Observational and Genetic Associations of Resting Heart Rate With Aortic Valve Calcium.

PubMed

Whelton, Seamus P; Mauer, Andreas C; Pencina, Karol M; Massaro, Joseph M; D'Agostino, Ralph B; Fox, Caroline S; Hoffmann, Udo; Michos, Erin D; Peloso, Gina M; Dufresne, Line; Engert, James C; Kathiresan, Sekar; Budoff, Matthew; Post, Wendy S; Thanassoulis, George; O'Donnell, Christopher J

2018-05-15

It is unknown if lifelong exposure to increased hemodynamic stress from an elevated resting heart rate (HR) may contribute to aortic valve calcium (AVC). We performed multivariate regression analyses using data from 1,266 Framingham Heart Study (FHS) Offspring cohort participants and 6,764 Multi-Ethnic Study of Atherosclerosis (MESA) participants. We constructed a genetic risk score (GRS) for HR using summary-level data in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) AVC Consortium to investigate if there was evidence in favor of a causal relation. AVC was present in 39% of FHS Offspring cohort participants and in 13% of MESA cohort participants. In multivariate adjusted models, participants in the highest resting HR quartiles had significantly greater prevalence of AVC, with a prevalence ratio of 1.19 (95% confidence interval [CI] 0.99 to 1.44) for the FHS Offspring cohort and 1.32 (95% CI 1.12 to 1.63) for the MESA cohort, compared with those in the lowest quartile. There was a similar increase in the prevalence of AVC per standard deviation increase in resting HR in both FHS Offspring (prevalence ratio 1.08, 95% CI 1.01 to 1.15) and MESA (1.10, 95% CI 1.03 to 1.17). In contrast with these observational findings, a HR associated GRS was not significantly associated with AVC. Although our observational analysis indicates that a higher resting HR is associated with AVC, our genetic results do not support a causal relation. Unmeasured environmental and/or lifestyle factors associated with both increased resting HR and AVC that are not fully explained by covariates in our observational models may account for the association between resting HR and AVC. Copyright © 2018. Published by Elsevier Inc.

Longitudinal association between dairy consumption and changes of body weight and waist circumference: the Framingham Heart Study

USDA-ARS?s Scientific Manuscript database

Dairy foods are nutrient dense and may be protective against long-term weight gain. We aimed to examine the longitudinal association between dairy consumption and annualized changes in weight and waist circumference (WC) in adults. Members of the Framingham Heart Study Offspring Cohort who participa...

Longitudinal association of dairy consumption with the changes in blood pressure and the risk of incident hypertension: the Framingham Heart Study

USDA-ARS?s Scientific Manuscript database

We aimed to examine the longitudinal association of dairy consumption with the changes in blood pressure (BP) and the risk of incident hypertension (HTN) among adults. This study included 2636 Framingham Heart Study Offspring Cohort members who participated in the 5th through 8th examinations (1991-...

Lipoprotein(a) levels, apo(a) isoform size, and coronary heart disease risk in the Framingham Offspring Study

USDA-ARS?s Scientific Manuscript database

The aim of this study was to assess the independent contributions of plasma levels of lipoprotein(a) [Lp(a)], Lp(a) cholesterol, and of apo(a) isoform size to prospective coronary heart disease (CHD) risk. Plasma Lp(a) and Lp(a) cholesterol levels, and apo(a) isoform size were measured at examinati...

Influence of maternal obesity on the long-term health of offspring

PubMed Central

Godfrey, Keith M.; Reynolds, Rebecca M.; Prescott, Susan L.; Nyirenda, Moffat; Jaddoe, Vincent W.V.; Eriksson, Johan G.; Broekman, Birit F.P

2017-01-01

Alongside its immediate implications for pregnancy complications, increasing evidence implicates maternal obesity as a major determinant of health in the offspring during childhood and later adult life. Observational studies provide evidence for effects of maternal obesity on the offspring’s risks of obesity, coronary heart disease, stroke, type 2 diabetes and asthma. Maternal obesity may also lead to poorer cognitive performance in the offspring and an increased risk of neurodevelopmental disorders including cerebral palsy. Preliminary evidence suggests potential implications for immune and infectious disease related outcomes. Insights from experimental studies support causal effects of maternal obesity on offspring outcomes, mediated at least in part through changes in epigenetic processes including alternations in DNA methylation, and perhaps through alterations in the gut microbiome. Although the offspring of obese women who lose weight prior to pregnancy have a reduced risk of obesity, to date few controlled intervention studies have reversed maternal obesity and examined the consequences for the offspring. The long term effects of maternal obesity may have profound public health implications and indicate the urgency of studies on causality, underlying mechanisms and effective interventions to reverse the epidemic of obesity in women of child-bearing age and to mitigate its consequences for the offspring. PMID:27743978

Maternal and infant genetic variants, maternal periconceptional use of selective serotonin reuptake inhibitors, and risk of congenital heart defects in offspring: population based study.

PubMed

Nembhard, Wendy N; Tang, Xinyu; Hu, Zhuopei; MacLeod, Stewart; Stowe, Zachary; Webber, Daniel

2017-03-06

Objective  To evaluate whether the association between maternal periconceptional use of selective serotonin reuptake inhibitors (SSRIs) and increased risk of congenital heart defects in offspring is modified by maternal or infant genetic variants in folate, homocysteine, or transsulfuration pathways. Design  Population based study. DNA from mothers, fathers, and infants was genotyped with an Illumina GoldenGate custom single nucleotide polymorphism panel. A hybrid design based on a log linear model was used to calculate relative risks and Bayesian false discovery probabilities (BFDP) to identify polymorphisms associated with congenital heart defects modified by SSRI use. Data sources  Data from the US National Birth Defects Prevention Study on 1180 liveborn infants with congenital heart defects and 1644 controls, born 1997-2008. Main outcome measures  Cases included infants with selected congenital heart defects and control infants had no major defects. SSRI use was obtained from telephone interviews with mothers. Results  For women who reported taking SSRIs periconceptionally, maternal SHMT1 (rs9909104) GG and AGgenotypes were associated with a 5.9 and 2.4 increased risk of select congenital heart defects in offspring, respectively, versus the AA genotype (BFDP=0.69). Compared with the AA genotype, BHMT (rs492842 and rs542852) GG and AG genotypes were associated with twice the riskof congenital heart defects (BFDP=0.74 and 0.79, respectively). MGST1 (rs2075237) CC and ACgenotypes were associated with an increased risk compared with the GG genotype (8.0 and 2.8, respectively; BFDP=0.79). Single nucleotide polymorphism in infant genes in the folate (MTHFS rs12438477), homocysteine (TRDMT1 rs6602178 and GNMT rs11752813) and transsulfuration (GSTP1 rs7941395 and MGST1 rs7294985) pathways were also associated with an increased risk of congenital heart defects. Conclusions  Common maternal or infant genetic variants in folate, homocysteine, or transsulfuration pathways are associated with an increased risk of certain congenital heart defects among children of women taking SSRIs during cardiogenesis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Sex-specific effects of nicotine exposure on developmental programming of blood pressure and vascular reactivity in the C57Bl/6J mouse.

PubMed

Fox, Karin A; Longo, Monica; Tamayo, Esther; Gamble, Phyllis; Makhlouf, Michel; Mateus, Julio F; Saade, George R

2012-09-01

The objective of the study was to determine whether perinatal nicotine exposure adversely affects cardiovascular health in adulthood. C57Bl/6J female mice were randomized to 200 μg/mL nicotine in 2% saccharin or 2% saccharin alone from 2 weeks before breeding until weaning. Offspring weight, vital signs, and carotid artery vascular reactivity were studied. A second cohort was subjected to shaker stress on day 4 of 7 days. Selected mediators of vascular tone were evaluated by molecular studies. Student t or Mann-Whitney U test was performed for statistical analysis (significance: P < .05). Nicotine-exposed compared with control female offspring had significantly elevated mean blood pressure under normal and stress conditions. Nicotine females lacked heart rate elevation after stress. Nicotine males had higher mean heart rate and a blunted contractile response to phenylephrine compared with controls, without an increase in blood pressure. Perinatal nicotine exposure has an impact on the developmental programming of future cardiovascular health, with adverse effects more evident in female offspring. Copyright © 2012 Mosby, Inc. All rights reserved.

Small dense low density lipoprotein cholesterol and coronary heart disease: results from the Framingham Offspring Study

USDA-ARS?s Scientific Manuscript database

We sought to establish reference values for a new direct assay for small dense LDL cholesterol (sdLDL-C) and to measure sdLDL-C concentrations in patients with established coronary heart disease (CHD) vs controls. Direct LDL-C and sdLDL-C were measured in samples from 3188 male and female participan...

Disturbed nitric oxide and homocysteine production are involved in the increased risk of cardiovascular diseases in the F1 offspring of maternal obesity and malnutrition.

PubMed

Moussa, Y Y; Tawfik, S H; Haiba, M M; Saad, M I; Hanafi, M Y; Abdelkhalek, T M; Oriquat, G A; Kamel, M A

2017-06-01

The present study aimed to evaluate the changes in levels of different independent risk factors for vascular diseases in the rat offspring of maternal obesity and malnutrition as maternal health disturbances are thought to have direct consequences on the offspring health. The effect of postnatal diet on the offspring was also assessed. Three groups of female Wistar rats were used (control, obese and malnourished). After the pregnancy and delivery, the offspring were weaned to control diet or high-caloric (HCD) diet and followed up for 30 weeks. Every 5 weeks postnatal, 20 pups (10 males and 10 females) of each subgroup were sacrificed after overnight fasting, the blood sample was obtained, and the rats were dissected out to obtain heart muscle. The following parameters were assessed; lipid profile, NEFA, homocysteine (Hcy), nitric oxide end product (NOx) and myocardial triglyceride content. Maternal obesity and malnutrition caused significant elevation in the body weight, triglycerides, NEFA, Hcy and NOx in the F1 offspring especially those maintained under HCD. Also, the male offspring showed more prominent changes than female offspring. Maternal malnutrition and obesity may increase the risk of the development of cardiovascular diseases in the offspring, especially the male ones.

In Utero Exposure to a Cardiac Teratogen Causes Reversible Deficits in Postnatal Cardiovascular Function, But Altered Adaptation to the Burden of Pregnancy.

PubMed

Aasa, Kristiina L; Maciver, Rebecca D; Ramchandani, Shyamlal; Adams, Michael A; Ozolinš, Terence R S

2015-11-01

Congenital heart defects (CHD) are the most common birth anomaly and while many resolve spontaneously by 1 year of age, the lifelong burden on survivors is poorly understood. Using a rat model of chemically induced CHD that resolve postnatally, we sought to characterize the postnatal changes in cardiac function, and to investigate whether resolved CHD affects the ability to adapt to the increased the cardiovascular (CV) burden of pregnancy. To generate rats with resolved CHD, pregnant rats were administered distilled water or dimethadione (DMO) [300 mg/kg b.i.d. on gestation day (gd) 9 and 10] and pups delivered naturally. To characterize structural and functional changes in the heart, treated and control offspring were scanned by echocardiography on postnatal day 4, 21, and 10-12 weeks. Radiotelemeters were implanted for continuous monitoring of hemodynamics. Females were mated and scanned by echocardiography on gd12 and gd18 during pregnancy. On gd18, maternal hearts were collected for structural and molecular assessment. Postnatal echocardiography revealed numerous structural and functional differences in treated offspring compared with control; however, these resolved by 10-12 weeks of age. The CV demand of pregnancy revealed differences between treated and control offspring with respect to mean arterial pressure, CV function, cardiac strain, and left ventricular gene expression. In utero exposure to DMO also affected the subsequent generation. Gd18 fetal and placental weights were increased in treated F2 offspring. This study demonstrates that in utero chemical exposure may permanently alter the capacity of the postnatal heart to adapt to pregnancy and this may have transgenerational effects. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A Review of the Impact of Maternal Obesity on the Cognitive Function and Mental Health of the Offspring.

PubMed

Contu, Laura; Hawkes, Cheryl A

2017-05-19

Globally, more than 20% of women of reproductive age are currently estimated to be obese. Children born to obese mothers are at higher risk of developing obesity, coronary heart disease, diabetes, stroke, and asthma in adulthood. Increasing clinical and experimental evidence suggests that maternal obesity also affects the health and function of the offspring brain across the lifespan. This review summarizes the current findings from human and animal studies that detail the impact of maternal obesity on aspects of learning, memory, motivation, affective disorders, attention-deficit hyperactivity disorder, autism spectrum disorders, and neurodegeneration in the offspring. Epigenetic mechanisms that may contribute to this mother-child interaction are also discussed.

Circadian rhythm of autonomic activity in non diabetic offsprings of type 2 diabetic patients

PubMed Central

Fiorentini, A; Perciaccante, A; Paris, A; Serra, P; Tubani, L

2005-01-01

The aim of the present study was to evaluate, by heart rate variability (HRV) with 24-hours ECG Holter (HRV), the circadian autonomic activity in offspring of type 2 diabetic subjects and the relation with insulin-resistance. METHODS: 50 Caucasian offsprings of type 2 diabetic subjects were divided in two groups: insulin-resistant offsprings (IR) and non insulin-resistant offsprings (NIR). Autonomic nervous activity was studied by HRV. Time domain and spectral analysis (low frequency, LF, and high frequency, HF, provide markers of sympathetic and parasympathetic modulation when assessed in normalized units) were evaluated. RESULTS. Time domain showed a reduction of total SDNN in IR (p < 0.001) and NIR (p 0.047) versus controls. Spectral analysis showed a total and night LF higher in IR and NIR than in control group (all p < 0.001). CONCLUSION. In frequency domain, the analysis of sympathetic (LF) and parasympathetic (HF) component evidenced an association between the offspring of type 2 diabetic subjects and a sympathetic overactivity. A global reduction and alteration of circadian rhythm of autonomic activity are present in offspring of type 2 diabetic patients with and without insulin resistance. The data of our study suggested that an autonomic impairment is associated with the familiarity for type 2 diabetes independently to insulin resistance and that an impairment of autonomic system activity could precede the insulin resistance. PMID:16197556

A genetic risk score based on direct associations with coronary heart disease improves coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC), but not in the Rotterdam and Framingham Offspring, Studies

PubMed Central

Brautbar, Ariel; Pompeii, Lisa A.; Dehghan, Abbas; Ngwa, Julius S.; Nambi, Vijay; Virani, Salim S.; Rivadeneira, Fernando; Uitterlinden, André G.; Hofman, Albert; Witteman, Jacqueline C.M.; Pencina, Michael J.; Folsom, Aaron R.; Cupples, L. Adrienne; Ballantyne, Christie M.; Boerwinkle, Eric

2013-01-01

Objective Multiple studies have identified single-nucleotide polymorphisms (SNPs) that are associated with coronary heart disease (CHD). We examined whether SNPs selected based on predefined criteria will improve CHD risk prediction when added to traditional risk factors (TRFs). Methods SNPs were selected from the literature based on association with CHD, lack of association with a known CHD risk factor, and successful replication. A genetic risk score (GRS) was constructed based on these SNPs. Cox proportional hazards model was used to calculate CHD risk based on the Atherosclerosis Risk in Communities (ARIC) and Framingham CHD risk scores with and without the GRS. Results The GRS was associated with risk for CHD (hazard ratio [HR] = 1.10; 95% confidence interval [CI]: 1.07–1.13). Addition of the GRS to the ARIC risk score significantly improved discrimination, reclassification, and calibration beyond that afforded by TRFs alone in non-Hispanic whites in the ARIC study. The area under the receiver operating characteristic curve (AUC) increased from 0.742 to 0.749 (Δ= 0.007; 95% CI, 0.004–0.013), and the net reclassification index (NRI) was 6.3%. Although the risk estimates for CHD in the Framingham Offspring (HR = 1.12; 95% CI: 1.10–1.14) and Rotterdam (HR = 1.08; 95% CI: 1.02–1.14) Studies were significantly improved by adding the GRS to TRFs, improvements in AUC and NRI were modest. Conclusion Addition of a GRS based on direct associations with CHD to TRFs significantly improved discrimination and reclassification in white participants of the ARIC Study, with no significant improvement in the Rotterdam and Framingham Offspring Studies. PMID:22789513

Prenatal exposure to dexamethasone in the mouse alters cardiac growth patterns and increases pulse pressure in aged male offspring.

PubMed

O'Sullivan, Lee; Cuffe, James S M; Paravicini, Tamara M; Campbell, Sally; Dickinson, Hayley; Singh, Reetu R; Gezmish, Oksan; Black, M Jane; Moritz, Karen M

2013-01-01

Exposure to synthetic glucocorticoids during development can result in later cardiovascular and renal disease in sheep and rats. Although prenatal glucocorticoid exposure is associated with impaired renal development, less is known about effects on the developing heart. This study aimed to examine the effects of a short-term exposure to dexamethasone (60 hours from embryonic day 12.5) on the developing mouse heart, and cardiovascular function in adult male offspring. Dexamethasone (DEX) exposed fetuses were growth restricted compared to saline treated controls (SAL) at E14.5, but there was no difference between groups at E17.5. Heart weights of the DEX fetuses also tended to be smaller at E14.5, but not different at E17.5. Cardiac AT1aR, Bax, and IGF-1 mRNA expression was significantly increased by DEX compared to SAL at E17.5. In 12-month-old offspring DEX exposure caused an increase in basal blood pressure of ~3 mmHg. In addition, DEX exposed mice had a widened pulse pressure compared to SAL. DEX exposed males at 12 months had an approximate 25% reduction in nephron number compared to SAL, but no difference in cardiomyocyte number. Exposure to DEX in utero appears to adversely impact on nephrogenesis and heart growth but is not associated with a cardiomyocyte deficit in male mice in adulthood, possibly due to compensatory growth of the myocardium following the initial insult. However, the widened pulse pressure may be indicative of altered vascular compliance.

Maternal residential proximity to chlorinated solvent emissions and birth defects in offspring: a case-control study.

PubMed

Brender, Jean D; Shinde, Mayura U; Zhan, F Benjamin; Gong, Xi; Langlois, Peter H

2014-11-19

Some studies have noted an association between maternal occupational exposures to chlorinated solvents and birth defects in offspring, but data are lacking on the potential impact of industrial air emissions of these solvents on birth defects. With data from the Texas Birth Defects Registry for births occurring in 1996-2008, we examined the relation between maternal residential proximity to industrial air releases of chlorinated solvents and birth defects in offspring of 60,613 case-mothers and 244,927 control-mothers. Maternal residential exposures to solvent emissions were estimated with metrics that took into account residential distances to industrial sources and annual amounts of chemicals released. Logistic regression was used to generate odds ratios and 95% confidence intervals for the associations between residential proximity to emissions of 14 chlorinated solvents and selected birth defects, including neural tube, oral cleft, limb deficiency, and congenital heart defects. All risk estimates were adjusted for year of delivery and maternal age, education, race/ethnicity, and public health region of residence. Relative to exposure risk values of 0, neural tube defects were associated with maternal residential exposures (exposure risk values >0) to several types of chlorinated solvents, most notably carbon tetrachloride (adjusted odds ratio [aOR] 1.42, 95% confidence interval [CI] 1.09, 1.86); chloroform (aOR 1.40, 95% CI 1.04, 1.87); ethyl chloride (aOR 1.39, 95% CI 1.08, 1.79); 1,1,2-trichloroethane (aOR 1.56, 95% CI 1.11, 2.18); and 1,2,3-trichloropropane (aOR 1.49, 95% CI 1.08, 2.06). Significant associations were also noted between a few chlorinated solvents and oral cleft, limb deficiency, and congenital heart defects. We observed stronger associations between some emissions and neural tube, oral cleft, and heart defects in offspring of mothers 35 years or older, such as spina bifida with carbon tetrachloride (aOR 2.49, 95% CI 1.09, 5.72), cleft palate with 1,2-dichloroethane (aOR 1.93, 95% 1.05, 3.54), cleft lip with or without cleft palate with ethyl chloride (aOR 1.81, 95% CI 1.06, 3.07), and obstructive heart defects with trichloroethylene (aOR 1.43, 95% CI 1.08, 1.88). These findings suggest that maternal residential proximity to industrial emissions of chlorinated solvents might be associated with selected birth defects in offspring, especially among older mothers.

Risk of major congenital malformations in relation to maternal overweight and obesity severity: cohort study of 1.2 million singletons

PubMed Central

Cnattingius, Sven; Villamor, Eduardo; Söderling, Jonas; Pasternak, Björn; Stephansson, Olof; Neovius, Martin

2017-01-01

Objective To estimate the risks of major congenital malformations in the offspring of mothers who are underweight (body mass index (BMI) <18.5), overweight (BMI 25 to <30), or in obesity classes I (BMI 30 to <35), II (35 to <40), or III (≥40) compared with offspring of normal weight mothers (BMI 18.5 to <25) in early pregnancy. Design Population based cohort study. Setting Nationwide Swedish registries. Participants 1 243 957 liveborn singleton infants from 2001 to 2014 in Sweden. Data on maternal and pregnancy characteristics were obtained by individual record linkages. Exposure Maternal BMI at the first prenatal visit. Main outcome measures Offspring with any major congenital malformation, and subgroups of organ specific malformations diagnosed during the first year of life. Risk ratios were estimated using generalised linear models adjusted for maternal factors, sex of offspring, and birth year. Results A total of 43 550 (3.5%) offspring had any major congenital malformation, and the most common subgroup was for congenital heart defects (n=20 074; 1.6%). Compared with offspring of normal weight mothers (risk of malformations 3.4%), the proportions and adjusted risk ratios of any major congenital malformation among the offspring of mothers with higher BMI were: overweight, 3.5% and 1.05 (95% confidence interval 1.02 to 1.07); obesity class I, 3.8% and 1.12 (1.08 to 1.15), obesity class II, 4.2% and 1.23 (1.17 to 1.30), and obesity class III, 4.7% and 1.37 (1.26 to 1.49). The risks of congenital heart defects, malformations of the nervous system, and limb defects also progressively increased with BMI from overweight to obesity class III. The largest organ specific relative risks related to maternal overweight and increasing obesity were observed for malformations of the nervous system. Malformations of the genital and digestive systems were also increased in offspring of obese mothers. Conclusions Risks of any major congenital malformation and several subgroups of organ specific malformations progressively increased with maternal overweight and increasing severity of obesity. For women who are planning pregnancy, efforts should be encouraged to reduce adiposity in those with a BMI above the normal range. PMID:28615173

Association of parental obesity with concentrations of select systemic biomarkers in nonobese offspring: the Framingham Heart Study.

PubMed

Lieb, Wolfgang; Pencina, Michael J; Lanier, Katherine J; Tofler, Geoffrey H; Levy, Daniel; Fox, Caroline S; Wang, Thomas J; D'Agostino, Ralph B; Vasan, Ramachandran S

2009-01-01

Parental obesity is a risk factor for offspring obesity. It is unclear whether parental obesity also confers risk for obesity-associated conditions (e.g., a proinflammatory or prothrombotic state) in the absence of offspring obesity. We compared concentrations of multiple biomarkers representing distinct biological pathways (C-reactive protein [CRP], aldosterone, renin, B-type natriuretic peptide, NH(2)-terminal proatrial natriuretic peptide, fibrinogen, and plasminogen activator inhibitor-1) in nonobese Framingham Offspring Study participants with no parents (n = 665), one parent (n = 488), or two parents (n = 119) with obesity (BMI > or =30 kg/m(2)). Nonobese offspring with both parents with obesity had higher CRP levels (median 2.16 mg/l) than offspring with one parent (1.58 mg/l) or no parents (1.35 mg/l) with obesity. After multivariable adjustment, a nonlinear relationship with parental obesity became evident: compared with those without parental obesity, CRP levels were higher in offspring with two obese parents (P = 0.04) but not in offspring with only one obese parent (P = 0.76). Renin levels were more linearly related to parental obesity status, being significantly higher in offspring with one parent (P = 0.04) or two parents (P = 0.09) with obesity (P = 0.02 for trend). The other systemic biomarkers did not vary according to parental obesity status (all P > 0.05). Our findings suggest that offspring with a high risk of developing obesity have an altered biomarker profile, characterized by systemic inflammation and increased neurohormonal activity, even in the absence of obesity. This is consistent with the notion that parental obesity may confer an increased susceptibility to other adiposity-associated traits.

Adiposity, Dysmetabolic Traits, and Earlier Onset of Female Puberty in Adolescent Offspring of Women With Gestational Diabetes Mellitus: A Clinical Study Within the Danish National Birth Cohort.

PubMed

Grunnet, Louise G; Hansen, Susanne; Hjort, Line; Madsen, Camilla M; Kampmann, Freja B; Thuesen, Anne Cathrine B; Granstrømi, Charlotta; Strøm, Marin; Maslova, Ekaterina; Frikke-Schmidt, Ruth; Damm, Peter; Chavarro, Jorge E; Hu, Frank B; Olsen, Sjurdur F; Vaag, Allan

2017-12-01

Offspring of pregnancies affected by gestational diabetes mellitus (GDM) are at increased risk of the development of type 2 diabetes. However, the extent to which these dysmetabolic traits may be due to offspring and/or maternal adiposity is unknown. We examined body composition and associated cardiometabolic traits in 561 9- to 16-year-old offspring of mothers with GDM and 597 control offspring. We measured anthropometric characteristics; puberty status; blood pressure; and fasting glucose, insulin, C-peptide, and lipid levels; and conducted a DEXA scan in a subset of the cohort. Differences in the outcomes between offspring of mothers with GDM and control subjects were examined using linear and logistic regression models. After adjustment for age and sex, offspring of mothers with GDM displayed higher weight, BMI, waist-to-hip ratio (WHR), systolic blood pressure, and resting heart rate and lower height. Offspring of mothers with GDM had higher total and abdominal fat percentages and lower muscle mass percentages, but these differences disappeared after correction for offspring BMI. The offspring of mothers with GDM displayed higher fasting plasma glucose, insulin, C-peptide, HOMA-insulin resistance (IR), and plasma triglyceride levels, whereas fasting plasma HDL cholesterol levels were decreased. Female offspring of mothers with GDM had an earlier onset of puberty than control offspring. Offspring of mothers with GDM had significantly higher BMI, WHR, fasting glucose, and HOMA-IR levels after adjustment for maternal prepregnancy BMI, and glucose and HOMA-IR remained elevated in the offspring of mothers with GDM after correction for both maternal and offspring BMIs. In summary, adolescent offspring of women with GDM show increased adiposity, an adverse cardiometabolic profile, and earlier onset of puberty among girls. Increased fasting glucose and HOMA-IR levels among the offspring of mothers with GDM may be explained by the programming effects of hyperglycemia in pregnancy. © 2017 by the American Diabetes Association.

A genome-wide search for genes affecting circulating fibrinogen levels in the Framingham Heart Study.

PubMed

Yang, Qiong; Tofler, Geoffrey H; Cupples, L Adrienne; Larson, Martin G; Feng, DaLi; Lindpaintner, Klaus; Levy, Daniel; D'Agostino, Ralph B; O'Donnell, Christopher J

2003-04-15

Circulating levels of fibrinogen are associated with atherosclerosis and predict future coronary heart disease and stroke. Levels of fibrinogen are correlated among family members, suggesting a heritable component. Variants of the beta-fibrinogen gene subunit on 4q28 are associated with fibrinogen levels but explain only a small proportion of the total genetic variability. It remains unknown what role, if any, is played by other genetic variants in the inter-individual variability in levels of fibrinogen in the general population. We conducted a 10-cM spaced genome-wide scan using 402 original cohort subjects and 1193 offspring subjects from 330 extended families of the Framingham Heart Study. Heritability and linkage analyses were carried out using variance component methods. Regression analyses were performed to adjust for traditional risk factors and HindIII beta-148 genotypes. The total heritability was estimated as 0.24. The highest and second highest LOD scores of linkage were found on chromosomes 2 (LOD=1.5 at 243 cM) and 10 (LOD=2.4 at 87 cM) using only offspring subjects in the analysis, and on chromosomes 2 (LOD=2.1 at 242 cM) and 10(LOD=1.4 at 86 cM), 17 (LOD=1.4 at 96 cM) and 20 (LOD=1.4 at 80 cM) using both original cohort and offspring. These results suggest that there may be influential genetic regions on these chromosomes. While no linkage with genome-wide significance was detected, further research to confirm our findings is warranted.

Cardiac remodelling in a baboon model of intrauterine growth restriction mimics accelerated ageing.

PubMed

Kuo, Anderson H; Li, Cun; Li, Jinqi; Huber, Hillary F; Nathanielsz, Peter W; Clarke, Geoffrey D

2017-02-15

Rodent models of intrauterine growth restriction (IUGR) successfully identify mechanisms that can lead to short-term and long-term detrimental cardiomyopathies but differences between rodent and human cardiac physiology and placental-fetal development indicate a need for models in precocial species for translation to human development. We developed a baboon model for IUGR studies using a moderate 30% global calorie restriction of pregnant mothers and used cardiac magnetic resonance imaging to evaluate offspring heart function in early adulthood. Impaired diastolic and systolic cardiac function was observed in IUGR offspring with differences between male and female subjects, compared to their respective controls. Aspects of cardiac impairment found in the IUGR offspring were similar to those found in normal controls in a geriatric cohort. Understanding early cardiac biomarkers of IUGR using non-invasive imaging in this susceptible population, especially taking into account sexual dimorphisms, will aid recognition of the clinical presentation, development of biomarkers suitable for use in humans and management of treatment strategies. Extensive rodent studies have shown that reduced perinatal nutrition programmes chronic cardiovascular disease. To enable translation to humans, we developed baboon offspring cohorts from mothers fed ad libitum (control) or 70% of the control ad libitum diet in pregnancy and lactation, which were growth restricted at birth. We hypothesized that intrauterine growth restriction (IUGR) offspring hearts would show impaired function and a premature ageing phenotype. We studied IUGR baboons (8 male, 8 female, 5.7 years), control offspring (8 male, 8 female, 5.6 years - human equivalent approximately 25 years), and normal elderly (OLD) baboons (6 male, 6 female, mean 15.9 years). Left ventricular (LV) morphology and systolic and diastolic function were evaluated with cardiac MRI and normalized to body surface area. Two-way ANOVA by group and sex (with P < 0.05) indicated ejection fraction, 3D sphericity indices, cardiac index, normalized systolic volume, normalized LV wall thickness, and average filling rate differed by group. Group and sex differences were found for normalized LV wall thickening and normalized myocardial mass, without interactions. Normalized peak LV filling rate and diastolic sphericity index were not correlated in control but strongly correlated in OLD and IUGR baboons. IUGR programming in baboons produces myocardial remodelling, reduces systolic and diastolic function, and results in the emergence of a premature ageing phenotype in the heart. To our knowledge, this is the first demonstration of the specific characteristics of cardiac programming and early life functional decline with ageing in an IUGR non-human primate model. Further studies across the life span will determine progression of cardiac dysfunction. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

The Quantitative-MFG Test: A Linear Mixed Effect Model to Detect Maternal-Offspring Gene Interactions.

PubMed

Clark, Michelle M; Blangero, John; Dyer, Thomas D; Sobel, Eric M; Sinsheimer, Janet S

2016-01-01

Maternal-offspring gene interactions, aka maternal-fetal genotype (MFG) incompatibilities, are neglected in complex diseases and quantitative trait studies. They are implicated in birth to adult onset diseases but there are limited ways to investigate their influence on quantitative traits. We present the quantitative-MFG (QMFG) test, a linear mixed model where maternal and offspring genotypes are fixed effects and residual correlations between family members are random effects. The QMFG handles families of any size, common or general scenarios of MFG incompatibility, and additional covariates. We develop likelihood ratio tests (LRTs) and rapid score tests and show they provide correct inference. In addition, the LRT's alternative model provides unbiased parameter estimates. We show that testing the association of SNPs by fitting a standard model, which only considers the offspring genotypes, has very low power or can lead to incorrect conclusions. We also show that offspring genetic effects are missed if the MFG modeling assumptions are too restrictive. With genome-wide association study data from the San Antonio Family Heart Study, we demonstrate that the QMFG score test is an effective and rapid screening tool. The QMFG test therefore has important potential to identify pathways of complex diseases for which the genetic etiology remains to be discovered. © 2015 John Wiley & Sons Ltd/University College London.

A novel healthy blood pressure phenotype in the Long Life Family Study.

PubMed

Marron, Megan M; Singh, Jatinder; Boudreau, Robert M; Christensen, Kaare; Cosentino, Stephanie; Feitosa, Mary F; Minster, Ryan L; Perls, Thomas; Schupf, Nicole; Sebastiani, Paola; Ukraintseva, Svetlana; Wojczynski, Mary K; Newman, Anne B

2018-01-01

Hypertension tends to run in families and has both genetic and environmental determinants. We assessed the hypothesis that a novel healthy blood pressure (BP) phenotype is also familial and sought to identify its associated factors. We developed a healthy BP phenotype in the Long Life Family Study, a cohort of two-generation families selected for longevity. Participants from the offspring generation (n = 2211, ages 32-88) were classified as having healthy BP if their age-adjusted and sex-adjusted SBP z-score was between -1.5 and -0.5. Offspring on antihypertensive medications were classified as not having healthy BP. Families with at least two offspring (n = 419 families) were defined as meeting the healthy BP phenotype if at least two and at least 50% of their offspring had healthy BP. Among 2211 offspring, 476 (21.5%) met the healthy BP phenotype. When examining the 419 families, only 44 (10.5%) families met the criteria for the healthy BP phenotype. Both offspring and probands from families with healthy BP performed better on neuropsychological tests that place demands on complex attention and executive function when compared with offspring and probands from remaining families. Among families with the healthy BP phenotype compared with families without, a higher proportion of offspring met the American Heart Association definition of ideal cardiovascular health (10.8 versus 3.8%, respectively; driven by BP, smoking status, and BMI components). In this cohort of familial longevity, few families had a novel healthy BP phenotype in multiple members. Families with this healthy BP phenotype may represent a specific pathway to familial longevity.

Maternal exposure to cadmium during gestation perturbs the vascular system of the adult rat offspring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ronco, Ana Maria, E-mail: amronco@inta.cl; Montenegro, Marcela; Castillo, Paula

2011-03-01

Several cardiovascular diseases (CVD) observed in adulthood have been associated with environmental influences during fetal growth. Here, we show that maternal exposure to cadmium, a ubiquitously distributed heavy metal and main component of cigarette smoke is able to induce cardiovascular morpho-functional changes in the offspring at adult age. Heart morphology and vascular reactivity were evaluated in the adult offspring of rats exposed to 30 ppm of cadmium during pregnancy. Echocardiographic examination shows altered heart morphology characterized by a concentric left ventricular hypertrophy. Also, we observed a reduced endothelium-dependent reactivity in isolated aortic rings of adult offspring, while endothelium-independent reactivity remainedmore » unaltered. These effects were associated with an increase of hem-oxygenase 1 (HO-1) expression in the aortas of adult offspring. The expression of HO-1 was higher in females than males, a finding likely related to the sex-dependent expression of the vascular cell adhesion molecule 1 (VCAM-1), which was lower in the adult female. All these long-term consequences were observed along with normal birth weights and absence of detectable levels of cadmium in fetal and adult tissues of the offspring. In placental tissues however, cadmium levels were detected and correlated with increased NF-{kappa}B expression - a transcription factor sensitive to inflammation and oxidative stress - suggesting a placentary mechanism that affect genes related to the development of the cardiovascular system. Our results provide, for the first time, direct experimental evidence supporting that exposure to cadmium during pregnancy reprograms cardiovascular development of the offspring which in turn may conduce to a long term increased risk of CVD.« less

Alterations in cholesterol absorption and synthesis characterize Framingham offspring study participants with coronary heart disease

USDA-ARS?s Scientific Manuscript database

Data is limited on measures influencing cholesterol homeostasis in subjects at high risk of developing cardiovascular disease (CVD) relative to established risk factors. To address this, we quantified circulating indicators of cholesterol homeostasis (plasma phytosterols and cholesterol precursor co...

Parental intermittent claudication as risk factor for claudication in adults.

PubMed

Prushik, Scott G; Farber, Alik; Gona, Philimon; Shrader, Peter; Pencina, Michael J; D'Agostino, Ralph B; Murabito, Joanne M

2012-03-01

Little is known about the familial aggregation of intermittent claudication (IC). Our objective was to examine whether parental IC increased the risk of IC in adult offspring, independent of the established cardiovascular risk factors. We evaluated the Offspring Cohort Participants of the Framingham Heart Study who were ≥30 years old, cardiovascular disease free, and had both parents enrolled in the Framingham Heart Study (n = 2,970 unique participants, 53% women). Pooled proportional hazards regression analysis was used to examine whether the 12-year risk of incident IC in offspring participants was associated with parental IC, adjusting for age, gender, diabetes, smoking, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, and antihypertensive and lipid treatment. Of the 909 person-examinations in the parental IC history group and 5,397 person-examinations in the no-parental IC history group, there were 101 incident IC events (29 with parental IC history and 72 without a parental IC history) during follow-up. The age- and gender-adjusted 12-year cumulative incidence rate per 1,000 person-years was 5.08 (95% confidence interval [CI] 2.74 to 7.33) and 2.34 (95% CI 1.46 to 3.19) in participants with and without a parental IC history. A parental history of IC significantly increased the risk of incident IC in the offspring (multivariable adjusted hazard ratio 1.81, 95% CI 1.14 to 2.88). The hazard ratio was unchanged, with an adjustment for the occurrence of cardiovascular disease (hazard ratio 1.83, 95% CI 1.15 to 2.91). In conclusion, IC in parents increases the risk of IC in adult offspring, independent of the established risk factors. These data suggest a genetic component of peripheral artery disease and support future research into genetic causes. Copyright © 2012 Elsevier Inc. All rights reserved.

A genetic risk score based on direct associations with coronary heart disease improves coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC), but not in the Rotterdam and Framingham Offspring, Studies.

PubMed

Brautbar, Ariel; Pompeii, Lisa A; Dehghan, Abbas; Ngwa, Julius S; Nambi, Vijay; Virani, Salim S; Rivadeneira, Fernando; Uitterlinden, André G; Hofman, Albert; Witteman, Jacqueline C M; Pencina, Michael J; Folsom, Aaron R; Cupples, L Adrienne; Ballantyne, Christie M; Boerwinkle, Eric

2012-08-01

Multiple studies have identified single-nucleotide polymorphisms (SNPs) that are associated with coronary heart disease (CHD). We examined whether SNPs selected based on predefined criteria will improve CHD risk prediction when added to traditional risk factors (TRFs). SNPs were selected from the literature based on association with CHD, lack of association with a known CHD risk factor, and successful replication. A genetic risk score (GRS) was constructed based on these SNPs. Cox proportional hazards model was used to calculate CHD risk based on the Atherosclerosis Risk in Communities (ARIC) and Framingham CHD risk scores with and without the GRS. The GRS was associated with risk for CHD (hazard ratio [HR] = 1.10; 95% confidence interval [CI]: 1.07-1.13). Addition of the GRS to the ARIC risk score significantly improved discrimination, reclassification, and calibration beyond that afforded by TRFs alone in non-Hispanic whites in the ARIC study. The area under the receiver operating characteristic curve (AUC) increased from 0.742 to 0.749 (Δ = 0.007; 95% CI, 0.004-0.013), and the net reclassification index (NRI) was 6.3%. Although the risk estimates for CHD in the Framingham Offspring (HR = 1.12; 95% CI: 1.10-1.14) and Rotterdam (HR = 1.08; 95% CI: 1.02-1.14) Studies were significantly improved by adding the GRS to TRFs, improvements in AUC and NRI were modest. Addition of a GRS based on direct associations with CHD to TRFs significantly improved discrimination and reclassification in white participants of the ARIC Study, with no significant improvement in the Rotterdam and Framingham Offspring Studies. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Improving cardiometabolic and mental health in women with gestational diabetes mellitus and their offspring: study protocol for MySweetHeart Trial, a randomised controlled trial

PubMed Central

Horsch, Antje; Gilbert, Leah; Lanzi, Stefano; Gross, Justine; Kayser, Bengt; Vial, Yvan; Simeoni, Umberto; Hans, Didier; Berney, Alexandre; Scholz, Urte; Barakat, Ruben; Puder, Jardena J

2018-01-01

Introduction Gestational diabetes mellitus (GDM) carries prenatal and perinatal risk for the mother and her offspring as well as longer-term risks for both the mother (obesity, diabetes, cardiovascular disease) and her child (obesity, type 2 diabetes). Compared with women without GDM, women with GDM are twice as likely to develop perinatal or postpartum depression. Lifestyle interventions for GDM are generally limited to physical activity and/or nutrition, often focus separately on the mother or the child and take place either during or after pregnancy, while their results are inconsistent. To increase efficacy of intervention, the multifactorial origins of GDM and the tight link between mental and metabolic as well as maternal and child health need to be heeded. This calls for an interdisciplinary transgenerational approach starting in, but continuing beyond pregnancy. Methods and analysis This randomised controlled trial will assess the effect of a multidimensional interdisciplinary lifestyle and psychosocial intervention aimed at improving the metabolic and mental health of 200 women with GDM and their offspring. Women with GDM at 24–32 weeks gestational age who understand French or English, and their offspring and partners can participate. The intervention components will be delivered on top of usual care during pregnancy and the first year postpartum. Metabolic and mental health outcomes will be measured at 24–32 weeks of pregnancy, shortly after birth and at 6–8 weeks and 1 year after childbirth. Data will be analysed using intention-to-treat analyses. The MySweetHeart Trial is linked to the MySweetHeart Cohort (clinicaltrials.gov/ct2/show/NCT02872974). Ethics and dissemination We will disseminate the findings through regional, national and international conferences and through peer-reviewed journals. Trial registration number NCT02890693; Pre-results. PMID:29487077

Improving cardiometabolic and mental health in women with gestational diabetes mellitus and their offspring: study protocol for MySweetHeart Trial, a randomised controlled trial.

PubMed

Horsch, Antje; Gilbert, Leah; Lanzi, Stefano; Gross, Justine; Kayser, Bengt; Vial, Yvan; Simeoni, Umberto; Hans, Didier; Berney, Alexandre; Scholz, Urte; Barakat, Ruben; Puder, Jardena J

2018-02-27

Gestational diabetes mellitus (GDM) carries prenatal and perinatal risk for the mother and her offspring as well as longer-term risks for both the mother (obesity, diabetes, cardiovascular disease) and her child (obesity, type 2 diabetes). Compared with women without GDM, women with GDM are twice as likely to develop perinatal or postpartum depression. Lifestyle interventions for GDM are generally limited to physical activity and/or nutrition, often focus separately on the mother or the child and take place either during or after pregnancy, while their results are inconsistent. To increase efficacy of intervention, the multifactorial origins of GDM and the tight link between mental and metabolic as well as maternal and child health need to be heeded. This calls for an interdisciplinary transgenerational approach starting in, but continuing beyond pregnancy. This randomised controlled trial will assess the effect of a multidimensional interdisciplinary lifestyle and psychosocial intervention aimed at improving the metabolic and mental health of 200 women with GDM and their offspring. Women with GDM at 24-32 weeks gestational age who understand French or English, and their offspring and partners can participate. The intervention components will be delivered on top of usual care during pregnancy and the first year postpartum. Metabolic and mental health outcomes will be measured at 24-32 weeks of pregnancy, shortly after birth and at 6-8 weeks and 1 year after childbirth. Data will be analysed using intention-to-treat analyses. The MySweetHeart Trial is linked to the MySweetHeart Cohort (clinicaltrials.gov/ct2/show/NCT02872974). We will disseminate the findings through regional, national and international conferences and through peer-reviewed journals. NCT02890693; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Increased risk of death with congenital anomalies in the offspring of male semiconductor workers.

PubMed

Lin, Ching-Chun; Wang, Jung-Der; Hsieh, Gong-Yih; Chang, Yu-Yin; Chen, Pau-Chung

2008-01-01

Female workers in the semiconductor industry have higher risks of subfertility and spontaneous abortion, but no studies exploring male-mediated developmental toxicity have been published. This study aimed to investigate whether the offspring of male workers employed in the semiconductor manufacturing industry had an increased risk of death with congenital anomalies. The 6,834 male workers had been employed in the eight semiconductor companies in Taiwan between 1980 and 1994. We identified the live born children with or without congenital anomalies of the workers using the National Birth and Death Registries from the Department of Health, Taiwan. Multiple logistic regression models were used to estimate the odds ratios (OR) of birth outcomes and deaths, controlling for infant sex, maternal age, and paternal education. A total of 5,702 children were born to male workers during the period 1980-1994. There were increased risks of deaths with congenital anomalies (adjusted OR, 3.26; and 95% confidence interval [CI], 1.12-9.44) and heart anomalies (OR, 4.15; 95% CI, 1.08-15.95) in the offspring of male workers who were employed during the two months before conception. We found evidence of a possible link between paternal preconception exposure of semiconductor manufacturing and an increased risk of congenital anomalies, especially of the heart. The possible etiological basis needs to be corroborated in further research.

Risk of major congenital malformations in relation to maternal overweight and obesity severity: cohort study of 1.2 million singletons.

PubMed

Persson, Martina; Cnattingius, Sven; Villamor, Eduardo; Söderling, Jonas; Pasternak, Björn; Stephansson, Olof; Neovius, Martin

2017-06-14

Objective  To estimate the risks of major congenital malformations in the offspring of mothers who are underweight (body mass index (BMI) <18.5), overweight (BMI 25 to <30), or in obesity classes I (BMI 30 to <35), II (35 to <40), or III (≥40) compared with offspring of normal weight mothers (BMI 18.5 to <25) in early pregnancy. Design  Population based cohort study. Setting  Nationwide Swedish registries. Participants  1 243 957 liveborn singleton infants from 2001 to 2014 in Sweden. Data on maternal and pregnancy characteristics were obtained by individual record linkages. Exposure  Maternal BMI at the first prenatal visit. Main outcome measures  Offspring with any major congenital malformation, and subgroups of organ specific malformations diagnosed during the first year of life. Risk ratios were estimated using generalised linear models adjusted for maternal factors, sex of offspring, and birth year. Results  A total of 43 550 (3.5%) offspring had any major congenital malformation, and the most common subgroup was for congenital heart defects (n=20 074; 1.6%). Compared with offspring of normal weight mothers (risk of malformations 3.4%), the proportions and adjusted risk ratios of any major congenital malformation among the offspring of mothers with higher BMI were: overweight, 3.5% and 1.05 (95% confidence interval 1.02 to 1.07); obesity class I, 3.8% and 1.12 (1.08 to 1.15), obesity class II, 4.2% and 1.23 (1.17 to 1.30), and obesity class III, 4.7% and 1.37 (1.26 to 1.49). The risks of congenital heart defects, malformations of the nervous system, and limb defects also progressively increased with BMI from overweight to obesity class III. The largest organ specific relative risks related to maternal overweight and increasing obesity were observed for malformations of the nervous system. Malformations of the genital and digestive systems were also increased in offspring of obese mothers. Conclusions  Risks of any major congenital malformation and several subgroups of organ specific malformations progressively increased with maternal overweight and increasing severity of obesity. For women who are planning pregnancy, efforts should be encouraged to reduce adiposity in those with a BMI above the normal range. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Maternal exposure to an environmentally relevant dose of triclocarban results in perinatal exposure and potential alterations in offspring development in the mouse model.

PubMed

Enright, Heather A; Falso, Miranda J S; Malfatti, Michael A; Lao, Victoria; Kuhn, Edward A; Hum, Nicholas; Shi, Yilan; Sales, Ana Paula; Haack, Kurt W; Kulp, Kristen S; Buchholz, Bruce A; Loots, Gabriela G; Bench, Graham; Turteltaub, Kenneth W

2017-01-01

Triclocarban (TCC) is among the top 10 most commonly detected wastewater contaminants in both concentration and frequency. Its presence in water, as well as its propensity to bioaccumulate, has raised numerous questions about potential endocrine and developmental effects. Here, we investigated whether exposure to an environmentally relevant concentration of TCC could result in transfer from mother to offspring in CD-1 mice during gestation and lactation using accelerator mass spectrometry (AMS). 14C-TCC (100 nM) was administered to dams through drinking water up to gestation day 18, or from birth to post-natal day 10. AMS was used to quantify 14C-concentrations in offspring and dams after exposure. We demonstrated that TCC does effectively transfer from mother to offspring, both trans-placentally and via lactation. TCC-related compounds were detected in the tissues of offspring with significantly higher concentrations in the brain, heart and fat. In addition to transfer from mother to offspring, exposed offspring were heavier in weight than unexposed controls demonstrating an 11% and 8.5% increase in body weight for females and males, respectively. Quantitative real-time polymerase chain reaction (qPCR) was used to examine changes in gene expression in liver and adipose tissue in exposed offspring. qPCR suggested alterations in genes involved in lipid metabolism in exposed female offspring, which was consistent with the observed increased fat pad weights and hepatic triglycerides. This study represents the first report to quantify the transfer of an environmentally relevant concentration of TCC from mother to offspring in the mouse model and evaluate bio-distribution after exposure using AMS. Our findings suggest that early-life exposure to TCC may interfere with lipid metabolism and could have implications for human health.

Pregnant mothers with resolved anxiety disorders and their offspring have reduced heart rate variability: implications for the health of children.

PubMed

Braeken, Marijke A K A; Kemp, Andrew H; Outhred, Tim; Otte, Renée A; Monsieur, Geert J Y J; Jones, Alexander; Van den Bergh, Bea R H

2013-01-01

Active anxiety disorders have lasting detrimental effects on pregnant mothers and their offspring but it is unknown if historical, non-active, maternal anxiety disorders have similar effects. Anxiety-related conditions, such as reduced autonomic cardiac control, indicated by reduced heart rate variability (HRV) could persist despite disorder resolution, with long-term health implications for mothers and children. The objective in this study is to test the hypotheses that pregnant mothers with a history of, but not current anxiety and their children have low HRV, predicting anxiety-like offspring temperaments. The participants in this case-control study consist of 56 women during their first trimester and their offspring (15 male, 29 female). Women had a history of an anxiety disorder (n=22) or no psychopathology (n=34) determined using the Mini-International Neuropsychiatric Interview. The main outcome measures were indices of autonomic cardiac control including root mean square of successive differences (RMSSD) and high frequency (HF) variability. Children's fearfulness was also assessed using the Laboratory Temperament Assessment Battery (Lab-TAB)-Locomotor Version. HRV was lower in women and children in the past anxiety group compared to controls. HRV measures for mothers and children were positively correlated in the anxiety group only. In all children, low HRV measures at 2-4 months were associated with a higher chance of fearful behavior at 9-10 months. Pregnant women with previous but not current anxiety and their children have low HRV. Children with low HRV tend to show more fearfulness. These findings have implications for identifying children at risk of anxiety disorders and point to possible underlying mechanisms of child psychopathology.

Pregnant Mothers with Resolved Anxiety Disorders and Their Offspring Have Reduced Heart Rate Variability: Implications for the Health of Children

PubMed Central

Braeken, Marijke A. K. A.; Kemp, Andrew H.; Outhred, Tim; Otte, Renée A.; Monsieur, Geert J. Y. J.; Jones, Alexander; Van den Bergh, Bea R. H.

2013-01-01

Objective Active anxiety disorders have lasting detrimental effects on pregnant mothers and their offspring but it is unknown if historical, non-active, maternal anxiety disorders have similar effects. Anxiety-related conditions, such as reduced autonomic cardiac control, indicated by reduced heart rate variability (HRV) could persist despite disorder resolution, with long-term health implications for mothers and children. The objective in this study is to test the hypotheses that pregnant mothers with a history of, but not current anxiety and their children have low HRV, predicting anxiety-like offspring temperaments. Methods The participants in this case-control study consist of 56 women during their first trimester and their offspring (15 male, 29 female). Women had a history of an anxiety disorder (n=22) or no psychopathology (n=34) determined using the Mini-International Neuropsychiatric Interview. The main outcome measures were indices of autonomic cardiac control including root mean square of successive differences (RMSSD) and high frequency (HF) variability. Children’s fearfulness was also assessed using the Laboratory Temperament Assessment Battery (Lab-TAB)-Locomotor Version. Results HRV was lower in women and children in the past anxiety group compared to controls. HRV measures for mothers and children were positively correlated in the anxiety group only. In all children, low HRV measures at 2-4 months were associated with a higher chance of fearful behavior at 9-10 months. Conclusions Pregnant women with previous but not current anxiety and their children have low HRV. Children with low HRV tend to show more fearfulness. These findings have implications for identifying children at risk of anxiety disorders and point to possible underlying mechanisms of child psychopathology. PMID:24340091

Win some, lose some: parental hypertension and heart rate change in an incentive versus response cost paradigm.

PubMed

Hastrup, J L; Johnson, C A; Hotchkiss, A P; Kraemer, D L

1986-11-01

Fowles (1983), citing evidence from separate studies, suggests that both incentive and response cost paradigms increase heart rate and should be subsumed under Gray's (1975) 'appetitive motivational system'. Shock avoidance and loss of reward (response cost) contingencies, while aversive, appear to evoke this motivational system; consequently both should elicit heart rate increases independent of anxiety. The present investigation compared magnitude of heart rate changes observed under conditions of winning and losing money. Results showed: no differences between incentive and response cost conditions; no effect of state anxiety on heart rate in these conditions, despite an elevation of state anxiety on the task day relative to a subsequent relaxation day assessment; and some evidence for the presence under both such appetitive conditions of cardiovascular hyperresponsivity among offspring of hypertensive parents. The results suggest a need for systematic parametric studies of experimental conditions.

A novel healthy blood pressure phenotype in the Long Life Family Study

PubMed Central

Marron, Megan M.; Singh, Jatinder; Boudreau, Robert M.; Christensen, Kaare; Cosentino, Stephanie; Feitosa, Mary F.; Minster, Ryan L.; Perls, Thomas; Schupf, Nicole; Sebastiani, Paola; Ukraintseva, Svetlana; Wojczynski, Mary K.; Newman, Anne B.

2018-01-01

Background Hypertension tends to run in families and has both genetic and environmental determinants. We assessed the hypothesis that a novel healthy blood pressure (BP) phenotype is also familial and sought to identify its associated factors. Methods We developed a healthy BP phenotype in the Long Life Family Study, a cohort of two-generation families selected for longevity. Participants from the offspring generation (n = 2211, ages 32–88) were classified as having healthy BP if their age-adjusted and sex-adjusted SBP z-score was between −1.5 and −0.5. Offspring on antihypertensive medications were classified as not having healthy BP. Families with at least two offspring (n = 419 families) were defined as meeting the healthy BP phenotype if at least two and at least 50% of their offspring had healthy BP. Results Among 2211 offspring, 476 (21.5%) met the healthy BP phenotype. When examining the 419 families, only 44 (10.5%) families met the criteria for the healthy BP phenotype. Both offspring and probands from families with healthy BP performed better on neuropsychological tests that place demands on complex attention and executive function when compared with offspring and probands from remaining families. Among families with the healthy BP phenotype compared with families without, a higher proportion of offspring met the American Heart Association definition of ideal cardiovascular health (10.8 versus 3.8%, respectively; driven by BP, smoking status, and BMI components). Conclusion In this cohort of familial longevity, few families had a novel healthy BP phenotype in multiple members. Families with this healthy BP phenotype may represent a specific pathway to familial longevity. PMID:28837423

Metabolic factors and genetic risk mediate familial type 2 diabetes risk in the Framingham Heart Study

PubMed Central

Raghavan, Sridharan; Porneala, Bianca; McKeown, Nicola; Fox, Caroline S.; Dupuis, Josée; Meigs, James B.

2015-01-01

Aims/hypothesis Type 2 diabetes mellitus in parents is a strong determinant of diabetes risk in their offspring. We hypothesise that offspring diabetes risk associated with parental diabetes is mediated by metabolic risk factors. Methods We studied initially non-diabetic participants of the Framingham Offspring Study. Metabolic risk was estimated using beta cell corrected insulin response (CIR), HOMA-IR or a count of metabolic syndrome components (metabolic syndrome score [MSS]). Dietary risk and physical activity were estimated using questionnaire responses. Genetic risk score (GRS) was estimated as the count of 62 type 2 diabetes risk alleles. The outcome of incident diabetes in offspring was examined across levels of parental diabetes exposure, accounting for sibling correlation and adjusting for age, sex and putative mediators. The proportion mediated was estimated by comparing regression coefficients for parental diabetes with (βadj) and without (βunadj) adjustments for CIR, HOMA-IR, MSS and GRS (percentage mediated = 1 – βadj / βunadj). Results Metabolic factors mediated 11% of offspring diabetes risk associated with parental diabetes, corresponding to a reduction in OR per diabetic parent from 2.13 to 1.96. GRS mediated 9% of risk, corresponding to a reduction in OR per diabetic parent from 2.13 to 1.99. Conclusions/interpretation Metabolic risk factors partially mediated offspring type 2 diabetes risk conferred by parental diabetes to a similar magnitude as genetic risk. However, a substantial proportion of offspring diabetes risk associated with parental diabetes remains unexplained by metabolic factors, genetic risk, diet and physical activity, suggesting that important familial influences on diabetes risk remain undiscovered. PMID:25619168

The effects of experimental gestational hypertension on maternal blood pressure and fluid intake and pre-weanling hypothalamic neuronal activity.

PubMed

Arguelles, Juan; Perillan, Carmen; Beltz, Terry G; Xue, Baojian; Badaue-Passos, Daniel; Vega, Jose A; Johnson, Alan Kim

2017-09-01

To examine the fetal programming effects of maternal hypertension, natriophilia and hyperreninemia [experimentally induced in rats by partial inter-renal aortic ligature (PAL) prior to mating] fos immunoreactivity was studied in 6-day-old offspring of PAL and control mothers. The purposes of the present set of experiments were twofold. The first was to characterize the effects of PAL on the mother's arterial blood pressure and intake of salt (1.8% NaCl solution) and water over the course of gestation. Second, was to study the pattern of neuronal activation in key brain areas of 6-day-old offspring treated with the dipsogen isoproterenol that were from PAL and control mothers. Beta-adrenergic receptor agonist-treated pups allowed the determination whether there were neuroanatomical correlates within the neural substrates controlling thirst and the enhanced water intake evidenced by the isoproterenol treated pups of PAL mothers. Hydromineral ingestive behavior along with blood pressure and heart rate of PAL (M-PAL) and control (M-sPAL) dams throughout gestation was studied. Higher salt and water intakes along with blood pressures and heart rates were found during gestation and lactation in the M-PAL group. Maternal PAL evoked significantly increased isoproterenol-elicited Fos staining in brain regions (e.g. subfornical organ, organum vasculosum of the lamina terminalis, supraoptic nucleus, hypothalamic paraventricular nucleus and median preoptic nucleus) of 6-day-old pups, which is the age of animals shown enhanced thirst responses in PAL offspring. These results indicate that PAL is compatible with pregnancy, producing a sustained increase in blood pressure and heart rate, along with increased water and salt intake. The present study demonstrates that the neural substrates involved in cardiovascular homeostasis and fluid balance in adult rats are responsive in six-day-old rats, and can be altered by fetal programming. Copyright © 2017 Elsevier Ltd. All rights reserved.

Feasibility of recruiting families into a heart disease prevention program based on dietary patterns

USDA-ARS?s Scientific Manuscript database

Offspring of parents with a history of cardiovascular disease (CVD) inherit a similar genetic profile and share diet and lifestyle behaviors. This study aimed to evaluate the feasibility of recruiting families at risk of CVD to a dietary prevention program, determine the changes in diet achieved, an...

Prenatal exposure to angiotensin II increases blood pressure and decreases salt sensitivity in rats.

PubMed

Svitok, Pavel; Senko, Tomas; Panakova, Zuzana; Olexova, Lucia; Krskova, Lucia; Okuliarova, Monika; Zeman, Michal

2017-01-01

Renin angiotensin aldosterone system (RAAS) plays an essential role in the homeostatic control of arterial blood pressure, perfusion of tissues, and control of extracellular fluid. Its components are highly expressed in the developing kidney, general vasculature, brain, and heart. A modified intrauterine environment alters mechanisms controlling blood pressure (BP) and can lead to hypertension in the adult offspring and developmentally programmed RAAS can be involved in this process. There are very little data about the effects of increased angiotensin II (Ang II) concentrations during pregnancy on in utero development of the fetus. In our study, we administered Ang II to pregnant female rats via osmotic mini-pumps and evaluated the postnatal development and BP control in the offspring. To estimate possible developmental changes in sensitivity to salt, we exposed the offspring to a diet with increased salt content and measured plasma aldosterone levels and plasma renin activity. Increased Ang II during pregnancy raised BP in the offspring; however, salt sensitivity was decreased in comparison to controls. Relative weight of the left ventricle was decreased in the offspring prenatally exposed to Ang II, while relative kidney weight was reduced only in female offspring. Prenatal treatment led to increased aldosterone levels and decreased plasma renin activity, suggesting a complex physiological response. Our results suggest that conditions leading to upregulation of RAAS during pregnancy can influence the cardiovascular system of the fetus and have a long-term impact on the offspring's health.

Maternal residential proximity to waste sites and industrial facilities and conotruncal heart defects in offspring.

PubMed

Langlois, Peter H; Brender, Jean D; Suarez, Lucina; Zhan, F Benjamin; Mistry, Jatin H; Scheuerle, Angela; Moody, Karen

2009-07-01

Most studies of the relationship between maternal residential proximity to sources of environmental pollution and congenital cardiovascular malformations have combined heart defects into one group or broad subgroups. The current case-control study examined whether risk of conotruncal heart defects, including subsets of specific defects, was associated with maternal residential proximity to hazardous waste sites and industrial facilities with recorded air emissions. Texas Birth Defects Registry cases were linked to their birth or fetal death certificate. Controls without birth defects were randomly selected from birth certificates. Distances from maternal addresses at delivery to National Priority List (NPL) waste sites, state superfund waste sites, and Toxic Release Inventory (TRI) facilities were determined for 1244 cases (89.5% of those eligible) and 4368 controls (88.0%). Living within 1 mile of a hazardous waste site was not associated with risk of conotruncal heart defects [adjusted odds ratio (aOR) = 0.83, 95% confidence interval (CI) = 0.54, 1.27]. This was true whether looking at most types of defects or waste sites. Only truncus arteriosus showed statistically elevated ORs with any waste site (crude OR: 2.80, 95% CI 1.19, 6.54) and with NPL sites (crude OR: 4.63, 95% CI 1.18, 13.15; aOR 4.99, 95% CI 1.26, 14.51), but the latter was based on only four exposed cases. There was minimal association between conotruncal heart defects and proximity to TRI facilities (aOR = 1.10, 95% CI = 0.91, 1.33). Stratification by maternal age or race/ethnic group made little difference in effect estimates for waste sites or industrial facilities. In this study population, maternal residential proximity to waste sites or industries with reported air emissions was not associated with conotruncal heart defects or its subtypes in offspring, with the exception of truncus arteriosus.

Postnatal Cardiovascular Consequences in the Offspring of Pregnant Rats Exposed to Smoking and Smoking Cessation Pharmacotherapies.

PubMed

Gopalakrishnan, Kathirvel; More, Amar S; Hankins, Gary D; Nanovskaya, Tatiana N; Kumar, Sathish

2017-06-01

Approximately 20% of pregnant women smoke despite intentions to quit. Smoking cessation drugs, such as nicotine replacement therapy (NRT) and bupropion, are recommended treatments. Adverse cardiovascular outcomes in offspring have raised concerns about NRT's safety during pregnancy. However, the effect of bupropion is unknown. Using a rat model, we determined whether NRT and bupropion interventions during pregnancy are safer than continued smoking on offspring's cardiovascular function. Male offspring of controls and dams exposed to cigarette smoke (1.6 packs/day, inhalation), nicotine (2 mg/kg/d subcutaneously), and bupropion (13 mg/kg twice daily orally) were assessed for fetoplacental weight, cardiac function, blood pressure, and vascular reactivity. Fetoplacental weights were decreased and spontaneous beating and intracellular calcium in neonatal cardiomyocytes were increased in smoking, nicotine, and bupropion offspring; however, these effects were more accentuated in smoking followed by nicotine and bupropion offspring. Increased heart rate and decreased cardiac output, stroke volume, and left ventricular percent posterior wall thickening were observed in smoking, nicotine, and bupropion offspring. The left ventricular mass was reduced in smoking and nicotine but not in bupropion offspring. Blood pressure was higher with decreased endothelium-dependent relaxation and exaggerated vascular contraction to angiotensin II in smoking and nicotine offspring, with more pronounced dysfunctions in smoking than nicotine offspring. Maternal bupropion did not impact offspring's blood pressure, endothelium-dependent relaxation, and vascular contraction. In conclusion, maternal nicotine intervention adversely affects offspring's cardiovascular outcomes, albeit less severely than continued smoking. However, bupropion causes cardiac derangement in offspring but does not adversely affect blood pressure and vascular function.

Maternal occupational exposure to polycyclic aromatic hydrocarbons and congenital heart defects among offspring in the national birth defects prevention study.

PubMed

Lupo, Philip J; Symanski, Elaine; Langlois, Peter H; Lawson, Christina C; Malik, Sadia; Gilboa, Suzanne M; Lee, Laura J; Agopian, A J; Desrosiers, Tania A; Waters, Martha A; Romitti, Paul A; Correa, Adolfo; Shaw, Gary M; Mitchell, Laura E

2012-11-01

There is evidence in experimental model systems that exposure to polycyclic aromatic hydrocarbons (PAHs) results in congenital heart defects (CHDs); however, to our knowledge, this relationship has not been examined in humans. Therefore, we conducted a case-control study assessing the association between estimated maternal occupational exposure to PAHs and CHDs in offspring. Data on CHD cases and control infants were obtained from the National Birth Defects Prevention Study for the period of 1997 to 2002. Exposure to PAHs was assigned by industrial hygienist consensus, based on self-reported maternal occupational histories from 1 month before conception through the third month of pregnancy. Logistic regression was used to evaluate the association between maternal occupational PAH exposure and specific CHD phenotypic subtypes among offspring. The prevalence of occupational PAH exposure was 4.0% in CHD case mothers (76/1907) and 3.6% in control mothers (104/2853). After adjusting for maternal age, race or ethnicity, education, smoking, folic acid supplementation, and study center, exposure was not associated with conotruncal defects (adjusted odds ratio [AOR], 0.98; 95% confidence interval [CI], 0.58-1.67), septal defects (AOR, 1.28; 95% CI, 0.86-1.90), or with any isolated CHD subtype. Our findings do not support an association between potential maternal occupational exposure to PAHs and various CHDs in a large, population-based study. For CHD phenotypic subtypes in which modest nonsignificant associations were observed, future investigations could be improved by studying populations with a higher prevalence of PAH exposure and by incorporating information on maternal and fetal genotypes related to PAH metabolism. Birth Defects Research (Part A), 2012. Copyright © 2012 Wiley Periodicals, Inc.

Maternal Gestational Hypertension-Induced Sensitization of Angiotensin II Hypertension Is Reversed by Renal Denervation or Angiotensin-Converting Enzyme Inhibition in Rat Offspring.

PubMed

Xue, Baojian; Yin, Haifeng; Guo, Fang; Beltz, Terry G; Thunhorst, Robert L; Johnson, Alan Kim

2017-04-01

Numerous findings demonstrate that there is a strong association between maternal health during pregnancy and cardiovascular disease in adult offspring. The purpose of the present study was to test whether maternal gestational hypertension modulates brain renin-angiotensin-aldosterone system (RAAS) and proinflammatory cytokines that sensitizes angiotensin II-elicited hypertensive response in adult offspring. In addition, the role of renal nerves and the RAAS in the sensitization process was investigated. Reverse transcription polymerase chain reaction analyses of structures of the lamina terminalis and paraventricular nucleus indicated upregulation of mRNA expression of several RAAS components and proinflammatory cytokines in 10-week-old male offspring of hypertensive dams. Most of these increases were significantly inhibited by either renal denervation performed at 8 weeks of age or treatment with an angiotensin-converting enzyme inhibitor, captopril, in drinking water starting at weaning. When tested beginning at 10 weeks of age, a pressor dose of angiotensin II resulted in enhanced upregulation of mRNA expression of RAAS components and proinflammatory cytokines in the lamina terminalis and paraventricular nucleus and an augmented pressor response in male offspring of hypertensive dams. The augmented blood pressure change and most of the increases in gene expression in the offspring were abolished by either renal denervation or captopril. The results suggest that maternal hypertension during pregnancy enhances pressor responses to angiotensin II through overactivity of renal nerves and the RAAS in male offspring and that upregulation of the brain RAAS and proinflammatory cytokines in these offspring may contribute to maternal gestational hypertension-induced sensitization of the hypertensive response to angiotensin II. © 2017 American Heart Association, Inc.

Maternal exposure to an environmentally relevant dose of triclocarban results in perinatal exposure and potential alterations in offspring development in the mouse model

DOE PAGES

Enright, Heather A.; Falso, Miranda J. S.; Malfatti, Michael A.; ...

2017-08-09

Triclocarban (TCC) is among the top 10 most commonly detected wastewater contaminants in both concentration and frequency. Its presence in water, as well as its propensity to bioaccumulate, has raised numerous questions about potential endocrine and developmental effects. Here in this paper, we investigated whether exposure to an environmentally relevant concentration of TCC could result in transfer from mother to offspring in CD-1 mice during gestation and lactation using accelerator mass spectrometry (AMS). 14C-TCC (100 nM) was administered to dams through drinking water up to gestation day 18, or from birth to post-natal day 10. AMS was used to quantifymore » 14C-concentrations in offspring and dams after exposure. We demonstrated that TCC does effectively transfer from mother to offspring, both trans-placentally and via lactation. TCC-related compounds were detected in the tissues of offspring with significantly higher concentrations in the brain, heart and fat. In addition to transfer from mother to offspring, exposed offspring were heavier in weight than unexposed controls demonstrating an 11% and 8.5% increase in body weight for females and males, respectively. Quantitative real-time polymerase chain reaction (qPCR) was used to examine changes in gene expression in liver and adipose tissue in exposed offspring. qPCR suggested alterations in genes involved in lipid metabolism in exposed female offspring, which was consistent with the observed increased fat pad weights and hepatic triglycerides. This study represents the first report to quantify the transfer of an environmentally relevant concentration of TCC from mother to offspring in the mouse model and evaluate bio-distribution after exposure using AMS. Our findings suggest that early-life exposure to TCC may interfere with lipid metabolism and could have implications for human health.« less

Maternal exposure to an environmentally relevant dose of triclocarban results in perinatal exposure and potential alterations in offspring development in the mouse model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Enright, Heather A.; Falso, Miranda J. S.; Malfatti, Michael A.

Triclocarban (TCC) is among the top 10 most commonly detected wastewater contaminants in both concentration and frequency. Its presence in water, as well as its propensity to bioaccumulate, has raised numerous questions about potential endocrine and developmental effects. Here in this paper, we investigated whether exposure to an environmentally relevant concentration of TCC could result in transfer from mother to offspring in CD-1 mice during gestation and lactation using accelerator mass spectrometry (AMS). 14C-TCC (100 nM) was administered to dams through drinking water up to gestation day 18, or from birth to post-natal day 10. AMS was used to quantifymore » 14C-concentrations in offspring and dams after exposure. We demonstrated that TCC does effectively transfer from mother to offspring, both trans-placentally and via lactation. TCC-related compounds were detected in the tissues of offspring with significantly higher concentrations in the brain, heart and fat. In addition to transfer from mother to offspring, exposed offspring were heavier in weight than unexposed controls demonstrating an 11% and 8.5% increase in body weight for females and males, respectively. Quantitative real-time polymerase chain reaction (qPCR) was used to examine changes in gene expression in liver and adipose tissue in exposed offspring. qPCR suggested alterations in genes involved in lipid metabolism in exposed female offspring, which was consistent with the observed increased fat pad weights and hepatic triglycerides. This study represents the first report to quantify the transfer of an environmentally relevant concentration of TCC from mother to offspring in the mouse model and evaluate bio-distribution after exposure using AMS. Our findings suggest that early-life exposure to TCC may interfere with lipid metabolism and could have implications for human health.« less

Perinatal mortality and congenital anomalies in babies of women with type 1 or type 2 diabetes in England, Wales, and Northern Ireland: population based study

PubMed Central

Macintosh, Mary C M; Fleming, Kate M; Bailey, Jaron A; Doyle, Pat; Modder, Jo; Acolet, Dominique; Golightly, Shona; Miller, Alison

2006-01-01

Objective To provide perinatal mortality and congenital anomaly rates for babies born to women with type 1 or type 2 diabetes in England, Wales, and Northern Ireland. Design National population based pregnancy cohort. Setting 231 maternity units in England, Wales, and Northern Ireland. Participants 2359 pregnancies to women with type 1 or type 2 diabetes who delivered between 1 March 2002 and 28 February 2003. Main outcome measures Stillbirth rates; perinatal and neonatal mortality; prevalence of congenital anomalies. Results Of 2359 women with diabetes, 652 had type 2 diabetes and 1707 had type 1 diabetes. Women with type 2 diabetes were more likely to come from a Black, Asian, or other ethnic minority group (type 2, 48.8%; type 1, 9.1%) and from a deprived area (type 2, 46.3% in most deprived fifth; type 1, 22.8%). Perinatal mortality in babies of women with diabetes was 31.8/1000 births. Perinatal mortality was comparable in babies of women with type 1 (31.7/1000 births) and type 2 diabetes (32.3/1000) and was nearly four times higher than that in the general maternity population. 141 major congenital anomalies were confirmed in 109 offspring. The prevalence of major congenital anomaly was 46/1000 births in women with diabetes (48/1000 births for type 1 diabetes; 43/1000 for type 2 diabetes), more than double that expected. This increase was driven by anomalies of the nervous system, notably neural tube defects (4.2-fold), and congenital heart disease (3.4-fold). Anomalies in 71/109 (65%) offspring were diagnosed antenatally. Congenital heart disease was diagnosed antenatally in 23/42 (54.8%) offspring; anomalies other than congenital heart disease were diagnosed antenatally in 48/67 (71.6%) offspring. Conclusion Perinatal mortality and prevalence of congenital anomalies are high in the babies of women with type 1 or type 2 diabetes. The rates do not seem to differ between the two types of diabetes. PMID:16782722

Are there intergenerational and population-specific effects of oxidative stress in sockeye salmon (Oncorhynchus nerka)?

PubMed

Taylor, Jessica J; Wilson, Samantha M; Sopinka, Natalie M; Hinch, Scott G; Patterson, David A; Cooke, Steven J; Willmore, William G

2015-06-01

Intergenerational effects of stress have been reported in a wide range of taxa; however, few researchers have examined the intergenerational consequences of oxidative stress. Oxidative stress occurs in living organisms when reactive oxygen species remain unquenched by antioxidant defense systems and become detrimental to cells. In fish, it is unknown how maternal oxidative stress and antioxidant capacity influence offspring quality. The semelparous, migratory life history of Pacific salmon (Oncorhynchus spp.) provides a unique opportunity to explore intergenerational effects of oxidative stress. This study examined the effects of population origin on maternal and developing offspring oxidative stress and antioxidant capacity, and elucidated intergenerational relationships among populations of sockeye salmon (Oncorhynchus nerka) with varying migration effort. For three geographically distinct populations of Fraser River sockeye salmon (British Columbia, Canada), antioxidant capacity and oxidative stress were measured in adult female plasma, heart, brain, and liver, as well as in developing offspring until time of emergence. Maternal and offspring oxidative stress and antioxidant capacity varied among populations but patterns were not consistent across tissue/developmental stage. Furthermore, maternal oxidative stress and antioxidant capacity did not affect offspring oxidative stress and antioxidant capacity across any of the developmental stages or populations sampled. Our results revealed that offspring develop their endogenous antioxidant systems at varying rates across populations; however, this variability is overcome by the time of emergence. While offspring may be relying on maternally derived antioxidants in the initial stages of development, they rapidly develop their own antioxidant systems (mainly glutathione) during later stages of development. Copyright © 2015 Elsevier Inc. All rights reserved.

Exposure to a high-fat diet during development alters leptin and ghrelin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits.

PubMed

Prior, Larissa J; Davern, Pamela J; Burke, Sandra L; Lim, Kyungjoon; Armitage, James A; Head, Geoffrey A

2014-02-01

Exposure to maternal obesity or a maternal diet rich in fat during development may have adverse outcomes in offspring, such as the development of obesity and hypertension. The present study examined the effect of a maternal high-fat diet (m-HFD) on offspring blood pressure and renal sympathetic nerve activity, responses to stress, and sensitivity to central administration of leptin and ghrelin. Offspring of New Zealand white rabbits fed a 13% HFD were slightly heavier than offspring from mothers fed a 4% maternal normal fat diet (P<0.05) but had 64% greater fat pad mass (P=0.015). Mean arterial pressure, heart rate, and renal sympathetic nerve activity at 4 months of age were 7%, 7%, and 24% greater, respectively (P<0.001), in m-HFD compared with maternal normal fat diet rabbits, and the renal sympathetic nerve activity response to airjet stress was enhanced in the m-HFD group. m-HFD offspring had markedly elevated pressor and renal sympathetic nerve activity responses to intracerebroventricular leptin (5-100 µg) and enhanced sympathetic responses to intracerebroventricular ghrelin (1-5 nmol). In contrast, there was resistance to the anorexic effects of intracerebroventricular leptin and less neuronal activation as detected by Fos immunohistochemistry in the arcuate (-57%; P<0.001) and paraventricular (-37%; P<0.05) nuclei of the hypothalamus in m-HFD offspring compared with maternal normal fat diet rabbits. We conclude that offspring from mothers consuming an HFD exhibit an adverse cardiovascular profile in adulthood because of altered central hypothalamic sensitivity to leptin and ghrelin.

Increased congenital heart defects in children born to women with systemic lupus erythematosus: results from the offspring of Systemic Lupus Erythematosus Mothers Registry Study.

PubMed

Vinet, Évelyne; Pineau, Christian A; Scott, Susan; Clarke, Ann E; Platt, Robert W; Bernatsky, Sasha

2015-01-13

In a large population-based study, we aimed to determine whether children born to women with systemic lupus erythematosus (SLE) have an increased risk of congenital heart defects (CHDs) in comparison with children born to women without SLE. The Offspring of SLE Mothers Registry (OSLER) includes all women who had ≥1 hospitalization for delivery after SLE diagnosis, identified through Quebec's healthcare databases (1989-2009), and a randomly selected control group of women, matched ≥4:1 for age and year of delivery. We identified children born live to SLE mothers and their matched controls, and ascertained CHD based on ≥1 hospitalization or physician visit with relevant diagnostic codes, within the first 12 months of life. We performed multivariable logistic regression analyses, using the generalized estimating equation method, to adjust for relevant covariates. Five hundred nine women with SLE had 719 children, whereas 5824 matched controls had 8493 children. In comparison with controls, children born to women with SLE experienced more CHD (5.2% [95% confidence interval (CI), 3.7-7.1] versus 1.9% [95% CI, 1.6-2.2], difference 3.3% [95% CI, 1.9-5.2]). In multivariable analyses, children born to women with SLE had a substantially increased risk of CHD (odds ratio, 2.62; 95% CI, 1.77-3.88) in comparison with controls. In addition, in comparison with controls, offspring of SLE mothers had a substantially increased risk of having a CHD repair procedure (odds ratio, 5.82; 95% CI, 1.77-19.09). In comparison with children from the general population, children born to women with SLE have an increased risk of CHD, and an increased risk of having a CHD repair procedure, as well. © 2014 American Heart Association, Inc.

Marital status, marital strain, and risk of coronary heart disease or total mortality: the Framingham Offspring Study.

PubMed

Eaker, Elaine D; Sullivan, Lisa M; Kelly-Hayes, Margaret; D'Agostino, Ralph B; Benjamin, Emelia J

2007-01-01

To determine if marriage and marital strain are related to the 10-year coronary heart disease (CHD) incidence or total mortality. Research has demonstrated associations between marital strain and prognosis of heart disease, but little research has addressed the association between specific aspects of marital strain and incident CHD. From 1984 to 1987, 3682 participants (mean age 48.5 +/- 10.1 (standard deviation) years; 52% women) of the Framingham Offspring Study were examined; measures of marital status, marital strain, and risk factors for CHD were collected at the baseline examination. The present study describes the 10-year follow-up for incident CHD and total mortality. After adjusting for age, systolic blood pressure, body mass index, cigarette smoking, diabetes, and total cholesterol/high density cholesterol, the married men compared with unmarried men were almost half as likely to die during follow-up (hazard ratio (HR) = 0.54; 95% confidence interval (CI): 0.34-0.83). Women who "self-silenced" during conflict with their spouse, compared with women who did not, had four times the risk of dying (HR = 4.01; 95% CI: 1.75-9.20). Men with wives who were upset by work were 2.7 times more likely to develop CHD (HR = 2.71; 95% CI: 1.22-6.03). Marital happiness, satisfaction, and disagreements were not related to the development of CHD or death in men or women. Our study suggests that marital communication, conflict, and strain are associated with adverse health outcomes. Further research into the influence of marital stress on health is merited.

Hypertension in Pregnancy and Offspring Cardiovascular Risk in Young Adulthood: Prospective and Sibling Studies in the HUNT Study (Nord-Trøndelag Health Study) in Norway.

PubMed

Alsnes, Ingvild V; Vatten, Lars J; Fraser, Abigail; Bjørngaard, Johan Håkon; Rich-Edwards, Janet; Romundstad, Pål R; Åsvold, Bjørn O

2017-04-01

Women with hypertensive disorders in pregnancy are at increased lifetime risk for cardiovascular disease. We examined the offspring's cardiovascular risk profile in young adulthood and their siblings' cardiovascular risk profile. From the HUNT study (Nord-Trøndelag Health Study) in Norway, 15 778 participants (mean age: 29 years), including 210 sibling groups, were linked to information from the Medical Birth Registry of Norway. Blood pressure, anthropometry, serum lipids, and C-reactive protein were assessed. Seven hundred and six participants were born after exposure to maternal hypertension in pregnancy: 336 mothers had gestational hypertension, 343 had term preeclampsia, and 27 had preterm preeclampsia. Offspring whose mothers had hypertension in pregnancy had 2.7 (95% confidence interval, 1.8-3.5) mm Hg higher systolic blood pressure, 1.5 (0.9-2.1) mm Hg higher diastolic blood pressure, 0.66 (0.31-1.01) kg/m 2 higher body mass index, and 1.49 (0.65-2.33) cm wider waist circumference, compared with offspring of normotensive pregnancies. Similar differences were observed for gestational hypertension and term preeclampsia. Term preeclampsia was also associated with higher concentrations of non-high-density lipoprotein cholesterol (0.14 mmol/L, 0.03-0.25) and triglycerides (0.13 mmol/L, 0.06-0.21). Siblings born after a normotensive pregnancy had nearly identical risk factor levels as siblings born after maternal hypertension. Offspring born after maternal hypertension in pregnancy have a more adverse cardiovascular risk profile in young adulthood than offspring of normotensive pregnancies. Their siblings, born after a normotensive pregnancy, have a similar risk profile, suggesting that shared genes or lifestyle may account for the association, rather than an intrauterine effect. All children of mothers who have experienced hypertension in pregnancy may be at increased lifetime risk of cardiovascular disease. © 2017 American Heart Association, Inc.

Right Ventricular Volumes and Systolic Function by Cardiac Magnetic Resonance and the Impact of Sex, Age, and Obesity in a Longitudinally Followed Cohort Free of Pulmonary and Cardiovascular Disease: The Framingham Heart Study.

PubMed

Foppa, Murilo; Arora, Garima; Gona, Philimon; Ashrafi, Arman; Salton, Carol J; Yeon, Susan B; Blease, Susan J; Levy, Daniel; O'Donnell, Christopher J; Manning, Warren J; Chuang, Michael L

2016-03-01

Cardiac magnetic resonance is uniquely well suited for noninvasive imaging of the right ventricle. We sought to define normal cardiac magnetic resonance reference values and to identify the main determinants of right ventricular (RV) volumes and systolic function using a modern imaging sequence in a community-dwelling, longitudinally followed cohort free of clinical cardiovascular and pulmonary disease. The Framingham Heart Study Offspring cohort has been followed since 1971. We scanned 1794 Offspring cohort members using steady-state free precession cardiac magnetic resonance and identified a reference group of 1336 adults (64±9 years, 576 men) free of prevalent cardiovascular and pulmonary disease. RV trabeculations and papillary muscles were considered cavity volume. Men had greater RV volumes and cardiac output before and after indexation to body size (all P<0.001). Women had higher RV ejection fraction than men (68±6% versus 64±7%; P<0.0001). RV volumes and cardiac output decreased with advancing age. There was an increase in raw and height-indexed RV measurements with increasing body mass index, but this trend was weakly inverted after indexation of RV volumes to body surface area. Sex, age, height, body mass index, and heart rate account for most of the variability in RV volumes and function in this community-dwelling population. We report sex-specific normative values for RV measurements among principally middle-aged and older adults. RV ejection fraction is greater in women. RV volumes increase with body size, are greater in men, and are smaller in older people. Body surface area seems to be appropriate for indexation of cardiac magnetic resonance-derived RV volumes. © 2016 American Heart Association, Inc.

Mouse models for the study of postnatal cardiac hypertrophy.

PubMed

Del Olmo-Turrubiarte, A; Calzada-Torres, A; Díaz-Rosas, G; Palma-Lara, I; Sánchez-Urbina, R; Balderrábano-Saucedo, N A; González-Márquez, H; Garcia-Alonso, P; Contreras-Ramos, A

2015-06-01

The main objective of this study was to create a postnatal model for cardiac hypertrophy (CH), in order to explain the mechanisms that are present in childhood cardiac hypertrophy. Five days after implantation, intraperitoneal (IP) isoproterenol (ISO) was injected for 7 days to pregnant female mice. The fetuses were obtained at 15, 17 and 19 dpc from both groups, also newborns (NB), neonates (7-15 days) and young adults (6 weeks of age). Histopathological exams were done on the hearts. Immunohistochemistry and western blot demonstrated GATA4 and PCNA protein expression, qPCR real time the mRNA of adrenergic receptors (α-AR and β-AR), alpha and beta myosins (α-MHC, β-MHC) and GATA4. After the administration of ISO, there was no change in the number of offsprings. We observed significant structural changes in the size of the offspring hearts. Morphometric analysis revealed an increase in the size of the left ventricular wall and interventricular septum (IVS). Histopathological analysis demonstrated loss of cellular compaction and presence of left ventricular small fibrous foci after birth. Adrenergic receptors might be responsible for changing a physiological into a pathological hypertrophy. However GATA4 seemed to be the determining factor in the pathology. A new animal model was established for the study of pathologic CH in early postnatal stages.

Examining the relationships between egg cortisol and oxidative stress in developing wild sockeye salmon (Oncorhynchus nerka).

PubMed

Taylor, Jessica J; Sopinka, Natalie M; Wilson, Samantha M; Hinch, Scott G; Patterson, David A; Cooke, Steven J; Willmore, William G

2016-10-01

Maternally-derived hormones in oocytes, such as glucocorticoids (GCs), play a crucial role in embryo development in oviparous taxa. In fishes, maternal stressor exposure increases circulating and egg cortisol levels, the primary GC in fishes, as well as induces oxidative stress. Elevated egg cortisol levels modify offspring traits but whether maternal oxidative stress correlates with circulating and egg cortisol levels, and whether maternal/egg cortisol levels correlate with offspring oxidative stress have yet to be determined. The objective of this study was to examine the relationships among maternal and egg cortisol, and maternal and offspring oxidative stress to provide insight into the potential intergenerational effects of stressor exposure in sockeye salmon (Oncorhynchus nerka). Antioxidant concentration and oxidative stress were measured in maternal tissues (plasma, brain, heart and liver) as well as offspring developmental stages (pre-fertilization, 24h post-fertilization, eyed, and hatch), and were compared to both naturally-occurring and experimentally-elevated (via cortisol egg bath) levels of cortisol in eggs. Oxygen radical absorptive capacity of tissues from maternal sockeye salmon was measured spectrophotometrically and was not correlated with maternal or egg cortisol concentrations. Also, naturally-occurring and experimentally-elevated cortisol levels in eggs (to mimic maternal stress) did not affect oxidative stress or antioxidant capacity of the offspring. We conclude that the metrics of maternal stress examined in sockeye salmon (i.e., maternal/egg cortisol, maternal oxidative stress) are independent of each other, and that egg cortisol content does not influence offspring oxidative stress. Copyright © 2016 Elsevier Inc. All rights reserved.

Parental Age of Onset of Cardiovascular Disease as a Predictor for Offspring Age of Onset of Cardiovascular Disease.

PubMed

Allport, Shannon Anjelica; Kikah, Ngum; Abu Saif, Nessim; Ekokobe, Fonkem; Atem, Folefac D

2016-01-01

The risk for cardiovascular disease (CVD) is higher for individuals with a first-degree relative who developed premature CVD (with a threshold at age 55 years for a male or 65 years for a female). However, little is known about the effect that each unit increase or decrease of maternal or paternal age of onset of CVD has on offspring age of onset of CVD. We hypothesized that there is an association between maternal and paternal age of onset of CVD and offspring age of onset of CVD. We used the Framingham Heart Study database and performed conditional imputation for CVD-censored parental age (i.e. parents that didn't experience onset of CVD) and Cox proportional regression analysis, with offspring's age of onset of CVD as the dependent variable and parental age of onset of CVD as the primary predictor. Modifiable risk factors in offspring, such as cigarette smoking, body mass index (BMI), diabetes mellitus, systolic blood pressure (SBP), high-density lipoprotein (HDL) level, and low-density lipoprotein (LDL) level, were controlled for. Separate analyses were performed for the association between maternal age of onset of CVD and offspring age of onset of CVD and the association between paternal age of onset of CVD and offspring age of onset of CVD. Parental age of onset of CVD was predictive of offspring age of onset of CVD for maternal age of onset of CVD (P < .0001; N = 1401) and for paternal age of onset of CVD (P = 0.0134; N = 1221). A negative estimate of the coefficient of interest signifies that late onset of cardiovascular events in parents is protective of onset of CVD in offspring. Cigarette smoking and HDL level were important associated confounders. Offspring age of onset of cardiovascular disease is significantly associated with both maternal and paternal age of onset CVD. The incorporation of the parameters, maternal or paternal age of onset of CVD, into risk estimate calculators may improve accuracy of identification of high-risk patients in clinical settings.

Scaling of Foraminifera Parent and Offspring Size through the Phanerozoic

NASA Astrophysics Data System (ADS)

Guo, D.; Holme, F.; Payne, J.; Skotheim, J.

2011-12-01

Since before the 1940s, scientists have studied the scaling of body mass with metabolic rate, heart rate, fecundity, cardiac cycling rate, and numerous other traits. Like these traits, offspring mass scales with parent body mass for plants and animals. However, the relationship is not well documented in single-celled organisms. In our study, we examined how adult size scales with embryo size in fusulinid foraminifera. Fusulinids, and most other foraminifera, are an exceptional study group because the proloculus (the initial shell chamber) can be used to measure the size of the daughter cell at the time it became independent of its parent. We find that proloculus size increases with adult test size across fusulinid species. This pattern may result because the genomic sizes and the cellular machinery necessary for a larger adult size place limits on how small the initial daughter cell can be.

Maternal Nutrition Induces Pervasive Gene Expression Changes but No Detectable DNA Methylation Differences in the Liver of Adult Offspring

PubMed Central

Cannon, Matthew V.; Buchner, David A.; Hester, James; Miller, Hadley; Sehayek, Ephraim; Nadeau, Joseph H.; Serre, David

2014-01-01

Aims Epidemiological and animal studies have shown that maternal diet can influence metabolism in adult offspring. However, the molecular mechanisms underlying these changes remain poorly understood. Here, we characterize the phenotypes induced by maternal obesity in a mouse model and examine gene expression and epigenetic changes induced by maternal diet in adult offspring. Methods We analyzed genetically identical male mice born from dams fed a high- or low-fat diet throughout pregnancy and until day 21 postpartum. After weaning, half of the males of each group were fed a high-fat diet, the other half a low-fat diet. We first characterized the genome-wide gene expression patterns of six tissues of adult offspring - liver, pancreas, white adipose, brain, muscle and heart. We then measured DNA methylation patterns in liver at selected loci and throughout the genome. Results Maternal diet had a significant effect on the body weight of the offspring when they were fed an obesogenic diet after weaning. Our analyses showed that maternal diet had a pervasive effect on gene expression, with a pronounced effect in liver where it affected many genes involved in inflammation, cholesterol synthesis and RXR activation. We did not detect any effect of the maternal diet on DNA methylation in the liver. Conclusions Overall, our findings highlighted the persistent influence of maternal diet on adult tissue regulation and suggested that the transcriptional changes were unlikely to be caused by DNA methylation differences in adult liver. PMID:24594983

Potential benefits of mindfulness during pregnancy on maternal autonomic nervous system function and infant development.

PubMed

Braeken, Marijke A K A; Jones, Alexander; Otte, Renée A; Nyklíček, Ivan; Van den Bergh, Bea R H

2017-02-01

Mindfulness is known to decrease psychological distress. Possible benefits in pregnancy have rarely been explored. Our aim was to examine the prospective association of mindfulness with autonomic nervous system function during pregnancy and with later infant social-emotional development. Pregnant women (N = 156) completed self-report mindfulness and emotional distress questionnaires, and had their autonomic function assessed in their first and third trimesters, including heart rate (HR), indices of heart rate variability (HRV), preejection period (PEP), and systolic (SBP) and diastolic blood pressure (DBP). The social-emotional development of 109 infants was assessed at 4 months of age. More mindful pregnant women had less prenatal and postnatal emotional distress (p < .001) and higher cardiac parasympathetic activity: root mean square of successive differences (RMSSD: p = .03) and high-frequency (HF) HRV (p = .02). Between the first and third trimesters, women's overall HR increased (p < .001), and HRV (RMSSD, HF HRV, and low-frequency (LF) HRV: p < .001) and PEP decreased (p < .001). In more mindful mothers, parasympathetic activity decreased less (RMSSD: p = .01; HF HRV: p = .03) and sympathetic activity (inversely related to PEP) increased less (PEP: p = .02) between trimesters. Their offspring displayed less negative social-emotional behavior (p = .03) compared to offspring of less mindful mothers. Mindfulness in pregnancy was associated with ANS changes likely to be adaptive and with better social-emotional offspring development. Interventions to increase mindfulness during pregnancy might improve maternal and offspring health, but randomized trials are needed to demonstrate this. © 2016 Society for Psychophysiological Research.

Gestational Protein Restriction Increases Cardiac Connexin 43 mRNA levels in male adult rat offspring.

PubMed

Rossini, Kamila Fernanda; Oliveira, Camila Andrea de; Rebelato, Hércules Jonas; Esquisatto, Marcelo Augusto Marreto; Catisti, Rosana

2017-07-01

The dietary limitation during pregnancy influences the growth and development of the fetus and offspring and their health into adult life. The mechanisms underlying the adverse effects of gestational protein restriction (GPR) in the development of the offspring hearts are not well understood. The aim of this study was to evaluate the effects of GPR on cardiac structure in male rat offspring at day 60 after birth (d60). Pregnant Wistar rats were fed a normal-protein (NP, 17% casein) or low-protein (LP, 6% casein) diet. Blood pressure (BP) values from 60-day-old male offspring were measured by an indirect tail-cuff method using an electro sphygmomanometer. Hearts (d60) were collected for assessment of connexin 43 (Cx43) mRNA expression and morphological and morphometric analysis. LP offspring showed no difference in body weight, although they were born lighter than NP offspring. BP levels were significantly higher in the LP group. We observed a significant increase in the area occupied by collagen fibers, a decrease in the number of cardiomyocytes by 104 µm2, and an increase in cardiomyocyte area associated with an increased Cx43 expression. GPR changes myocardial levels of Cx43 mRNA in male young adult rats, suggesting that this mechanism aims to compensate the fibrotic process by the accumulation of collagen fibers in the heart interstitium. A limitação dietética durante a gravidez influencia o crescimento e desenvolvimento do feto e da prole e sua saúde na vida adulta. Os mecanismos subjacentes dos efeitos adversos da restrição proteica gestacional (RPG) no desenvolvimento dos corações da prole não são bem compreendidos. Avaliar os efeitos da RPG sobre a estrutura cardíaca em filhotes machos de ratas aos 60 dias após o nascimento (d60). Ratos fêmeas Wistar grávidas foram alimentadas com uma dieta de proteína normal (PN, 17% caseína) ou de baixa proteína (BP, caseína 6%). Os valores de pressão arterial (PA) de descendentes do sexo masculino de 60 dias de idade foram medidos por meio de um método indireto de manguito de cauda usando um eletro esfigmomanômetro. Os corações (d60) foram coletados para avaliação da expressão de RNAm da conexina 43 (Cx43) e análise morfológica e morfométrica. A prole BP não mostrou diferença no peso corporal, embora tenha nascido mais leve do que a prole PN. Os níveis de PA foram significativamente mais altos no grupo BP. Observou-se um aumento significativo na área ocupada pelas fibras colágenas, diminuição do número de cardiomiócitos em 104 µm2 e aumento da área de cardiomiócitos associada ao aumento da expressão de Cx43. A RPG altera os níveis miocárdicos de RNAm de Cx43 em ratos adultos jovens, sugerindo que este mecanismo visa compensar o processo fibrótico pelo acúmulo de fibras de colágeno no interstício cardíaco.

The effects of feeding rats diets deficient in folic acid and related methyl donors on the blood pressure and glucose tolerance of the offspring.

PubMed

Maloney, Christopher A; Hay, Susan M; Rees, William D

2009-05-01

In humans poor maternal folate status is associated with a decrease in infant birth weight. As low birth weight increases the risk of cardiovascular and metabolic disease in adults, an inadequate supply of folic acid in the mother's diet may increase the susceptibility of the offspring to disease. We have fed laboratory rats diets deficient in folic acid and the related methyl donors methionine and choline to examine the effects on growth, blood pressure and insulin action in the offspring. Poor folate status transiently increased fetal growth but did not produce a long-term change in body weight. There were, however, small changes in the hearts of the female offspring. When folate deficiency was combined with low intakes of methionine and choline, the kidneys of the male offspring were proportionately smaller, probably because of the limited availability of methionine. There was no effect on the blood pressure of either the male or female offspring. The pancreatic insulin content of fetuses from animals fed the folate-deficient diets were higher than those of the controls. Following an oral glucose challenge, there was a weak trend for glucose-stimulated insulin release to be increased in the offspring of dams fed the folate-deficient diet. The changes in insulin concentrations were, however, much smaller than the corresponding changes observed in the offspring of animals fed protein-deficient diets. These results suggest that folate deficiency during gestation causes modest changes to the insulin axis of the fetus.

Proximity to Food Establishments and Body Mass Index in the Framingham Heart Study Offspring Cohort Over 30 Years

PubMed Central

Block, Jason P.; Christakis, Nicholas A.; O’Malley, A. James; Subramanian, S. V.

2011-01-01

Existing evidence linking residential proximity to food establishments with body mass index (BMI; weight (kg)/height (m)2) has been inconclusive. In this study, the authors assessed the relation between BMI and proximity to food establishments over a 30-year period among 3,113 subjects in the Framingham Heart Study Offspring Cohort living in 4 Massachusetts towns during 1971–2001. The authors used novel data that included repeated measures of BMI and accounted for residential mobility and the appearance and disappearance of food establishments. They calculated proximity to food establishments as the driving distance between each subject’s residence and nearby food establishments, divided into 6 categories. The authors used cross-classified linear mixed models to account for time-varying attributes of individuals and residential neighborhoods. Each 1-km increase in distance to the closest fast-food restaurant was associated with a 0.11-unit decrease in BMI (95% credible interval: −0.20, −0.04). In sex-stratified analyses, this association was present only for women. Other aspects of the food environment were either inconsistently associated or not at all associated with BMI. Contrary to much prior research, the authors did not find a consistent relation between access to fast-food restaurants and individual BMI, necessitating a reevaluation of policy discussions on the anticipated impact of the food environment on weight gain. PMID:21965186

Perinatal Hypercholesterolemia Exacerbates Atherosclerosis Lesions in Offspring by Altering Metabolism of Trimethylamine-N-Oxide and Bile Acids.

PubMed

Trenteseaux, Charlotte; Gaston, Anh-Thu; Aguesse, Audrey; Poupeau, Guillaume; de Coppet, Pierre; Andriantsitohaina, Ramaroson; Laschet, Jamila; Amarger, Valérie; Krempf, Michel; Nobecourt-Dupuy, Estelle; Ouguerram, Khadija

2017-11-01

Experimental studies suggest that maternal hypercholesterolemia may be relevant for the early onset of cardiovascular disease in offspring. We investigated the effect of perinatal hypercholesterolemia on the atherosclerosis development in the offspring of apolipoprotein E-deficient mice and the underlying mechanism. Atherosclerosis and related parameters were studied in adult male or female apolipoprotein E-deficient mice offspring from either normocholesterolemic or hypercholesterolemic mothers and normocholesterolemic fathers. Female born to hypercholesterolemic mothers had more aortic root lesions than female born to normocholesterolemic mothers. Lesions in whole aorta did not differ between groups. Higher trimethylamine-N-oxide levels and Fmo3 hepatic gene expression were higher in female born to hypercholesterolemic mothers offspring compared with female born to normocholesterolemic mothers and male. Trimethylamine-N-oxide levels were correlated with the size of atherosclerotic root lesions. Levels of hepatic cholesterol and gallbladder bile acid were greater in male born to hypercholesterolemic mothers compared with male born to normocholesterolemic mothers. At 18 weeks of age, female born to hypercholesterolemic mothers showed lower hepatic Scarb1 and Cyp7a1 but higher Nr1h4 gene expression compared with female born to normocholesterolemic mothers. Male born to hypercholesterolemic mothers showed an increase in Scarb1 and Ldlr gene expression compared with male born to normocholesterolemic mothers. At 25 weeks of age, female born to hypercholesterolemic mothers had lower Cyp7a1 gene expression compared with female born to normocholesterolemic mothers. DNA methylation of Fmo3, Scarb1 , and Ldlr promoter regions was slightly modified and may explain the mRNA expression modulation. Our findings suggest that maternal hypercholesterolemia may exacerbate the development of atherosclerosis in female offspring by affecting metabolism of trimethylamine-N-oxide and bile acids. These data could be explained by epigenetic alterations. © 2017 American Heart Association, Inc.

Cardiac tissue injury resistance during myocardial infarction at adulthood by developmental exposure to cadmium.

PubMed

Zepeda, Ramiro; Castillo, Paula; Sáez, Daniel; Llanos, Miguel N; Ronco, Ana M

2012-03-01

It has been suggested that prenatal exposure to cadmium may alter the cardiovascular function during adulthood. Using the left coronary artery ligation model of acute myocardial infarction, we studied the cardiac function of female adult offspring rats exposed to cadmium (30 ppm) during gestation. The cardiac ischemic zone in the control and cadmium-exposed groups was measured 72 h post-ligation using the TPT staining technique. Offspring from cadmium-treated dams showed a significantly smaller infarcted area compared with the control group (7.1 ± 1.5 vs. 19.6 ± 2.8%, P ≤ 0.05). We also performed echocardiographic and biochemical studies, which positively correlated with the differences observed previously. To evaluate whether the effects were associated to pre-infarct tissue damage and/or angiogenic molecules, we performed histological studies and measured the expression of vascular endothelial growth factor (VEGF), and platelet endothelial cellular adhesion molecule-1 (PECAM-1). Results revealed a higher heart vascularization in the exposed offspring that was associated with an increase in PECAM and a decrease in VEGF expression. We conclude that prenatal exposure to cadmium induces fetal adaptive responses involving changes in the expression of some cardiac angiogenic molecules resulting in long-term resistance to infarction.

Undernutrition during pregnancy in mice leads to dysfunctional cardiac muscle respiration in adult offspring.

PubMed

Beauchamp, Brittany; Thrush, A Brianne; Quizi, Jessica; Antoun, Ghadi; McIntosh, Nathan; Al-Dirbashi, Osama Y; Patti, Mary-Elizabeth; Harper, Mary-Ellen

2015-04-10

Intrauterine growth restriction (IUGR) is associated with an increased risk of developing obesity, insulin resistance and cardiovascular disease. However, its effect on energetics in heart remains unknown. In the present study, we examined respiration in cardiac muscle and liver from adult mice that were undernourished in utero. We report that in utero undernutrition is associated with impaired cardiac muscle energetics, including decreased fatty acid oxidative capacity, decreased maximum oxidative phosphorylation rate and decreased proton leak respiration. No differences in oxidative characteristics were detected in liver. We also measured plasma acylcarnitine levels and found that short-chain acylcarnitines are increased with in utero undernutrition. Results reveal the negative impact of suboptimal maternal nutrition on adult offspring cardiac energy metabolism, which may have life-long implications for cardiovascular function and disease risk. © 2015 Authors.

Estimated Maternal Pesticide Exposure from Drinking Water and Heart Defects in Offspring

PubMed Central

Kim, Jihye; Swartz, Michael D.; Langlois, Peter H.; Romitti, Paul A.; Weyer, Peter; Mitchell, Laura E.; Ramakrishnan, Anushuya; Malik, Sadia; Lupo, Philip J.; Feldkamp, Marcia L.; Meyer, Robert E.; Winston, Jennifer J.; Reefhuis, Jennita; Blossom, Sarah J.; Bell, Erin; Agopian, A. J.

2017-01-01

Our objective was to examine the relationship between estimated maternal exposure to pesticides in public drinking water and the risk of congenital heart defects (CHD). We used mixed-effects logistic regression to analyze data from 18,291 nonsyndromic cases with heart defects from the Texas Birth Defects Registry and 4414 randomly-selected controls delivered in Texas from 1999 through 2005. Water district-level pesticide exposure was estimated by linking each maternal residential address to the corresponding public water supply district’s measured atrazine levels. We repeated analyses among independent subjects from the National Birth Defects Prevention Study (NBDPS) (1620 nonsyndromic cases with heart defects and 1335 controls delivered from 1999 through 2005). No positive associations were observed between high versus low atrazine level and eight CHD subtypes or all included heart defects combined. These findings should be interpreted with caution, in light of potential misclassification and relatively large proportions of subjects with missing atrazine data. Thus, more consistent and complete monitoring and reporting of drinking water contaminants will aid in better understanding the relationships between pesticide water contaminants and birth defects. PMID:28786932

Estimated Maternal Pesticide Exposure from Drinking Water and Heart Defects in Offspring.

PubMed

Kim, Jihye; Swartz, Michael D; Langlois, Peter H; Romitti, Paul A; Weyer, Peter; Mitchell, Laura E; Luben, Thomas J; Ramakrishnan, Anushuya; Malik, Sadia; Lupo, Philip J; Feldkamp, Marcia L; Meyer, Robert E; Winston, Jennifer J; Reefhuis, Jennita; Blossom, Sarah J; Bell, Erin; Agopian, A J

2017-08-08

Our objective was to examine the relationship between estimated maternal exposure to pesticides in public drinking water and the risk of congenital heart defects (CHD). We used mixed-effects logistic regression to analyze data from 18,291 nonsyndromic cases with heart defects from the Texas Birth Defects Registry and 4414 randomly-selected controls delivered in Texas from 1999 through 2005. Water district-level pesticide exposure was estimated by linking each maternal residential address to the corresponding public water supply district's measured atrazine levels. We repeated analyses among independent subjects from the National Birth Defects Prevention Study (NBDPS) (1620 nonsyndromic cases with heart defects and 1335 controls delivered from 1999 through 2005). No positive associations were observed between high versus low atrazine level and eight CHD subtypes or all included heart defects combined. These findings should be interpreted with caution, in light of potential misclassification and relatively large proportions of subjects with missing atrazine data. Thus, more consistent and complete monitoring and reporting of drinking water contaminants will aid in better understanding the relationships between pesticide water contaminants and birth defects.

Transient Congenital Hypothyroidism Alters Gene Expression of Glucose Transporters and Impairs Glucose Sensing Apparatus in Young and Aged Offspring Rats.

PubMed

Gholami, Hanieh; Jeddi, Sajad; Zadeh-Vakili, Azita; Farrokhfall, Khadije; Rouhollah, Fatemeh; Zarkesh, Maryam; Ghanbari, Mahboubeh; Ghasemi, Asghar

2017-01-01

Transient congenital hypothyroidism (TCH) could disturb carbohydrate metabolism in adulthood. Aging is associated with increased risk of type 2 diabetes. This study aims to address effects of TCH on mRNA expressions of glucose transporters (GLUTs) and glucokinase (GcK) in islets and insulin target tissues of aged offspring rats. The TCH group received water containing 0.025% 6-propyl-2-thiouracil during gestation. Offspring from control and TCH groups (n=6 in each group) were followed until month 19. Gene expressions of GLUTs and GcK were measured at months 3 and 19. Compared to controls, aged TCH rats had higher GLUT4 expression in heart (4.88 fold) and soleus (6.91 fold), while expression was lower in epididymal fat (12%). In TCH rats, GLUT2 and GcK expressions in islets were lower in young (12% and 10%, respectively) and higher in aged (10.85 and 8.42 fold, respectively) rats. In addition, liver GLUT2 and GcK expressions were higher in young (13.11 and 21.15 fold, respectively) and lower in aged rats (44% and 5%, respectively). Thyroid hormone deficiency during fetal period impaired glucose sensing apparatus and changed glucose transporter expression in insulin-sensitive tissues of aged offspring rats. These changes may contribute to impaired carbohydrate metabolism. © 2017 The Author(s). Published by S. Karger AG, Basel.

Possible Common Aetiology behind Maternal Preeclampsia and Congenital Heart Defects in the Child: a Cardiovascular Diseases in Norway Project Study.

PubMed

Brodwall, Kristoffer; Leirgul, Elisabeth; Greve, Gottfried; Vollset, Stein Emil; Holmstrøm, Henrik; Tell, Grethe S; Øyen, Nina

2016-01-01

The aetiology of congenital heart defects (CHD) is mostly unknown, but maternal factors may modify the infant risk of CHD. We investigated the association between maternal preeclampsia and offspring risk of severe CHD in a nation-wide cohort study. Information on all births registered in the Medical Birth Registry of Norway, 1994-2009, was completed with information on CHD diagnoses from national health registries and the Cardiovascular Diseases in Norway Project (CVDNOR). Among 914 703 singleton births without chromosomal abnormalities, 32 864 (3.6%) were born after a pregnancy with preeclampsia. The preeclampsia was diagnosed before the 34th week of pregnancy (early-onset preeclampsia) in 2618 (8.0% of preeclamptic pregnancies). CHDs were diagnosed in 10 691 infants; of these, 2473 had severe CHD. The risk of severe CHD was compared between births with and without maternal preeclampsia and estimated with binomial log-linear regression. When adjusting for year of birth, maternal age, parity, and pregestational diabetes, the risk ratio (RR) for severe CHD in offspring of mothers with any preeclampsia was 1.3 [95% confidence interval (CI) 1.1, 1.5], and in pregnancies with early-onset preeclampsia, the RR was 2.8 (95% CI 1.8, 4.4). The association between early-onset preeclampsia and specific types of severe CHD was stronger for atrioventricular septal defects (AVSD), with adjusted RR 13.5 (95% CI 6.8, 26.8). Early-onset preeclampsia was strongly associated with infant risk of severe CHD, specifically; the risk of AVSD was 15-fold higher if the mother was diagnosed with early-onset preeclampsia, suggesting common aetiological factors for early-onset preeclampsia and erroneous fetal heart development. © 2015 John Wiley & Sons Ltd.

MINIMAL ROLE FOR REACTIVE OXYGEN SPECIES IN DICHLOROACETIC ACID-INDUCED DYSMORPHOLOGY IN MOUSE WHOLE EMBRYO CULTURE.

EPA Science Inventory

Administration of dichloroacetate (DCA) to pregnant rats produces craniofacial, heart and other defects in their offspring. Exposure of zebrafish to DCA induces malformations and increases superoxide and nitric oxide production suggesting that reactive oxygen species (ROS) are as...

Maternal high-fat diet associated with altered gene expression, DNA methylation, and obesity risk in mouse offspring.

PubMed

Keleher, Madeline Rose; Zaidi, Rabab; Shah, Shyam; Oakley, M Elsa; Pavlatos, Cassondra; El Idrissi, Samir; Xing, Xiaoyun; Li, Daofeng; Wang, Ting; Cheverud, James M

2018-01-01

We investigated maternal obesity in inbred SM/J mice by assigning females to a high-fat diet or a low-fat diet at weaning, mating them to low-fat-fed males, cross-fostering the offspring to low-fat-fed SM/J nurses at birth, and weaning the offspring onto a high-fat or low-fat diet. A maternal high-fat diet exacerbated obesity in the high-fat-fed daughters, causing them to weigh more, have more fat, and have higher serum levels of leptin as adults, accompanied by dozens of gene expression changes and thousands of DNA methylation changes in their livers and hearts. Maternal diet particularly affected genes involved in RNA processing, immune response, and mitochondria. Between one-quarter and one-third of differentially expressed genes contained a differentially methylated region associated with maternal diet. An offspring high-fat diet reduced overall variation in DNA methylation, increased body weight and organ weights, increased long bone lengths and weights, decreased insulin sensitivity, and changed the expression of 3,908 genes in the liver. Although the offspring were more affected by their own diet, their maternal diet had epigenetic effects lasting through adulthood, and in the daughters these effects were accompanied by phenotypic changes relevant to obesity and diabetes.

Maternal high-fat diet associated with altered gene expression, DNA methylation, and obesity risk in mouse offspring

PubMed Central

Zaidi, Rabab; Shah, Shyam; Oakley, M. Elsa; Pavlatos, Cassondra; El Idrissi, Samir; Xing, Xiaoyun; Li, Daofeng; Wang, Ting; Cheverud, James M.

2018-01-01

We investigated maternal obesity in inbred SM/J mice by assigning females to a high-fat diet or a low-fat diet at weaning, mating them to low-fat-fed males, cross-fostering the offspring to low-fat-fed SM/J nurses at birth, and weaning the offspring onto a high-fat or low-fat diet. A maternal high-fat diet exacerbated obesity in the high-fat-fed daughters, causing them to weigh more, have more fat, and have higher serum levels of leptin as adults, accompanied by dozens of gene expression changes and thousands of DNA methylation changes in their livers and hearts. Maternal diet particularly affected genes involved in RNA processing, immune response, and mitochondria. Between one-quarter and one-third of differentially expressed genes contained a differentially methylated region associated with maternal diet. An offspring high-fat diet reduced overall variation in DNA methylation, increased body weight and organ weights, increased long bone lengths and weights, decreased insulin sensitivity, and changed the expression of 3,908 genes in the liver. Although the offspring were more affected by their own diet, their maternal diet had epigenetic effects lasting through adulthood, and in the daughters these effects were accompanied by phenotypic changes relevant to obesity and diabetes. PMID:29447215

Tobacco Smoking: Patterns, Health Consequences for Adults, and the Long-term Health of the Offspring

PubMed Central

Maritz, Gert S.; Mutemwa, Muyunda

2012-01-01

Tobacco use started several centuries ago and increased markedly after the invention of the cigarette making machine. Once people start smoking they find it difficult to quit the habit. This is due to the addictive effect of nicotine in tobacco smoke. Various epidemiologic and laboratory studies clearly showed that smoking is associated with various diseases such as heart diseases, asthma and emphysema and the associated increase in morbidity and mortality of smokers. Several studies implicate nicotine as the causative factor in tobacco smoke. Apart from nicotine, various carcinogens also occur in tobacco smoke resulting in an increase in the incidence of cancer in smokers. While the smoking habit is decreasing in developed countries, tobacco use increases in the developing countries. Smoking prevalence is also highest in poor communities and amongst those with low education levels. It is important to note that, although ther is a decline in the number of smokers in the developed countries, there is a three to four decades lag between the peak in smoking prevalence and the subsequent peak in smoking related mortality. It has been shown that maternal smoking induces respiratory diseases in the offspring. There is also evidence that parental smoking may program the offspring to develop certain diseases later in life. Various studies showed that maternal nicotine exposure during pregnancy and lactation via tobacco smoke of nicotine replacement therapy (NRT), program the offspring to develop compromised lung structure later in life with the consequent compromised lung function. This implies that NRT is not an option to assist pregnant or lactating smokers to quit the habit. Even paternal smoking may have an adverse effect on the health of the offspring since it has been shown that 2nd and 3rd hand smoking have adverse health consequences for those exposed to it. PMID:22980343

Impact of gestational chronodisruption on fetal cardiac genomics.

PubMed

Galdames, Hugo A; Torres-Farfan, Claudia; Spichiger, Carlos; Mendez, Natalia; Abarzua-Catalan, Lorena; Alonso-Vazquez, Pamela; Richter, Hans G

2014-01-01

We recently reported that gestational chronodisruption induces fetal growth restriction and marked effects on fetal adrenal physiology. Here, whole-transcriptome profiling was used to test whether gestational chronodisruption modifies gene expression in the fetal heart, potentially altering cardiac development. At day 10 of gestation (E10), pregnant rats were randomized in two groups: constant light (LL) and control 12 h light/12 h dark photoperiod (LD). RNA isolated from E18 heart was subjected to microarray analysis (Affymetrix platform for 28,000 genes). Integrated transcriptional changes were assessed by gene ontology and pathway analysis. Significant differential expression was found for 383 transcripts in LL relative to LD fetal heart (280 up-regulated and 103 down-regulated); with 42 of them displaying a 1.5-fold or greater change in gene expression. Deregulated markers of cardiovascular disease accounted for alteration of diverse gene networks in LL fetal heart, including local steroidogenesis and vascular calcification, as well as cardiac hypertrophy, stenosis and necrosis/cell death. DNA integrity was also overrepresented, including a 2.1-fold increase of Hmga1 mRNA, which encodes for a profuse architectural transcription factor. microRNA analysis revealed up-regulation of miRNAs 218-1 and 501 and concurrent down-regulation of their validated target genes. In addition, persistent down-regulation of Kcnip2 mRNA and hypertrophy of the left ventricle were found in the heart from 90 days-old offspring from LL mothers. The dysregulation of a relevant fraction of the fetal cardiac transcriptome, together with the diversity and complexity of the gene networks altered by gestational chronodisruption, suggest enduring molecular changes which may shape the hypertrophy observed in the left ventricle of adult LL offspring. © 2013.

Association of Parental Obesity and Diabetes Mellitus With Circulating Adipokines in Nonobese Nondiabetic Offspring.

PubMed

Zachariah, Justin P; Quiroz, Rene; Enserro, Danielle; Andersson, Charlotte; Keaney, John F; Sullivan, Lisa M; Vasan, Ramachandran S

2017-07-16

Adipokines are implicated in the development of obesity-related traits. We hypothesized that nonobese participants without diabetes mellitus (DM) whose parents were obese or had DM would have altered circulating adipokines compared with those without parental history of these conditions. Participants in the community-based Framingham Third Generation cohort who were not obese (body mass index <30) and not diabetic with both parents in the Framingham Offspring cohort were included in this analysis (n=2034, mean age 40 years, 54% women). Circulating concentrations of fetuin A, RBP4 (retinol binding protein 4), FABP4 (fatty acid binding protein 4), leptin, LEP-R (leptin receptor), and adiponectin were assayed. Parental DM was defined as occurring before age 60 years, and obesity was defined as body mass index ≥30 before age 60 years. General estimating equations were used to compare concentrations of adipokines among participants with 0, 1, or 2 parents affected by obesity or DM (separate analyses for each), adjusting for known correlates of adipokines. Overall, 44% had at least 1 parent who was obese and 15% had parents with DM. Parental obesity was associated with higher serum levels of FABP4 and LEP-R in their offspring ( P =0.02 for both). Parental DM was associated with lower adiponectin but higher RBP4 concentrations in offspring ( P ≤0.02 for both). In our community-based sample, a parental history of DM or obesity was associated with an altered adipokine profile in nonobese nondiabetic offspring. Additional studies are warranted to evaluate whether such preclinical biomarker alterations presage future risk of disease. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Antenatal exercise in overweight and obese women and its effects on offspring and maternal health: design and rationale of the IMPROVE (Improving Maternal and Progeny Obesity Via Exercise) randomised controlled trial.

PubMed

Seneviratne, Sumudu N; Parry, Graham K; McCowan, Lesley Me; Ekeroma, Alec; Jiang, Yannan; Gusso, Silmara; Peres, Geovana; Rodrigues, Raquel O; Craigie, Susan; Cutfield, Wayne S; Hofman, Paul L

2014-04-26

Obesity during pregnancy is associated with adverse outcomes for the offspring and mother. Lifestyle interventions in pregnancy such as antenatal exercise, are proposed to improve both short- and long-term health of mother and child. We hypothesise that regular moderate-intensity exercise during the second half of pregnancy will result in improved maternal and offspring outcomes, including a reduction in birth weight and adiposity in the offspring, which may be protective against obesity in later life. The IMPROVE (Improving Maternal and Progeny Risks of Obesity Via Exercise) study is a two-arm parallel randomised controlled clinical trial being conducted in Auckland, New Zealand. Overweight and obese women (BMI ≥25 kg/m2) aged 18-40 years, with a singleton pregnancy of <20 weeks of gestation, from the Auckland region, are eligible for the trial. Exclusion criteria are ongoing smoking or medical contra-indications to antenatal exercise.Participants are randomised with 1:1 allocation ratio to either intervention or control group, using computer-generated randomisation sequences in variable block sizes, stratified on ethnicity and parity, after completion of baseline assessments. The intervention consists of a 16-week structured home-based moderate-intensity exercise programme utilising stationary cycles and heart rate monitors, commencing at 20 weeks of gestation. The control group do not receive any exercise intervention. Both groups undergo regular fetal ultrasonography and receive standard antenatal care. Due to the nature of the intervention, participants are un-blinded to group assignment during the trial.The primary outcome is offspring birth weight. Secondary offspring outcomes include fetal and neonatal body composition and anthropometry, neonatal complications and cord blood metabolic markers. Maternal outcomes include weight gain, pregnancy and delivery complications, aerobic fitness, quality of life, metabolic markers and post-partum body composition. The results of this trial will provide valuable insights on the effects of antenatal exercise on health outcomes in overweight and obese mothers and their offspring. Australian New Zealand Clinical Trials Registry ACTRN12612000932864.

Folic acid supplementation and the occurrence of congenital heart defects, orofacial clefts, multiple births, and miscarriage.

PubMed

Bailey, Lynn B; Berry, Robert J

2005-05-01

Key research findings relative to the question of whether maternal use of folic acid before and during pregnancy reduces the chance that offspring will be born with a congenital heart defect or an orofacial cleft are reviewed in this paper. Observational studies in general support an association between maternal use of multivitamins containing folic acid and a reduction in the occurrence of congenital heart defects and orofacial clefts. Results from one randomized controlled trial (RCT) provide the strongest evidence that multivitamins prevent congenital heart defects, but this RCT did not provide evidence that multivitamins prevent orofacial clefts. In addition, most observational and interventional studies are not designed to detect an independent effect from folic acid. Early studies suggested that periconceptional multivitamin use was associated with an increased occurrence of both miscarriages and multiple births, which has resulted in a great deal of controversy about the safety of folic acid use during pregnancy. We also review reports that were designed to answer these questions with more definitive data. When more substantial evidence about the effect of periconceptional folic acid on the occurrence of congenital heart defects and orofacial clefts is reported, we will have additional support for promoting folic acid intervention programs. All women capable of becoming pregnant should continue to consume 400 mug/d of folic acid in addition to a healthy diet as advised.

Longer Duration and Earlier Age of Onset of Paternal Betel Chewing and Smoking Increase Metabolic Syndrome Risk in Human Offspring, Independently, in a Community-Based Screening Program in Taiwan.

PubMed

Yen, Amy Ming-Fang; Boucher, Barbara J; Chiu, Sherry Yueh-Hsia; Fann, Jean Ching-Yuan; Chen, Sam Li-Sheng; Huang, Kuo-Chin; Chen, Hsiu-Hsi

2016-08-02

Transgenerational effects of paternal Areca catechu nut chewing on offspring metabolic syndrome (MetS) risk in humans, on obesity and diabetes mellitus experimentally, and of paternal smoking on offspring obesity, are reported, likely attributable to genetic and epigenetic effects previously reported in betel-associated disease. We aimed to determine the effects of paternal smoking, and betel chewing, on the risks of early MetS in human offspring. The 13 179 parent-child trios identified from 238 364 Taiwanese aged ≥20 years screened at 2 community-based integrated screening sessions were tested for the effects of paternal smoking, areca nut chewing, and their duration prefatherhood on age of detecting offspring MetS at screen by using a Cox proportional hazards regression model. Offspring MetS risks increased with prefatherhood paternal areca nutusage (adjusted hazard ratio, 1.77; 95% confidence interval [CI], 1.23-2.53) versus nonchewing fathers (adjusted hazard ratio, 3.28; 95% CI, 1.67-6.43) with >10 years paternal betel chewing, 1.62 (95% CI, 0.88-2.96) for 5 to 9 years, and 1.42 (95% CI, 0.80-2.54) for <5 years betel usage prefatherhood (Ptrend=0.0002), with increased risk (adjusted hazard ratio, 1.95; 95% CI, 1.26-3.04) for paternal areca nut usage from 20 to 29 years of age, versus from >30 years of age (adjusted hazard ratio,1.61; 95% CI, 0.22-11.69). MetS offspring risk for paternal smoking increased dosewise (Ptrend<0.0001) with earlier age of onset (Ptrend=0.0009), independently. Longer duration of paternal betel quid chewing and smoking, prefatherhood, independently predicted early occurrence of incident MetS in offspring, corroborating previously reported transgenerational effects of these habits, and supporting the need for habit-cessation program provision. © 2016 American Heart Association, Inc.

Maternal obesity and congenital heart defects: a population-based study123

PubMed Central

Mills, James L; Troendle, James; Conley, Mary R; Carter, Tonia; Druschel, Charlotte M

2010-01-01

Background: Obesity affects almost one-third of pregnant women and causes many complications, including neural tube defects. It is not clear whether the risk of congenital heart defects, the most common malformations, is also increased. Objective: This study was conducted to determine whether obesity is associated with an increased risk of congenital heart defects. Design: A population-based, nested, case-control study was conducted in infants born with congenital heart defects and unaffected controls from the cohort of all births (n = 1,536,828) between 1993 and 2003 in New York State, excluding New York City. The type of congenital heart defect, maternal body mass index (BMI; in kg/m2), and other risk factors were obtained from the Congenital Malformations Registry and vital records. Mothers of 7392 congenital heart defect cases and 56,304 unaffected controls were studied. Results: All obese women (BMI ≥ 30) were significantly more likely than normal-weight women (BMI: 19–24.9) to have children with a congenital heart defect [odds ratio (OR): 1.15; 95% CI: 1.07, 1.23; P < 0.0001]. Overweight women were not at increased risk (OR: 1.00; 95% CI: 0.94, 1.06). The risk in morbidly obese women (BMI ≥ 40) was higher (OR: 1.33; 95% CI: 1.15, 1.54; P = 0.0001) than that in obese women with a BMI of 30–39.9 (OR: 1.11; 95% CI: 1.04, 1.20; P = 0.004). There was a highly significant trend of increasing OR for congenital heart defects with increasing maternal obesity (P < 0.0001). The offspring of obese women had significantly higher ORs for atrial septal defects, hypoplastic left heart syndrome, aortic stenosis, pulmonic stenosis, and tetralogy of Fallot. Conclusions: Obese, but not overweight, women are at significantly increased risk of bearing children with a range of congenital heart defects, and the risk increases with increasing BMI. Weight reduction as a way to reduce risk should be investigated. PMID:20375192

Maternal nicotine exposure leads to decreased cardiac protein disulfide isomerase and impaired mitochondrial function in male rat offspring.

PubMed

Barra, Nicole G; Lisyansky, Maria; Vanduzer, Taylor A; Raha, Sandeep; Holloway, Alison C; Hardy, Daniel B

2017-12-01

Smoking throughout pregnancy can lead to complications during gestation, parturition and neonatal development. Thus, nicotine replacement therapies are a popular alternative thought to be safer than cigarettes. However, recent studies in rodents suggest that fetal and neonatal nicotine exposure alone results in cardiac dysfunction and high blood pressure. While it is well known that perinatal nicotine exposure causes increased congenital abnormalities, the mechanisms underlying longer-term deficits in cardiac function are not completely understood. Recently, our laboratory demonstrated that nicotine impairs placental protein disulfide isomerase (PDI) triggering an increase in endoplasmic reticulum stress, leading us to hypothesize that this may also occur in the heart. At 3 months of age, nicotine-exposed offspring had 45% decreased PDI levels in the absence of endoplasmic reticulum stress. Given the association of PDI and superoxide dismutase enzymes, we further observed that antioxidant superoxide dismutase-2 levels were reduced by 32% in these offspring concomitant with a 26-49% decrease in mitochondrial complex proteins (I, II, IV and V) and tissue inhibitor of metalloproteinase-4, a critical matrix metalloprotease for cardiac contractility and health. Collectively, this study suggests that perinatal nicotine exposure decreases PDI, which can promote oxidative damage and mitochondrial damage, associated with a premature decline in cardiac function. Copyright © 2017 John Wiley & Sons, Ltd.

Hypertension, Obesity, Diabetes, and Heart Failure-Free Survival: The Cardiovascular Disease Lifetime Risk Pooling Project.

PubMed

Ahmad, Faraz S; Ning, Hongyan; Rich, Jonathan D; Yancy, Clyde W; Lloyd-Jones, Donald M; Wilkins, John T

2016-12-01

This study was designed to quantify the relationship between the absence of heart failure risk factors in middle age and incident heart failure, heart failure-free survival, and overall survival. Quantification of years lived free from heart failure in the context of risk factor burden in mid-life may improve risk communication and prevention efforts. We conducted a pooled, individual-level analysis sampling from communities across the United States as part of 4 cohort studies: the Framingham Heart, Framingham Offspring, Chicago Heart Association Detection Project in Industry, and ARIC (Atherosclerosis Risk In Communities) studies. Participants with and without hypertension (blood pressure ≥140/90 mm Hg or treatment), obesity (body mass index ≥30 kg/m 2 ), or diabetes (fasting glucose ≥126 mg/dl or treatment), and combinations of these factors, at index ages of 45 years and 55 years through 95 years. Competing risk-adjusted Cox models, a modified Kaplan-Meier estimator, and Irwin's restricted mean were used to estimate the association between the absence of risk factors at mid-life and incident heart failure, heart failure-free survival, and overall survival. For participants at age 45 years, over 516,537 person-years of follow-up, 1,677 incident heart failure events occurred. Men and women with no risk factors, compared to those with all 3, had 73% to 85% lower risks of incident heart failure. Men and women without hypertension, obesity, or diabetes at age 45 years lived on average 34.7 years and 38.0 years without incident heart failure, and they lived on average an additional 3 years to 15 years longer free of heart failure than those with 1, 2, or 3 risk factors. Similar trends were seen when stratified by race and at index age 55 years. Prevention of hypertension, obesity, and diabetes by ages 45 years and 55 years may substantially prolong heart failure-free survival, decrease heart failure-related morbidity, and reduce the public health impact of heart failure. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Number of Offspring and Cardiovascular Disease Risk in Men and Women

PubMed Central

Iliodromiti, Stamatina; Lawlor, Debbie A.; Catov, Janet M.; Nelson, Scott M.; Fraser, Abigail

2017-01-01

Background: Previous studies of the number of offspring and cardiovascular disease (CVD) report conflicting findings. We re-examined this association in both sexes to clarify the role of the cardiometabolic changes that women experience during pregnancy versus shared lifestyle characteristics. Methods: We studied 180,626 women and 133,259 men participating in the UK Biobank cohort who were free of CVD at baseline. CVD events were obtained from hospital and death registers. Analyses were conducted using Cox proportional hazards regression. Results: The incidence rates of overall CVD were six per 1000 person-years for women and nine per 1000 person-years for men. Number of children showed an association with risk of CVD among women; the adjusted HR (95% CI) was 1.2 (1.1, 1.3) for one, 1.1 (1.0, 1.2) for two, 1.2 (1.1, 1.3) for three, and 1.2 (1.1, 1.4) for four or more as compared to none. Number of children was also associated with CVD among men; the adjusted HR (95% CI) was 1.1 (1.0, 1.2) for one, 1.0 (0.96, 1.1) for two, 1.1 (1.0, 1.2) for three, and 1.1 (1.0, 1.3) for four or more as compared to none. There was no evidence of heterogeneity in the associations between sexes (Pinteraction = 0.80). Number of offspring also showed similar associations with ischemic heart disease and hypertensive disorders in both sexes. Conclusions: We observed similar associations between number of offspring and CVD in both sexes. The association among women might therefore be largely explained by unobserved behavioral and lifestyle characteristics. PMID:28696997

A genome-wide association study of red-blood cell fatty acids and ratios incorporating dietary covariates: Framingham Heart Study Offspring Cohort.

PubMed

Kalsbeek, Anya; Veenstra, Jenna; Westra, Jason; Disselkoen, Craig; Koch, Kristin; McKenzie, Katelyn A; O'Bott, Jacob; Vander Woude, Jason; Fischer, Karen; Shearer, Greg C; Harris, William S; Tintle, Nathan L

2018-01-01

Recent analyses have suggested a strong heritable component to circulating fatty acid (FA) levels; however, only a limited number of genes have been identified which associate with FA levels. In order to expand upon a previous genome wide association study done on participants in the Framingham Heart Study Offspring Cohort and FA levels, we used data from 2,400 of these individuals for whom red blood cell FA profiles, dietary information and genotypes are available, and then conducted a genome-wide evaluation of potential genetic variants associated with 22 FAs and 15 FA ratios, after adjusting for relevant dietary covariates. Our analysis found nine previously identified loci associated with FA levels (FADS, ELOVL2, PCOLCE2, LPCAT3, AGPAT4, NTAN1/PDXDC1, PKD2L1, HBS1L/MYB and RAB3GAP1/MCM6), while identifying four novel loci. The latter include an association between variants in CALN1 (Chromosome 7) and eicosapentaenoic acid (EPA), DHRS4L2 (Chromosome 14) and a FA ratio measuring delta-9-desaturase activity, as well as two loci associated with less well understood proteins. Thus, the inclusion of dietary covariates had a modest impact, helping to uncover four additional loci. While genome-wide association studies continue to uncover additional genes associated with circulating FA levels, much of the heritable risk is yet to be explained, suggesting the potential role of rare genetic variation, epistasis and gene-environment interactions on FA levels as well. Further studies are needed to continue to understand the complex genetic picture of FA metabolism and synthesis.

A genome-wide association study of red-blood cell fatty acids and ratios incorporating dietary covariates: Framingham Heart Study Offspring Cohort

PubMed Central

Veenstra, Jenna; Westra, Jason; Disselkoen, Craig; Koch, Kristin; McKenzie, Katelyn A.; O’Bott, Jacob; Vander Woude, Jason; Fischer, Karen; Shearer, Greg C.; Harris, William S.; Tintle, Nathan L.

2018-01-01

Recent analyses have suggested a strong heritable component to circulating fatty acid (FA) levels; however, only a limited number of genes have been identified which associate with FA levels. In order to expand upon a previous genome wide association study done on participants in the Framingham Heart Study Offspring Cohort and FA levels, we used data from 2,400 of these individuals for whom red blood cell FA profiles, dietary information and genotypes are available, and then conducted a genome-wide evaluation of potential genetic variants associated with 22 FAs and 15 FA ratios, after adjusting for relevant dietary covariates. Our analysis found nine previously identified loci associated with FA levels (FADS, ELOVL2, PCOLCE2, LPCAT3, AGPAT4, NTAN1/PDXDC1, PKD2L1, HBS1L/MYB and RAB3GAP1/MCM6), while identifying four novel loci. The latter include an association between variants in CALN1 (Chromosome 7) and eicosapentaenoic acid (EPA), DHRS4L2 (Chromosome 14) and a FA ratio measuring delta-9-desaturase activity, as well as two loci associated with less well understood proteins. Thus, the inclusion of dietary covariates had a modest impact, helping to uncover four additional loci. While genome-wide association studies continue to uncover additional genes associated with circulating FA levels, much of the heritable risk is yet to be explained, suggesting the potential role of rare genetic variation, epistasis and gene-environment interactions on FA levels as well. Further studies are needed to continue to understand the complex genetic picture of FA metabolism and synthesis. PMID:29652918

Effects of fried potato chip supplementation on mouse pregnancy and fetal development.

PubMed

El-Sayyad, Hassan I; Abou-Egla, Mohamed H; El-Sayyad, Fawkia I; El-Ghawet, Heba A; Gaur, Rajiv L; Fernando, Augusta; Raj, Madhwa H G; Ouhtit, Allal

2011-03-01

Acrylamide (ACR), a proven rodent carcinogen, is present at significantly high quantities in commonly consumed foods such as potato chips, raising a health concern worldwide. The effects of ACR and fried potato chips (FPC) on pregnant mice and their offspring before and after birth were investigated and compared. In the pregnant mice, similar histologic abnormalities were found in various tissues for ACR intoxication and FPC supplementation. Drastic alterations were mainly seen in the liver, kidney, heart muscle, and epiphyseal cartilage of experimental dams. ACR and FPC increased the rate of abortion and neonatal mortality and decreased the total number, body weight, size, and crown-rump length of the offspring before and after birth. Interestingly, however, higher rates of congenital malformations were observed in the FPC-treated group. Although ossification of axial and appendicular bones was markedly retarded during fetal development, some ossified bones were missing in newly born offspring of treated groups. Furthermore, the incidence of missing ossification centers was higher in the FPC-treated than in the ACR-treated neonates. These results suggest that FPC can cause hazardous health effects and warrant a systematic study on the health effects of consumption of FPC and French fries in the general population. Copyright © 2011 Elsevier Inc. All rights reserved.

Thyroid hormone modulates offspring sex ratio in a turtle with temperature-dependent sex determination

PubMed Central

Li, Teng; Mu, Yi; McGlashan, Jessica K.; Georges, Arthur

2016-01-01

The adaptive significance of temperature-dependent sex determination (TSD) has attracted a great deal of research, but the underlying mechanisms by which temperature determines the sex of a developing embryo remain poorly understood. Here, we manipulated the level of a thyroid hormone (TH), triiodothyronine (T3), during embryonic development (by adding excess T3 to the eggs of the red-eared slider turtle Trachemys scripta, a reptile with TSD), to test two competing hypotheses on the proximate basis for TSD: the developmental rate hypothesis versus the hormone hypothesis. Exogenous TH accelerated embryonic heart rate (and hence metabolic rate), developmental rate, and rates of early post-hatching growth. More importantly, hyperthyroid conditions depressed expression of Cyp19a1 (the gene encoding for aromatase) and levels of oestradiol, and induced more male offspring. This result is contrary to the direction of sex-ratio shift predicted by the developmental rate hypothesis, but consistent with that predicted by the hormone hypothesis. Our results suggest an important role for THs in regulating sex steroid hormones, and therefore, in affecting gonadal sex differentiation in TSD reptiles. Our study has implications for the conservation of TSD reptiles in the context of global change because environmental contaminants may disrupt the activity of THs, and thereby affect offspring sex in TSD reptiles. PMID:27798296

Respiratory modulation of sympathetic nerve activity is enhanced in male rat offspring following uteroplacental insufficiency.

PubMed

Menuet, C; Wlodek, M E; Fong, A Y; Allen, A M

2016-06-01

Sympathetic nerve activity to the cardiovascular system displays prominent respiratory-related modulation which leads to the generation of rhythmic oscillations in blood pressure called Traube-Hering waves. An amplification of this respiratory modulation of sympathetic activity is observed in hypertension of both genetic, the spontaneously hypertensive rat, and induced, chronic intermittent hypoxia or maternal protein restriction during gestation, origin. Male offspring of mothers with uteroplacental insufficiency, induced by bilateral uterine vessel ligation at 18 days of gestation, are also hypertensive in adulthood. In this study we examined whether these male offspring display altered respiratory modulation of sympathetic activity at pre-hypertensive ages compared to controls. Respiratory, cardiovascular and sympathetic parameters were examined using the working heart-brainstem preparation in 35 day old male rats that had reduced birth weight due to uteroplacental insufficiency. Whilst all respiratory parameters were not different between groups, we observed an enhanced respiratory-related burst of thoracic sympathetic nerve activity and amplified Traube-Hering waves in the growth-restricted group. This group also showed an increased sympathetic and bradycardic response to activation of peripheral chemoreceptors. The observations add support to the view that altered respiratory modulation of sympathetic activity represents a common mechanism involved in the development of several forms of hypertension. Copyright © 2015 Elsevier B.V. All rights reserved.

Production of transgenic cloned pigs expressing the far-red fluorescent protein monomeric Plum.

PubMed

Watanabe, Masahito; Kobayashi, Mirina; Nagaya, Masaki; Matsunari, Hitomi; Nakano, Kazuaki; Maehara, Miki; Hayashida, Gota; Takayanagi, Shuko; Sakai, Rieko; Umeyama, Kazuhiro; Watanabe, Nobuyuki; Onodera, Masafumi; Nagashima, Hiroshi

2015-01-01

Monomeric Plum (Plum), a far-red fluorescent protein with photostability and photopermeability, is potentially suitable for in vivo imaging and detection of fluorescence in body tissues. The aim of this study was to generate transgenic cloned pigs exhibiting systemic expression of Plum using somatic cell nuclear transfer (SCNT) technology. Nuclear donor cells for SCNT were obtained by introducing a Plum-expression vector driven by a combination of the cytomegalovirus early enhancer and chicken beta-actin promoter into porcine fetal fibroblasts (PFFs). The cleavage and blastocyst formation rates of reconstructed SCNT embryos were 81.0% (34/42) and 78.6% (33/42), respectively. At 36-37 days of gestation, three fetuses systemically expressing Plum were obtained from one recipient to which 103 SCNT embryos were transferred (3/103, 2.9%). For generation of offspring expressing Plum, rejuvenated PFFs were established from one cloned fetus and used as nuclear donor cells. Four cloned offspring and one stillborn cloned offspring were produced from one recipient to which 117 SCNT embryos were transferred (5/117, 4.3%). All offspring exhibited high levels of Plum fluorescence in blood cells, such as lymphocytes, monocytes and granulocytes. In addition, the skin, heart, kidney, pancreas, liver and spleen also exhibited Plum expression. These observations demonstrated that transfer of the Plum gene did not interfere with the development of porcine SCNT embryos and resulted in the successful generation of transgenic cloned pigs that systemically expressed Plum. This is the first report of the generation and characterization of transgenic cloned pigs expressing the far-red fluorescent protein Plum.

Prepregnancy Diabetes and Offspring Risk of Congenital Heart Disease

PubMed Central

Diaz, Lars J.; Leirgul, Elisabeth; Boyd, Heather A.; Priest, James; Mathiesen, Elisabeth R.; Quertermous, Thomas; Wohlfahrt, Jan; Melbye, Mads

2016-01-01

Background— Maternal diabetes mellitus is associated with an increased risk of offspring congenital heart defects (CHD); however, the causal mechanism is poorly understood. We further investigated this association in a Danish nationwide cohort. Methods and Results— In a national cohort study, we identified 2 025 727 persons born from 1978 to 2011; among them were 7296 (0.36%) persons exposed to maternal pregestational diabetes mellitus. Pregestational diabetes mellitus was identified by using the National Patient Register and individual-level information on all prescriptions filled in Danish pharmacies. Persons with CHD (n=16 325) were assigned to embryologically related cardiac phenotypes. The CHD prevalence in the offspring of mothers with pregestational diabetes mellitus was 318 per 10 000 live births (n=232) in comparison with a baseline risk of 80 per 10 000; the adjusted relative risk for CHD was 4.00 (95% confidence interval, 3.51–4.53). The association was not modified by year of birth, maternal age at diabetes onset, or diabetes duration, and CHD risks associated with type 1 (insulin-dependent) and type 2 (insulin-independent) diabetes mellitus did not differ significantly. Persons born to women with previous acute diabetes complications had a higher CHD risk than those exposed to maternal diabetes mellitus without complications (relative risk, 7.62; 95% confidence interval, 5.23–10.6, and relative risk, 3.49; 95% confidence interval, 2.91–4.13, respectively; P=0.0004). All specific CHD phenotypes were associated with maternal pregestational diabetes mellitus (relative risk range, 2.74–13.8). Conclusions— The profoundly increased CHD risk conferred by maternal pregestational diabetes mellitus neither changed over time nor differed by diabetes subtype. The association with acute pregestational diabetes complications was particularly strong, suggesting a role for glucose in the causal pathway. PMID:27166384

Influences of maternal nutritional status on vascular function in the offspring.

PubMed

Poston, Lucilla

2007-08-01

Fetal growth restriction leading to low birthweight is associated with increased risk of ischaemic heart disease and hypertension in later life. Increasingly, it is recognised that cardiovascular risk may also be initiated in early life when the fetus and neonate are exposed to maternal nutritional excess. This review summarises the studies in man and animals that have investigated the potential role of vascular disorders in the aetiology of atherosclerosis and hypertension arising from early life nutritional deprivation or excess. Malfunction of the arterial endothelial cell layer in the offspring has been frequently described in association with both maternal under and overnutritional states and may play a permissive role in the origin of these disorders. Also prevalent is evidence for increased stiffness of the large arteries which may contribute to systolic hypertension. Further investigation is required into the intriguing suggestion that early life nutritional imbalance may adversely influence vascular angiogenesis leading to rarefaction and increased peripheral vascular resistance.

Aortic Arch Width and Cardiovascular Disease in Men and Women in the Community.

PubMed

Chuang, Michael L; Gona, Philimon N; Qazi, Saadia; Musgrave, Rebecca M; Fox, Caroline S; Massaro, Joseph M; Hoffmann, Udo; O'Donnell, Christopher J

2018-06-16

We sought to determine whether increased aortic arch width (AAW) adds to standard Framingham risk factors and coronary artery calcium (CAC) for prediction of incident adverse cardiovascular disease (CVD) events in community-dwelling adults. A total of 3026 Framingham Heart Study Offspring and Third Generation cohort participants underwent noncontrast multidetector computed tomography from 2002 to 2005 to quantify CAC. We measured AAW as the distance between the centroids of the ascending and descending thoracic aorta, at the level of main pulmonary artery bifurcation or the right pulmonary artery. We determined sex, age group, and body size specific cut points for high (≥90th percentile) AAW from a healthy referent group (N=1471) and dichotomized AAW as high or not high across all study participants. Clinical covariates were obtained at Offspring cycle 7 (1998-2001) or Third Generation cycle 1 (2002-2005) examinations. The primary CVD outcome was a composite of myocardial infarction, coronary insufficiency, cerebrovascular accident, first hospitalization for heart failure, or CVD death. Cox proportional hazards models were used to estimate hazard ratio of high AAW on time-to-incident CVD after adjustment for Framingham risk factors and CAC. Net reclassification improvement was used to assess the effect of adding AAW to the baseline Framingham risk factor+CAC model. A total of 2826 participants (aged 51±11 years, 48% women) had complete covariates and were free of CVD at multidetector computed tomography. Over a median 8.9 years of follow-up, there were 135 incident CVD events. High AAW was independently predictive of CVD events (hazard ratio, 1.55; P =0.032) and appropriately reclassified participants at risk: net reclassification improvement, 0.31 (95% confidence interval, 0.15-0.48). AAW augments traditional CVD risk factors and CAC for prediction of incident adverse CVD events among community-dwelling adults. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring

PubMed Central

Watkins, Adam J; Wilkins, Adrian; Cunningham, Colm; Perry, V Hugh; Seet, Meei J; Osmond, Clive; Eckert, Judith J; Torrens, Christopher; Cagampang, Felino R A; Cleal, Jane; Gray, William P; Hanson, Mark A; Fleming, Tom P

2008-01-01

Early embryonic development is known to be susceptible to maternal undernutrition, leading to a disease-related postnatal phenotype. To determine whether this sensitivity extended into oocyte development, we examined the effect of maternal normal protein diet (18% casein; NPD) or isocaloric low protein diet (9% casein; LPD) restricted to one ovulatory cycle (3.5 days) prior to natural mating in female MF-1 mice. After mating, all females received NPD for the remainder of gestation and all offspring were litter size adjusted and fed standard chow. No difference in gestation length, litter size, sex ratio or postnatal growth was observed between treatments. Maternal LPD did, however, induce abnormal anxiety-related behaviour in open field activities in male and female offspring (P < 0.05). Maternal LPD offspring also exhibited elevated systolic blood pressure (SBP) in males at 9 and 15 weeks and in both sexes at 21 weeks (P < 0.05). Male LPD offspring hypertension was accompanied by attenuated arterial responsiveness in vitro to vasodilators acetylcholine and isoprenaline (P < 0.05). LPD female offspring adult kidneys were also smaller, but had increased nephron numbers (P < 0.05). Moreover, the relationship between SBP and kidney or heart size or nephron number was altered by diet treatment (P < 0.05). These data demonstrate the sensitivity of mouse maturing oocytes in vivo to maternal protein undernutrition and identify both behavioural and cardiovascular postnatal outcomes, indicative of adult disease. These outcomes probably derive from a direct effect of protein restriction, although indirect stress mechanisms may also be contributory. Similar and distinct postnatal outcomes were observed here compared with maternal LPD treatment during post-fertilization preimplantation development which may reflect the relative contribution of the paternal genome. PMID:18308825

Impact of Age, Sex and Indexation Method on MR Left Ventricular Reference Values in the Framingham Heart Study Offspring Cohort

PubMed Central

Yeon, Susan B.; Salton, Carol J.; Gona, Philimon; Chuang, Michael L.; Blease, Susan J.; Han, Yuchi; Tsao, Connie W.; Danias, Peter G.; Levy, Daniel; O’Donnell, Christopher J.; Manning, Warren J.

2014-01-01

Purpose To determine normative values for left ventricular (LV) volumes, mass, concentricity and ejection fraction (EF) and investigate associations between sex, age and body size with LV parameters in community dwelling adults. Materials and Methods 1794 Framingham Heart Study Offspring cohort members underwent LV short-axis oriented, contiguous multislice ciné SSFP MR of the left ventricle; from these a healthy referent group (N=852, 61±9 years, 40% men) free of clinical cardiac disease and hypertension (SBP<140, DBP<90 mmHg, never used antihypertensive medication ≥ 30 years prior to scanning) was identified. Referent participants were stratified by sex and age group (≤55, 56-65, >65 years); LV parameters were indexed to measures of body size. Results Men have greater LV volumes and mass than women both before and after indexation to height, powers of height, and body surface area (p<0.01 all), but indexation to fat-free mass yielded greater LV volume and mass in women. In both sexes, LV volumes and mass decrease with advancing age, though indexation attenuates this association. LVEF is greater in women than men (68±5% vs. 66±5%, p<0.01) and increases with age in both sexes (p<0.05). Conclusion Among non-hypertensive adults free of cardiac disease, men have greater LV volumes and mass with sex differences generally persisting after indexation to body size. LV volumes and mass tend to decrease with greater age in both sexes. Female sex and advanced age were both associated with greater LVEF. PMID:24817313

Mainstream smoke and sidestream smoke affect the cardiac differentiation of mouse embryonic stem cells discriminately.

PubMed

Cheng, Wei; Zhou, Ren; Feng, Yan; Wang, Yan

2016-05-16

Epidemiology studies suggest that maternal smoking and passive smoking have strongly resulted in the occurrence of congenital heart defects (CHD) in offspring. Cigarette smoke (CS) can be divided into mainstream smoke (MS) and sidestream smoke (SS); CS chemistry study indicates that significant differences exist in the composition of MS and SS. Therefore, MS and SS were suspected to process toxicity dissimilarly. However, much less was known about the difference in the developmental effects induced by MS and SS. In the current study, heart development was mimicked by mouse embryonic stem cells (ESCs) differentiation. After MS and SS exposure, by tracing the bone morphogenetic protein (BMP)-Smad4 signalling pathway, interruption of downstream gene expression was observed, including Gata4, Mef2c and Nkx2.5, as well as myosin heavy chain and myosin light chain. Specifically, SS caused inhibition of Gata4 expression, even at non-cytotoxic concentration. Further, SS-induced hypoacetylation in promoter regions of Gata4 reflected the orchestration of CS-gene modulation-epigenetic regulation. Even though SS induced apoptosis in ESC-derived cardiomyocytes, the partial clearance in cells with down-regulated Gata4 caused these cells to survive and undergo further differentiation, which laid potential risk for abnormal heart development. These data uncovered the difference between MS and SS on heart development preliminarily. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Is maternal transmission of coronary heart disease risk stronger than paternal transmission?

PubMed

Kinra, S; Davey Smith, G; Okasha, M; McCarron, P; McEwen, J

2003-08-01

To test whether intergenerational transmission of coronary heart disease (CHD) to offspring is greater from the mother than from the father, the association between parental history of CHD and coronary mortality in male offspring was examined. Prospective cohort study with 43 years of follow up. University of Glasgow. Male students (n = 8402) aged 16-30 years when examined in 1948 to 1968. Fatal CHD. Of the 8402 men studied, 615 (7.3%) reported a history of CHD in at least one of the parents: 479 (5.8%) for fathers only, 124 (1.6%) for mothers only, and a further 12 (0.2%) for both their parents. During follow up, 373 (4.4%) men died of CHD. Parental history of disease was associated with fatal CHD and controlling for personal risk factors such as cigarette smoking, body mass index, systolic blood pressure, and father's social class did not attenuate this relation. The fully adjusted hazard ratios were 1.53 (95% confidence interval (CI) 1.08 to 2.18), 1.19 (95% CI 0.61 to 2.32), and 8.65 (95% CI 2.65 to 28.31) for father only, mother only, and both parents with CHD, respectively, compared with men whose parents did not have CHD. There was some evidence for interaction between parental histories (p = 0.049), with particularly high risk if both parents reported a history of CHD. This study found no differential transmission of CHD. Paternal history of CHD was at least as important as maternal history. Data from other comparable cohorts provide no consistent evidence of differential transmission. Intergenerational transmission of CHD does not appear to have differential effects between mothers and fathers.

Mother-offspring aggregation in home versus conventional blood pressure in the Tohoku Study of Child Development (TSCD).

PubMed

Asayama, Kei; Staessen, Jan A; Hayashi, Katsuhisa; Hosaka, Miki; Tatsuta, Nozomi; Kurokawa, Naoyuki; Satoh, Michihiro; Hashimoto, Takanao; Hirose, Takuo; Obara, Taku; Metoki, Hirohito; Inoue, Ryusuke; Kikuya, Masahiro; Ohkubo, Takayoshi; Nakai, Kunihiko; Imai, Yutaka; Satoh, Hiroshi

2012-08-01

Few studies described the home blood pressure (HBP) in young children. Using intrafamilial correlations of blood pressure as research focus, we assessed the feasibility of HBP monitoring in this age group. We enrolled 382 mothers (mean age 38.8 years) and singletons (7.0 years) in theTohoku Study of Child Development.We measured their conventional blood pressure (CBP; single reading) at an examination centre. Participants monitored HBP in the morning. We used the OMRON HEM-70801C for CBP and HBP measurement. In a separate group of 84 children (mean age 7.7 years), we compared blood pressure readings obtained by the OMRON monitor and the Dinamap Pro 100, a device approved by FDA for use in children. We used correlation coefficients as measure of intrafamilial aggregation, while accounting for the mothers' age, body mass index, heart rate and smoking and drinking habits and the children's age, height, and heart rate. Mother-offspring correlations were closer (P < or = 0.003) for HBP than CBP for systolic pressure [0.28 (P < 0.0001) vs 0.06 (P = 0.26)] and diastolic pressure [0.28 (P < 0.0001) vs 0.02 (P = 0.65)].The between-device differences (OMRON minus Dinamap) averaged 7.8 +/- 6.0 mmHg systolic and 5.8 +/- 5.5 mmHg diastolic. HBP monitoring is an easily applicable method to assess intrafamilial blood pressure aggregation in young children and outperforms CBP. Validation protocols for HBP devices in young children need revision, because the Korotkoff method is not practicable at this age and there is no agreed alternative reference method.

Consanguineous marriage in an urban area of Saudi Arabia: rates and adverse health effects on the offspring.

PubMed

al-Abdulkareem, A A; Ballal, S G

1998-02-01

The objective of this cross-sectional study was to determine the pattern and time trend of consanguineous marriage and its adverse health effects on the offspring in Dammam city, Eastern Province, in the Kingdom of Saudi Arabia. This city is known to attract Saudis from different parts of the country because it is in the heart of this industrial region. Five primary health care centers were randomly selected from different sectors of the city in addition to the city's only Maternity and Children's Hospital. For inclusion in the study a wife must have at least one pregnancy that terminated in either full term liveborn baby, still birth, or abortion. A total of 1307 ever-married Saudis completed a pre-structured questionnaire during an interview. The rate of consanguineous marriage was 52.0% with an average inbreeding coefficient of 0.0312. First-cousin marriages were the commonest (39.3%) of all matings. The consanguineous groups had a significantly higher number of pregnancies. The mean birth weight of the offspring of consanguineous couples was not statistically significant being less than that of the non-consanguineous. However, within the consanguineous groups the more closely related couples had smaller babies on average. No significant differences were noted for the rates of inherited diseases and reproductive wastage. The rate of consanguineous marriage in this city was high and so was the inbreeding coefficient. These figures place this nation among the countries with a high rate of consanguineous marriages. A nationwide study to determine accurately the relationship between consanguinity and inherited diseases has much to commend it.

Insulin and branched-chain amino acid depletion during mouse preimplantation embryo culture programmes body weight gain and raised blood pressure during early postnatal life.

PubMed

Velazquez, Miguel A; Sheth, Bhavwanti; Smith, Stephanie J; Eckert, Judith J; Osmond, Clive; Fleming, Tom P

2018-02-01

Mouse maternal low protein diet exclusively during preimplantation development (Emb-LPD) is sufficient to programme altered growth and cardiovascular dysfunction in offspring. Here, we use an in vitro model comprising preimplantation culture in medium depleted in insulin and branched-chain amino acids (BCAA), two proposed embryo programming inductive factors from Emb-LPD studies, to examine the consequences for blastocyst organisation and, after embryo transfer (ET), postnatal disease origin. Two-cell embryos were cultured to blastocyst stage in defined KSOM medium supplemented with four combinations of insulin and BCAA concentrations. Control medium contained serum insulin and uterine luminal fluid amino acid concentrations (including BCAA) found in control mothers from the maternal diet model (N-insulin+N-bcaa). Experimental medium (three groups) contained 50% reduction in insulin and/or BCAA (L-insulin+N-bcaa, N-insulin+L-bcaa, and L-insulin+N-bcaa). Lineage-specific cell numbers of resultant blastocysts were not affected by treatment. Following ET, a combined depletion of insulin and BCAA during embryo culture induced a non sex-specific increase in birth weight and weight gain during early postnatal life. Furthermore, male offspring displayed relative hypertension and female offspring reduced heart/body weight, both characteristics of Emb-LPD offspring. Combined depletion of metabolites also resulted in a strong positive correlation between body weight and glucose metabolism that was absent in the control group. Our results support the notion that composition of preimplantation culture medium can programme development and associate with disease origin affecting postnatal growth and cardiovascular phenotypes and implicate two important nutritional mediators in the inductive mechanism. Our data also have implications for human assisted reproductive treatment (ART) practice. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Nutrition has a pervasive impact on cardiac microRNA expression in isogenic mice

PubMed Central

Wing-Lun, Edwina; Eaton, Sally A.; Hur, Suzy S. J.; Aiken, Alastair; Young, Paul E.; Buckland, Michael E.; Li, Cheryl C. Y.; Cropley, Jennifer E.; Suter, Catherine M.

2016-01-01

ABSTRACT The complex interaction between obesity, Western-style diets, and cardiovascular disease is of increasing interest, with a growing number of children being born to obese parents with poor lifestyle choices. These offspring have themselves an increased susceptibility to obesity and subsequent cardiovascular disease in adult life, which may be ‘programmed’ by their intrauterine environment. Cardiac microRNAs (miRNAs) are affected by multiple disease states, and have also been shown to be capable of exerting a hormone-like control on whole body metabolism. Here we sought to determine the effect of prenatal exposure to maternal obesity and/or postnatal exposure to a Western diet on miRNA expression in the heart. Unbiased small RNA sequencing was carried out on cardiac tissue from young adult mice born to lean or obese mothers; offspring were weaned onto either a low-fat control diet or a high-fat Western-style diet. We found 8 cardiac miRNAs that were significantly altered in response to maternal obesity, but only when the offspring were challenged postnatally with the Western diet. In contrast, postnatal exposure to the diet alone induced significant changes to the expression of a much larger number of miRNAs (33 in offspring of lean and 46 in offspring of obese). Many of the affected miRNAs have previously been implicated in various cardiac pathologies. The pervasive cardiac miRNA changes induced by a Western diet suggest that an individual's lifestyle choices outweigh the impact of any programming effects by maternal obesity on miRNA-related cardiac health. PMID:27216962

Nutrition has a pervasive impact on cardiac microRNA expression in isogenic mice.

PubMed

Wing-Lun, Edwina; Eaton, Sally A; Hur, Suzy S J; Aiken, Alastair; Young, Paul E; Buckland, Michael E; Li, Cheryl C Y; Cropley, Jennifer E; Suter, Catherine M

2016-07-02

The complex interaction between obesity, Western-style diets, and cardiovascular disease is of increasing interest, with a growing number of children being born to obese parents with poor lifestyle choices. These offspring have themselves an increased susceptibility to obesity and subsequent cardiovascular disease in adult life, which may be 'programmed' by their intrauterine environment. Cardiac microRNAs (miRNAs) are affected by multiple disease states, and have also been shown to be capable of exerting a hormone-like control on whole body metabolism. Here we sought to determine the effect of prenatal exposure to maternal obesity and/or postnatal exposure to a Western diet on miRNA expression in the heart. Unbiased small RNA sequencing was carried out on cardiac tissue from young adult mice born to lean or obese mothers; offspring were weaned onto either a low-fat control diet or a high-fat Western-style diet. We found 8 cardiac miRNAs that were significantly altered in response to maternal obesity, but only when the offspring were challenged postnatally with the Western diet. In contrast, postnatal exposure to the diet alone induced significant changes to the expression of a much larger number of miRNAs (33 in offspring of lean and 46 in offspring of obese). Many of the affected miRNAs have previously been implicated in various cardiac pathologies. The pervasive cardiac miRNA changes induced by a Western diet suggest that an individual's lifestyle choices outweigh the impact of any programming effects by maternal obesity on miRNA-related cardiac health.

The maternal-age-associated risk of congenital heart disease is modifiable.

PubMed

Schulkey, Claire E; Regmi, Suk D; Magnan, Rachel A; Danzo, Megan T; Luther, Herman; Hutchinson, Alayna K; Panzer, Adam A; Grady, Mary M; Wilson, David B; Jay, Patrick Y

2015-04-09

Maternal age is a risk factor for congenital heart disease even in the absence of any chromosomal abnormality in the newborn. Whether the basis of this risk resides with the mother or oocyte is unknown. The impact of maternal age on congenital heart disease can be modelled in mouse pups that harbour a mutation of the cardiac transcription factor gene Nkx2-5 (ref. 8). Here, reciprocal ovarian transplants between young and old mothers establish a maternal basis for the age-associated risk in mice. A high-fat diet does not accelerate the effect of maternal ageing, so hyperglycaemia and obesity do not simply explain the mechanism. The age-associated risk varies with the mother's strain background, making it a quantitative genetic trait. Most remarkably, voluntary exercise, whether begun by mothers at a young age or later in life, can mitigate the risk when they are older. Thus, even when the offspring carry a causal mutation, an intervention aimed at the mother can meaningfully reduce their risk of congenital heart disease.

The potential reproductive, neurobehavioral and systemic effects of soluble sodium tungstate exposure in Sprague-Dawley rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

McInturf, S.M.; Bekkedal, M.Y.V.; Wilfong, E.

2011-07-15

The debate on tungsten (W) is fostered by its continuous usage in military munitions. Reports demonstrate W solubilizes in soil and can migrate into drinking water supplies and, therefore, is a potential health risk to humans. This study evaluated the reproductive, systemic and neurobehavioral effects of sodium tungstate (NaW) in rats following 70 days of daily pre-and postnatal exposure via oral gavage to 5, 62.5 and 125 mg/kg/day of NaW through mating, gestation and weaning (PND 0-20). Daily administration of NaW produced no overt evidence of toxicity and had no apparent effect on mating success or offspring physical development. Distressmore » vocalizations were elevated in F{sub 1} offspring from the high dose group, whereas righting reflex showed unexpected sex differences where males demonstrated faster righting than females; however, the effects were not dose-dependent. Locomotor activity was affected in both low and high-dose groups of F{sub 1} females. Low-dose group showed increased distance traveled, more time in ambulatory movements and less time in stereotypic behavior than controls or high dose animals. The high-dose group had more time in stereotypical movements than controls, and less time resting than controls and the lowest exposure group. Maternal retrieval was not affected by NaW exposure. Tungsten analysis showed a systemic distribution of NaW in both parents and offspring, with preferential uptake within the immune organs, including the femur, spleen and thymus. Histopathological evidence suggested no severe chronic injury or loss of function in these organs. However, the heart showed histological lesions, histiocytic inflammation from minimal to mild with cardiomyocyte degeneration and necrosis in several P{sub 0} animals of 125 mg NaW dose group. The result of this study suggests that pre and postnatal exposure to NaW may produce subtle neurobehavioral effects in offspring related to motor activity and emotionality.« less

Identification and comparative analyses of myocardial miRNAs involved in the fetal response to maternal obesity.

PubMed

Maloyan, Alina; Muralimanoharan, Sribalasubashini; Huffman, Steven; Cox, Laura A; Nathanielsz, Peter W; Myatt, Leslie; Nijland, Mark J

2013-10-01

Human and animal studies show that suboptimal intrauterine environments lead to fetal programming, predisposing offspring to disease in later life. Maternal obesity has been shown to program offspring for cardiovascular disease (CVD), diabetes, and obesity. MicroRNAs (miRNAs) are small, noncoding RNA molecules that act as key regulators of numerous cellular processes. Compelling evidence links miRNAs to the control of cardiac development and etiology of cardiac pathology; however, little is known about their role in the fetal cardiac response to maternal obesity. Our aim was to sequence and profile the cardiac miRNAs that are dysregulated in the hearts of baboon fetuses born to high fat/high fructose-diet (HFD) fed mothers for comparison with fetal hearts from mothers eating a regular diet. Eighty miRNAs were differentially expressed. Of those, 55 miRNAs were upregulated and 25 downregulated with HFD. Twenty-two miRNAs were mapped to human; 14 of these miRNAs were previously reported to be dysregulated in experimental or human CVD. We used an Ingenuity Pathway Analysis to integrate miRNA profiling and bioinformatics predictions to determine miRNA-regulated processes and genes potentially involved in fetal programming. We found a correlation between miRNA expression and putative gene targets involved in developmental disorders and CVD. Cellular death, growth, and proliferation were the most affected cellular functions in response to maternal obesity. Thus, the current study reveals significant alterations in cardiac miRNA expression in the fetus of obese baboons. The epigenetic modifications caused by adverse prenatal environment may represent one of the mechanisms underlying fetal programming of CVD.

Impact of age, sex, and indexation method on MR left ventricular reference values in the Framingham Heart Study offspring cohort.

PubMed

Yeon, Susan B; Salton, Carol J; Gona, Philimon; Chuang, Michael L; Blease, Susan J; Han, Yuchi; Tsao, Connie W; Danias, Peter G; Levy, Daniel; O'Donnell, Christopher J; Manning, Warren J

2015-04-01

To determine normative values for left ventricular (LV) volumes, mass, concentricity, and ejection fraction (EF) and investigate associations between sex, age, and body size with LV parameters in community-dwelling adults. In all, 1794 Framingham Heart Study Offspring cohort members underwent LV short-axis oriented, contiguous multislice cine steady-state free precession MR of the left ventricle; from these a healthy referent group (n = 852, 61 ± 9 years, 40% men) free of clinical cardiac disease and hypertension (SBP < 140, DBP < 90 mmHg, never used antihypertensive medication ≥30 years prior to scanning) was identified. Referent participants were stratified by sex and age group (≤55, 56-65, >65 years); LV parameters were indexed to measures of body size. Men have greater LV volumes and mass than women both before and after indexation to height, powers of height, and body surface area (P < 0.01 all), but indexation to fat-free mass yielded greater LV volume and mass in women. In both sexes, LV volumes and mass decrease with advancing age, although indexation attenuates this association. LVEF is greater in women than men (68 ± 5% vs. 66 ± 5%, P < 0.01) and increases with age in both sexes (P < 0.05). Among nonhypertensive adults free of cardiac disease, men have greater LV volumes and mass with sex differences generally persisting after indexation to body size. LV volumes and mass tend to decrease with greater age in both sexes. Female sex and advanced age were both associated with greater LVEF. J. Magn. Reson. Imaging 2015;41:1038-1045. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

Adaptogen

NASA Astrophysics Data System (ADS)

Mikhaylenko, E. A.; Stepchenko, L. M.

2009-04-01

The mechanism of adaptive action of peat preparations needs further understanding. Therefore, the research studied of the effects of the peat "Hydrohumate", on the adaptation processes of young rats, born from mothers who received this preparation togethewater durinr with g a lengthy time psycho-emotional stress (swimming). The test measured selected activity of proteolytic lysosomol cathepsin L in the spleen, heart and liver tissues, and in the grey matter of the large hemispheres of the cerebrum and cerebellum. The amount of cathepsin L activity was determined in 15- and 30-day-old rats with azocasein as substrate. The experiment established that rats, born from stressed mothers that drank plain water during stress had less body mass and altered organ indexes, including the adrenal gland index, compared to rats born from mothers who drank water with the peat preparation added. The change of cathepsin L activity in offspring of treated rats compared to controls demonstrates that structural adaptations occurred, affecting a perceptible and labile system such as the activity of lysosomal enzymes. Discussion will include the effect of humic preparations added to water on rats in the adaptive mechanisms of offspring after prenatal stress.

Trade-offs in the effects of the apolipoprotein E polymorphism on risks of diseases of the heart, cancer, and neurodegenerative disorders: insights on mechanisms from the Long Life Family Study.

PubMed

Kulminski, Alexander M; Arbeev, Konstantin G; Culminskaya, Irina; Ukraintseva, Svetlana V; Stallard, Eric; Province, Michael A; Yashin, Anatoli I

2015-04-01

The lack of evolutionary established mechanisms linking genes to age-related traits makes the problem of genetic susceptibility to health span inherently complex. One complicating factor is genetic trade-off. Here we focused on long-living participants of the Long Life Family Study (LLFS), their offspring, and spouses to: (1) Elucidate whether trade-offs in the effect of the apolipoprotein E e4 allele documented in the Framingham Heart Study (FHS) are a more general phenomenon, and (2) explore potential mechanisms generating age- and gender-specific trade-offs in the effect of the e4 allele on cancer, diseases of the heart, and neurodegenerative disorders assessed retrospectively in the LLFS populations. The e4 allele can diminish risks of cancer and diseases of the heart and confer risks of diseases of the heart in a sex-, age-, and LLFS-population-specific manner. A protective effect against cancer is seen in older long-living men and, potentially, their sons (>75 years, relative risk [RR]>75=0.48, p=0.086), which resembles our findings in the FHS. The protective effect against diseases of the heart is limited to long-living older men (RR>76=0.50, p=0.016), as well. A detrimental effect against diseases of the heart is characteristic for a normal LLFS population of male spouses and is specific for myocardial infarction (RR=3.07, p=2.1×10(-3)). These trade-offs are likely associated with two inherently different mechanisms, including disease-specific (detrimental; characteristic for a normal male population) and systemic, aging-related (protective; characteristic for older long-living men) mechanisms. The e4 allele confers risks of neurological disorders in men and women (RR=1.98, p=0.046). The results highlight the complex role of the e4 allele in genetic susceptibility to health span.

Persistence of Positive Carryover Effects in the Oyster, Saccostrea glomerata, following Transgenerational Exposure to Ocean Acidification.

PubMed

Parker, Laura M; O'Connor, Wayne A; Raftos, David A; Pörtner, Hans-Otto; Ross, Pauline M

2015-01-01

Ocean acidification (OA) is predicted to have widespread implications for marine organisms, yet the capacity for species to acclimate or adapt over this century remains unknown. Recent transgenerational studies have shown that for some marine species, exposure of adults to OA can facilitate positive carryover effects to their larval and juvenile offspring that help them to survive in acidifying oceanic conditions. But whether these positive carryover effects can persist into adulthood or the next generation is unknown. Here we tested whether positive carryover effects found in larvae of the oyster, Saccostrea glomerata following transgenerational exposure to elevated CO2, could persist into adulthood and whether subsequent transgenerational exposure of adults to elevated CO2 would facilitate similar adaptive responses in the next generation of larvae and juveniles. Following our previous transgenerational exposure of parental adults and first generation (F1) larvae to ambient (385 μatm) and elevated (856 μatm) CO2, newly settled F1 juveniles were transferred to the field at ambient CO2 for 14 months, until they reached reproductive maturity. At this time, the F1 adults were returned to the laboratory and the previous transgenerational CO2 exposure was repeated to produce F2 offspring. We found that the capacity of adults to regulate extracellular pH at elevated CO2 was improved if they had a prior history of transgenerational exposure to elevated CO2. In addition, subsequent transgenerational exposure of these adults led to an increase in the resilience of their larval and juvenile offspring. Offspring with a history of transgenerational exposure to elevated CO2 had a lower percentage abnormality, faster development rate, faster shell growth and increased heart rate at elevated CO2 compared with F2 offspring with no prior history of exposure to elevated CO2. Our results suggest that positive carryover effects originating during parental and larval exposure will be important in mediating some of the impacts of OA for later life-history stages and generations.

Gender differences and normal left ventricular anatomy in an adult population free of hypertension. A cardiovascular magnetic resonance study of the Framingham Heart Study Offspring cohort.

PubMed

Salton, Carol J; Chuang, Michael L; O'Donnell, Christopher J; Kupka, Michelle J; Larson, Martin G; Kissinger, Kraig V; Edelman, Robert R; Levy, Daniel; Manning, Warren J

2002-03-20

We sought to derive gender-specific cardiovascular magnetic resonance (CMR) reference values for normative left ventricular (LV) anatomy and function in a healthy adult population of clinically relevant age. Cardiovascular magnetic resonance imaging is increasingly applied in the clinical setting, but age-relevant, gender-specific normative values are currently unavailable. A representative sample of 318 Framingham Heart Study (FHS) Offspring participants free of clinically overt cardiovascular disease underwent CMR examination to determine LV end-diastolic and end-systolic volume (EDV and ESV, respectively), mass, ejection fraction (EF) and linear dimensions (wall thickness, cavity length). Subjects with a clinical history of hypertension or those with a systolic blood pressure > or =140 mm Hg or diastolic pressure > or =90 mm Hg at any FHS cycle examination were excluded, leaving 142 subjects (63 men, 79 women; age 57 +/- 9 years). All volumetric (EDV, ESV, mass) and unidimensional measures were significantly greater (p < 0.001) in men than in women and remained greater (p < 0.02) after adjustment for subject height. Volumetric measures were greater (p < 0.001) in men than in women after adjustment for body surface area (BSA), but there were increased linear dimensions in women after adjustment for BSA. In particular, end-diastolic dimension indexed to BSA was greater in women (p < 0.001) than in men. There were no gender differences in global LVEF (men = 0.69; women = 0.70). Cardiovascular magnetic resonance measures of LV volumes, mass and linear dimensions differ significantly according to gender and body size. This study provides gender-specific normal CMR reference values, uniquely derived from a population-based sample of persons free of cardiovascular disease and clinical hypertension. These data may serve as a reference to identify LV pathology in the adult population.

Psychiatric disorders in child and adolescent offspring of patients with schizophrenia and bipolar disorder: A controlled study.

PubMed

Sanchez-Gistau, Vanessa; Romero, Soledad; Moreno, Dolores; de la Serna, Elena; Baeza, Inmaculada; Sugranyes, Gisela; Moreno, Carmen; Sanchez-Gutierrez, Teresa; Rodriguez-Toscano, Elisa; Castro-Fornieles, Josefina

2015-10-01

Early clinical manifestations predating schizophrenia (SZ) and bipolar disorder (BP) have not been fully characterized. Child offspring studies are a valuable opportunity to study the natural history of the illness from its earliest stages. However, there is limited evidence assessing young offspring of SZ and BP simultaneously. We set out to assess rates of psychiatric disorders in child and adolescent offspring of SZ and BP, relative to offspring of community controls, so as to characterize the early phenotype of the disorders comparatively. SZ and BP parents with offspring aged 7-17years were recruited through adult mental health services of two tertiary hospitals. Community control (CC) parents were recruited from the same geographical area. Ninety BP-offspring, 41 SZ-offspring and 107 CC-offspring were assessed using the K-SADS-PL by child psychiatrists blinded to parental status. Differences in prevalence of psychiatric disorders between groups were adjusted for confounders and for sibling correlation using generalised estimating equations. We found a gradient of clinical severity and social disadvantage between SZ, BP and CC-offspring. After adjusting for socio-demographic confounders, SZ and BP-offspring presented higher rates of attention deficit hyperactivity disorder (ADHD) than CC-offspring. ADHD was more prevalent in SZ-offspring than BP-offspring, and BP-offspring presented a higher prevalence of depression than CC-offspring. The higher rates of ADHD in SZ-offspring suggest that abnormal neurodevelopmental processes may exert a stronger influence in SZ than BP. Follow-up of these children will help elucidate the role of ADHD and depression phenotypes in predicting future transition to SZ or BP. Copyright © 2015 Elsevier B.V. All rights reserved.

Why does offspring size affect performance? Integrating metabolic scaling with life-history theory

PubMed Central

Pettersen, Amanda K.; White, Craig R.; Marshall, Dustin J.

2015-01-01

Within species, larger offspring typically outperform smaller offspring. While the relationship between offspring size and performance is ubiquitous, the cause of this relationship remains elusive. By linking metabolic and life-history theory, we provide a general explanation for why larger offspring perform better than smaller offspring. Using high-throughput respirometry arrays, we link metabolic rate to offspring size in two species of marine bryozoan. We found that metabolism scales allometrically with offspring size in both species: while larger offspring use absolutely more energy than smaller offspring, larger offspring use proportionally less of their maternally derived energy throughout the dependent, non-feeding phase. The increased metabolic efficiency of larger offspring while dependent on maternal investment may explain offspring size effects—larger offspring reach nutritional independence (feed for themselves) with a higher proportion of energy relative to structure than smaller offspring. These findings offer a potentially universal explanation for why larger offspring tend to perform better than smaller offspring but studies on other taxa are needed. PMID:26559952

Depressed parents' attachment: effects on offspring suicidal behavior in a longitudinal, family study

PubMed Central

MacGregor, Erica K.; Grunebaum, Michael F.; Galfalvy, Hanga C.; Melhem, Nadine; Burke, Ainsley K.; Brent, David A.; Oquendo, Maria A.; Mann, J. John

2015-01-01

Objective To investigate relationships of depressed parents' attachment style to offspring suicidal behavior. Method 244 parents diagnosed with a DSM-IV depressive episode completed the Adult Attachment Questionnaire at study entry. Baseline and yearly follow-up interviews of their 488 offspring tracked suicidal behavior and psychopathology. Survival analysis and marginal regression models with correlated errors for siblings investigated the relationship between parent insecure attachment traits and offspring characteristics. Data analyzed were collected 1992–2008 during a longitudinal family study completed January 31, 2014. Results Parent avoidant attachment predicted offspring suicide attempts at a trend level (p=0.083). Parent anxious attachment did not predict offspring attempts (p=0.961). In secondary analyses, anxious attachment in parents was associated with offspring impulsivity (p=0.034), and in offspring suicide attempters, was associated with greater intent (p=0.045) and lethality of attempts (p=0.003). Avoidant attachment in parents was associated with offspring impulsivity (p=0.025) and major depressive disorder (p=0.012). Parent avoidant attachment predicted a greater number of suicide attempts (p=0.048) and greater intent in offspring attempters (p=0.003). Results were comparable after adjusting for parent diagnosis of borderline personality disorder. Conclusion Insecure avoidant, but not anxious, attachment in depressed parents may predict offspring suicide attempt. Insecure parent attachment traits were associated with impulsivity and major depressive disorder in all offspring, and with more severe suicidal behavior in offspring attempters. Insecure parental attachment merits further study as a potential target to reduce risk of offspring psychopathology and more severe suicidal behavior. PMID:25098943

Depressed parents' attachment: effects on offspring suicidal behavior in a longitudinal family study.

PubMed

MacGregor, Erica K; Grunebaum, Michael F; Galfalvy, Hanga C; Melhem, Nadine; Burke, Ainsley K; Brent, David A; Oquendo, Maria A; Mann, J John

2014-08-01

To investigate relationships of depressed parents' attachment style to offspring suicidal behavior. 244 parents diagnosed with a DSM-IV depressive episode completed the Adult Attachment Questionnaire at study entry. Baseline and yearly follow-up interviews of their 488 offspring tracked suicidal behavior and psychopathology. Survival analysis and marginal regression models with correlated errors for siblings investigated the relationship between parent insecure attachment traits and offspring characteristics. Data analyzed were collected 1992-2008 during a longitudinal family study completed January 31, 2014. Parental avoidant attachment predicted offspring suicide attempts at a trend level (P = .083). Parental anxious attachment did not predict offspring attempts (P = .961). In secondary analyses, anxious attachment in parents was associated with offspring impulsivity (P = .034) and, in offspring suicide attempters, was associated with greater intent (P = .045) and lethality of attempts (P = .003). Avoidant attachment in parents was associated with offspring impulsivity (P = .025) and major depressive disorder (P = .012). Parental avoidant attachment predicted a greater number of suicide attempts (P = .048) and greater intent in offspring attempters (P = .003). Results were comparable after adjusting for parent diagnosis of borderline personality disorder. Insecure avoidant, but not anxious, attachment in depressed parents may predict offspring suicide attempt. Insecure parental attachment traits were associated with impulsivity and major depressive disorder in all offspring and with more severe suicidal behavior in offspring attempters. Insecure parental attachment merits further study as a potential target to reduce risk of offspring psychopathology and more severe suicidal behavior. © Copyright 2014 Physicians Postgraduate Press, Inc.

Maternal depression during pregnancy and offspring depression in adulthood: role of child maltreatment

PubMed Central

Plant, Dominic T.; Pariante, Carmine M.; Sharp, Deborah; Pawlby, Susan

2015-01-01

Background Studies have shown that maternal depression during pregnancy predicts offspring depression in adolescence. Child maltreatment is also a risk factor for depression. Aims To investigate (a) whether there is an association between offspring exposure to maternal depression in pregnancy and depression in early adulthood, and (b) whether offspring child maltreatment mediates this association. Method Prospectively collected data on maternal clinical depression in pregnancy, offspring child maltreatment and offspring adulthood (18–25 years) DSM-IV depression were analysed in 103 mother–offspring dyads of the South London Child Development Study. Results Adult offspring exposed to maternal depression in pregnancy were 3.4 times more likely to have a DSM-IV depressive disorder, and 2.4 times more likely to have experienced child maltreatment, compared with non-exposed offspring. Path analysis revealed that offspring experience of child maltreatment mediated the association between exposure to maternal depression in pregnancy and depression in adulthood. Conclusions Maternal depression in pregnancy is a key vulnerability factor for offspring depression in early adulthood. PMID:26045352

Effects of Bisphenol A on Incidence and Severity of Cardiac Lesions in the NCTR- Sprague-Dawley Rat: A CLARITY-BPA Study

PubMed Central

Gear, Robin; Kendziorski, Jessica A.; Belcher, Scott M.

2017-01-01

The goal of this study was to determine whether bisphenol A (BPA) had adverse effects indicative of cardiac toxicity. As part of the “Consortium Linking Academic and Regulatory Insights on BPA Toxicity” (CLARITY-BPA), study dams and offspring were exposed by daily gavage to five doses of BPA ranging from 2.5 to 25000 μg/kg/day, 0.05 or 0.5 μg/kg/day 17α-ethinyl-estradiol (EE) or 0.3% carboxymethylcellulose vehicle. Exposure-related effects were analyzed in isolated hearts by quantitative morphometry and histopathology. No dose-related changes in body weight were detected. Across all exposure groups including vehicle controls, body weight of continuously dosed males was reduced compared to males dosed only until PND21. Heart weight was increased only in females exposed to EE, and consistent alterations in LV wall thickness were not observed. Exposure-related changes in collagen accumulation were minor and limited to highest EE exposure groups with increased collagen accumulation in PND21 males. Decreased collagen was observed in hearts of BPA or EE exposed females at PND90 and PND180. In BPA or EE treated females cardiomyopathy incidence and severity was significantly increased compared to control females at PND21 with myocardial degeneration observed in both males and females at PND21 and PND90. PMID:28499613

Getting to the Heart of Emotion Regulation in Youth: The Role of Interoceptive Sensitivity, Heart Rate Variability, and Parental Psychopathology

PubMed Central

Sütterlin, Stefan; Braet, Caroline; Mueller, Sven C.

2016-01-01

Emotion regulation and associated autonomic activation develop throughout childhood and adolescence under the influence of the family environment. Specifically, physiological indicators of autonomic nervous system activity such as interoceptive sensitivity and vagally mediated heart rate variability (HRV) can inform on emotion regulation. Although the effect of parental emotion socialization on emotion regulation appears to be influenced by autonomic processes, research on physiological regulation and the influence of parental factors remains scarce. This study investigated the relationship between self-reported habitual emotion regulation strategies and HRV at rest as well as interoceptive sensitivity in forty-six youngsters (27 female; age: M = 13.00, SD = 2.13). Secondly, the association between these autonomic correlates and parental psychopathology was also studied. Whereas better interoceptive sensitivity was related to reduced maladaptive emotion regulation, specifically rumination, high HRV was related to more use of external emotion regulation strategies (i.e., support seeking). In addition, increased HRV and decreased interoceptive sensitivity were associated with maternal internalizing and there was evidence for a possible mediation effect of HRV in the relationship between maternal internalizing and child external emotion regulation. This study elucidates the link between cognitive emotion regulation strategies and underlying physiological regulation in adolescents but also indicates a putative influence of maternal internalizing symptoms on emotion regulation in their offspring. PMID:27741261

In vitro fertilization affects growth and glucose metabolism in a sex-specific manner in an outbred mouse model.

PubMed

Donjacour, Annemarie; Liu, Xiaowei; Lin, Wingka; Simbulan, Rhodel; Rinaudo, Paolo F

2014-04-01

The preimplantation period is a time of reprogramming that may be vulnerable to disruption. This question has wide clinical relevance since the number of children conceived by in vitro fertilization (IVF) is rising. To examine this question, outbred mice (CF1 × B6D2F1) conceived by IVF and cultured using Whitten medium and 20% O2 (IVFWM group, less optimal) or K simplex optimized medium with amino acids and 5% O2 (IVFKAA group, more optimal and similar to conditions used in human IVF) were studied postnatally. We found that flushed blastocysts transferred to recipient mice provided the best control group (FB group), as this accounted for the effects of superovulation, embryo transfer, and litter size. We observed that many physiological parameters were normal. Reassuringly, IVFKAA offspring did not differ significantly from FB offspring. However, male IVFWM mice (but not females) were larger during the first 19 wk of life and exhibited glucose intolerance. Male IVFWM mice also showed enlarged left heart despite normal blood pressure. Expression of candidate imprinted genes (H19, Igf2, and Slc38a4) in multiple adult tissues did not show differences among the groups; only Slc38a4 was down-regulated following IVF (in both culture conditions) in female adipose tissue. These studies demonstrate that adult metabolism is affected by the type of conditions encountered during the preimplantation stage. Further, the postnatal growth trajectory and glucose homeostasis following ex vivo manipulation may be sexual dimorphic. Future work on the long-term effects of IVF offspring should focus on glucose metabolism and the cardiovascular system.

Relation of parental history of coronary heart disease to obesity in young adults.

PubMed

Grotto, I; Huerta, M; Kark, J D; Shpilberg, O; Meyerovitch, J

2003-03-01

To assess the association between obesity and parental coronary heart disease (CHD) history. Analysis of data from an ongoing, large-scale survey on medical status, health behaviour and attitudes. Representative samples of Israeli military personnel upon discharge from compulsory service at age 20-22 y. Overall 14297 men and 11638 women were interviewed and examined upon release from military service between 1989 and 1999. Data on demographic characteristics, family history of CHD, lifestyle, weight and height were collected. Analysis of variance and logistic regression were used. Higher mean body mass index (BMI) and obesity (BMI>30 kg/m(2)) were associated with paternal CHD history in both sexes, and with maternal CHD history among men. Offspring of a parent with a positive CHD history had a higher mean BMI (23.22 vs 22.86 kg/m(2), P<0.001) and were more likely to be obese (5.4 vs 3.7%, P<0.001) than offspring of parents with no history of CHD. Multivariate adjustment for demographic and behavioural variables associated with obesity attenuated the association (adjusted odds ratio for obesity 1.37, 95% confidence interval: 1.15, 1.64). When stratified by sex, this association remained statistically significant only among males. Young adults with a parental history of CHD are more likely to be overweight. This high-risk group should be targeted for early preventive activities.

Relations of long-term and contemporary lipid levels and lipid genetic risk scores with coronary artery calcium in the framingham heart study.

PubMed

Tsao, Connie W; Preis, Sarah Rosner; Peloso, Gina M; Hwang, Shih-Jen; Kathiresan, Sekar; Fox, Caroline S; Cupples, L Adrienne; Hoffmann, Udo; O'Donnell, Christopher J

2012-12-11

This study evaluated the association of timing of lipid levels and lipid genetic risk score (GRS) with subclinical atherosclerosis. Atherosclerosis is a slowly progressive disorder influenced by suboptimal lipid levels. Long-term versus contemporary lipid levels may more strongly impact the development of coronary artery calcium (CAC). Framingham Heart Study (FHS) Offspring Cohort participants (n = 1,156, 44% male, 63 ± 9 years) underwent serial fasting lipids (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein, and triglycerides), Exam 1 (1971 to 1975) to Exam 7 (1998 to 2001). FHS Third Generation Cohort participants (n = 1,954, 55% male, 45 ± 6 years) had fasting lipid profiles assessed, 2002 to 2005. Computed tomography (2002 to 2005) measured CAC. Lipid GRSs were computed from significantly associated single-nucleotide polymorphisms. The association between early, long-term average, and contemporary lipids, and lipid GRS with elevated CAC was assessed using logistic regression. In FHS Offspring, Exam 1 and long-term average as compared with Exam 7 lipid measurements, including untreated lipid levels, were strongly associated with elevated CAC. In the FHS Third Generation, contemporary lipids were associated with CAC. The LDL-C GRS was associated with CAC (age-/sex-adjusted odds ratio: 1.14, 95% confidence interval: 1.00 to 1.29, p = 0.04). However, addition of the GRS to the lipid models did not result in a significant increase in the odds ratio or C-statistic for any lipid measure. Early and long-term average lipid levels, as compared with contemporary measures, are more strongly associated with elevated CAC. Lipid GRS was associated with lipid levels but did not predict elevated CAC. Adult early and long-term average lipid levels provide important information when assessing subclinical atherosclerosis and cardiovascular risk. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Gene variants in the folate-mediated one-carbon metabolism (FOCM) pathway as risk factors for conotruncal heart defects.

PubMed

Zhu, Huiping; Yang, Wei; Lu, Wei; Etheredge, Analee J; Lammer, Edward J; Finnell, Richard H; Carmichael, Suzan L; Shaw, Gary M

2012-05-01

We evaluated 35 variants among four folate-mediated one-carbon metabolism pathway genes, MTHFD1, SHMT1, MTHFR, and DHFR as risk factors for conotruncal heart defects. Cases with a diagnosis of single gene disorders or chromosomal aneusomies were excluded. Controls were randomly selected from area hospitals in proportion to their contribution to the total population of live-born infants. Odds ratios (OR) and the 95% confidence intervals (CI) were computed for each genotype (homozygous variant or heterozygote, vs. homozygous wildtype) and for increase of each less common allele (log-additive model). Interactions between each variant and three folate intake variables (maternal multivitamin use, maternal dietary folate intake, and combined maternal folate intake) were also evaluated under the log-additive model. In general, we did not identify notable associations. The A allele of MTHFD1 rs11627387 was associated with a 1.7-fold increase in conotruncal defects risk in both Hispanic mothers (OR = 1.7, 95% CI = 1.1-2.5) and Hispanic infants (OR = 1.7, 95% CI = 1.2-2.3). The T allele of MTHFR rs1801133 was associated with a 2.8-fold increase of risk among Hispanic women whose dietary folate intake was ≤ 25th centile. The C allele of MTHFR rs1801131 was associated with a two-fold increase of risk (OR = 2.0, 95% CI = 1.0-3.9) only among those whose dietary folate intake was >25th centile. Our study suggested that MTHFD1 rs11627387 may be associated with risk of conotruncal defects through both maternal and offspring genotype effect among the Hispanics. Maternal functional variants in MTHFR gene may interact with dietary folate intake and modify the conotruncal defects risk in the offspring. Copyright © 2012 Wiley Periodicals, Inc.

Usefulness of Desirable Lifestyle Factors to Attenuate the Risk of Heart Failure Among Offspring whose Parents had Myocardial Infarction before Age 55 Years

PubMed Central

Khawaja, Owais; Kotler, Gregory; Gaziano, John Michael; Djoussé, Luc

2012-01-01

Heart failure (HF) is one of the leading causes of hospitalization and death in United States and throughout Europe. While a higher risk of HF with antecedent myocardial infarction (MI) has been reported in offspring whose parents had MI before age 55, it is unclear whether adherence to healthful behaviors could mitigate that risk. The aim of the current study was therefore to prospectively examine if adherence to healthy weight, regular exercise, moderate alcohol consumption, and abstinence from smoking can attenuate such increased HF risk. The information on parental history of MI and lifestyle factors was collected using questionnaires. Subjects adhering to at least three healthy lifestyle factors were classified as having good vs. poor lifestyle score. Incident HF was assessed via yearly follow-up questionnaires and validated in a subsample. During an average follow up of 21.7 (6.5) years, 1,323 new HF cases (6.6%) of which 190 (14.4%) were preceded by MI occurred. Compared to subjects with good lifestyle score and no parental history of premature MI, multivariable adjusted hazard ratios (95% CI) for incident HF with antecedent MI was 3.21 (1.74–5.91) for people with good lifestyle score and parental history of premature MI; 1.52 (1.12–2.07) for individuals with poor lifestyle score and no parental history of premature MI; and 4.60 (2.55–8.30) for people with poor lifestyle score and parental history of premature MI. In conclusion, our data suggest that even in people at higher risk of HF due to genetic predisposition, adherence to healthful lifestyle factors may attenuate such an elevated HF risk. PMID:22516528

Prenatal stress and balance of the child's cardiac autonomic nervous system at age 5-6 years.

PubMed

van Dijk, Aimée E; van Eijsden, Manon; Stronks, Karien; Gemke, Reinoud J B J; Vrijkotte, Tanja G M

2012-01-01

Autonomic nervous system (ANS) misbalance is a potential causal factor in the development of cardiovascular disease. The ANS may be programmed during pregnancy due to various maternal factors. Our aim is to study maternal prenatal psychosocial stress as a potential disruptor of cardiac ANS balance in the child. Mothers from a prospective birth cohort (ABCD study) filled out a questionnaire at gestational week 16 [IQR 12-20], that included validated instruments for state anxiety, depressive symptoms, pregnancy-related anxiety, parenting daily hassles and job strain. A cumulative stress score was also calculated (based on 80(th) percentiles). Indicators of cardiac ANS in the offspring at age 5-6 years are: pre-ejection period (PEP), heart rate (HR), respiratory sinus arrhythmia (RSA) and cardiac autonomic balance (CAB), measured with electrocardiography and impedance cardiography in resting supine and sitting positions. 2,624 mother-child pairs, only single births, were available for analysis. The stress scales were not significantly associated with HR, PEP, RSA and CAB (p≥0.17). Accumulation of maternal stress was also not associated with HR, PEP, RSA and CAB (p≥0.07). Results did not support the hypothesis that prenatal maternal psychosocial stress deregulates cardiac ANS balance in the offspring, at least in rest, and at the age of five-six years.

Academic Achievement in Primary School in Offspring Born to Mothers With Type 1 Diabetes (the EPICOM Study): A Register-Based Prospective Cohort Study.

PubMed

Knorr, Sine; Clausen, Tine D; Vlachová, Zuzana; Bytoft, Birgitte; Damm, Peter; Beck-Nielsen, Henning; Jensen, Dorte M; Juul, Svend; Gravholt, Claus Højbjerg

2015-07-01

This study examined the effect of maternal pregestational type 1 diabetes on offspring primary school performance. We performed a prospective combined clinical and register-based cohort study comparing primary school performance in offspring (n = 707) of women with pregestational type 1 diabetes with matched control offspring (n = 60,341). We also examined the association between HbA1c levels during pregnancy and later school performance among offspring born to women with pregestational type 1 diabetes. Offspring of mothers with pregestational type 1 diabetes obtained similar school grades as control offspring when finishing primary school (regression coefficient [β] = -0.13; 95% CI = -0.30 to 0.03; P = 0.12). Adjusting for parental education also resulted in an insignificant difference between the two groups (β = -0.07; 95% CI = -0.23 to 0.09; P = 0.37). Among offspring of women with type 1 diabetes, increasing maternal HbA1c pregestationally and throughout the pregnancy was associated with lower average school grades. Offspring born to mothers with good glycemic control in the third trimester obtained higher average school grades compared with control offspring. The opposite applied to offspring born to mothers with inadequate glycemic control, who obtained significantly lower average school grades compared with control offspring. Offspring of mothers with pregestational type 1 diabetes obtained similar average grades when finishing primary school compared with matched control offspring. Among offspring of women with type 1 diabetes, we found a consistent negative association between maternal HbA1c in pregnancy and primary school grades. However, whether this association reflects a direct causal influence of intrauterine hyperglycemia is uncertain. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

The Relationship Between Stressful Life Events and Axis I Diagnoses Among Adolescent Offspring of Probands With Bipolar and Non-Bipolar Psychiatric Disorders and Healthy Controls: The Pittsburgh Bipolar Offspring Study (BIOS).

PubMed

Pan, Lisa A; Goldstein, Tina R; Rooks, Brian T; Hickey, Mary; Fan, Jie Yu; Merranko, John; Monk, Kelly; Diler, Rasim S; Sakolsky, Dara J; Hafeman, Danella; Iyengar, Satish; Goldstein, Benjamin; Kupfer, David J; Axelson, David A; Brent, David A; Birmaher, Boris

2017-03-01

Previous studies have explored the role of stressful life events in the development of mood disorders. We examined the frequency and nature of stressful life events as measured by the Stressful Life Events Schedule (SLES) among 3 groups of adolescent offspring of probands with bipolar (BD), with non-BD psychiatric disorders, and healthy controls. Furthermore, we examined the relationship between stressful life events and the presence of DSM-IV Axis I disorders in these offspring. Stressful life events were characterized as dependent, independent, or uncertain (neither dependent nor independent) and positive, negative, or neutral (neither positive nor negative). Offspring of probands with BD aged 13-18 years (n = 269), demographically matched offspring of probands with non-BD Axis I disorders (n = 88), and offspring of healthy controls (n = 81) from the Pittsburgh Bipolar Offspring Study were assessed from 2002 to 2007 with standardized instruments at intake. Probands completed the SLES for their offspring for life events within the prior year. Life events were evaluated with regard to current Axis I diagnoses in offspring after adjusting for confounds. After adjusting for demographic and clinical between-group differences (in probands and offspring), offspring of probands with BD had greater independent (χ² = 11.96, P < .04) and neutral (χ² = 17.99, P < .003) life events compared with offspring of healthy controls and greater number of more severe stressful life events than offspring of healthy controls, but not offspring of probands with non-BD. Offspring of BD probands with comorbid substance use disorder reported more independent stressful life events compared to those without comorbid substance use disorder (P = .024). Greater frequency and severity of stressful life events were associated with current Axis I disorder in offspring of both probands with BD and probands with other Axis I disorders regardless of dependency or valence. Greater frequency and severity of stressful life events were associated with greater current Axis I disorder in all offspring. Offspring of probands with BD have greater exposure to independent and neutral life events than offspring of healthy controls. Greater frequency and severity of stressful life events were associated with Axis I disorder in offspring of both BD and non-BD affected probands. © Copyright 2017 Physicians Postgraduate Press, Inc.

The Role of Depression in the Differential Effect of Childhood Parental Divorce on Male and Female Adult Offspring Suicide Attempt Risk

PubMed Central

Lizardi, Dana; Thompson, Ronald G.; Keyes, Katherine; Hasin, Deborah

2013-01-01

In previous studies by our group, we found that female offspring of parental divorce and parental remarriage are more susceptible to suicide attempt than male offspring. In this study, we examine whether these findings remain even after controlling for offspring depression. The sample consists of respondents from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions. Multivariable regressions controlled for offspring depression, parental depression, age, race/ethnicity, income, and marital status. Our previous findings that female offspring of parental divorce and parental remarriage are more likely to report a lifetime suicide attempt than male offspring remained even after controlling for offspring depression. Findings suggest that focusing on engaging female offspring who demonstrate symptoms of depression is not sufficient to reduce suicide attempt risk in this group as many at risk individuals will remain unrecognized. PMID:20823733

The role of depression in the differential effect of childhood parental divorce on male and female adult offspring suicide attempt risk.

PubMed

Lizardi, Dana; Thompson, Ronald G; Keyes, Katherine; Hasin, Deborah

2010-09-01

In previous studies by our group, we found that female offspring of parental divorce and parental remarriage are more susceptible to suicide attempt than male offspring. In this study, we examine whether these findings remain even after controlling for offspring depression. The sample consists of respondents from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions. Multivariable regressions controlled for offspring depression, parental depression, age, race/ethnicity, income, and marital status. Our previous findings that female offspring of parental divorce and parental remarriage are more likely to report a lifetime suicide attempt than male offspring remained even after controlling for offspring depression. Findings suggest that focusing on engaging female offspring who demonstrate symptoms of depression is not sufficient to reduce suicide attempt risk in this group as many at risk individuals will remain unrecognized.

Parental Legacy in Insects: Variation of Transgenerational Immune Priming during Offspring Development

PubMed Central

Trauer, Ute; Hilker, Monika

2013-01-01

In insects, a parental immune challenge can prepare and enhance offspring immune activity. Previous studies of such transgenerational immune priming (TGIP) mainly focused on a single offspring life stage. However, different developmental stages may be exposed to different risks and show different susceptibility to parental immune priming. Here we addressed the question (i) whether TGIP effects on the immunity of Manduca sexta offspring vary among the different developmental offspring stages. We differentiated between unchallenged and immunochallenged offspring; for the latter type of offspring, we further investigated (ii) whether TGIP has an impact on the time that enhanced immune levels persist after offspring immune challenge. Finally, we determined (iii) whether TGIP effects on offspring performance depend on the offspring stage. Our results show that TGIP effects on phenoloxidase (PO) activity, but not on antibacterial activity, vary among unchallenged offspring stages. In contrast, TGIP effects on PO and antibacterial activity did not vary among immunochallenged offspring stages. The persistence of enhanced immune levels in immunochallenged offspring was dependent on the parental immune state. Antibacterial (but not PO) activity in offspring of immunochallenged parents decreased over five days after pupal immune challenge, whereas no significant change over time was detectable in offspring of control parents. Finally, TGIP effects on the developmental time of unchallenged offspring varied among stages; young larvae of immunochallenged parents developed faster and gained more weight than larvae of control parents. However, offspring females of immunochallenged parents laid fewer eggs than females derived from control parents. These findings suggest that the benefits which the offspring gains from TGIP during juvenile development are paid by the adults with reduced reproductive power. Our study shows that TGIP effects vary among offspring stages and depend on the type of immunity (PO or antibacterial activity) as well as the time past offspring immune challenge. PMID:23700423

Unique dietary patterns and chronic disease risk profiles of adult men: the Framingham nutrition studies.

PubMed

Millen, Barbara E; Quatromoni, Paula A; Pencina, Michael; Kimokoti, Ruth; Nam, Byung-H O; Cobain, Sonia; Kozak, Waldemar; Appugliese, Danielle P; Ordovas, Jose; D'Agostino, Ralph B

2005-11-01

To identify the dietary patterns of adult men and examine their relationships with nutrient intake and chronic disease risk over long-term follow-up. Baseline 145-item food frequency questionnaires from 1,666 Framingham Offspring-Spouse cohort men were used to identify comprehensive dietary patterns. Independent 3-day dietary records at baseline and 8 years later provided estimates of subjects' nutrient intake by dietary pattern. Chronic disease risk factor status was compared at baseline and 16-year follow-up across all male dietary patterns. Cluster analysis was applied to food frequency data to identify non-overlapping male dietary patterns. Analysis of covariance and logistic regression were used to compare nutrient intake, summary nutritional risk scores, and chronic disease risk status at baseline and follow-up by male dietary pattern. Five distinct and comprehensive dietary patterns of Framingham Offspring-Spouse men were identified and ordered according to overall nutritional risk: Transition to Heart Healthy, Higher Starch, Average Male, Lower Variety, and Empty Calories. Nutritional risk was high and varied by dietary pattern; key nutrient contrasts were stable over 8-year follow-up. Chronic disease risk also varied by dietary pattern and specific subgroup differences persisted over 16 years, notably rates of overweight/obesity and smoking. Quantitative cluster analysis applied to food frequency questionnaire data identified five distinct, comprehensive, and stable dietary patterns of adult Framingham Offspring-Spouse cohort men. The close associations between the dietary patterns, nutritional risk, and chronic disease profiles of men emphasize the importance of targeted preventive nutrition interventions to promote health in the male population.

Pathways to suicide-related behavior in offspring of mothers with depression: the role of offspring psychopathology.

PubMed

Hammerton, Gemma; Zammit, Stanley; Mahedy, Liam; Pearson, Rebecca M; Sellers, Ruth; Thapar, Anita; Collishaw, Stephan

2015-05-01

Offspring of mothers with depression are a high-risk group for the development of suicide-related behavior. These offspring are therefore a priority for preventive interventions; however, pathways contributing to risk, including specific aspects of offspring psychopathology, remain unclear. The aim of this study was to examine whether offspring symptoms of major depressive disorder (MDD), generalized anxiety disorder (GAD), disruptive behavior disorder (DBD), attention-deficit/hyperactivity disorder (ADHD), and alcohol abuse independently mediate the association between maternal depression and offspring suicide-related behavior. Data were used from a population-based birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Three distinct classes of depression symptoms across the mothers' first 11 years of their child's life were identified (minimal, moderate, chronic-severe). Offspring psychopathology was assessed at age 15 years and suicide-related behavior at age 16 years. Data were analyzed using structural equation modeling. There was evidence for increased risk of suicidal ideation in offspring of mothers with chronic-severe depression symptoms in comparison to offspring of mothers with minimal symptoms (odds ratio = 3.04, 95% CI = 2.19, 4.21). This association was independently mediated by offspring MDD, GAD, and DBD symptoms. The same mechanisms were found for offspring of mothers with moderate depression symptoms over time. Results were similar for offspring suicide attempt except for additional evidence of an indirect effect through offspring ADHD symptoms. Findings highlight that suicide prevention efforts in offspring of mothers with depression should not only be targeted at offspring with MDD; it is also important to consider offspring with other forms of psychopathology. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Pathways to Suicide-Related Behavior in Offspring of Mothers With Depression: The Role of Offspring Psychopathology

PubMed Central

Hammerton, Gemma; Zammit, Stanley; Mahedy, Liam; Pearson, Rebecca M.; Sellers, Ruth; Thapar, Anita; Collishaw, Stephan

2015-01-01

Objective Offspring of mothers with depression are a high-risk group for the development of suicide-related behavior. These offspring are therefore a priority for preventive interventions; however, pathways contributing to risk, including specific aspects of offspring psychopathology, remain unclear. The aim of this study was to examine whether offspring symptoms of major depressive disorder (MDD), generalized anxiety disorder (GAD), disruptive behavior disorder (DBD), attention-deficit/hyperactivity disorder (ADHD), and alcohol abuse independently mediate the association between maternal depression and offspring suicide-related behavior. Method Data were used from a population-based birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Three distinct classes of depression symptoms across the mothers’ first 11 years of their child’s life were identified (minimal, moderate, chronic-severe). Offspring psychopathology was assessed at age 15 years and suicide-related behavior at age 16 years. Data were analyzed using structural equation modeling. Results There was evidence for increased risk of suicidal ideation in offspring of mothers with chronic-severe depression symptoms in comparison to offspring of mothers with minimal symptoms (odds ratio = 3.04, 95% CI = 2.19, 4.21). This association was independently mediated by offspring MDD, GAD, and DBD symptoms. The same mechanisms were found for offspring of mothers with moderate depression symptoms over time. Results were similar for offspring suicide attempt except for additional evidence of an indirect effect through offspring ADHD symptoms. Conclusion Findings highlight that suicide prevention efforts in offspring of mothers with depression should not only be targeted at offspring with MDD; it is also important to consider offspring with other forms of psychopathology. PMID:25901775

Parental Post-traumatic Stress Disorder Symptoms Are Related to Successful Aging in Offspring of Holocaust Survivors

PubMed Central

Shrira, Amit; Ayalon, Liat; Bensimon, Moshe; Bodner, Ehud; Rosenbloom, Tova; Yadid, Gal

2017-01-01

A fascinating, yet underexplored, question is whether traumatic events experienced by previous generations affect the aging process of subsequent generations. This question is especially relevant for offspring of Holocaust survivors (OHS), who begin to face the aging process. Some preliminary findings point to greater physical dysfunction among middle-aged OHS, yet the mechanisms behind this dysfunction need further clarification. Therefore, the current studies assess aging OHS using the broad-scoped conceptualization of successful aging, while examining whether offspring successful aging relates to parental post-traumatic stress disorder (PTSD) symptoms and offspring’s secondary traumatization symptoms. In Study 1, 101 adult offspring (mean age = 62.31) completed measures of parental PTSD, secondary traumatization, as well as successful aging indices – objective (medical conditions, disability and somatic symptoms) and subjective (perceptions of one’s aging). Relative to comparisons and OHS who reported that none of their parents suffered from probable PTSD, OHS who reported that their parents suffered from probable PTSD had lower scores in objective and subjective measures of successful aging. Mediation analyses showed that higher level of secondary traumatization mediated the relationship between parental PTSD and less successful aging in the offspring. Study 2 included 154 dyads of parents (mean age = 81.86) and their adult offspring (mean age = 54.48). Parents reported PTSD symptoms and offspring reported secondary traumatization and completed measures of objective successful aging. Relative to comparisons, OHS whose parent had probable PTSD have aged less successfully. Once again, offspring secondary traumatization mediated the effect. The findings suggest that parental post-traumatic reactions assessed both by offspring (Study 1) and by parents themselves (Study 2) take part in shaping the aging of the subsequent generation via reactions of secondary traumatization in the offspring. The studies also provide initial evidence that these processes can transpire even when offspring do not have probable PTSD or when controlling offspring anxiety symptoms. Our findings allude to additional behavioral and epigenetic processes that are potentially involved in the effect of parental PTSD on offspring aging, and further imply the need to develop interdisciplinary interventions aiming at promoting successful aging among offspring of traumatized parents. PMID:28706503

Parental obesity and risk factors for cardiovascular disease among their offspring in mid-life: findings from the 1958 British Birth Cohort Study.

PubMed

Cooper, R; Pinto Pereira, S M; Power, C; Hyppönen, E

2013-12-01

Few studies have investigated whether parental adiposity is associated with offspring cardiovascular health or the underlying pathways. Studying these associations may help to illuminate the paradox of increasing prevalence of obesity and declining trends in cardiovascular disease (CVD) mortality, which may be partially explained by beneficial adaptations to an obesogenic environment among people exposed to such environments from younger ages. To investigate associations between parental body mass index (BMI) and risk factors for CVD among their offspring in mid-life and to test whether associations of offspring BMI with CVD risk factors were modified by parental BMI. Data from parents and offspring in the 1958 British birth cohort were used (N=9328). Parental BMI was assessed when offspring were aged 11 years; offspring BMI, waist circumference and CVD risk factors (lipid levels, blood pressure, glycosylated haemoglobin (HbA1c) and inflammatory and haemostatic markers) were measured at 44-45 years. Higher parental BMI was associated with less favourable levels of offspring risk factors for CVD. Most associations were maintained after adjustment for offspring lifestyle and socioeconomic factors but were largely abolished or reversed after adjustment for offspring adiposity. For some CVD risk factors, there was evidence of effect modification; the association between higher BMI and an adverse lipid profile among offspring was weaker if maternal BMI had been higher. Conversely, offspring BMI was more strongly associated with HbA1c if parental BMI had been higher. Intergenerational influences may be important in conferring the effect of high BMI on CVD risk among offspring.

Psychosocial functioning in offspring of parents with bipolar disorder.

PubMed

Bella, Tolulope; Goldstein, Tina; Axelson, David; Obreja, Mihaela; Monk, Kelly; Hickey, Mary Beth; Goldstein, Benjamin; Brent, David; Diler, Rasim Somer; Kupfer, David; Sakolsky, Dara; Birmaher, Boris

2011-09-01

Offspring of parents with bipolar disorder are at increased risk for a range of psychopathology, including bipolar disorder. It is not clear if they also have impairments in their psychosocial functioning. We compared the psychosocial functioning of three groups of children enrolled in the Pittsburgh Bipolar Offspring Study (BIOS): offspring of probands with bipolar disorder (n=388), offspring of probands with other types of psychopathology (n=132), and offspring of healthy probands (n=118). Psychosocial functioning was assessed at study intake using the schedule of the Adolescent Longitudinal Interval Follow-Up Evaluation (A-LIFE), the Child Behavior Check List (CBCL) and the Children's Global Assessment Scale (CGAS). Offspring of probands with bipolar disorder exhibited impairments in various aspects of psychosocial functioning. On all measures, they had worse functioning in comparison with offspring of healthy probands. Offspring of probands with bipolar disorder generally exhibited more impairment than offspring of probands with nonbipolar psychopathology. After adjusting for proband parent functioning and the child's Axis I psychopathology, functioning of offspring of probands with bipolar disorder was similar to that of offspring of healthy probands. Data are cross-sectional and therefore do not allow for causal conclusions about the association between parental psychopathology, child psychopathology and offspring psychosocial functioning. Offspring of parents with bipolar disorder exhibit impairments in psychosocial functioning which appear largely attributable to proband parent functional impairment and the child's own psychopathology. As such, interventions to improve parental functioning, as well as early interventions to treat the child's psychopathology may help reduce the risk for long-term functional impairment in offspring. Copyright © 2011 Elsevier B.V. All rights reserved.

Physiological reactivity in children of Oklahoma City bombing survivors 7 years postdisaster: a pilot study.

PubMed

Pfefferbaum, Betty; Tucker, Phebe; North, Carol S; Jeon-Slaughter, Haekyung

2011-08-01

Relatively few studies of children exposed to trauma have used objective indicators such as heart rate and blood pressure measurements to assess physiological reactivity. This pilot study examined physiological reactivity (heart rate, systolic blood pressure, and diastolic blood pressure) and emotional indicators (posttraumatic stress and depressive symptoms) in 17 children of directly exposed Oklahoma City bombing survivors and in 17 demographically matched community comparison children, 7 years after the incident. Despite generally low levels of subjectively reported posttraumatic stress and depressive symptoms 7 years after the disaster, the children of survivors showed heightened objectively measured physiological reactivity relative to the comparison group. The extent to which this heightened physiological reactivity in the children of survivors was pathologic is unclear. Only 1 participant reported high levels of posttraumatic stress and depressive symptoms; this individual also demonstrated physiological reactivity. Results suggest children of disaster survivors may experience physiological reactivity despite absence of direct exposure to the trauma or acknowledgement of symptoms. These findings indicate the physiological effects of trauma may endure separate from subjective affect in the offspring of highly exposed disaster survivors. More research is needed to determine the potential consequences of persistent physiological reactivity.

Changes in the food environment over time: examining 40 years of data in the Framingham Heart Study.

PubMed

James, Peter; Seward, Michael W; James O'Malley, A; Subramanian, S V; Block, Jason P

2017-06-24

Research has explored associations between diet, body weight, and the food environment; however, few studies have examined historical trends in food environments. In the Framingham Heart Study Offspring (N = 3321) and Omni (N = 447) cohorts, we created food environment metrics in four Massachusetts towns utilizing geocoded residential, workplace, and food establishment addresses from 1971 to 2008. We created multilevel models adjusted for age, sex, education, and census tract poverty to examine trends in home, workplace, and commuting food environments. Proximity to and density of supermarkets, fast-food, full service restaurants, convenience stores, and bakeries increased over time for residential, workplace, and commuting environments; exposure to grocery stores decreased. The greatest increase in access was for supermarkets, with residential distance to the closest supermarket 1406 m closer (95% CI 1303 m, 1508 m) by 2005-2008 than in 1971-1975. Although poorer census tracts had higher access to fast-food restaurants consistently across follow-up, this disparity dissipated over time, due to larger increases in proximity to fast-food in wealthier neighborhoods. Access to most food establishment types increased over time, with similar trends across home, workplace, and commuter environments.

Adrenocortical responses to offspring-directed threats in two open-nesting birds.

PubMed

Butler, Luke K; Bisson, Isabelle-Anne; Hayden, Timothy J; Wikelski, Martin; Romero, L Michael

2009-07-01

Dependent young are often easy targets for predators, so for many parent vertebrates, responding to offspring-directed threats is a fundamental part of reproduction. We tested the parental adrenocortical response of the endangered black-capped vireo (Vireo atricapilla) and the common white-eyed vireo (V. griseus) to acute and chronic threats to their offspring. Like many open-nesting birds, our study species experience high offspring mortality. Parents responded behaviorally to a predator decoy or human 1-2m from their nests, but, in contrast to similar studies of cavity-nesting birds, neither these acute threats nor chronic offspring-directed threats altered plasma corticosterone concentrations of parents. Although parents in this study showed no corticosterone response to offspring-directed threats, they always increased corticosterone concentrations in response to capture. To explain these results, we propose that parents perceive their risk of nest-associated death differently depending on nest type, with cavity-nesting adults perceiving greater risk to themselves than open-nesters that can readily detect and escape from offspring-directed threats. Our results agree with previous studies suggesting that the hypothalamic-pituitary-adrenal axis, a major physiological mechanism for coping with threats to survival, probably plays no role in coping with threats to offspring when risks to parents and offspring are not correlated. We extend that paradigm by demonstrating that nest style may influence how adults perceive the correlation between offspring-directed and self-directed threats.

A mouse model of pre-pregnancy maternal obesity combined with offspring exposure to a high-fat diet resulted in cognitive impairment in male offspring.

PubMed

Zhu, Chen; Han, Ting-Li; Zhao, Yalan; Zhou, Xiaobo; Mao, Xun; Qi, Hongbo; Baker, Philip N; Zhang, Hua

2018-04-23

Cognitive impairment is a brain dysfunction characterized by neuropsychological deficits in attention, working memory, and executive function. Maternal obesity and consumption of a high-fat diet (HFD) in the offspring has been suggested to have detrimental consequences for offspring cognitive function through its effect on the hippocampus and prefrontal cortex. Therefore, our study aimed to investigate the effects of maternal obesity and offspring HFD exposure on the brain metabolome of the offspring. In our pilot study, a LepRdb/+ mouse model was used to model pre-pregnancy maternal obesity and the c57bl/6 wildtype was used as a control group. Offspring were fed either a HFD or a low-fat control diet (LFD) after weaning (between 8 and 10 weeks). The Mirrors water maze was performed between 28 and 30 weeks to measure cognitive function. Fatty acid metabolomic profiles of the prefrontal cortex and hippocampus from the offspring at 30-32 weeks were analyzed using gas chromatography-mass spectrometry. The memory of male offspring from obese maternal mice, consuming a HFD post-weaning, was significantly impaired when compared to the control offspring mice. No significant differences were observed in female offspring. In male mice, the fatty acid metabolites in the prefrontal cortex were most affected by maternal obesity, whereas, the fatty acid metabolites in the hippocampus were most affected by the offspring's diet. Hexadecanoic acid and octadecanoic acid were significantly affected in both the hippocampus and pre-frontal cortex, as a result of maternal obesity and a HFD in the offspring. Our findings suggest that the combination of maternal obesity and HFD in the offspring can result in spatial cognitive deficiency in the male offspring, by influencing the fatty acid metabolite profiles in the prefrontal cortex and hippocampus. Further research is needed to validate the results of our pilot study. Copyright © 2018 Elsevier Inc. All rights reserved.

Functional impairment due to bereavement after the death of adolescent or young adult offspring in a national population study of 1,051,515 parents.

PubMed

Wilcox, Holly C; Mittendorfer-Rutz, Ellenor; Kjeldgård, Linnea; Alexanderson, Kristina; Runeson, Bo

2015-08-01

This study addresses the burden of grief after the death of an adolescent or young adult offspring. Parental bereavement following the death of an adolescent or young adult offspring is associated with considerable psychiatric and somatic impairment. Our aim is to fill a research gap by examining offspring death due to suicide, accidents, or natural causes in relation to risk of parental sickness absence with psychiatric or somatic disorders. This whole population-based prospective study included mothers and fathers of all offspring aged 16-24 years in Sweden on December 31, 2004 (n = 1,051,515). This study had no loss to follow-up and exposure, confounders, and the outcome were recorded independently of each other. Cox survival analysis was used to model time to sickness absence exceeding 30 days, adjusting for parental demographic characteristics, previous parental sickness absence and disability pension, and inpatient and outpatient psychiatric and somatic healthcare prior to offspring death in 2001-2004. This large study population provided satisfactory statistical power for stratification by parents' sex and adolescent and young adults' cause of death. Mothers and fathers of offspring suicide and accident decedents both had over tenfold higher risk for psychiatric sickness absence exceeding 30 days as compared to parents of live offspring. Fathers of suicide decedents were at 40 % higher risk for somatic sickness absence. This is the largest study to date of parents who survived their offspring's death and the first study of work-related outcomes in bereaved parents. This study uses a broad metric of work-related functional impairment, sickness absence, for capturing the burden of sudden offspring death.

The Effects of Parental Mood on Reports of Their Children's Psychopathology

PubMed Central

Maoz, Hagai; Goldstein, Tina; Goldstein, Benjamin I.; Axelson, David A.; Fan, Jieyu; Hickey, Mary Beth; Monk, Kelly; Sakolsky, Dara; Diler, Rasim S.; Brent, David; Kupfer, David J.; Birmaher, Boris

2014-01-01

Objective In this study, we aim to assess whether current mood state (depressed or manic/hypomanic) among parents with a mood disorder affects their reports of their offspring's psychopathology. Method Sixty-five parents with current depression, 42 with current mania/hypomania, 181 with mood disorder in remission, and their offspring (n=479, ages 6-18) completed assessments of offspring IP psychopathology as part of the Pittsburgh Bipolar Offspring Study (BIOS). We compared rates of offspring psychopathology assessed using the following: a clinician-administered semi-structured interview with parent and child using the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS); parent-reported Child Behavior Checklist (CBCL); offspring self-reported Youth Self Reports (YSR) for those 11 years and older (n=250); and teachers’ reports when available (n= 209). Results There were no between-group differences in rates of psychopathology yielded from the K-SADS, except for more depressive disorders in offspring of parents with current mania/hypomania compared to offspring of parents in remission. Conversely, using the CBCL and comparing with parents who were in remission, parents with current depression reported significantly more externalizing psychopathology in offspring, whereas parents with current mania/hypomania reported more externalizing and internalizing psychopathology in their offspring. On the YSR, offspring of parents with current mania/hypomania had more internalizing psychopathology compared to offspring of parents in remission. Teacher's reports showed no between-group differences in rates of any psychopathology. Conclusion Parental active mood symptomatology, especially during a manic/hypomanic episode, significantly affects their reports of their offspring's psychopathology. Trained interviewers reduce potential report bias. Clinicians and studies assessing children's psychopathology should take into account parental current mood state. PMID:25245355

Risk of mental illness in offspring of parents with schizophrenia, bipolar disorder, and major depressive disorder: a meta-analysis of family high-risk studies.

PubMed

Rasic, Daniel; Hajek, Tomas; Alda, Martin; Uher, Rudolf

2014-01-01

Offspring of parents with severe mental illness (SMI; schizophrenia, bipolar disorder, major depressive disorder) are at an increased risk of developing mental illness. We aimed to quantify the risk of mental disorders in offspring and determine whether increased risk extends beyond the disorder present in the parent. Meta-analyses of absolute and relative rates of mental disorders in offspring of parents with schizophrenia, bipolar disorder, or depression in family high-risk studies published by December 2012. We included 33 studies with 3863 offspring of parents with SMI and 3158 control offspring. Offspring of parents with SMI had a 32% probability of developing SMI (95% CI: 24%-42%) by adulthood (age >20). This risk was more than twice that of control offspring (risk ratio [RR] 2.52; 95% CI 2.08-3.06, P < .001). High-risk offspring had a significantly increased rate of the disorder present in the parent (RR = 3.59; 95% CI: 2.57-5.02, P < .001) and of other types of SMI (RR = 1.92; 95% CI: 1.48-2.49, P < .001). The risk of mood disorders was significantly increased among offspring of parents with schizophrenia (RR = 1.62; 95% CI: 1.02-2.58; P = .042). The risk of schizophrenia was significantly increased in offspring of parents with bipolar disorder (RR = 6.42; 95% CI: 2.20-18.78, P < .001) but not among offspring of parents with depression (RR = 1.71; 95% CI: 0.19-15.16, P = .631). Offspring of parents with SMI are at increased risk for a range of psychiatric disorders and one third of them may develop a SMI by early adulthood.

Parental obesity and risk factors for cardiovascular disease among their offspring in mid-life: findings from the 1958 British Birth Cohort Study

PubMed Central

Cooper, R; Pinto Pereira, S M; Power, C; Hyppönen, E

2013-01-01

Background: Few studies have investigated whether parental adiposity is associated with offspring cardiovascular health or the underlying pathways. Studying these associations may help to illuminate the paradox of increasing prevalence of obesity and declining trends in cardiovascular disease (CVD) mortality, which may be partially explained by beneficial adaptations to an obesogenic environment among people exposed to such environments from younger ages. Objective: To investigate associations between parental body mass index (BMI) and risk factors for CVD among their offspring in mid-life and to test whether associations of offspring BMI with CVD risk factors were modified by parental BMI. Methods: Data from parents and offspring in the 1958 British birth cohort were used (N=9328). Parental BMI was assessed when offspring were aged 11 years; offspring BMI, waist circumference and CVD risk factors (lipid levels, blood pressure, glycosylated haemoglobin (HbA1c) and inflammatory and haemostatic markers) were measured at 44–45 years. Results: Higher parental BMI was associated with less favourable levels of offspring risk factors for CVD. Most associations were maintained after adjustment for offspring lifestyle and socioeconomic factors but were largely abolished or reversed after adjustment for offspring adiposity. For some CVD risk factors, there was evidence of effect modification; the association between higher BMI and an adverse lipid profile among offspring was weaker if maternal BMI had been higher. Conversely, offspring BMI was more strongly associated with HbA1c if parental BMI had been higher. Conclusions: Intergenerational influences may be important in conferring the effect of high BMI on CVD risk among offspring. PMID:23567929

Cross-sectional relations of arterial stiffness, pressure pulsatility, wave reflection, and arterial calcification.

PubMed

Tsao, Connie W; Pencina, Karol M; Massaro, Joseph M; Benjamin, Emelia J; Levy, Daniel; Vasan, Ramachandran S; Hoffmann, Udo; O'Donnell, Christopher J; Mitchell, Gary F

2014-11-01

Arterial hemodynamics and vascular calcification are associated with increased risk for cardiovascular disease, but their inter-relations remain unclear. We sought to examine the associations of arterial stiffness, pressure pulsatility, and wave reflection with arterial calcification in individuals free of prevalent cardiovascular disease. Framingham Heart Study Third Generation and Offspring Cohort participants free of cardiovascular disease underwent applanation tonometry to measure arterial stiffness, pressure pulsatility, and wave reflection, including carotid-femoral pulse wave velocity, central pulse pressure, forward wave amplitude, and augmentation index. Participants in each cohort (n=1905, 45±6 years and n=1015, 65±9 years, respectively) underwent multidetector computed tomography to assess the presence and quantity of thoracic aortic calcification, abdominal aortic calcification, and coronary artery calcification. In multivariable-adjusted models, both higher carotid-femoral pulse wave velocity and central pulse pressure were associated with greater thoracic aortic calcification and abdominal aortic calcification, whereas higher augmentation index was associated with abdominal aortic calcification. Among the tonometry measures, carotid-femoral pulse wave velocity was the strongest correlate of all calcification measures in multivariable-adjusted models (odds ratio per SD for thoracic aortic calcification, 2.69 [95% confidence interval, 2.17-3.35]; abdominal aortic calcification, 1.47 [95% confidence interval, 1.26-1.73]; and coronary artery calcification, 1.48 [95% confidence interval, 1.28-1.72]; all P<0.001, respectively). We observed stronger relations of carotid-femoral pulse wave velocity, central pulse pressure, and forward wave amplitude with nearly all continuous calcification measures in the younger Third Generation Cohort as compared with the Offspring Cohort. In community-dwelling individuals without prevalent cardiovascular disease, abnormal central arterial hemodynamics were positively associated with vascular calcification and were observed at younger ages than previously recognized. The mechanisms of these associations may be bidirectional and deserve further study. © 2014 American Heart Association, Inc.

Intergenerational Transmission of Stress in Humans

PubMed Central

Bowers, Mallory E; Yehuda, Rachel

2016-01-01

The hypothesis that offspring are affected by parental trauma or stress exposure, first noted anecdotally, is now supported empirically by data from Holocaust survivor offspring cohorts and other populations. These findings have been extended to less extreme forms of stress, where differential physical, behavioral, and cognitive outcomes are observed in affected offspring. Parental stress-mediated effects in offspring could be explained by genetics or social learning theory. Alternatively, biological variations stemming from stress exposure in parents could more directly have an impact on offspring, a concept we refer to here as ‘intergenerational transmission', via changes to gametes and the gestational uterine environment. We further extend this definition to include the transmission of stress to offspring via early postnatal care, as animal studies demonstrate the importance of early maternal care of pups in affecting offsprings' long-term behavioral changes. Here, we review clinical observations in offspring, noting that offspring of stress- or trauma-exposed parents may be at greater risk for physical, behavioral, and cognitive problems, as well as psychopathology. Furthermore, we review findings concerning offspring biological correlates of parental stress, in particular, offspring neuroendocrine, epigenetic, and neuroanatomical changes, in an attempt to determine the extent of parental stress effects. Although understanding the etiology of effects in offspring is currently impeded by methodological constraints, and limitations in our knowledge, we summarize current information and conclude by presenting hypotheses that have been prompted by recent studies in the field. PMID:26279078

The relationship between stressful life events and Axis I diagnoses among adolescent offspring of probands with bipolar and non-bipolar psychiatric disorders and healthy controls

PubMed Central

Pan, Lisa A.; Goldstein, Tina R.; Rooks, Brian T.; Hickey, Mary; Fan, Jie Yu; Merranko, John; Monk, Kelly; Diler, Rasim S.; Sakolsky, Dara J.; Hafeman, Daniella; Iyengar, Satish; Goldstein, Benjamin; Kupfer, David J.; Axelson, David; Brent, David A.; Birmaher, Boris

2018-01-01

Background Previous studies have explored the role of stressful life events in the development of mood disorders. We examined the frequency and nature of stressful life events as measured by the Stressful Life Events Scale(SLES) among three groups of adolescent offspring of probands: with bipolar(BD), with non-BD psychiatric disorders, and healthy control(HC). Furthermore, we examined the relationship between stressful life events and presence of DSM-IV Axis I disorders in these offspring. Stressful life events were characterized as dependent, independent, or uncertain (neither dependent or independent), and positive, negative, and neutral (neither positive or negative). Method Offspring of probands with BD aged 13–18 years(N=269), demographically-matched offspring of probands with non-BD Axis I disorders(N=88), and HC probands(N=81) from the Pittsburgh Bipolar Offspring Study were assessed from 2002–2007 with standardized instruments at intake. Probands completed the SLES for their offspring for life events within the prior year. Life events were evaluated with regard to current offspring Axis I diagnoses after adjusting for confounds. Results After adjusting for demographic and clinical between-group differences(in probands and offspring), offspring of BD probands had greater independent and neutral life events compared with HC offspring and greater number of more severe stressful life events than HC offspring, but not non-BD offspring. Offspring of BD probands with comorbid substance use disorder reported more independent stressful life events. Greater frequency and severity of stressful life events were associated with current Axis I disorder in offspring of both BD and non-BD affected probands regardless of dependency or valence. Greater frequency and severity of stressful life events were associated with greater current Axis I disorder in all offspring. Conclusions Offspring of BD probands have greater exposure to independent and neutral life events than HC offspring. Greater frequency and severity of stressful life events was associated with Axis I disorder in offspring of both BD and non-BD affected probands. PMID:28199068

Effects of bisphenol A on incidence and severity of cardiac lesions in the NCTR-Sprague-Dawley rat: A CLARITY-BPA study.

PubMed

Gear, Robin; Kendziorski, Jessica A; Belcher, Scott M

2017-06-05

The goal of this study was to determine whether bisphenol A (BPA) had adverse effects indicative of cardiac toxicity. As part of the "Consortium Linking Academic and Regulatory Insights on BPA Toxicity" (CLARITY-BPA), study dams and offspring were exposed by daily gavage to five doses of BPA ranging from 2.5 to 25000μg/kg/day, 0.05 or 0.5μg/kg/day 17α-ethinyl-estradiol (EE) or 0.3% carboxymethylcellulose vehicle. Exposure-related effects were analyzed in isolated hearts by quantitative morphometry and histopathology. No dose-related changes in body weight were detected. Across all exposure groups including vehicle controls, body weight of continuously dosed males was reduced compared to males dosed only until PND21. Heart weight was increased only in females exposed to EE, and consistent alterations in LV wall thickness were not observed. Exposure-related changes in collagen accumulation were minor and limited to highest EE exposure groups with increased collagen accumulation in PND21 males. Decreased collagen was observed in hearts of BPA or EE exposed females at PND90 and PND180. In BPA or EE treated females cardiomyopathy incidence and severity was significantly increased compared to control females at PND21 with myocardial degeneration observed in both males and females at PND21 and PND90. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical, Demographic, and Familial Correlates of Bipolar Spectrum Disorders among Offspring of Parents with Bipolar Disorder

ERIC Educational Resources Information Center

Goldstein, Benjamin I.; Shamseddeen, Wael; Axelson, David A.; Kalas, Cathy; Monk, Kelly; Brent, David A.; Kupfer, David J.; Birmaher, Boris

2010-01-01

Objective: Despite increased risk, most offspring of parents with bipolar disorder (BP) do not manifest BP. The identification of risk factors for BP among offspring could improve preventive and treatment strategies. We examined this topic in the Pittsburgh Bipolar Offspring Study (BIOS). Method: Subjects included 388 offspring, ages 7-17 years,…

Trends in dietary carbohydrate consumption from 1991 to 2008 in the Framingham Heart Study Offspring Cohort.

PubMed

Makarem, Nour; Scott, Marc; Quatromoni, Paula; Jacques, Paul; Parekh, Niyati

2014-06-14

The intake of carbohydrates has been evaluated cross-sectionally, but not longitudinally in an ageing American adult population. The aim of the present study was to examine trends in the intake of dietary carbohydrates and their major food sources among the Framingham Heart Study Offspring (FOS) cohort, which had been uniquely tracked for 17 years in the study. The FOS cohort was recruited in 1971-1975. Follow-up examinations were conducted, on average, every 4 years. Dietary data collection began in 1991 (examination 5) using a validated semi-quantitative FFQ. The study included 2894 adults aged ≥ 25 years with complete dietary data in at least three examinations from 1991 to 2008. Descriptive statistics were generated using SAS version 9.3, and a repeated-measures model was used to examine trends in the intake of carbohydrates and their food sources in the whole sample, and by sex and BMI category. Over 17 years of follow-up, the percentage of energy from total carbohydrates (51·0-46·8 %; P for trend < 0·001) and total sugars (18·2-16·6 %; P for trend < 0·001) decreased. There was a decrease in the percentage of energy from fructose (5·4-4·7 %; P for trend < 0·001) and sucrose (9·8-8·8 %; P for trend < 0·001). Dietary fibre intake increased (18·0-19·2 g/d; P for trend < 0·001). The number of weekly servings of yeast bread, soft drinks/soda, cakes/cookies/quick breads/doughnuts, potatoes, milk, pasta, rice and cooked grains, fruit juice/drinks, potato chips/maize chips/popcorn, and lunch foods (e.g. pizzas and burgers) decreased significantly (P for trend < 0·001), while the intake of ready-to-eat cereals, legumes, fruits, dairy products, candy and ice cream/sherbet/frozen yogurt increased significantly (P for trend<0·04). Similar trends were observed when the analyses were stratified by sex and BMI. The present results suggest favourable trends in dietary carbohydrate consumption, but dietary guidelines for fruits, vegetables and fibre were not met in this cohort.

Maternal early pregnancy lipid profile and offspring's lipids and glycaemic control at age 5-6 years: The ABCD study.

PubMed

van Lieshout, Noekie; Oostvogels, Adriëtte J J M; Gademan, Maaike G J; Vrijkotte, Tanja G M

2017-12-01

Maternal early pregnancy lipid profile might influence offspring's lipids and glycaemic control, through an increased offspring's fat percentage. This explorative study investigates whether maternal early pregnancy lipid profile is associated with offspring's lipids and glycaemic control independently of offspring's fat percentage and if these associations are mediated by offspring's fat percentage. Possible sex differences in these associations are also examined. 1133 mother-child pairs of the prospective ABCD-study were included. Maternal non-fasting lipids were collected in early pregnancy: triglycerides, total cholesterol (TC), Apolipoprotein A1 (ApoA1), Apolipoprotein B (ApoB) and free fatty acids (FFA). Fasting triglycerides, TC, high density lipoprotein (HDL), low density lipoprotein (LDL), glucose and C-peptide were assessed in offspring aged 5-6 years and HOMA2-IR was calculated. After adjustment for covariates, strongest associations were found between maternal TC and offspring's TC (boys β(95%CI) = 0.141 (0.074-0.207); girls β(95%CI) = 0.268 (0.200; 0.336)) and LDL (boys β(95%CI) = 0.114 (0.052; 0.176); girls β(95%CI) = 0.247 (0.181-0.312)), maternal ApoB and offspring's TC (boys β(95%CI) = 0.638 (0.311-0.965); girls β(95%CI) = 1.121 (0.766-1.475)) and LDL (boys β(95%CI) = 0.699 (0.393-1.005); girls β(95%CI) = 1.198 (0.868-1.529)), and maternal ApoA1 and offspring's HDL (only boys β(95%CI) = 0.221 (0.101-0.341)). No significant association was found between maternal lipids and offspring's glycaemic control, and offspring's fat percentage played no mediating role. Maternal early pregnancy lipid profile is associated with offspring's lipid profile in childhood, with overall stronger associations in girls. This study provides further evidence that lowering lipid levels during pregnancy might be beneficial for the long term health of the offspring. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Temperament and major depression: How does difficult temperament affect frequency, severity, and duration of major depressive episodes among offspring of parents with or without depression?

PubMed Central

Sherman, Brian J.; Vousoura, Eleni; Wickramaratne, Priya; Warner, Virginia; Verdeli, Helen

2016-01-01

Introduction The current study examined the relationships between parental depression, offspring depression, and offspring temperament among 203 offspring of parents with or without depression. The specific aim was to investigate how offspring difficult temperament affects frequency, severity, and duration of offspring major depressive episodes (MDEs). Methods As part of an ongoing multigenerational study assessing familial transmission of depression, offspring were assessed over a 20-year study period. Offspring temperament was assessed at baseline using the Dimensions of Temperament Survey and diagnostic interviews were conducted at each of the four waves using best estimate procedures. Results Difficult temperament predicted greater frequency of lifetime MDEs. Parental depression moderated the relationship between offspring difficult temperament and severity of MDEs, such that difficult temperament was associated with increased severity ratings among high-risk, but not low-risk offspring. Dimensional analysis revealed that lower rhythmicity and adaptability were associated with greater number of lifetime MDEs, while higher inattention/distractibility was associated with shorter duration of MDEs. Discussion Certain limitations must be noted, namely the self-report nature of temperament data and the relatively small sample size drawn from a clinical and predominantly Caucasian and Christian sample. Notwithstanding these limitations, our results suggest that the clinical presentation of major depression may reflect temperamental profiles and should be considered in diagnostic and treatment settings. PMID:27130957

Weight Status and Blood Pressure among Adolescent African American Males: The Jackson Heart KIDS Pilot Study.

PubMed

Bruce, Marino A; Beech, Bettina M; Griffith, Derek M; Thorpe, Roland J

2015-08-07

Obesity had not been considered a significant factor contributing to high levels of hypertension among African American males until recently. Epidemiologic research on heart disease among males has primarily focused on adults; however, the significant rise in obesity and hypertension prevalence among African American boys indicates that studies examining the relationship between excess body weight and elevated blood pressure among this high-risk population are critically needed. The purpose of our study was to examine the degree to which weight status has implications for elevated blood pressure among young African American males. The data for this cross-sectional study were drawn from adolescent males (N=105), aged 12-19 years and who participated in the Jackson Heart KIDS Pilot Study - an offspring cohort study examining cardiovascular disease risks among adolescent descendants of Jackson Heart Study participants. Blood pressure was the primary outcome of interest and weight status was a key independent variable. Other covariates were fruit and vegetable consumption, physical activity, sleep, and stress. Approximately 49% of adolescent males in the study were overweight or obese. Bivariate and multiple variable analyses suggest that obesity may be correlated with elevated diastolic blood pressure (DBP) levels among African American boys. Results from ordinary least squared regression analysis indicate that the DBP for boys carrying excess weight was 4.2 mm Hg (P<.01) higher than the corresponding DBP for their normal weight counterparts, after controlling for age, fruit and vegetable consumption, physical activity, and sleep. Additional studies are needed to specify the manner through which excess weight and weight gain can accelerate the development and progression of CVD-related diseases among African American males over the life course, thereby providing evidenced-based information for tailored interventions that can reduce risks for premature morbidity, disability, and mortality among this group.

Effects of Low-Dose Developmental Bisphenol A Exposure on Metabolic Parameters and Gene Expression in Male and Female Fischer 344 Rat Offspring

PubMed Central

Lejonklou, Margareta H.; Dunder, Linda; Bladin, Emelie; Pettersson, Vendela; Rönn, Monika; Lind, Lars; Waldén, Tomas B.

2017-01-01

Background: Bisphenol A (BPA) is an endocrine-disrupting chemical that may contribute to development of obesity and metabolic disorders. Humans are constantly exposed to low concentrations of BPA, and studies support that the developmental period is particularly sensitive. Objectives: The aim was to investigate the effects of low-dose developmental BPA exposure on metabolic parameters in male and female Fischer 344 (F344) rat offspring. Methods: Pregnant F344 rats were exposed to BPA via their drinking water, corresponding to 0.5μg/kg BW/d (BPA0.5; n=21) or 50μg/kg BW/d (BPA50; n=16), from gestational day (GD) 3.5 until postnatal day (PND) 22, and controls were given vehicle (n=26). Body weight (BW), adipose tissue, liver (weight, histology, and gene expression), heart weight, and lipid profile were investigated in the 5-wk-old offspring. Results: Males and females exhibited differential susceptibility to the different doses of BPA. Developmental BPA exposure increased plasma triglyceride levels (0.81±0.10 mmol/L compared with 0.57±0.03 mmol/L, females BPA50 p=0.04; 0.81±0.05 mmol/L compared with 0.61±0.04 mmol/L, males BPA0.5 p=0.005) in F344 rat offspring compared with controls. BPA exposure also increased adipocyte cell density by 122% in inguinal white adipose tissue (iWAT) of female offspring exposed to BPA0.5 compared with controls (68.2±4.4 number of adipocytes/HPF compared with 55.9±1.5 number of adipocytes/HPF; p=0.03) and by 123% in BPA0.5 females compared with BPA50 animals (68.2±4.4 number of adipocytes/high power field (HPF) compared with 55.3±2.9 number of adipocytes/HPF; p=0.04). In iWAT of male offspring, adipocyte cell density was increased by 129% in BPA50-exposed animals compared with BPA0.5-exposed animals (69.9±5.1 number of adipocytes/HPF compared with 54.0±3.4 number of adipocytes/HPF; p=0.03). Furthermore, the expression of genes involved in lipid and adipocyte homeostasis was significantly different between exposed animals and controls depending on the tissue, dose, and sex. Conclusions: Developmental exposure to 0.5μg/kg BW/d of BPA, which is 8–10 times lower than the current preliminary EFSA (European Food Safety Authority) tolerable daily intake (TDI) of 4μg/kg BW/d and is within the range of environmentally relevant levels, was associated with sex-specific differences in the expression of genes in adipose tissue plasma triglyceride levels in males and adipocyte cell density in females when F344 rat offspring of dams exposed to BPA at 0.5μg/kg BW/d were compared with the offspring of unexposed controls. https://doi.org/10.1289/EHP505 PMID:28657538

The psychological, social, and behavioural impact of a parent's cancer on adolescent and young adult offspring aged 10-24 at time of diagnosis: A systematic review.

PubMed

Morris, Julia; Turnbull, Deborah; Preen, David; Zajac, Ian; Martini, Angelita

2018-06-01

This study reviewed the literature regarding the psychological, social, and behavioural impact of parental cancer on offspring aged 10-24 years, at the time of the parent's first diagnosis. A systematic literature review was conducted following 2015 PRISMA guidelines. Seven studies met inclusion criteria. Offspring were impacted by their parent's cancer and experienced psychological and behavioural problems. Daughters and offspring who experienced more problems at their parent's diagnosis appeared to be most impacted. Offspring refrained from communicating their disease-related concerns, but expected their parents to communicate openly. Turning to oneself and peer-support were coping strategies used by offspring. The majority of offspring were significantly impacted by their parent's cancer. The paucity of literature focusing on offspring aged 10-24 years at the time of their parent's incident cancer diagnosis indicates that research has overlooked offspring age at their parent's cancer onset as a factor that may influence their future outcomes. Copyright © 2018. Published by Elsevier Ltd.

Psychopathology in the adolescent and young adult offspring of parents with dysthymic disorder and major depressive disorder.

PubMed

Lizardi, Humberto; Klein, Daniel N; Shankman, Stewart A

2004-03-01

This study addressed the following question: are the adolescent and young adult offspring of parents with early-onset dysthymic disorder (DD) at increased risk for psychopathology? Participants included 41 offspring of 21 outpatients with early-onset DD, 19 offspring of nine outpatients with episodic major depressive disorder (MDD), and 32 offspring of 11 normal controls (NCs). Lifetime best-estimate diagnoses were determined for each offspring using a team consensus method. Diagnoses were derived blind to all information about the index parents. The offspring of outpatients with early-onset DD exhibited significantly higher lifetime rates of a broad range of psychiatric disorders than the offspring of NCs. In addition, the offspring of outpatients with early-onset DD exhibited significantly higher lifetime rates of DD, anxiety disorders, and phobia than the offspring of outpatients with episodic MDD. These results support the importance of early-onset DD in parents as a risk factor for psychopathology in their offspring.

Risk/protective factors among addicted mothers' offspring: a replication study.

PubMed

Weissman, M M; McAvay, G; Goldstein, R B; Nunes, E V; Verdeli, H; Wickramaratne, P J

1999-11-01

There are few systematic studies of the school-aged offspring of drug-dependent patients, although this information is useful for planning evidence-based prevention programs. We have completed such a study, which we compare to a similar study independently conducted in 1998. In both studies, both the parent and offspring were assessed blindly and independently by direct diagnostic interviews, and parental assessment of offspring was also obtained. The similarity in design and methods between studies provided an opportunity for replication by reanalysis of data. The major findings are a replication in two independently conducted studies of school-aged offspring of opiate- and/or cocaine-addicted mothers of the high rates of any psychiatric disorder (60% in both studies), major depression (20%, 26%), oppositional defiant disorder (ODD) (18%, 23%), conduct disorder (17%, 9%), attention-deficit/hyperactivity disorder (ADHD) (13%, 8%), and substance abuse (5%, 10%) among offspring. Both studies also found high rates of comorbid alcohol abuse, depression, and multiple drugs of abuse in the mothers. We conclude that efforts to replicate findings by analyses of independently conducted studies are an inexpensive way to test the sturdiness of findings that can provide the empirical basis for preventive efforts. Clinically, the data in both studies suggest that both drug dependence and associated psychopathology should be assessed and treated in opiate addicts with young offspring, and the offspring should be monitored for the development of conduct and mood disorders and substance use.

Does relationship satisfaction and financial aid from offspring influence the quality of life of older parents?: a longitudinal study based on findings from the Korean longitudinal study of aging, 2006-2012.

PubMed

Ju, Yeong Jun; Han, Kyu-Tae; Lee, Tae-Hoon; Kim, Woorim; Kim, Juyeong; Park, Eun-Cheol

2016-07-26

Quality of life (QoL) in old age is of major importance because the global population is aging rapidly. Offspring support, including financial and emotional support, is important in later life and directly affects the wellbeing of elderly individuals. The aim of this study was to examine the relationship between QoL in older parents and offspring support. We used baseline data from the 2006-2012 Korean Longitudinal Study of Aging, from 3,274 individuals aged 65 years or older. We measured the individual's QoL using a visual analog scale and included both relationship satisfaction and regular economic support as variables. A generalized estimating equation (GEE) model was used to perform longitudinal regression analysis on the data. Regarding the QoL of older parents, those with an unsatisfying relationship with their offspring had a QoL of -21.93 (SE = 0.55; P < 0.0001) compared to those with satisfying offspring relationships. Those receiving no regular financial aid from their offspring had a QoL of -0.92 (SE = 0.38; P = 0.0171) compared to those who received such economic support. Combination effects were observed, with cases living alone - and having poor offspring relationships and no regular financial support from their offspring - showing the most drastic decrease in QoL (-23.46; SE = 1.03; P < 0.0001). Offspring support influences the QoL of elderly individuals, and Korean children appear to play a crucial role in the QoL of their (older) parents. Considering that the role of offspring is rapidly diminishing due to industrialization policies, initiatives are required to revitalize offspring support for elderly parents.

The role of the mother-child relationship for anxiety disorders and depression: results from a prospective-longitudinal study in adolescents and their mothers.

PubMed

Asselmann, Eva; Wittchen, Hans-Ulrich; Lieb, Roselind; Beesdo-Baum, Katja

2015-04-01

This study aims to examine whether (a) low child valence (emotional connectedness) within the mother-child relationship increases the risk for offspring depression, (b) low child potency (individual autonomy) increases the risk for offspring anxiety, and (c) maternal psychopathology pronounces these associations. We used data from a prospective-longitudinal study of adolescents (aged 14-17 at baseline) and their mothers (N = 1,015 mother-child dyads). Anxiety disorders and depression were assessed repeatedly over 10 years in adolescents (T0, T1, T2, T3) and their mothers (T1, T3) using the DSM-IV/M-CIDI. Valence and potency were assessed in mothers (T1) with the Subjective Family Image Questionnaire. Odds ratios (OR) from logistic regression were used to estimate associations between low child valence/potency and offspring psychopathology (cumulated lifetime incidences; adjusted for sex and age). In separate models (low valence or low potency as predictor), low child valence predicted offspring depression only (OR = 1.26 per SD), while low child potency predicted offspring anxiety (OR = 1.24) and depression (OR = 1.24). In multiple models (low valence and low potency as predictors), low child valence predicted offspring depression only (OR = 1.19), while low child potency predicted offspring anxiety only (OR = 1.22). Low child potency interacted with maternal anxiety on predicting offspring depression (OR = 1.49), i.e. low child potency predicted offspring depression only in the presence of maternal anxiety (OR = 1.33). These findings suggest that low child valence increases the risk for offspring depression, while low child potency increases the risk for offspring anxiety and depression and interacts with maternal psychopathology on predicting offspring depression.

Using Response Surface Analysis to Interpret the Impact of Parent–Offspring Personality Similarity on Adolescent Externalizing Problems

PubMed Central

Laceulle, Odillia M.; Van Aken, Marcel A.G.; Ormel, Johan

2017-01-01

Abstract Personality similarity between parent and offspring has been suggested to play an important role in offspring's development of externalizing problems. Nonetheless, much remains unknown regarding the nature of this association. This study aimed to investigate the effects of parent–offspring similarity at different levels of personality traits, comparing expectations based on evolutionary and goodness‐of‐fit perspectives. Two waves of data from the TRAILS study (N = 1587, 53% girls) were used to study parent–offspring similarity at different levels of personality traits at age 16 predicting externalizing problems at age 19. Polynomial regression analyses and Response Surface Analyses were used to disentangle effects of different levels and combinations of parents and offspring personality similarity. Although several facets of the offspring's personality had an impact on offspring's externalizing problems, few similarity effects were found. Therefore, there is little support for assumptions based on either an evolutionary or a goodness‐of‐fit perspective. Instead, our findings point in the direction that offspring personality, and at similar levels also parent personality might impact the development of externalizing problems during late adolescence. © 2017 The Authors. European Journal of Personality published by John Wiley & Sons Ltd on behalf of European Association of Personality Psychology PMID:28303077

Family functioning in the context of parental bipolar disorder: associations with offspring age, sex, and psychopathology.

PubMed

Freed, Rachel D; Tompson, Martha C; Wang, Christine H; Otto, Michael W; Hirshfeld-Becker, Dina R; Nierenberg, Andrew A; Henin, Aude

2015-02-01

Previous research has shown that families with a parent who has bipolar disorder (BD) may experience family functioning difficulties. However, the association between family functioning and psychopathology among offspring of parents with BD, and offspring characteristics that may moderate this association, remains poorly understood. This study examined the cross-sectional associations between family functioning (cohesion, expressiveness, and conflict) and psychopathology in 117 offspring (ages 5-18) of 75 parents with BD. We also examined whether age and sex differences moderated these associations. We measured offspring psychopathology by examining current dimensional symptoms and DSM-IV emotional and behavioral disorders. Correlational analyses indicated that higher family conflict and lower cohesion were associated with higher internalizing and externalizing symptoms in offspring. Lower family cohesion was also associated with current offspring mood disorders. Moderation analyses indicated, first, that the link between lower family cohesion and internalizing symptoms was stronger for younger offspring compared to older offspring. Second, higher family conflict and current mood disorder were associated in younger males but not in older males or in females. Results remained the same after controlling for parental anxiety or substance use disorder comorbidity. Our study highlights the importance of accounting for family functioning when working with offspring at risk for BD, while also recognizing that the connections between family functioning and offspring outcomes are complex and differ based on offspring sex and developmental stage. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Cross-generational environmental effects and the evolution of offspring size in the Trinidadian guppy Poecilia reticulata.

PubMed

Bashey, Farrah

2006-02-01

The existence of adaptive phenotypic plasticity demands that we study the evolution of reaction norms, rather than just the evolution of fixed traits. This approach requires the examination of functional relationships among traits not only in a single environment but across environments and between traits and plasticity itself. In this study, I examined the interplay of plasticity and local adaptation of offspring size in the Trinidadian guppy, Poecilia reticulata. Guppies respond to food restriction by growing and reproducing less but also by producing larger offspring. This plastic difference in offspring size is of the same order of magnitude as evolved genetic differences among populations. Larger offspring sizes are thought to have evolved as an adaptation to the competitive environment faced by newborn guppies in some environments. If plastic responses to maternal food limitation can achieve the same fitness benefit, then why has guppy offspring size evolved at all? To explore this question, I examined the plastic response to food level of females from two natural populations that experience different selective environments. My goals were to examine whether the plastic responses to food level varied between populations, test the consequences of maternal manipulation of offspring size for offspring fitness, and assess whether costs of plasticity exist that could account for the evolution of mean offspring size across populations. In each population, full-sib sisters were exposed to either a low- or high-food treatment. Females from both populations produced larger, leaner offspring in response to food limitation. However, the population that was thought to have a history of selection for larger offspring was less plastic in its investment per offspring in response to maternal mass, maternal food level, and fecundity than the population under selection for small offspring size. To test the consequences of maternal manipulation of offspring size for offspring fitness, I raised the offspring of low- and high-food mothers in either low- or high-food environments. No maternal effects were detected at high food levels, supporting the prediction that mothers should increase fecundity rather than offspring size in noncompetitive environments. For offspring raised under low food levels, maternal effects on juvenile size and male size at maturity varied significantly between populations, reflecting their initial differences in maternal manipulation of offspring size; nevertheless, in both populations, increased investment per offspring increased offspring fitness. Several correlates of plasticity in investment per offspring that could affect the evolution of offspring size in guppies were identified. Under low-food conditions, mothers from more plastic families invested more in future reproduction and less in their own soma. Similarly, offspring from more plastic families were smaller as juveniles and female offspring reproduced earlier. These correlations suggest that a fixed, high level of investment per offspring might be favored over a plastic response in a chronically low-resource environment or in an environment that selects for lower reproductive effort.

Familial association of anxiety sensitivity and psychopathology.

PubMed

East, Allison J; Berman, Mitchell E; Stoppelbein, Laura

2007-01-01

The purpose of this study was to examine the association between parental (biological mother and father) and adult-offspring anxiety sensitivity (AS), and to determine whether parental AS is related to psychopathology in offspring. We obtained offspring (N=174) self-ratings of anxiety, mood, and stress symptoms, and assigned psychiatric diagnoses using a semistructured clinical interview. Biological mothers, fathers, and offspring independently completed a self-report measure of AS. We hypothesized that (1) there would be a positive relation between parental and offspring AS, and (2) AS in parents would be positively associated with psychopathology in offspring. Results indicated that paternal (but not maternal) AS was associated with offspring AS and psychopathology.

Sugared water consumption by adult offspring of mothers fed a protein-restricted diet during pregnancy results in increased offspring adiposity: the second hit effect.

PubMed

Cervantes-Rodríguez, M; Martínez-Gómez, M; Cuevas, E; Nicolás, L; Castelán, F; Nathanielsz, P W; Zambrano, E; Rodríguez-Antolín, J

2014-02-01

Poor maternal nutrition predisposes offspring to metabolic disease. This predisposition is modified by various postnatal factors. We hypothesised that coupled to the initial effects of developmental programming due to a maternal low-protein diet, a second hit resulting from increased offspring postnatal sugar consumption would lead to additional changes in metabolism and adipose tissue function. The objective of the present study was to determine the effects of sugared water consumption (5% sucrose in the drinking-water) on adult offspring adiposity as a 'second hit' following exposure to maternal protein restriction during pregnancy. We studied four offspring groups: (1) offspring of mothers fed the control diet (C); (2) offspring of mothers fed the restricted protein diet (R); (3) offspring of control mothers that drank sugared water (C-S); (4) offspring of restricted mothers that drank sugared water (R-S). Maternal diet in pregnancy was considered the first factor and sugared water consumption as the second factor - the second hit. Body weight and total energy consumption, before and after sugared water consumption, were similar in all the groups. Sugared water consumption increased TAG, insulin and cholesterol concentrations in both the sexes of the C-S and R-S offspring. Sugared water consumption increased leptin concentrations in the R-S females and males but not in the R offspring. There was also an interaction between sugared water and maternal diet in males. Sugared water consumption increased adipocyte size and adiposity index in both females and males, but the interaction with maternal diet was observed only in females. Adiposity index and plasma leptin concentrations were positively correlated in both the sexes. The present study shows that a second hit during adulthood can amplify the effects of higher adiposity arising due to poor maternal pregnancy diet in an offspring sex dependent fashion.

Deficits in social behavior and reversal learning are more prevalent in male offspring of VIP deficient female mice

PubMed Central

Stack, Conor M.; Lim, Maria A.; Cuasay, Katrina; Stone, Madeleine M.; Seibert, Kimberly. M.; Spivak-Pohis, Irit; Crawley, Jacqueline N.; Waschek, James A.; Hill, Joanna M.

2008-01-01

Blockage of vasoactive intestinal peptide (VIP) receptors during early embryogenesis in the mouse has been shown to result in developmental delays in neonates, and social behavior deficits selectively in adult male offspring. Offspring of VIP deficient mothers (VIP +/−) also exhibited developmental delays, and reductions in maternal affiliation and play behavior. In the current study, comparisons among the offspring of VIP deficient mothers (VIP +/−) mated to VIP +/− males with the offspring of wild type (WT) mothers mated to VIP +/− males allowed assessment of the contributions of both maternal and offspring VIP genotype to general health measures, social behavior, fear conditioning, and spatial learning and memory in the water maze. These comparisons revealed few differences in general health among offspring of WT and VIP deficient mothers, and all offspring exhibited normal responses in fear conditioning and in the acquisition phase of spatial discrimination in the water maze. WT mothers produced offspring that were normal in all tests; the reduced VIP in their VIP +/− offspring apparently did not contribute to any defects in the measures under study. However, regardless of their own VIP genotype, all male offspring of VIP deficient mothers exhibited severe deficits in social approach behavior and reversal learning. The deficits in these behaviors in the female offspring of VIP deficient mothers were less severe than in their male littermates, and the extent of their impairment was related to their own VIP genotype. This study has shown that intrauterine conditions had a greater influence on behavioral outcome than did genetic inheritance. In addition, the greater prevalence of deficits in social behavior and the resistance to change seen in reversal learning in the male offspring of VIP deficient mothers indicate a potential usefulness of the VIP knockout mouse in furthering the understanding of neurodevelopmental disorders such as autism. PMID:18316078

Diastolic dysfunction is associated with insulin resistance, but not with aldosterone level in normotensive offspring of hypertensive families.

PubMed

Zizek, Bogomir; Poredos, Pavel; Trojar, Andrej; Zeljko, Tadej

2008-01-01

We investigated left ventricular (LV) morphology and function in association with insulin level/insulin resistance (IR) and aldosterone level in normotensive offspring of subjects with essential hypertension (familial trait, FT). The study encompassed 76 volunteers of whom 44 were normotensive with FT (aged 28-39 years) and 32 age-matched controls without FT. LV mass and function were measured using conventional echocardiography and tissue Doppler imaging. LV diastolic function was reported as peak septal annular velocities (E(m) and E(m)/A(m) ratio) in tissue Doppler imaging. Fasting insulin and aldosterone were determined. In subjects with FT, the LV mass was higher than in controls (92.14 +/- 24.02 vs. 70.08 +/- 20.58 g; p < 0.001). The study group had a worse LV diastolic function than control subjects (lower E(m) and E(m)/A(m) ratio; p < 0.001). In subjects with FT, the E(m)/A(m) ratio was independently associated with IR (partial p = 0.029 in multivariate model, R(2) = 0.51), but not with LV mass. The aldosterone level was comparable in both groups. In normotensive individuals with FT, LV morphological and functional abnormalities were found. LV dysfunction but not an increase in LV mass is associated with IR. The aldosterone level is probably not responsible for the development of early hypertensive heart disease. (c) 2008 S. Karger AG, Basel.

Metabolic dysregulation of the insulin-glucose axis and risk of obesity-related cancers in the Framingham heart study-offspring cohort (1971-2008).

PubMed

Parekh, Niyati; Lin, Yong; Vadiveloo, Maya; Hayes, Richard B; Lu-Yao, Grace L

2013-10-01

Obesity-related dysregulation of the insulin-glucose axis is hypothesized in carcinogenesis. We studied impaired fasting glucose (IFG) and other markers of insulin-glucose metabolism in the Framingham Heart Study-Offspring Cohort, which uniquely tracks these markers and cancer >37 years. Participants were recruited between 1971 and 1975 and followed until 2008 (n = 4,615; mean age 66.8 years in 2008). Serum glucose, insulin, and hemoglobin A1c were determined from fasting blood in quart-annual exams. Lifestyle and demographic information was self-reported. HRs and 95% confidence intervals (CI) of cancer risk were computed using time-dependent survival analysis (SASv9.3), while accounting for temporal changes for relevant variables. We identified 787 obesity-related cancers, including 136 colorectal, 217 breast, and 219 prostate cancers. Absence versus presence of IFG 10 to 20 years and 20+ years before the event or last follow-up was associated with 44% (95% CI, 1.15-1.79) and 57% (95% CI, 1.17-2.11) increased risk of obesity-related cancers, respectively. When time-dependent variables were used, after adjusting for age, sex, smoking, alcohol, and body mass index, IFG was associated with a 27% increased risk of obesity-related cancer (HR = 1.27; CI, 1.1-1.5). Associations were stronger in smokers (HR = 1.41; CI, 1.13-1.76). Increased risk was noted among persons with higher insulin (HR = 1.47; CI, 1.15-1.88) and hemoglobin A1c (HR = 1.54; CI, 1.13-2.10) for the highest (≥ 5.73%) versus lowest (≤ 5.25%) category. A >2-fold increase in colorectal cancer risk was observed for all blood biomarkers of insulin-glucose metabolism, particularly with earlier IFG exposure. Nonsignificant increased risk of breast and prostate cancer was observed for blood biomarkers. Earlier IFG exposure (>10 years before) increased obesity-related cancer risk, particularly for colorectal cancer. Our study explicitly recognizes the importance of prolonged IFG exposure in identifying links between glucose dysregulation and obesity-related cancers.

Assessing the roles of population density and predation risk in the evolution of offspring size in populations of a placental fish

PubMed Central

Schrader, Matthew; Travis, Joseph

2012-01-01

Population density is an ecological variable that is hypothesized to be a major agent of selection on offspring size. In high-density populations, high levels of intraspecific competition are expected to favor the production of larger offspring. In contrast, lower levels of intraspecific competition and selection for large offspring should be weaker and more easily overridden by direct selection for increased fecundity in low-density populations. Some studies have found associations between population density and offspring size consistent with this hypothesis. However, their interpretations are often clouded by a number of issues. Here, we use data from a 10-year study of nine populations of the least killifish, Heterandria formosa, to describe the associations of offspring size with habitat type, population density, and predation risk. We found that females from spring populations generally produced larger offspring than females from ponds; however, the magnitude of this difference varied among years. Across all populations, larger offspring were associated with higher densities and lower risks of predation. Interestingly, the associations between the two ecological variables (density and predation risk) and offspring size were largely independent of one another. Our results suggest that previously described genetic differences in offspring size are due to density-dependent natural selection. PMID:22957156

Intergenerational Transmission of Overweight and Obesity from Parents to Their Adolescent Offspring - The HUNT Study.

PubMed

Næss, Marit; Holmen, Turid Lingaas; Langaas, Mette; Bjørngaard, Johan Håkon; Kvaløy, Kirsti

2016-01-01

The main aim of this study was to examine weight associations between parents and offspring at two time points: 1995-97 and 2006-08, taking into account body mass index (BMI) and waist circumference. The study included 8425 parent-offspring trios who participated in the population based Health Study of Nord Trøndelag (the HUNT Study), Norway, at either the HUNT2 (1995-97) or the HUNT3 (2006-08) survey. We used linear mixed effects models with siblings clustered within mothers to analyze the associations between 1) parental grouped BMI and offspring BMI z-scores and 2) parental grouped waist circumference and offspring waist circumference z-scores. Adolescent and adult overweight and obesity were higher in 2006-08 than in 1995-97, with the greatest increase observed in waist circumference. Both mother's and father's BMI and waist circumference were strongly associated with corresponding measures in offspring. Compared with both parents being normal weight (BMI <25 kg/m2), having two overweight or obese parents (BMI ≥25 kg/m2) was associated with a higher offspring BMI z-score of 0.76 (95% CI; 0.65, 0.87) and 0.64 (95% CI; 0.48, 0.80) in daughters, and 0.76 (95% CI; 0.65, 0.87) and 0.69 (95% CI; 0.53, 0.80) in sons, in 1995-97 and 2006-08 respectively. Offspring with one parent being overweight/obese had BMI z-scores of approximately half of offspring with two parents categorized as overweight/obese. The results of the waist circumference based analyses did not differ substantially from the BMI based analyses. Parental overweight was strongly positively associated with offspring weight both in 1995-97 and 2006-08 where both parents being overweight/obese gave the largest effect. This seemingly stable association, strongly address the importance of public health initiatives towards preventing obesity in parents of both sexes to decrease further obesity expansion in offspring.

Temperament and major depression: How does difficult temperament affect frequency, severity, and duration of major depressive episodes among offspring of parents with or without depression?

PubMed

Sherman, Brian J; Vousoura, Eleni; Wickramaratne, Priya; Warner, Virginia; Verdeli, Helen

2016-08-01

The current study examined the relationships between parental depression, offspring depression, and offspring temperament among 203 offspring of parents with or without depression. The specific aim was to investigate how parental depression and offspring difficult temperament affect frequency, severity, and duration of offspring major depressive episodes (MDEs). As part of an ongoing multigenerational study assessing familial transmission of depression, offspring were assessed over a 20-year study period. Offspring temperament was assessed at baseline using the Dimensions of Temperament Survey and diagnostic interviews were conducted at each of the four waves using best estimate procedures. Difficult temperament predicted greater frequency of lifetime MDEs. Parental depression moderated the relationship between offspring difficult temperament and severity of MDEs, such that difficult temperament was associated with increased severity ratings among high-risk, but not low-risk offspring. Dimensional analysis revealed that lower rhythmicity and adaptability were associated with greater number of lifetime MDEs, higher inattention/distractibility was associated with shorter duration of MDEs, and greater activity was associated with decreased severity of MDEs. Certain limitations must be noted, namely the self-report nature of temperament data and the relatively small sample size drawn from a clinical and predominantly Caucasian and Christian sample. Notwithstanding these limitations, our results suggest that the clinical presentation of major depression may reflect temperamental profiles and should be considered in diagnostic and treatment settings. Copyright © 2016 Elsevier B.V. All rights reserved.

Higher oily fish consumption in late pregnancy is associated with reduced aortic stiffness in the child at age 9 years.

PubMed

Bryant, Jennifer; Hanson, Mark; Peebles, Charles; Davies, Lucy; Inskip, Hazel; Robinson, Sian; Calder, Philip C; Cooper, Cyrus; Godfrey, Keith M

2015-03-27

Higher pulse wave velocity (PWV) reflects increased arterial stiffness and is an established cardiovascular risk marker associated with lower long-chain n-3 polyunsaturated fatty acid intake in adults. Experimentally, maternal fatty acid intake in pregnancy has lasting effects on offspring arterial stiffness. To examine the association between maternal consumption of oily fish, a source of long-chain n-3 polyunsaturated fatty acids, in pregnancy and child's aortic stiffness age 9 years. In a mother-offspring study (Southampton Women's Survey), the child's descending aorta PWV was measured at the age of 9 years using velocity-encoded phase-contrast MRI and related to maternal oily fish consumption assessed prospectively during pregnancy. Higher oily fish consumption in late pregnancy was associated with lower childhood aortic PWV (sex-adjusted β=-0.084 m/s per portion per week; 95% confidence interval, -0.137 to -0.031; P=0.002; n=226). Mother's educational attainment was independently associated with child's PWV. PWV was not associated with the child's current oily fish consumption. Level of maternal oily fish consumption in pregnancy may influence child's large artery development, with potential long-term consequences for later cardiovascular risk. © 2015 American Heart Association, Inc.

Protective effects of Allium sativum against defects of hypercholesterolemia on pregnant rats and their offspring.

PubMed

El-Sayyad, Hassan I; Abou-El-Naga, Amoura M; Gadallah, Abdelalim A; Bakr, Iman H

2010-06-10

Sixty fertile female and male albino rats of Wistar strain (I male/ 3 females) were used in the present study. The females were divided into four groups of ten rats each. Group 1 received water and standard feeds for thirty-four days. Group 2 was fed with a cholesterol-containing diet (1%) for two weeks prior to onset of gestation and maintained administration till parturition, produce atherosclerosis (34 days). Group 3 received intragastric administration of 100mg homogenate of garlic (Allium sativum)/kg body weight for three weeks prior to onset of gestation as well as throughout the gestation period. Group 4 intragastrically administered garlic for one week of group B and maintained with combined garlic-treatment for the mentioned period. At parturition, the pregnant were sacrificed and serum total cholesterol (TCL), triglycerides (TG), HDL, LDL and creatine kinase activity (CK) were determined. The total numbers of offspring were recorded and examined morphological for congenital abnormalities. Biopsies of heart and dorsal aorta of both pregnant and their offspring (1 day-age) were processed for investigation at light and transmission electron microscopy. The skeleton of the newborn of different experimental groups were stained with alizarin red s and mor-phometric assessment of mandibular and appendicular bone length. The study revealed that the myocardium of atherosclerotic mother exhibited leuhkocytic inflammatory cell infiltration associated with necrosis, eosinophilia of myocardiai fibers, and edema of blood vessels. Ultrastructural studies revealed swelling of mitochondria, disruption of cristae in the myocardiai muscle fibers. The dorsal aorta possessed accumulation of extra-cellular lipid in intima lining of endothelium. The collagenous fibrils in the tunica adventitia became fragile and loosely separated from each other. Numerous foamy lipid loaden cells were detected within the tunica intima causing deterioration of the elastic fibers, resulting in fibrinoid necrosis. Oral supplementation with Allium sativum (100 mg/ kg) ameliorated these effects in myocardium muscle of mothers and offspring; however the dorsal aorta of mothers showed partial amelioration. Hypercholesterolemic mothers exhibited marked alterations in serum TCL, TG, LDL and CK activity. Supplementation with Allium sativum ameliorated the drastic biochemical alterations. Concerning pregnancy, hypercholesterolemia increased the incidence of abortion and abnormalities of the newborn including decreased body weight, reduced ossification of axial (mandible) and appendicular bones. All these effects were markedly ameliorated by supplementation with Allium sativum. The author finally concluded that hypercholesterolemia exhibits pathological alterations of myocardiai muscles reducing its optimal capacity for pumping blood to different body organs along with atherosclerosis of dorsal aorta which intern affect the progress of gestation and development of both morphological and skeletal abnormalities. Allium sativum-supplementation leads to amelioration of both mother and their offspring investigated parameters as a result of its antioxidant activity.

Protective effects of Allium sativum against defects of hypercholesterolemia on pregnant rats and their offspring

PubMed Central

El-Sayyad, Hassan I; Abou-El-Naga, Amoura M; Gadallah, Abdelalim A; Bakr, Iman H

2010-01-01

Sixty fertile female and male albino rats of Wistar strain (I male/ 3 females) were used in the present study. The females were divided into four groups of ten rats each. Group 1 received water and standard feeds for thirty-four days. Group 2 was fed with a cholesterol-containing diet (1%) for two weeks prior to onset of gestation and maintained administration till parturition, produce atherosclerosis (34 days). Group 3 received intragastric administration of 100mg homogenate of garlic (Allium sativum)/kg body weight for three weeks prior to onset of gestation as well as throughout the gestation period. Group 4 intragastrically administered garlic for one week of group B and maintained with combined garlic-treatment for the mentioned period. At parturition, the pregnant were sacrificed and serum total cholesterol (TCL), triglycerides (TG), HDL, LDL and creatine kinase activity (CK) were determined. The total numbers of offspring were recorded and examined morphological for congenital abnormalities. Biopsies of heart and dorsal aorta of both pregnant and their offspring (1 day-age) were processed for investigation at light and transmission electron microscopy. The skeleton of the newborn of different experimental groups were stained with alizarin red s and mor-phometric assessment of mandibular and appendicular bone length. The study revealed that the myocardium of atherosclerotic mother exhibited leuhkocytic inflammatory cell infiltration associated with necrosis, eosinophilia of myocardiai fibers, and edema of blood vessels. Ultrastructural studies revealed swelling of mitochondria, disruption of cristae in the myocardiai muscle fibers. The dorsal aorta possessed accumulation of extra-cellular lipid in intima lining of endothelium. The collagenous fibrils in the tunica adventitia became fragile and loosely separated from each other. Numerous foamy lipid loaden cells were detected within the tunica intima causing deterioration of the elastic fibers, resulting in fibrinoid necrosis. Oral supplementation with Allium sativum (100 mg/ kg) ameliorated these effects in myocardium muscle of mothers and offspring; however the dorsal aorta of mothers showed partial amelioration. Hypercholesterolemic mothers exhibited marked alterations in serum TCL, TG, LDL and CK activity. Supplementation with Allium sativum ameliorated the drastic biochemical alterations. Concerning pregnancy, hypercholesterolemia increased the incidence of abortion and abnormalities of the newborn including decreased body weight, reduced ossification of axial (mandible) and appendicular bones. All these effects were markedly ameliorated by supplementation with Allium sativum. The author finally concluded that hypercholesterolemia exhibits pathological alterations of myocardiai muscles reducing its optimal capacity for pumping blood to different body organs along with atherosclerosis of dorsal aorta which intern affect the progress of gestation and development of both morphological and skeletal abnormalities. Allium sativum-supplementation leads to amelioration of both mother and their offspring investigated parameters as a result of its antioxidant activity. PMID:20607041

A theoretical model of the evolution of maternal effects under parent-offspring conflict.

PubMed

Uller, Tobias; Pen, Ido

2011-07-01

The evolution of maternal effects on offspring phenotype should depend on the extent of parent-offspring conflict and costs and constraints associated with maternal and offspring strategies. Here, we develop a model of maternal effects on offspring dispersal phenotype under parent-offspring conflict to evaluate such dependence. In the absence of evolutionary constraints and costs, offspring evolve dispersal rates from different patch types that reflect their own, rather than the maternal, optima. This result also holds true when offspring are unable to assess their own environment because the maternal phenotype provides an additional source of information. Consequently, maternal effects on offspring diapause, dispersal, and other traits that do not necessarily represent costly resource investment are more likely to maximize offspring than maternal fitness. However, when trait expression was costly, the evolutionarily stable dispersal rates tended to deviate from those under both maternal and offspring control. We use our results to (re)interpret some recent work on maternal effects and their adaptive value and provide suggestions for future work. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

Antenatal depression and offspring psychopathology: the influence of childhood maltreatment.

PubMed

Pawlby, Susan; Hay, Dale; Sharp, Deborah; Waters, Cerith S; Pariante, Carmine M

2011-08-01

Antenatal depression and childhood maltreatment have each been associated with offspring psychopathology, but have never been examined in the same sample. To determine whether childhood maltreatment influences the association between antenatal depression and offspring psychopathology. Prospectively collected data on antenatal depression, offspring maltreatment (age 11) and offspring psychopathology (age 11 and 16) were analysed in 120 mother-offspring dyads from the community-based South London Child Development Study. Antenatal depression increased the risk of maltreatment in the offspring by almost four times. Children exposed only to antenatal depression or only to childhood maltreatment were no more at risk of developing psychopathology; however, children exposed to both antenatal depression and childhood maltreatment were at almost 12 times greater risk of developing psychopathology than offspring not so exposed. Research investigating exposure to adverse events in utero and offspring psychopathology should take account of postnatal adverse events such as maltreatment.

Paternal stress prior to conception alters DNA methylation and behaviour of developing rat offspring.

PubMed

Mychasiuk, R; Harker, A; Ilnytskyy, S; Gibb, R

2013-06-25

Although there has been an abundance of research focused on offspring outcomes associated with maternal experiences, there has been limited examination of the relationship between paternal experiences and offspring brain development. As spermatogenesis is a continuous process, experiences that have the ability to alter epigenetic regulation in fathers may actually change developmental trajectories of offspring. The purpose of this study was to examine the effects of paternal stress prior to conception on behaviour and the epigenome of both male and female developing rat offspring. Male Long-Evans rats were stressed for 27 consecutive days and then mated with control female rats. Early behaviour was tested in offspring using the negative geotaxis task and the open field. At P21 offspring were sacrificed and global DNA methylation levels in the hippocampus and frontal cortex were analysed. Paternal stress prior to conception altered behaviour of all offspring on the negative geotaxis task, delaying acquisition of the task. In addition, male offspring demonstrated a reduction in stress reactivity in the open field paradigm spending more time than expected in the centre of the open field. Paternal stress also altered DNA methylation patterns in offspring at P21, global methylation was reduced in the frontal cortex of female offspring, but increased in the hippocampus of both male and female offspring. The results from this study clearly demonstrate that paternal stress during spermatogenesis can influence offspring behaviour and DNA methylation patterns, and these affects occur in a sex-dependent manner. Development takes place in the centre of a complex interaction between maternal, paternal, and environmental influences, which combine to produce the various phenotypes and individual differences that we perceive. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Gray Matter Volume Decrease Distinguishes Schizophrenia From Bipolar Offspring During Childhood and Adolescence.

PubMed

Sugranyes, Gisela; de la Serna, Elena; Romero, Soledad; Sanchez-Gistau, Vanessa; Calvo, Anna; Moreno, Dolores; Baeza, Inmaculada; Diaz-Caneja, Covadonga M; Sanchez-Gutierrez, Teresa; Janssen, Joost; Bargallo, Nuria; Castro-Fornieles, Josefina

2015-08-01

There is increasing support toward the notion that schizophrenia and bipolar disorder share neurodevelopmental underpinnings, although areas of divergence remain. We set out to examine gray matter volume characteristics of child and adolescent offspring of patients with schizophrenia or bipolar disorder comparatively. In this 2-center study, magnetic resonance structural neuroimaging data were acquired in 198 children and adolescents (aged 6-17 years): 38 offspring of patients with schizophrenia, 77 offspring of patients with bipolar disorder, and 83 offspring of community controls. Analyses of global brain volumes and voxel-based morphometry (using familywise error correction) were conducted. There was an effect of group on total cerebral gray matter volume (F = 3.26, p = .041), driven by a decrease in offspring of patients with schizophrenia relative to offspring of controls (p = .035). At a voxel-based level, we observed an effect of group in the left inferior frontal cortex/anterior insula (F = 14.7, p < .001), which was driven by gray matter volume reduction in offspring of patients with schizophrenia relative to both offspring of controls (p = .044) and of patients with bipolar disorder (p < .001). No differences were observed between offspring of patients with bipolar disorder and offspring of controls in either global or voxel-based gray matter volumes. This first comparative study between offspring of patients with schizophrenia and bipolar disorder suggests that gray matter volume reduction in childhood and adolescence may be specific to offspring of patients with schizophrenia; this may index a greater neurodevelopmental impact of risk for schizophrenia relative to bipolar disorder during youth. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Obesity and abnormal glucose tolerance in offspring of diabetic mothers: A systematic review and meta-analysis.

PubMed

Kawasaki, Maki; Arata, Naoko; Miyazaki, Celine; Mori, Rintaro; Kikuchi, Toru; Ogawa, Yoshihiro; Ota, Erika

2018-01-01

Rising prevalence of childhood obesity and type 2 diabetes mellitus (T2DM) is an emerging public health issue. To investigate the association of maternal hyperglycemia exposure during pregnancy with obesity and abnormal glucose tolerance in offspring, and the age at occurrence. We searched MEDLINE and EMBASE for observational studies on obesity and diabetes in offspring of diabetic mothers (gestational diabetes mellitus (GDM), type 1 diabetes mellitus (T1DM) and T2DM), and those on non-diabetic mothers. We performed fixed effect meta-analysis for all studies except when heterogeneity was detected. The quality of studies was evaluated using the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS). Twenty observational studies were included involving a total of 26,509 children. Offspring of GDM mother had higher BMI z-score in childhood (pooled MD: 0.14, 95%CI: 0.04-0.24, seven studies, 21,691children, low quality of evidence). Offspring of T1DM mothers had higher BMI z-score from prepubertal to adolescent (pooled MD: 0.35, 95% CI: 0.13-0.58, three studies, 844 children, low quality of evidence) compared with control. After adjustment for maternal pre-pregnancy BMI, this association remained in offspring of T1DM, but disappeared in those of GDM mothers. Offspring of GDM mother had higher 2-hour plasma glucose from prepubertal to early adulthood (pooled MD: 0.43 mmol/L, 95% CI: 0.18-0.69, five studies, 890 children), while those of T1DM mothers had higher rate of T2DM in 2-5 years old to early adulthood (pooled odds ratio [OR], 6.10: 95% CI: 1.23-30.37, two studies, 448 children, very low quality of evidence) compared with control. As there was only one study with offspring of T2DM mothers, evidence is sparse. Only observational studies were included, with a few adequately adjusted for covariables. Exposure to maternal hyperglycemia was associated with offspring obesity and abnormal glucose tolerance especially in offspring of T1DM mothers, but the evidence relies on observational studies with low quality of evidence only.

A Study on Mediation by Offspring BMI in the Association between Maternal Obesity and Child Respiratory Outcomes in the Amsterdam Born and Their Development Study Cohort.

PubMed

Harskamp-van Ginkel, Margreet W; London, Stephanie J; Magnus, Maria C; Gademan, Maaike G; Vrijkotte, Tanja G

2015-01-01

A causal relationship between maternal obesity and offspring asthma is hypothesized to begin during early development, but no underlying mechanism for the found association is identified. We quantitatively examined mediation by offspring body mass index (BMI) in the association of maternal pre-pregnancy BMI on risk of asthma and wheezing during the first 7-8 years of life in a large Amsterdam born birth cohort. For 3185 mother-child pairs, mothers reported maternal pre-pregnancy BMI and offspring outcomes "ever being diagnosed with asthma" and "wheezing in the past 12 months" on questionnaires. We measured offspring height and weight at age 5-6 years. We performed a multivariate log linear regression comparing outcomes in offspring of mothers with different BMI categories. For each category we quantified and tested mediation by offspring BMI and also investigated interaction by parental asthma. At the age of 7-8 years, 8% of the offspring ever had asthma and 7% had current wheezing. Maternal pre-pregnancy obesity was associated with higher risks of asthma (adjusted RR 2.32 (95% CI: 1.49-3.61) and wheezing (adjusted RR 2.16 (95% CI: 1.28-3.64). Offspring BMI was a mediator in the association between maternal BMI and offspring wheezing, but not for asthma. There was no interaction by parental asthma. Maternal pre-pregnancy obesity was associated with higher risks of offspring asthma and wheezing. The association between maternal obesity and offspring wheezing was both direct and indirect (mediated) through the child's own BMI.

Lifestyle, pregnancy and epigenetic effects.

PubMed

Barua, Subit; Junaid, Mohammed A

2015-01-01

Rapidly growing evidences link maternal lifestyle and prenatal factors with serious health consequences and diseases later in life. Extensive epidemiological studies have identified a number of factors such as diet, stress, gestational diabetes, exposure to tobacco and alcohol during gestation as influencing normal fetal development. In light of recent discoveries, epigenetic mechanisms such as alteration of DNA methylation, chromatin modifications and modulation of gene expression during gestation are believed to possibly account for various types of plasticity such as neural tube defects, autism spectrum disorder, congenital heart defects, oral clefts, allergies and cancer. The purpose of this article is to review a number of published studies to fill the gap in our understanding of how maternal lifestyle and intrauterine environment influence molecular modifications in the offspring, with an emphasis on epigenetic alterations. To support these associations, we highlighted laboratory studies of rodents and epidemiological studies of human based on sampling population cohorts.

Exploring the association between maternal prenatal multivitamin use and early infant growth: The Healthy Start Study.

PubMed

Sauder, K A; Starling, A P; Shapiro, A L; Kaar, J L; Ringham, B M; Glueck, D H; Dabelea, D

2016-10-01

Prenatal multivitamin supplementation is recommended to improve offspring outcomes, but effects on early infant growth are unknown. We examined whether multivitamin supplementation in the year before delivery predicts offspring mass, body composition and early infant growth. Multivitamin use was assessed longitudinally in 626 women from the Healthy Start Study. Offspring body size and composition was measured with air displacement plethysmography at birth (<3 days) and postnatally (median 5.2 months). Separate multiple linear regressions assessed the relationship of weeks of daily multivitamin use with offspring mass, body composition and postnatal growth, after adjustment for potential confounders (maternal age, race, pre-pregnant body mass index; offspring gestational age at birth, sex; breastfeeding exclusivity). Maternal multivitamin use was not related to offspring mass or body composition at birth, or rate of change in total or fat-free mass in the first 5 months. Multivitamin use was inversely associated with average monthly growth in offspring percent fat mass (β = -0.009, p = 0.049) between birth and postnatal exam. Offspring of non-users had a monthly increase in percent fat mass of 3.45%, while offspring at the top quartile of multivitamin users had a monthly increase in percent fat mass of 3.06%. This association was not modified by exclusive breastfeeding. Increased multivitamin use in the pre-conception and prenatal periods was associated with a slower rate of growth in offspring percent fat mass in the first 5 months of life. This study provides further evidence that in utero nutrient exposures may affect offspring adiposity beyond birth. © 2015 World Obesity.

Association of Rare Loss-Of-Function Alleles in HAL, Serum Histidine: Levels and Incident Coronary Heart Disease.

PubMed

Yu, Bing; Li, Alexander H; Muzny, Donna; Veeraraghavan, Narayanan; de Vries, Paul S; Bis, Joshua C; Musani, Solomon K; Alexander, Danny; Morrison, Alanna C; Franco, Oscar H; Uitterlinden, André; Hofman, Albert; Dehghan, Abbas; Wilson, James G; Psaty, Bruce M; Gibbs, Richard; Wei, Peng; Boerwinkle, Eric

2015-04-01

Histidine is a semiessential amino acid with antioxidant and anti-inflammatory properties. Few data are available on the associations between genetic variants, histidine levels, and incident coronary heart disease (CHD) in a population-based sample. By conducting whole exome sequencing on 1152 African Americans in the Atherosclerosis Risk in Communities (ARIC) study and focusing on loss-of-function (LoF) variants, we identified 3 novel rare LoF variants in HAL, a gene that encodes histidine ammonia-lyase in the first step of histidine catabolism. These LoF variants had large effects on blood histidine levels (β=0.26; P=1.2×10(-13)). The positive association with histidine levels was replicated by genotyping an independent sample of 718 ARIC African Americans (minor allele frequency=1%; P=1.2×10(-4)). In addition, high blood histidine levels were associated with reduced risk of developing incident CHD with an average of 21.5 years of follow-up among African Americans (hazard ratio=0.18; P=1.9×10(-4)). This finding was validated in an independent sample of European Americans from the Framingham Heart Study (FHS) Offspring Cohort. However, LoF variants in HAL were not directly significantly associated with incident CHD after meta-analyzing results from the CHARGE Consortium. Three LoF mutations in HAL were associated with increased histidine levels, which in turn were shown to be inversely related to the risk of CHD among both African Americans and European Americans. Future investigations on the association between HAL gene variation and CHD are warranted. © 2015 American Heart Association, Inc.

Moderate maternal food restriction in mice impairs physical growth, behavior, and neurodevelopment of offspring.

PubMed

Akitake, Yoshiharu; Katsuragi, Shinji; Hosokawa, Masato; Mishima, Kenichi; Ikeda, Tomoaki; Miyazato, Mikiya; Hosoda, Hiroshi

2015-01-01

Intrauterine growth retardation (IUGR) occurs in 3% to 7% of all pregnancies. Recent human studies have indicated that neurodevelopmental disabilities, learning disorders, memory impairment, and mood disturbance are common in IUGR offspring. However, the interactions between IUGR and neurodevelopmental disorders are unclear because of the wide range of causes of IUGR, such as maternal malnutrition, placental insufficiency, pregnancy toxemia, and fetal malformations. Meanwhile, many studies have shown that moderate food restriction enhances spatial learning and improves mood disturbance in adult humans and animals. To date, the effects of maternal moderate food restriction on fetal brain remain largely unknown. In this study, we hypothesized that IUGR would be caused by even moderate food restriction in pregnant females and that the offspring would have neurodevelopmental disabilities. Mid-pregnant mice received moderate food restriction through the early lactation period. The offspring were tested for aspects of physical development, behavior, and neurodevelopment. The results showed that moderate maternal food restriction induced IUGR. Offspring had low birth weight and delayed development of physical and coordinated movement. Moreover, IUGR offspring exhibited mental disabilities such as anxiety and poor cognitive function. In particular, male offspring exhibited significantly impaired cognitive function at 3 weeks of age. These results suggested that a restricted maternal diet could be a risk factor for developmental disability in IUGR offspring and that male offspring might be especially susceptible. Copyright © 2015 Elsevier Inc. All rights reserved.

Total and Trimester-Specific Gestational Weight Gain and Offspring Birth and Early Childhood Weight: A Prospective Cohort Study on Monozygotic Twin Mothers and Their Offspring.

PubMed

Scheers Andersson, Elina; Silventoinen, Karri; Tynelius, Per; Nohr, Ellen A; Sørensen, Thorkild I A; Rasmussen, Finn

2016-08-01

Gestational weight gain (GWG) has in numerous studies been associated with offspring birth weight (BW) and childhood weight. However, these associations might be explained by genetic confounding as offspring inherit their mother's genetic potential to gain weight. Furthermore, little is known about whether particular periods of pregnancy could influence offspring body weight differently. We therefore aimed to explore total and trimester-specific effects of GWG in monozygotic (MZ) twin mother-pairs on their offspring's BW, weight at 1 year and body mass index (BMI) at 5 and 10 years. MZ twin mothers born 1962-1975 were identified in national Swedish registers, and data on exposure and outcome variables was collected from medical records. We analyzed associations within and between twin pairs. We had complete data on the mothers' GWG and offspring BW for 82 pairs. The results indicated that total, and possibly also second and third trimester GWG were associated with offspring BW within the twin pairs in the fully adjusted model (β = 0.08 z-score units, 95% CI: 0.001, 0.17; β = 1.32 z-score units, 95% CI: -0.29, 2.95; and β = 1.02 z-score units, 95% CI: -0.50, 2.54, respectively). Our findings, although statistically weak, suggested no associations between GWG and offspring weight or BMI during infancy or childhood. Our study suggests that total, and possibly also second and third trimester, GWG are associated with offspring BW when taking shared genetic and environmental factors within twin pairs into account. Larger family-based studies with long follow-up are needed to confirm our findings.

Categorical and dimensional psychopathology in Dutch and US offspring of parents with bipolar disorder: A preliminary cross-national comparison.

PubMed

Mesman, Esther; Birmaher, Boris B; Goldstein, Benjamin I; Goldstein, Tina; Derks, Eske M; Vleeschouwer, Marloes; Hickey, Mary Beth; Axelson, David; Monk, Kelly; Diler, Rasim; Hafeman, Danella; Sakolsky, Dara J; Reichart, Catrien G; Wals, Marjolein; Verhulst, Frank C; Nolen, Willem A; Hillegers, Manon H J

2016-11-15

Accumulating evidence suggests cross-national differences in adults with bipolar disorder (BD), but also in the susceptibility of their offspring (bipolar offspring). This study aims to explore and clarify cross-national variation in the prevalence of categorical and dimensional psychopathology between bipolar offspring in the US and The Netherlands. We compared levels of psychopathology in offspring of the Pittsburgh Bipolar Offspring Study (n=224) and the Dutch Bipolar Offspring Study (n=136) (age 10-18). Categorical psychopathology was ascertained through interviews using the Schedule for Affective Disorders and Schizophrenia for School Age Children (K-SADS-PL), dimensional psychopathology by parental reports using the Child Behavior Checklist (CBCL). Higher rates of categorical psychopathology were observed in the US versus the Dutch samples (66% versus 44%). We found no differences in the overall prevalence of mood disorders, including BD-I or -II, but more comorbidity in mood disorders in US versus Dutch offspring (80% versus 34%). The strongest predictors of categorical psychopathology were maternal BD (OR: 1.72, p<.05), older age of the offspring (OR: 1.19, p<.05), and country of origin (US; OR: 2.17, p<.001). Regarding comorbidity, only country of origin (OR: 7.84, p<.001) was a significant predictor. In general, we found no differences in dimensional psychopathology based on CBCL reports. Preliminary measure of inter-site reliability. We found cross-national differences in prevalence of categorical diagnoses of non-mood disorders in bipolar offspring, but not in mood disorder diagnoses nor in parent-reported dimensional psychopathology. Cross-national variation was only partially explained by between-sample differences. Cultural and methodological explanations for these findings warrant further study. Copyright © 2016 Elsevier B.V. All rights reserved.

Categorical and dimensional psychopathology in Dutch and US offspring of parents with bipolar disorder: A preliminary cross-national comparison✩

PubMed Central

Mesman, Esther; Birmaher, Boris B.; Goldstein, Benjamin I.; Goldstein, Tina; Derks, Eske M.; Vleeschouwer, Marloes; Hickey, Mary Beth; Axelson, David; Monk, Kelly; Diler, Rasim; Hafeman, Danella; Sakolsky, Dara J.; Reichart, Catrien G.; Wals, Marjolein; Verhulst, Frank C.; Nolen, Willem A.; Hillegers, Manon H.J.

2017-01-01

Objective Accumulating evidence suggests cross-national differences in adults with bipolar disorder (BD), but also in the susceptibility of their offspring (bipolar offspring). This study aims to explore and clarify cross-national variation in the prevalence of categorical and dimensional psychopathology between bipolar offspring in the US and The Netherlands. Methods We compared levels of psychopathology in offspring of the Pittsburgh Bipolar Offspring Study (n=224) and the Dutch Bipolar Offspring Study (n=136) (age 10–18). Categorical psychopathology was ascertained through interviews using the Schedule for Affective Disorders and Schizophrenia for School Age Children (K-SADS-PL), dimensional psychopathology by parental reports using the Child Behavior Checklist (CBCL). Results Higher rates of categorical psychopathology were observed in the US versus the Dutch samples (66% versus 44%). We found no differences in the overall prevalence of mood disorders, including BD-I or -II, but more comorbidity in mood disorders in US versus Dutch offspring (80% versus 34%). The strongest predictors of categorical psychopathology were maternal BD (OR: 1.72, p<.05), older age of the offspring (OR: 1.19, p<.05), and country of origin (US; OR: 2.17, p<.001). Regarding comorbidity, only country of origin (OR: 7.84, p<.001) was a significant predictor. In general, we found no differences in dimensional psychopathology based on CBCL reports. Limitations Preliminary measure of inter-site reliability. Conclusions We found cross-national differences in prevalence of categorical diagnoses of non-mood disorders in bipolar offspring, but not in mood disorder diagnoses nor in parent-reported dimensional psychopathology. Cross-national variation was only partially explained by between-sample differences. Cultural and methodological explanations for these findings warrant further study. PMID:27423424

The effect of pre-laying maternal immunization on offspring growth and immunity differs across experimentally altered postnatal rearing conditions in a wild songbird.

PubMed

Martyka, Rafał; Śliwińska, Ewa B; Martyka, Mirosław; Cichoń, Mariusz; Tryjanowski, Piotr

2018-01-01

Prenatal antibody transfer is an immune-mediated maternal effect by which females can shape postnatal offspring resistance to pathogens and parasites. Maternal antibodies passed on to offspring provide primary protection to neonates against diverse pathogenic antigens, but they may also affect offspring growth and influence the development of an offspring's own immune response. The effects of maternal antibodies on offspring performance commonly require that the disease environment experienced by a mother prior to breeding matches the environment encountered by her offspring after hatching/birth. However, other circumstances, like postnatal rearing conditions that affect offspring food availability, may also determine the effects of maternal antibodies on offspring growth and immunity. To date, knowledge about how prenatal immune-mediated maternal effects interact with various postnatal rearing conditions to affect offspring development and phenotype in wild bird population remains elusive. Here we experimentally studied the interactive effects of pre-laying maternal immunization with a bacterial antigen (lipopolysaccharide) and post-hatching rearing conditions, altered by brood size manipulation, on offspring growth and humoral immunity of wild great tits ( Parus major ). We found that maternal immunization and brood size manipulation interactively affected the growth and specific humoral immune response of avian offspring. Among nestlings reared in enlarged broods, only those that originated from immunized mothers grew better and were heavier at fledging stage compared to those that originated from non-immunized mothers. In contrast, no such effects were observed among nestlings reared in non-manipulated (control) broods. Moreover, offspring of immunized females had a stronger humoral immune response to lipopolysaccharide during postnatal development than offspring of non-immunized females, but only when the nestling was reared in control broods. This study demonstrates that offspring development and their ability to cope with pathogens after hatching are driven by mutual influences of pathogen-induced prenatal maternal effects and post-hatching rearing conditions. Our findings suggest that immune-mediated maternal effects may have context-dependent influences on offspring growth and immune function, related to the postnatal environmental conditions experienced by the progeny.

Maternal Immune Activation During the Third Trimester Is Associated with Neonatal Functional Connectivity of the Salience Network and Fetal to Toddler Behavior.

PubMed

Spann, Marisa N; Monk, Catherine; Scheinost, Dustin; Peterson, Bradley S

2018-03-14

Prenatal maternal immune activation (MIA) is associated with altered brain development and risk of psychiatric disorders in offspring. Translational human studies of MIA are few in number. Alterations of the salience network have been implicated in the pathogenesis of the same psychiatric disorders associated with MIA. If MIA is pathogenic, then associated abnormalities in the salience network should be detectable in neonates immediately after birth. We tested the hypothesis that third trimester MIA of adolescent women who are at risk for high stress and inflammation is associated with the strength of functional connectivity in the salience network of their neonate. Thirty-six women underwent blood draws to measure interleukin-6 (IL-6) and C-reactive protein (CRP) and electrocardiograms to measure fetal heart rate variability (FHRV) at 34-37 weeks gestation. Resting-state imaging data were acquired in the infants at 40-44 weeks postmenstrual age (PMA). Functional connectivity was measured from seeds placed in the anterior cingulate cortex and insula. Measures of cognitive development were obtained at 14 months PMA using the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). Both sexes were studied. Regions in which the strength of the salience network correlated with maternal IL-6 or CRP levels included the medial prefrontal cortex, temporoparietal junction, and basal ganglia. Maternal CRP level correlated inversely with FHRV acquired at the same gestational age. Maternal CRP and IL-6 levels correlated positively with measures of cognitive development on the BSID-III. These results suggest that MIA is associated with short- and long-term influences on offspring brain and behavior. SIGNIFICANCE STATEMENT Preclinical studies in rodents and nonhuman primates and epidemiological studies in humans suggest that maternal immune activation (MIA) alters the development of brain circuitry and associated behaviors, placing offspring at risk for psychiatric illness. Consistent with preclinical findings, we show that maternal third trimester interleukin-6 and C-reactive protein levels are associated with neonatal functional connectivity and with both fetal and toddler behavior. MIA-related functional connectivity was localized to the salience, default mode, and frontoparietal networks, which have been implicated in the pathogenesis of psychiatric disorders. Our results suggest that MIA alters functional connectivity in the neonatal brain, that those alterations have consequences for cognition, and that these findings may provide pathogenetic links between preclinical and epidemiological studies associating MIA with psychiatric risk in offspring. Copyright © 2018 the authors 0270-6474/18/382877-10$15.00/0.

Face-Emotion Processing in Offspring at Risk for Panic Disorder.

ERIC Educational Resources Information Center

Pine, Daniel S.; Klein, Rachel G.; Mannuzza, Salvatore; Moulton, John L., III; Lissek, Shmuel; Guardino, Mary; Woldehawariat, Girma

2005-01-01

Objective: Panic disorder (PD) has been linked to perturbed processing of threats. This study tested the hypotheses that offspring of parents with PD and offspring with anxiety disorders display relatively greater sensitivity and attention allocation to fear provocation. Method: Offspring of adults with PD, major depressive disorder (MDD), or no…

Long-term influences of parental divorce on offspring affective disorders: A systematic review and meta-analysis.

PubMed

Sands, Amy; Thompson, Ellen J; Gaysina, Darya

2017-08-15

The prevalence of divorce in Western countries has increased in recent decades. However, there is no recent systematic review and/or meta-analysis of studies testing for long-term effects of parental divorce on offspring affective disorders. The present study conducted a systematic review and meta-analysis of studies published since 1980 testing for the association between parental divorce and offspring depression and anxiety in adulthood. PUBMED, Science Direct, Medline, PsychInfo, and PsychArticles databases were searched for eligible studies. Random-effect meta-analyses were used to synthesize effect sizes and to test whether associations of parental divorce with offspring affective disorders differed among three publication periods (i.e., before 1996, 1996-2005, 2006-2015). In total, 29 studies were eligible for the systematic review, and 18 studies were included in the meta-analyses (depression: n=21,581; anxiety: n=2472). There was significant association between parental divorce and offspring depression (OR=1.56; 95%CI [1.31, 1.86]), but not anxiety (OR=1.16; 95%CI [0.98, 1.38]). The effect of parental divorce on offspring depression was not weaker in the reports published in more recent decades. There is limited research in relation to offspring anxiety in adulthood. Parental divorce is associated with an increased risk of adult offspring depression, with no indication of the effect being weaker in recent publications. Copyright © 2017 Elsevier B.V. All rights reserved.

Transgenerational effects of parent and grandparent gender on offspring development in a biparental beetle species.

PubMed

Lock, Judith E

2012-06-23

Parental effects on offspring life-history traits are common and increasingly well-studied. However, the extent to which these effects persist into offspring in subsequent generations has received less attention. In this experiment, maternal and paternal effects on offspring and grand-offspring were investigated in the biparental burying beetle Nicrophorus vespilloides, using a split-family design. This allowed the separation of prenatal and postnatal transgenerational effects. Grandparent and parent gender were found to have a cumulative effect on offspring development and may provide a selection pressure on the division of parental investment in biparental species.

Maternal depression during pregnancy and the postnatal period: risks and possible mechanisms for offspring depression at age 18 years.

PubMed

Pearson, Rebecca M; Evans, Jonathan; Kounali, Daphne; Lewis, Glyn; Heron, Jon; Ramchandani, Paul G; O'Connor, Tom G; Stein, Alan

2013-12-01

Some small studies suggest that maternal postnatal depression is a risk factor for offspring adolescent depression. However, to our knowledge, no large cohort studies have addressed this issue. Furthermore, only 1 small study has examined the association between antenatal depression and later offspring depression. Understanding these associations is important to inform prevention. To investigate the hypothesis that there are independent associations between antenatal and postnatal depression with offspring depression and that the risk pathways are different, such that the risk is moderated by disadvantage (low maternal education) with postnatal depression but not with antenatal depression. Prospective investigation of associations between symptoms of antenatal and postnatal parental depression with offspring depression at age 18 years in a UK community-based birth cohort (Avon Longitudinal Study of Parents and Children) with data from more than 4500 parents and their adolescent offspring. Diagnosis of offspring aged 18 years with major depression using the International Classification of Diseases, 10th Revision. Antenatal depression was an independent risk factor. Offspring were 1.28 times (95% CI, 1.08-1.51; P = .003) more likely to have depression at age 18 years for each standard deviation increase in maternal depression score antenatally, independent of later maternal depression. Postnatal depression was also a risk factor for mothers with low education, with offspring 1.26 times (95% CI, 1.06-1.50; P = .01) more likely to have depression for each standard deviation increase in postnatal depression score. However, for more educated mothers, there was little association (odds ratio, 1.09; 95% CI, 0.88-1.36; P = .42). Analyses found that maternal education moderated the effects of postnatal but not antenatal depression. Paternal depression antenatally was not associated with offspring depression, while postnatally, paternal depression showed a similar pattern to maternal depression. The findings suggest that treating maternal depression antenatally could prevent offspring depression during adulthood and that prioritizing less advantaged mothers postnatally may be most effective.

Familial Risk of Chronic Musculoskeletal Pain and the Importance of Physical Activity and Body Mass Index: Prospective Data from the HUNT Study, Norway.

PubMed

Lier, Ragnhild; Mork, Paul Jarle; Holtermann, Andreas; Nilsen, Tom Ivar Lund

2016-01-01

The main objectives of the current study was i) to prospectively examine if chronic musculoskeletal pain in parents is associated with risk of chronic musculoskeletal pain in their adult offspring, and ii) to assess if these parent-offspring associations are modified by offspring body mass index and leisure time physical activity. We used data on 4,742 adult offspring linked with their parents who participated in the population-based HUNT Study in Norway in 1995-97 and in 2006-08. Family relations were established through the national Family Registry. A Poisson regression model was used to estimate relative risk (RR) with 95% confidence interval (CI). In total, 1,674 offspring (35.3%) developed chronic musculoskeletal pain during the follow-up period of approximately 11 years. Both maternal (RR: 1.26, 95% CI: 1.03, 1.55) and paternal chronic musculoskeletal pain (RR: 1.29, 95% CI: 1.06, 1.57) was associated with increased risk of offspring chronic musculoskeletal pain. Compared to offspring of parents without chronic musculoskeletal pain, the adverse effect of parental pain was somewhat stronger among offspring who reported a low (RR: 1.82, 95% CI: 1.32, 2.52) versus high (RR: 1.32, 95% CI: 0.95, 1.84) level of leisure time physical activity. Offspring of parents with chronic musculoskeletal pain and who were classified as obese had more than twofold increased risk (RR: 2.33, 95% CI: 1.68, 3.24) of chronic musculoskeletal pain compared to normal weight offspring of parents without pain. In conclusion, parental chronic musculoskeletal pain is positively associated with risk of chronic musculoskeletal pain in their adult offspring. Maintenance of normal body weight may reduce the risk of chronic musculoskeletal pain in offspring of pain-afflicted parents.

Familial Risk of Chronic Musculoskeletal Pain and the Importance of Physical Activity and Body Mass Index: Prospective Data from the HUNT Study, Norway

PubMed Central

Lier, Ragnhild; Mork, Paul Jarle; Holtermann, Andreas; Nilsen, Tom Ivar Lund

2016-01-01

The main objectives of the current study was i) to prospectively examine if chronic musculoskeletal pain in parents is associated with risk of chronic musculoskeletal pain in their adult offspring, and ii) to assess if these parent-offspring associations are modified by offspring body mass index and leisure time physical activity. We used data on 4,742 adult offspring linked with their parents who participated in the population-based HUNT Study in Norway in 1995–97 and in 2006–08. Family relations were established through the national Family Registry. A Poisson regression model was used to estimate relative risk (RR) with 95% confidence interval (CI). In total, 1,674 offspring (35.3%) developed chronic musculoskeletal pain during the follow-up period of approximately 11 years. Both maternal (RR: 1.26, 95% CI: 1.03, 1.55) and paternal chronic musculoskeletal pain (RR: 1.29, 95% CI: 1.06, 1.57) was associated with increased risk of offspring chronic musculoskeletal pain. Compared to offspring of parents without chronic musculoskeletal pain, the adverse effect of parental pain was somewhat stronger among offspring who reported a low (RR: 1.82, 95% CI: 1.32, 2.52) versus high (RR: 1.32, 95% CI: 0.95, 1.84) level of leisure time physical activity. Offspring of parents with chronic musculoskeletal pain and who were classified as obese had more than twofold increased risk (RR: 2.33, 95% CI: 1.68, 3.24) of chronic musculoskeletal pain compared to normal weight offspring of parents without pain. In conclusion, parental chronic musculoskeletal pain is positively associated with risk of chronic musculoskeletal pain in their adult offspring. Maintenance of normal body weight may reduce the risk of chronic musculoskeletal pain in offspring of pain-afflicted parents. PMID:27082110

Maternal effects on offspring depend on female mating pattern and offspring environment in yellow dung flies.

PubMed

Tregenza, Tom; Wedell, Nina; Hosken, David J; Ward, Paul I

2003-02-01

Direct costs and benefits to females of multiple mating have been shown to have large effects on female fecundity and longevity in several species. However, with the exception of studies examining genetic benefits of polyandry, little attention has been paid to the possible effects on offspring of multiple mating by females. We propose that nongenetic effects of maternal matings on offspring fitness are best viewed in the same context as other maternal phenotype effects on offspring that are well known even in species lacking parental care. Hence, matings can exert effects on offspring in the same way as other maternal environment variables, and are likely to interact with such effects. We have conducted a study using yellow dung flies (Scathophaga stercoraria), in which we independently manipulated female mating rate, number of mates and maternal thermal environment and measured subsequent fecundity, hatching success, and offspring life-history traits. To distinguish between direct effects of matings and potential genetic benefits of polyandry we split broods and reared offspring at three different temperature regimes. This allowed us to demonstrate that although we could not detect any simple benefits or costs to matings, there are effects of maternal environment on offspring and these effects interact with female mating regime affecting offspring fitness. Such interactions between female phenotype and the costs and benefits of matings have potentially broad implications for understanding female behavior.

[Psychopathological Profiles of Offspring of Subjects with Bipolar Disorder].

PubMed

Villa, Esteban Uribe; Briceño, Paola Gutiérrez; Palacio, Juan David; García, Jenny

2012-03-01

Bipolar Disorder (BD) has a high heritability and is more prevalent in first-degree relatives with family history. This makes the bipolar offspring (BO) an ideal study group to evaluate the natural history and the prodromal symptoms of this disorder. The main psychopathological findings for this group in various studies are described in this review. Articles comparing the psychopathology of bipolar offspring to either the offspring of other psychiatric patients or the offspring of healthy controls were reviewed. The reviewed studies showed that the BO group had higher rates of affective disorders when compared to the offspring of other psychiatric patients or the offspring of healthy controls. The high prevalence of anxiety disorders, ADHD, and disruptive behavior disorders in this population suggest that such disorders could be considered prodromes of mood disorders. The group of BO had a significantly higher risk of developing a wide range of psychiatric disorders besides BD. More longitudinal studies are needed to characterize this population at risk for BD and to elucidate the risk factors in the progression of this disorder. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Dietary sodium manipulation during critical periods in development sensitize adult offspring to amphetamines

PubMed Central

McBride, Shawna M.; Culver, Bruce; Flynn, Francis W.

2008-01-01

This study examined critical periods in development to determine when offspring were most susceptible to dietary sodium manipulation leading to amphetamine sensitization. Wistar dams (n = 6–8/group) were fed chow containing low (0.12% NaCl; LN), normal (1% NaCl; NN), or high sodium (4% NaCl; HN) during the prenatal or early postnatal period (birth to 5 wk). Offspring were fed normal chow thereafter until testing at 6 mo. Body weight (BW), blood pressure (BP), fluid intake, salt preference, response to amphetamine, open field behavior, plasma adrenocorticotropin hormone (ACTH), plasma corticosterone (Cort), and adrenal gland weight were measured. BW was similar for all offspring. Offspring from the prenatal and postnatal HN group had increased BP, NaCl intake, and salt preference and decreased water intake relative to NN offspring. Prenatal HN offspring had greater BP than postnatal HN offspring. In response to amphetamine, both prenatal and postnatal LN and HN offspring had increased locomotor behavior compared with NN offspring. In a novel open field environment, locomotion was also increased in prenatal and postnatal LN and HN offspring compared with NN offspring. ACTH and Cort levels 30 min after restraint stress and adrenal gland weight measurement were greater in LN and HN offspring compared with NN offspring. These results indicate that early life experience with low- and high-sodium diets, during the prenatal or early postnatal period, is a stress that produces long-term changes in responsiveness to amphetamines and to subsequent stressors. PMID:18614766

Maternal or paternal suicide and offspring's psychiatric and suicide-attempt hospitalization risk.

PubMed

Kuramoto, S Janet; Stuart, Elizabeth A; Runeson, Bo; Lichtenstein, Paul; Långström, Niklas; Wilcox, Holly C

2010-11-01

We examined whether the risk for psychiatric morbidity requiring inpatient care was higher for offspring who experienced parental suicide, compared with offspring of fatal accident decedents, and whether the association varied according to the deceased parent's gender. Children and adolescents (0-17 years of age) who experienced maternal (N = 5600) or paternal (N = 17,847) suicide in 1973-2003 in Sweden were identified by using national, longitudinal, population-based registries. Cox regression modeling was used to compare psychiatric hospitalization risks among offspring of suicide decedents and propensity score-matched offspring of accident decedents. Offspring of maternal suicide decedents had increased risk of suicide-attempt hospitalization, after controlling for psychiatric hospitalization for decedents and surviving parents, compared with offspring of maternal accidental decedents. Offspring of paternal suicide decedents had similar risk of suicide-attempt hospitalization, compared with offspring of accident decedents, but had increased risk of hospitalization attributable to depressive and anxiety disorders. The magnitude of risks for offspring suicide-attempt hospitalization was greater for those who experienced maternal versus paternal suicide, compared with their respective control offspring (interaction P = .05; offspring of maternal decedents, adjusted hazard ratio: 1.80 [95% confidence interval: 1.19-2.74]; offspring of paternal decedents, adjusted hazard ratio: 1.14 [95% confidence interval: 0.96-1.35]). Maternal suicide is associated with increased risk of suicide-attempt hospitalization for offspring, beyond the risk associated with maternal accidental death. However, paternal suicide is not associated with suicide-attempt hospitalization. Future studies should examine factors that might differ between offspring who experience maternal versus paternal suicide, including genetic or early environmental determinants.

Parental depression and offspring psychopathology: a children of twins study.

PubMed

Singh, A L; D'Onofrio, B M; Slutske, W S; Turkheimer, E; Emery, R E; Harden, K P; Heath, A C; Madden, P A F; Statham, D J; Martin, N G

2011-07-01

Associations between parental depression and offspring affective and disruptive disorders are well documented. Few genetically informed studies have explored the processes underlying intergenerational associations. A semi-structured interview assessing DSM-III-R psychiatric disorders was administered to twins (n=1296) from the Australian Twin Register (ATR), their spouses (n=1046) and offspring (n=2555). We used the Children of Twins (CoT) design to delineate the extent to which intergenerational associations were consistent with a causal influence or due to genetic confounds. In between-family analyses, parental depression was associated significantly with offspring depression [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.20-1.93] and conduct disorder (CD; HR 2.27, CI 1.31-3.93). Survival analysis indicated that the intergenerational transmission of depression is consistent with a causal (environmental) inference, with a significant intergenerational association in offspring of discordant monozygotic (MZ) twin pairs (HR 1.39, CI 1.00-1.94). Logistic regression analysis suggested that the parental depression-offspring CD association was due to shared genetic liability in the parents and offspring. No intergenerational association was found when comparing the offspring of discordant MZ twins [odds ratio (OR) 1.41, CI 0.63-3.14], but offspring of discordant dizygotic (DZ) twins differed in their rates of CD (OR 2.53, CI 0.95-6.76). All findings remained after controlling for several measured covariates, including history of depression and CD in the twins' spouses. The mechanisms underlying associations between parental depression and offspring psychopathology seem to differ depending on the outcome. The results are consistent with a causal environmental role of parental depression in offspring depression whereas common genetic factors account for the association of parental depression and offspring CD.

Maternal Age at Holocaust Exposure and Maternal PTSD Independently Influence Urinary Cortisol Levels in Adult Offspring

PubMed Central

Bader, Heather N.; Bierer, Linda M.; Lehrner, Amy; Makotkine, Iouri; Daskalakis, Nikolaos P.; Yehuda, Rachel

2014-01-01

Background: Parental traumatization has been associated with increased risk for the expression of psychopathology in offspring, and maternal posttraumatic stress disorder (PTSD) appears to increase the risk for the development of offspring PTSD. In this study, Holocaust-related maternal age of exposure and PTSD were evaluated for their association with offspring ambient cortisol and PTSD-associated symptom expression. Method: Ninety-five Holocaust offspring and Jewish comparison subjects received diagnostic and psychological evaluations, and 24 h urinary cortisol was assayed by RIA. Offspring completed the parental PTSD questionnaire to assess maternal PTSD status. Maternal Holocaust exposure was identified as having occurred in childhood, adolescence, or adulthood and examined in relation to offspring psychobiology. Results: Urinary cortisol levels did not differ for Holocaust offspring and comparison subjects but differed significantly in offspring based on maternal age of exposure and maternal PTSD status. Increased maternal age of exposure and maternal PTSD were each associated with lower urinary cortisol in offspring, but did not exhibit a significant interaction. In addition, offspring PTSD-associated symptom severity increased with maternal age at exposure and PTSD diagnosis. A regression analysis of correlates of offspring cortisol indicated that both maternal age of exposure and maternal PTSD were significant predictors of lower offspring urinary cortisol, whereas childhood adversity and offspring PTSD symptoms were not. Conclusion: Offspring low cortisol and PTSD-associated symptom expression are related to maternal age of exposure, with the greatest effects associated with increased age at exposure. These effects are relatively independent of the negative consequences of being raised by a trauma survivor. These observations highlight the importance of maternal age of exposure in determining a psychobiology in offspring that is consistent with increased risk for stress-related pathology. PMID:25071719

Maternal age at first birth and offspring criminality: Using the children-of-twins design to test causal hypotheses

PubMed Central

Coyne, Claire A; Långström, Niklas; Rickert, Martin E; Lichtenstein, Paul; D’Onofrio, Brian M

2013-01-01

Teenage childbirth is a risk factor for poor offspring outcomes, particularly offspring antisocial behaviour. It is not clear if maternal age at first birth (MAFB) is causally associated with offspring antisocial behavior or if this association is due to selection factors that influence both the likelihood that a young woman gives birth early and that her offspring engage in antisocial behavior. The current study addresses the limitations of previous research by using longitudinal data from Swedish national registries and children-of-siblings and children-of-twins comparisons to identify the extent to which the association between MAFB and offspring criminal convictions is consistent with a causal influence and confounded by genetic or environmental factors that make cousins similar. We found offspring born to mothers who began childbearing earlier were more likely to be convicted of a crime than offspring born to mothers who delayed childbearing. The results from comparisons of differentially exposed cousins, especially born to discordant MZ twin sisters, provide support for a causal association between MAFB and offspring criminal convictions. The analyses also found little evidence for genetic confounding due to passive gene-environment correlation. Future studies are needed to replicate these findings and to identify environmental risk factors that mediate this causal association. PMID:23398750

Reduced Intellectual Ability in Offspring of Ovarian Hyperstimulation Syndrome: A Cohort Study.

PubMed

Xu, Gu-Feng; Zhou, Cheng-Liang; Xiong, Yi-Meng; Li, Jing-Yi; Yu, Tian-Tian; Tian, Shen; Lin, Xian-Hua; Liao, Yun; Lv, Yuan; Zhang, Fang-Hong; Liu, Zhi-Wei; Shi, Yin-Yin; Shen, Yan; Sha, Jin; Zhang, Dan; Zhu, Yi-Min; Sheng, Jian-Zhong; Huang, He-Feng

2017-06-01

Ovarian hyperstimulation syndrome (OHSS), a complication of ovarian stimulation, has various adverse effects on both pregnant women and their offspring. However, whether OHSS will affect intellectual ability in offspring is still unknown. We recruited 86 Chinese children born to OHSS women and 172 children conceived with non-OHSS In Vitro Fertilization (IVF) in this cohort study. Their intellectual ability was assessed according to the Revised Chinese Version of the Wechsler Intelligence Scale for Children (C-WISC). Verbal Intelligence Quotient (VIQ), Performance Intelligence Quotient (PIQ), and Full Intelligence Quotient (FIQ) were calculated. The investigation was registered in Chinese Clinical Trial Registry (ChiCTR-SOC-16009555). OHSS offspring scored less on C-WISC (mean (standard deviation [SD]): (VIQ=92.7 (14.7), PIQ=108.9 (13.1), FIQ=100.6 (13.4)) compared with non-OHSS IVF offspring (VIQ=100.1 (13.2), PIQ=113.7 (10.8), FIQ=107.4 (11.5)). The prevalence of low IQ (<80) children was 4.7 times higher in OHSS offspring compared with non-OHSS offspring. Maternal estradiol level on hCG administration day was negatively associated with FIQ in offspring. OHSS offspring displayed reduced intellectual ability. Prenatal estradiol exposure might be involved in underlying mechanism. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Maternal age at first birth and offspring criminality: using the children of twins design to test causal hypotheses.

PubMed

Coyne, Claire A; Långström, Niklas; Rickert, Martin E; Lichtenstein, Paul; D'Onofrio, Brian M

2013-02-01

Teenage childbirth is a risk factor for poor offspring outcomes, particularly offspring antisocial behavior. It is not clear, however, if maternal age at first birth (MAFB) is causally associated with offspring antisocial behavior or if this association is due to selection factors that influence both the likelihood that a young woman gives birth early and that her offspring engage in antisocial behavior. The current study addresses the limitations of previous research by using longitudinal data from Swedish national registries and children of siblings and children of twins comparisons to identify the extent to which the association between MAFB and offspring criminal convictions is consistent with a causal influence and confounded by genetic or environmental factors that make cousins similar. We found offspring born to mothers who began childbearing earlier were more likely to be convicted of a crime than offspring born to mothers who delayed childbearing. The results from comparisons of differentially exposed cousins, especially born to discordant monozygotic twin sisters, provide support for a causal association between MAFB and offspring criminal convictions. The analyses also found little evidence for genetic confounding due to passive gene-environment correlation. Future studies are needed to replicate these findings and to identify environmental risk factors that mediate this causal association.

Current Parental Depression and Offspring Perceived Self-Competence: A Quasi-Experimental Examination

PubMed Central

Class, Quetzal A.; D’Onofrio, Brian M.; Singh, Amber L.; Ganiban, Jody M.; Spotts, E. L.; Lichtenstein, Paul; Reiss, David; Neiderhiser, Jenae M.

2013-01-01

A genetically-informed, quasi-experimental design was used to examine the genetic and environmental processes underlying associations between current parental depressive symptoms and offspring perceived self-competence. Participants, drawn from a population-based Swedish sample, were 852 twin pairs and their male (52%) and female offspring aged 15.7 ± 2.4 years. Parental depressive symptoms were measured using the Center for Epidemiological Studies Depression scale. Offspring perceived self-competence was measured using a modified Harter Perceived Competence Scale. Cousin comparisons and Children of Twins (CoT) designs suggested that associations between maternal depressive symptoms and offspring perceived self-competence were due to shared genetic/environmental liability. The mechanism responsible for father-offspring associations, however, was independent of genetic factors and of extended-family environmental factors, supporting a causal inference. Thus, mothers and fathers may impact offspring perceived self-competence via different mechanisms and unmeasured genetic and environmental selection factors must be considered when studying the intergenerational transmission of cognitive vulnerabilities for depression. PMID:22692226

Emotional and behavioral functioning of offspring of African American mothers with depression.

PubMed

Boyd, Rhonda C; Diamond, Guy S; Ten Have, Thomas R

2011-10-01

Extensive research demonstrates the negative impact of maternal depression on their offspring. Unfortunately, few studies have been explored in African American families. This study examined emotional and behavioral functioning among children of African American mothers with depression. African American mothers (n = 63), with a past year diagnosis of a depressive disorder, and one of their children (ages 7-14) completed behavioral rating scales in a cross-sectional design. Results showed that 6.5 and 15% scored within the clinical range for depression and anxiety symptoms, respectively. Approximately a third of the offspring reported suicidal ideation. Based on mothers' report, 25.4 and 20.6% of the offspring exhibited internalizing and externalizing symptoms in the clinical range, respectively. Offspring whose mothers were in treatment exhibited higher levels of self-reported anxiety symptoms. Offspring of African American mothers with depression were exhibiting socioemotional problems in ways that are similar to offspring of European American mothers with depression.

Suicidal risk in young adult offspring of mothers with bipolar or major depressive disorder: a longitudinal family risk study.

PubMed

Klimes-Dougan, Bonnie; Lee, Chih-Yuan S; Ronsaville, Donna; Martinez, Pedro

2008-04-01

Recent evidence has highlighted suicidal risk associated with bipolar disorder (BD). Using a family risk approach, the goal of this study was to evaluate suicidal thoughts and behaviors longitudinally from childhood to young adulthood in children of mothers with BD, Major depressive disorder (MDD), and well mothers. Few group differences were found for cross-sectional assessments of suicidal thoughts and behavior in young adulthood; the offspring of MDD demonstrate an earlier onset and more persistent suicidality than other groups, but by young adulthood, BD offspring appear to be comparable to MDD offspring in their rates of suicidality. The longitudinal assessments reveal a pattern of higher suicidal risk in MDD offspring, more intermediate risk in BD offspring, and lower risk in well offspring. Precursors and correlates of suicidal thoughts and behaviors were also examined. These findings suggest diverse developmental trajectories based on family risk and have implications for planning preventive intervention.

Emotional and Behavioral Functioning of Offspring of African American Mothers with Depression

PubMed Central

Boyd, Rhonda C.; Diamond, Guy S.; Ten Have, Thomas R.

2011-01-01

Extensive research demonstrates the negative impact of maternal depression on their offspring. Unfortunately, few studies have been explored in African American families. This study examined emotional and behavioral functioning among children of African American mothers with depression. African American mothers (n = 63), with a past year diagnosis of a depressive disorder, and one of their children (ages 7–14) completed behavioral rating scales in a cross-sectional design. Results showed that 6.5% and 15% scored within the clinical range for depression and anxiety symptoms, respectively. Approximately a third of the offspring reported suicidal ideation. Based on mothers’ report, 25.4% and 20.6% of the offspring exhibited internalizing and externalizing symptoms in the clinical range, respectively. Offspring whose mothers were in treatment exhibited higher levels of self-reported anxiety symptoms Offspring of African American mothers with depression were exhibiting socioemotional problems in ways that are similar to offspring of European American mothers with depression. PMID:21671005

Current parental depression and offspring perceived self-competence: a quasi-experimental examination.

PubMed

Class, Quetzal A; D'Onofrio, Brian M; Singh, Amber L; Ganiban, Jody M; Spotts, E L; Lichtenstein, Paul; Reiss, David; Neiderhiser, Jenae M

2012-09-01

A genetically-informed, quasi-experimental design was used to examine the genetic and environmental processes underlying associations between current parental depressive symptoms and offspring perceived self-competence. Participants, drawn from a population-based Swedish sample, were 852 twin pairs and their male (52 %) and female offspring aged 15.7 ± 2.4 years. Parental depressive symptoms were measured using the Center for Epidemiological Studies Depression scale. Offspring perceived self-competence was measured using a modified Harter Perceived Competence Scale. Cousin comparisons and Children of Twins designs suggested that associations between maternal depressive symptoms and offspring perceived self-competence were due to shared genetic/environmental liability. The mechanism responsible for father-offspring associations, however, was independent of genetic factors and of extended family environmental factors, supporting a causal inference. Thus, mothers and fathers may impact offspring perceived self-competence via different mechanisms and unmeasured genetic and environmental selection factors must be considered when studying the intergenerational transmission of cognitive vulnerabilities for depression.

Intrauterine growth restriction programs an accelerated age-related increase in cardiovascular risk in male offspring

PubMed Central

Dasinger, John Henry; Intapad, Suttira; Backstrom, Miles A.; Carter, Anthony J.

2016-01-01

Placental insufficiency programs an increase in blood pressure associated with a twofold increase in serum testosterone in male growth-restricted offspring at 4 mo of age. Population studies indicate that the inverse relationship between birth weight and blood pressure is amplified with age. Thus, we tested the hypothesis that intrauterine growth restriction programs an age-related increase in blood pressure in male offspring. Growth-restricted offspring retained a significantly higher blood pressure at 12 but not at 18 mo of age compared with age-matched controls. Blood pressure was significantly increased in control offspring at 18 mo of age relative to control counterparts at 12 mo; however, blood pressure was not increased in growth-restricted at 18 mo relative to growth-restricted counterparts at 12 mo. Serum testosterone levels were not elevated in growth-restricted offspring relative to control at 12 mo of age. Thus, male growth-restricted offspring no longer exhibited a positive association between blood pressure and testosterone at 12 mo of age. Unlike hypertension in male growth-restricted offspring at 4 mo of age, inhibition of the renin-angiotensin system with enalapril (250 mg/l for 2 wk) did not abolish the difference in blood pressure in growth-restricted offspring relative to control counterparts at 12 mo of age. Therefore, these data suggest that intrauterine growth restriction programs an accelerated age-related increase in blood pressure in growth-restricted offspring. Furthermore, this study suggests that the etiology of increased blood pressure in male growth-restricted offspring at 12 mo of age differs from that at 4 mo of age. PMID:27147668

Female partner preferences enhance offspring ability to survive an infection.

PubMed

Raveh, Shirley; Sutalo, Sanja; Thonhauser, Kerstin E; Thoß, Michaela; Hettyey, Attila; Winkelser, Friederike; Penn, Dustin J

2014-01-23

It is often suggested that mate choice enhances offspring immune resistance to infectious diseases. To test this hypothesis, we conducted a study with wild-derived house mice (Mus musculus musculus) in which females were experimentally mated either with their preferred or non-preferred male, and their offspring were infected with a mouse pathogen, Salmonella enterica (serovar Typhimurium). We found that offspring sired by preferred males were significantly more likely to survive the experimental infection compared to those sired by non-preferred males. We found no significant differences in the pathogen clearance or infection dynamics between the infected mice, suggesting that offspring from preferred males were better able to cope with infection and had improved tolerance rather than immune resistance. Our results provide the first direct experimental evidence within a single study that partner preferences enhance offspring resistance to infectious diseases.

Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands

PubMed Central

Jin, Sheng Chih; Homsy, Jason; Zaidi, Samir; Lu, Qiongshi; Morton, Sarah; DePalma, Steven R.; Zeng, Xue; Qi, Hongjian; Chang, Weni; Sierant, Michael C.; Hung, Wei-Chien; Haider, Shozeb; Zhang, Junhui; Knight, James; Bjornson, Robert D.; Castaldi, Christopher; Tikhonoa, Irina R.; Bilguvar, Kaya; Mane, Shrikant M.; Sanders, Stephan J.; Mital, Seema; Russell, Mark; Gaynor, William; Deanfield, John; Giardini, Alessandro; Porter, George A.; Srivastava, Deepak; Lo, Cecelia W.; Shen, Yufeng; Watkins, W. Scott; Yandell, Mark; Yost, H. Joseph; Tristani-Firouzi, Martin; Newburger, Jane W.; Roberts, Amy E.; Kim, Richard; Zhao, Hongyu; Kaltman, Jonathan R.; Goldmuntz, Elizabeth; Chung, Wendy K.; Seidman, Jonathan G.; Gelb, Bruce D.; Seidman, Christine E.; Lifton, Richard P.; Brueckner, Martina

2017-01-01

Congenital heart disease (CHD) is the leading cause of mortality from birth defects. Exome sequencing of a single cohort of 2,871 CHD probands including 2,645 parent-offspring trios implicated rare inherited mutations in 1.8%, including a recessive founder mutation in GDF1 accounting for ~5% of severe CHD in Ashkenazim, recessive genotypes in MYH6 accounting for ~11% of Shone complex, and dominant FLT4 mutations accounting for 2.3% of Tetralogy of Fallot. De novo mutations (DNMs) accounted for 8% of cases, including ~3% of isolated CHD patients and ~28% with both neurodevelopmental and extra-cardiac congenital anomalies. Seven genes surpassed thresholds for genome-wide significance and 12 genes not previously implicated in CHD had > 70% probability of being disease-related; DNMs in ~440 genes are inferred to contribute to CHD. There was striking overlap between genes with damaging DNMs in probands with CHD and autism. PMID:28991257

Association between parental psychopathology and suicidal behavior among adult offspring: results from the cross-sectional South African Stress and Health survey

PubMed Central

2014-01-01

Background Prior studies have demonstrated a link between parental psychopathology and offspring suicidal behavior. However, it remains unclear what aspects of suicidal behavior among adult offspring are predicted by specific parental mental disorders, especially in Africa. This study set out to investigate the association between parental psychopathology and suicidal behavior among their adult offspring in a South African general population sample. Method Parental psychopathology and suicidal behavior in offspring were assessed using structured interviews among 4,315 respondents from across South Africa. The WHO CIDI was used to collect data on suicidal behavior, while the Family History Research Diagnostic Criteria Interview was used to assess prior parental psychopathology. Bivariate and multivariate survival models tested the associations between the type and number parental mental disorders (including suicide) and lifetime suicidal behavior in the offspring. Associations between a range of parental disorders and the onset of subsequent suicidal behavior (suicidal ideation, plans, and attempts) among adult offspring were tested. Results The presence of parental psychopathology significantly increased the odds of suicidal behavior among their adult offspring. More specifically, parental panic disorder was associated with offspring suicidal ideation, while parental panic disorder, generalized anxiety disorder and suicide were significantly associated with offspring suicide attempts. Among those with suicidal ideation, none of the tested forms of parental psychopathology was associated with having suicide plans or attempts. There was a dose–response relationship between the number of parental disorders and odds of suicidal ideation. Conclusions Parental psychopathology increases the odds of suicidal behavior among their adult offspring in the South African context, replicating results found in other regions. Specific parental disorders predicted the onset and persistence of suicidal ideation or attempts in their offspring. Further research into these associations is recommended in order to determine the mechanisms through which parent psychopathology increases the odds of suicidal behavior among offspring. PMID:24592882

Obesity and abnormal glucose tolerance in offspring of diabetic mothers: A systematic review and meta-analysis

PubMed Central

Kawasaki, Maki; Miyazaki, Celine; Mori, Rintaro; Kikuchi, Toru; Ogawa, Yoshihiro; Ota, Erika

2018-01-01

Background Rising prevalence of childhood obesity and type 2 diabetes mellitus (T2DM) is an emerging public health issue. Objectives To investigate the association of maternal hyperglycemia exposure during pregnancy with obesity and abnormal glucose tolerance in offspring, and the age at occurrence. Methods We searched MEDLINE and EMBASE for observational studies on obesity and diabetes in offspring of diabetic mothers (gestational diabetes mellitus (GDM), type 1 diabetes mellitus (T1DM) and T2DM), and those on non-diabetic mothers. We performed fixed effect meta-analysis for all studies except when heterogeneity was detected. The quality of studies was evaluated using the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS) Results Twenty observational studies were included involving a total of 26,509 children. Offspring of GDM mother had higher BMI z-score in childhood (pooled MD: 0.14, 95%CI: 0.04–0.24, seven studies, 21,691children, low quality of evidence). Offspring of T1DM mothers had higher BMI z-score from prepubertal to adolescent (pooled MD: 0.35, 95% CI: 0.13–0.58, three studies, 844 children, low quality of evidence) compared with control. After adjustment for maternal pre-pregnancy BMI, this association remained in offspring of T1DM, but disappeared in those of GDM mothers. Offspring of GDM mother had higher 2-hour plasma glucose from prepubertal to early adulthood (pooled MD: 0.43 mmol/L, 95% CI: 0.18–0.69, five studies, 890 children), while those of T1DM mothers had higher rate of T2DM in 2–5 years old to early adulthood (pooled odds ratio [OR], 6.10: 95% CI: 1.23–30.37, two studies, 448 children, very low quality of evidence) compared with control. As there was only one study with offspring of T2DM mothers, evidence is sparse. Limitations Only observational studies were included, with a few adequately adjusted for covariables. Conclusions Exposure to maternal hyperglycemia was associated with offspring obesity and abnormal glucose tolerance especially in offspring of T1DM mothers, but the evidence relies on observational studies with low quality of evidence only. PMID:29329330

Offspring of Parents with Chronic Pain: A Systematic Review and Meta-Analysis of Pain, Health, Psychological, and Family Outcomes

PubMed Central

Higgins, Kristen S.; Birnie, Kathryn A.; Chambers, Christine T.; Wilson, Anna C.; Caes, Line; Clark, Alexander J.; Lynch, Mary; Stinson, Jennifer; Campbell-Yeo, Marsha

2015-01-01

Offspring of parents with chronic pain may be at risk for poorer outcomes than offspring of healthy parents. The objective of this research was to provide a comprehensive mixed-methods, systematic synthesis of all available research on outcomes in offspring of parents with chronic pain. A systematic search was conducted for published articles in English examining pain, health, psychological, or family outcomes in offspring of parents with chronic pain. Fifty-nine eligible articles were identified (31 population-based, 25 clinical, 3 qualitative), including offspring from birth to adulthood and parents with varying chronic pain diagnoses (e.g., mixed pain samples, arthritis). Meta-analysis was used to synthesize the results from population-based and clinical studies, while meta-ethnography was used to synthesize the results of qualitative studies. Increased pain complaints were found in offspring of mothers and of fathers with chronic pain, and when both parents had chronic pain. Newborns of mothers with chronic pain were more likely to have adverse birth outcomes, including low birthweight, preterm delivery, caesarean section, intensive care admission, and mortality. Offspring of parents with chronic pain had greater externalizing and internalizing problems and poorer social competence and family outcomes. No significant differences were found on teacher-reported externalizing problems. The meta-ethnography identified six key concepts (developing independence, developing compassion, learning about health and coping, missing out, emotional health, and struggles communicating with parents). Across study designs, offspring of parents with chronic pain had poorer outcomes than other offspring, although the meta-ethnography noted some constructive impact of having a parent with chronic pain. PMID:26172553

Association of secondary sex ratio with smoking and parity.

PubMed

Beratis, Nicholas G; Asimacopoulou, Aspasia; Varvarigou, Anastasia

2008-03-01

To assess the sex ratio in offspring of smoking and nonsmoking mothers in relationship to parity. Prospective study. University hospital. The authors studied 2,108 term singleton neonates born between 1993 and 2002, 665 from smoking mothers and 1,443 from nonsmoking mothers. A prospective recording of maternal age, parity and smoking status, and gender of neonates delivered over a 10-year period. Secondary sex ratio in regard to maternal smoking and parity. The offspring sex ratio in the total sample studied was 1.09; in the offspring of smoking and nonsmoking mothers, it was 1.26 and 1.03, respectively, a statistically significant difference. In the offspring of smoking women who had parity 1, 2, and >or=3, it was 1.47, 1.35, and 0.92, whereas in those of nonsmoking women, it was 1.04, 1.00, and 1.03, respectively (the differences of the parity 1 and 2 groups between the offspring of smoking and nonsmoking mothers were statistically significant). Logistic regression analysis showed that the possibility of a boy being delivered by a mother who smoked was significantly greater in primiparous women than in women who had parity >or=3, independent of the maternal age. Conversely, parity did not affect significantly the sex ratio in the offspring of nonsmoking women. The findings suggest that among women who smoked, significantly more male than female offspring are born from primiparous women, whereas women who had parity >or=3 gave birth to more female offspring; biparous women give birth to significantly more male offspring, but the offspring sex ratio declined with the number of cigarettes when the mothers smoked >or=10 cigarettes per day.

Both paternal exercise and healthy diet are required to protect offspring from high fat diet-induced obesity and type 2 diabetes risk in mice

USDA-ARS?s Scientific Manuscript database

Objective: Paternal eating and physical activity behaviors peri-conception may influence offspring obesity and type 2 diabetes (T2D) risk. A recent study showed that paternal exercise increased offspring susceptibility to obesity when the offspring consumed a high fat (HF) diet. However, it is not y...

The relationship between parental depressive symptoms and offspring psychopathology: evidence from a children-of-twins study and an adoption study.

PubMed

McAdams, T A; Rijsdijk, F V; Neiderhiser, J M; Narusyte, J; Shaw, D S; Natsuaki, M N; Spotts, E L; Ganiban, J M; Reiss, David; Leve, L D; Lichtenstein, P; Eley, T C

2015-01-01

Parental depressive symptoms are associated with emotional and behavioural problems in offspring. However, genetically informative studies are needed to distinguish potential causal effects from genetic confounds, and longitudinal studies are required to distinguish parent-to-child effects from child-to-parent effects. We conducted cross-sectional analyses on a sample of Swedish twins and their adolescent offspring (n = 876 twin families), and longitudinal analyses on a US sample of children adopted at birth, their adoptive parents, and their birth mothers (n = 361 adoptive families). Depressive symptoms were measured in parents, and externalizing and internalizing problems measured in offspring. Structural equation models were fitted to the data. Results of model fitting suggest that associations between parental depressive symptoms and offspring internalizing and externalizing problems remain after accounting for genes shared between parent and child. Genetic transmission was not evident in the twin study but was evident in the adoption study. In the longitudinal adoption study child-to-parent effects were evident. We interpret the results as demonstrating that associations between parental depressive symptoms and offspring emotional and behavioural problems are not solely attributable to shared genes, and that bidirectional effects may be present in intergenerational associations.

Increased renal sympathetic nerve activity leads to hypertension and renal dysfunction in offspring from diabetic mothers.

PubMed

de Almeida Chaves Rodrigues, Aline Fernanda; de Lima, Ingrid Lauren Brites; Bergamaschi, Cássia Toledo; Campos, Ruy Ribeiro; Hirata, Aparecida Emiko; Schoorlemmer, Guus Hermanus Maria; Gomes, Guiomar Nascimento

2013-01-15

The exposure of the fetus to a hyperglycemic environment promotes the development of hypertension and renal dysfunction in the offspring at adult age. We evaluated the role of renal nerves in the hypertension and renal changes seen in offspring of diabetic rats. Diabetes was induced in female Wistar rats (streptozotocin, 60 mg/kg ip) before mating. Male offspring from control and diabetic dams were studied at an age of 3 mo. Systolic blood pressure measured by tail cuff was increased in offspring of diabetic dams (146 ± 1.6 mmHg, n = 19, compared with 117 ± 1.4 mmHg, n = 18, in controls). Renal function, baseline renal sympathetic nerve activity (rSNA), and arterial baroreceptor control of rSNA were analyzed in anesthetized animals. Glomerular filtration rate, fractional sodium excretion, and urine flow were significantly reduced in offspring of diabetic dams. Two weeks after renal denervation, blood pressure and renal function in offspring from diabetic dams were similar to control, suggesting that renal nerves contribute to sodium retention in offspring from diabetic dams. Moreover, basal rSNA was increased in offspring from diabetic dams, and baroreceptor control of rSNA was impaired, with blunted responses to infusion of nitroprusside and phenylephrine. Thus, data from this study indicate that in offspring from diabetic mothers, renal nerves have a clear role in the etiology of hypertension; however, other factors may also contribute to this condition.

Filial anxiety and sense of obligation among offspring of Holocaust survivors.

PubMed

Shrira, Amit; Menashe, Ravit; Bensimon, Moshe

2018-03-13

Much is known about adult children caring for their aging parents, yet the potentially unique experience of offspring caring for traumatized parents is underexplored. Therefore, the current studies assessed filial anxiety and sense of obligation among offspring of Holocaust survivors (OHS) in caring for their parents. In Study 1, we interviewed 10 OHS (mean age = 61.0) in order to extract themes of filial anxiety. Based on Study 1's data, a newly constructed scale of filial anxiety was administered in Study 2 to 59 adult offspring (mean age = 56.4): 28 OHS and 31 comparisons. Study 3 included 143 dyads of parents and offspring (mean age = 55.4 and 81.7, respectively): 86 Holocaust dyads and 57 comparison dyads. Parents reported posttraumatic stress disorder (PTSD) symptoms and offspring reported filial anxiety and sense of obligation. In Study 1, interviewees referred to concerns about parent experiencing decline alongside caregiving difficulties. In Study 2, OHS reported higher filial anxiety and sense of obligation relative to comparisons. This group difference was mediated by sense of obligation. In Study 3, OHS with parental PTSD reported higher filial anxiety and sense of obligation relative to comparisons. Once more, filial sense of obligation served as a mediator. In Studies 2-3, results remained significant after adjusting for offspring symptoms. Parental exposure to the Holocaust, and especially parental PTSD, related to higher filial obligation, which in turn was related to higher filial anxiety. These findings bear important implications for practitioners working with survivors' families.

Psychiatric morbidity, violent crime, and suicide among children and adolescents exposed to parental death.

PubMed

Wilcox, Holly C; Kuramoto, Satoko J; Lichtenstein, Paul; Långström, Niklas; Brent, David A; Runeson, Bo

2010-05-01

This retrospective cohort study examined the risk for suicide, psychiatric hospitalization, and violent criminal convictions among offspring of parents who died from suicide, accidents, and other causes. Population-based data from multiple Swedish national registers were linked from 1969 to 2004. Participants were 44,397 offspring of suicide decedents, 41,467 offspring of accident decedents, 417,365 offspring of parents who died by other causes, and 3,807,867 offspring of alive parents. We estimated risk by mode of parental death (suicide, accident, other) and offspring age at parental death (childhood, adolescence, young adulthood). Offspring of suicide decedents were at greater risk for suicide than offspring of alive parents (incidence rate ratio [IRR] = 1.9; 95% confidence interval [CI] = 1.4 to 2.5), whereas offspring of accident decedents and other parental death were not at increased risk (p < .001). The risk for offspring suicide differed by the developmental period during which parental suicide occurred. Child and adolescent offspring of suicide decedents were at threefold greater risk for suicide (IRR = 3.0; 95% CI = 1.7 to 5.3; IRR = 3.1, 95% CI = 2.1 to 4.6, respectively). Young adults were not at increased risk for suicide (IRR = 1.3; 95% CI = 0.9 to 1.9). Offspring of suicide decedents had an especially high risk of hospitalization for suicide attempt, depressive, psychotic, and personality disorders. Child survivors of parental suicide were at particularly high risk for hospitalization for drug disorders and psychosis. All offspring who experienced parental death, regardless of mode or age, were at increased risk for violent criminal convictions. Mode of parental death and offspring age at parental death are associated with offspring long-term risk for suicide and hospitalization for specific psychiatric disorders.

Adult exercise effects on oxidative stress and reproductive programming in male offspring of obese rats.

PubMed

Santos, Mery; Rodríguez-González, Guadalupe L; Ibáñez, Carlos; Vega, Claudia C; Nathanielsz, Peter W; Zambrano, Elena

2015-02-01

Exercise improves health but few data are available regarding benefits of exercise in offspring exposed to developmental programming. There is currently a worldwide epidemic of obesity. Obesity in pregnant women predisposes offspring to obesity. Maternal obesity has well documented effects on offspring reproduction. Few studies address ability of offspring exercise to reduce adverse outcomes. We observed increased oxidative stress and impaired sperm function in rat offspring of obese mothers. We hypothesized that regular offspring exercise reverses adverse effects of maternal obesity on offspring sperm quality and fertility. Female Wistar rats ate chow (C) or high-energy, obesogenic diet (MO) from weaning through lactation, bred at postnatal day (PND) 120, and ate their pregnancy diet until weaning. All offspring ate C diet from weaning. Five male offspring (different litters) ran on a wheel for 15 min, 5 times/week from PND 330 to 450 and were euthanized at PND 450. Average distance run per session was lower in MO offspring who had higher body weight, adiposity index, and gonadal fat and showed increases in testicular oxidative stress biomarkers. Sperm from MO offspring had reduced antioxidant enzyme activity, lower sperm quality, and fertility. Exercise in MO offspring decreased testicular oxidative stress, increased sperm antioxidant activity and sperm quality, and improved fertility. Exercise intervention has beneficial effects on adiposity index, gonadal fat, oxidative stress markers, sperm quality, and fertility. Thus regular physical exercise in male MO offspring recuperates key male reproductive functions even at advanced age: it's never too late. Copyright © 2015 the American Physiological Society.

Association of Maternal Exposure to Childhood Abuse With Elevated Risk for Attention Deficit Hyperactivity Disorder in Offspring.

PubMed

Roberts, Andrea L; Liew, Zeyan; Lyall, Kristen; Ascherio, Alberto; Weisskopf, Marc G

2018-05-14

Children whose mothers experienced childhood abuse are more likely to suffer various neurodevelopmental deficits. Whether an association exists specifically for attention deficit hyperactivity disorder (ADHD) is unknown. We examined the association of maternal experience of childhood abuse with ADHD in offspring, assessed by maternal report of diagnosis and validated with the ADHD Rating Scale-IV in a subsample, in the Nurses' Health Study II (n = 49,497 mothers, N offspring cases = 7,607, N offspring controls = 102,151). We examined whether ten adverse perinatal circumstances (e.g., prematurity, smoking) or socioeconomic factors accounted for a possible association. Exposure to abuse was associated with greater prevalence of ADHD in offspring (8.7% of offspring of women exposed to severe abuse vs. 5.5% of offspring of women not abused, P = 0.0001) and with greater risk for ADHD adjusted for demographic factors (male offspring, risk ratio (RR) = 1.6; 95% CI: 1.3, 1.9; female offspring, RR = 2.3, 95% CI: 1.7, 3.0). Adjusted for perinatal factors, the association of maternal childhood abuse with ADHD in offspring was slightly attenuated (male offspring, RR = 1.5; 95% CI: 1.2, 1.8; female offspring, RR = 2.1, 95% CI: 1.6, 2.8). We identified an association between maternal experience of childhood abuse and risk for ADHD in offspring, which was not explained by several important perinatal risk factors or socioeconomic status.

Family environment and psychopathology in offspring of parents with bipolar disorder.

PubMed

Lau, Phoebe; Hawes, David J; Hunt, Caroline; Frankland, Andrew; Roberts, Gloria; Wright, Adam; Costa, Daniel S J; Mitchell, Philip B

2018-01-15

The aim of this study was to examine the relationship between family environment (cohesion and parental bonding), high-risk status, and psychopathology (internalizing and externalizing problems) among offspring of parents with bipolar disorder (BD), from the perspective of both offspring and their parents. We further tested if family environment mediated the relationship between bipolar risk status and internalizing and externalizing problems. High-risk (n = 90) BD offspring and control (n = 56) offspring aged 12-21 years old, and their parents, completed questionnaires on family cohesion and offspring internalizing and externalizing problems. Offspring also completed a parental bonding questionnaire. Group differences were examined, followed by multi-level mediation analysis with maximum likelihood and robust standard errors. Both offspring and parents in the high-risk group reported higher levels of internalizing and externalizing problems than controls. According to offspring reports, high-risk status, lower maternal and paternal care in parental bonding, was independently associated with internalizing problems. Lower maternal care alone predicted externalizing problems. Family environment did not mediate the relationship between bipolar risk status, and offspring problems. Due to rates of missing data from parent reports of offspring psychopathology, mediation analysis was completed using offspring reports. The offspring-report data presented indicate that low parental warmth and connection were associated with internalizing and externalizing problems as an independent risk factor, in addition to bipolar risk status. The parent-child relationship therefore warrants attention as a potential target for prevention strategies with such families. Copyright © 2017 Elsevier B.V. All rights reserved.

Offspring ADHD as a risk factor for parental marital problems: controls for genetic and environmental confounds.

PubMed

Schermerhorn, Alice C; D'Onofrio, Brian M; Slutske, Wendy S; Emery, Robert E; Turkheimer, Eric; Harden, K Paige; Heath, Andrew C; Martin, Nicholas G

2012-12-01

Previous studies have found that child attention-deficit/hyperactivity disorder (ADHD) is associated with more parental marital problems. However, the reasons for this association are unclear. The association might be due to genetic or environmental confounds that contribute to both marital problems and ADHD. Data were drawn from the Australian Twin Registry, including 1,296 individual twins, their spouses, and offspring. We studied adult twins who were discordant for offspring ADHD.Using a discordant twin pairs design, we examined the extent to which genetic and environmental confounds,as well as measured parental and offspring characteristics, explain the ADHD-marital problems association. Offspring ADHD predicted parental divorce and marital conflict. The associations were also robust when comparing differentially exposed identical twins to control for unmeasured genetic and environmental factors, when controlling for measured maternal and paternal psychopathology,when restricting the sample based on timing of parental divorce and ADHD onset, and when controlling for other forms of offspring psychopathology. Each of these controls rules out alternative explanations for the association. The results of the current study converge with those of prior research in suggesting that factors directly associated with offspring ADHD increase parental marital problems.

Are there subtle genome-wide epigenetic alterations in normal offspring conceived by assisted reproductive technologies?

PubMed

Batcheller, April; Cardozo, Eden; Maguire, Marcy; DeCherney, Alan H; Segars, James H

2011-12-01

To review recent data regarding subtle, but widespread, epigenetic alterations in phenotypically normal offspring conceived by assisted reproductive technologies (ART) compared with offspring conceived in vivo. A PubMed computer search was performed to identify relevant articles. Research institution. Not applicable. None. Not applicable. Studies in animals indicate that in vitro culture may be associated with widespread alterations in imprinted genes compared with in vivo-conceived offspring. Recently, studies in humans have likewise demonstrated widespread changes in DNA methylation, including genes linked to adipocyte development, insulin signaling, and obesity in offspring conceived by ART compared with in vivo-conceived children. Changes in multiple imprinted genes after ART also were noted in additional studies, which suggested that the diagnosis of infertility may explain the differences between in vivo-conceived and ART offspring. These data suggest that ART is associated with widespread epigenetic modifications in phenotypically normal children, and that these modifications may increase the risk of adverse cardiometabolic outcomes. Further research is needed to elucidate the possible relationship between ART, genome-wide alterations in imprinted genes, and their potential relevance to subtle cardiometabolic consequences reported in ART offspring. Published by Elsevier Inc.

Offspring ADHD as a Risk Factor for Parental Marital Problems: Controls for Genetic and Environmental Confounds

PubMed Central

Schermerhorn, Alice C.; D’Onofrio, Brian M.; Slutske, Wendy S.; Emery, Robert E.; Turkheimer, Eric; Harden, K. Paige; Heath, Andrew C.; Martin, Nicholas G.

2013-01-01

Background Previous studies have found that child attention-deficit/hyperactivity disorder (ADHD) is associated with more parental marital problems. The reasons for this association are unclear, however. The association might be due to genetic or environmental confounds that contribute to both marital problems and ADHD. Method Data were drawn from the Australian Twin Registry, including 1296 individual twins, their spouses, and offspring. We studied adult twins who were discordant for offspring ADHD. Using a discordant twin pairs design, we examined the extent to which genetic and environmental confounds, as well as measured parental and offspring characteristics, explain the ADHD-marital problems association. Results Offspring ADHD predicted parental divorce and marital conflict. The associations were also robust when comparing differentially exposed identical twins to control for unmeasured genetic and environmental factors, when controlling for measured maternal and paternal psychopathology, when restricting the sample based on timing of parental divorce and ADHD onset, and when controlling for other forms of offspring psychopathology. Each of these controls rules out alternative explanations for the association. Conclusion The results of the current study converge with those of prior research in suggesting that factors directly associated with offspring ADHD increase parental marital problems. PMID:22958575

A developmental approach to dimensional expression of psychopathology in child and adolescent offspring of parents with bipolar disorder.

PubMed

Morón-Nozaleda, María Goretti; Díaz-Caneja, Covadonga M; Rodríguez-Toscano, Elisa; Arango, Celso; Castro-Fornieles, Josefina; de la Serna, Elena; Espliego, Ana; Sanchez-Gistau, Vanessa; Romero, Soledad; Baeza, Immaculada; Sugranyes, Gisela; Moreno, Carmen; Moreno, Dolores

2017-10-01

The aim of this is to describe psychopathology, functioning and symptom dimensions accounting for subthreshold manifestations and developmental status in child and adolescent offspring of parents with bipolar disorder ("high-risk offspring"). The study population comprised 90 high-risk offspring (HR-offspring) and 107 offspring of community control parents (CC-offspring). Direct clinical observations and parental and offspring reports based on selected standardized clinical scales were used to assess offspring threshold and subthreshold diagnoses, symptoms and functioning. All outcomes were compared between the whole HR-offspring and CC-offspring samples and then by developmental status. After controlling for potential confounders, HR-offspring showed significantly poorer adjustment for childhood (r = 0.18, p = 0.014) and adolescence (r = 0.21, p = 0.048) than CC-offspring, as well as more emotional problems (r = 0.24, p = 0.001) and higher depression scores (r = 0.16, p = 0.021). As for differences in lifetime categorical diagnoses (threshold and subthreshold) between HR-offspring and CC-offspring, the prevalence of disruptive disorders was higher in pre-pubertal HR-offspring (OR 12.78 [1.45-112.42]), while prevalence of mood disorders was higher in post-pubertal HR-offspring (OR 3.39 [1.14-10.06]). Post-pubertal HR-offspring presented more prodromal (r = 0.40, p = 0.001), negative (r = 0.38, p = 0.002), manic (r = 0.22, p = 0.035) and depressive (r = 0.23, p = 0.015) symptoms than pre-pubertal HR-offspring, as well as more peer relationship problems (r = 0.31, p = 0.004), poorer childhood adjustment (r = 0.22, p = 0.044) and worse current psychosocial functioning (r = 0.27, p = 0.04). Externalizing psychopathology is more prevalent in pre-pubertal HR-offspring, while depressive and prodromal symptoms leading to functional impairment are more prominent in post-pubertal HR-offspring. Developmental approaches and dimensional measures may be useful for identifying children at high risk of developing bipolar disorder and help guide specific preventive strategies.

Maternal caloric restriction partially rescues the deleterious effects of advanced maternal age on offspring

PubMed Central

Gribble, Kristin E; Jarvis, George; Bock, Martha; Mark Welch, David B

2014-01-01

While many studies have focused on the detrimental effects of advanced maternal age and harmful prenatal environments on progeny, little is known about the role of beneficial non-Mendelian maternal inheritance on aging. Here, we report the effects of maternal age and maternal caloric restriction (CR) on the life span and health span of offspring for a clonal culture of the monogonont rotifer Brachionus manjavacas. Mothers on regimens of chronic CR (CCR) or intermittent fasting (IF) had increased life span compared with mothers fed ad libitum (AL). With increasing maternal age, life span and fecundity of female offspring of AL-fed mothers decreased significantly and life span of male offspring was unchanged, whereas body size of both male and female offspring increased. Maternal CR partially rescued these effects, increasing the mean life span of AL-fed female offspring but not male offspring and increasing the fecundity of AL-fed female offspring compared with offspring of mothers of the same age. Both maternal CR regimens decreased male offspring body size, but only maternal IF decreased body size of female offspring, whereas maternal CCR caused a slight increase. Understanding the genetic and biochemical basis of these different maternal effects on aging may guide effective interventions to improve health span and life span. PMID:24661622

Interspecific competition alters nonlinear selection on offspring size in the field.

PubMed

Marshall, Dustin J; Monro, Keyne

2013-02-01

Offspring size is one of the most important life-history traits with consequences for both the ecology and evolution of most organisms. Surprisingly, formal estimates of selection on offspring size are rare, and the degree to which selection (particularly nonlinear selection) varies among environments remains poorly explored. We estimate linear and nonlinear selection on offspring size, module size, and senescence rate for a sessile marine invertebrate in the field under three different intensities of interspecific competition. The intensity of competition strongly modified the strength and form of selection acting on offspring size. We found evidence for differences in nonlinear selection across the three environments. Our results suggest that the fitness returns of a given offspring size depend simultaneously on their environmental context, and on the context of other offspring traits. Offspring size effects can be more pervasive with regards to their influence on the fitness returns of other traits than previously recognized, and we suggest that the evolution of offspring size cannot be understood in isolation from other traits. Overall, variability in the form and strength of selection on offspring size in nature may reduce the efficacy of selection on offspring size and maintain variation in this trait. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

Investigation of implicit avoidance of displacement-related stimuli in offspring of trauma exposed, forcibly-displaced individuals.

PubMed

Wittekind, Charlotte E; Muhtz, Christoph; Moritz, Steffen; Jelinek, Lena

2017-04-01

There is an ongoing debate as to whether traumatization also affects the close relatives of trauma survivors who have symptoms of PTSD. Although many studies provide evidence favoring a transgenerational transmission, other studies have not found evidence to support this idea. The present study examined whether adult offspring of individuals exposed to trauma during forced displacement with (n=22) and without PTSD (n=24) exhibit an implicit avoidance of stimuli related to the parental trauma compared to children of non-trauma exposed control participants (n=23) using an Approach-Avoidance task (AAT). Offspring participants were requested to push (i.e., avoidance) or pull (i.e., approach) displacement-related and neutral pictures, whereby response direction depended on a non-affective dimension (color of the pictures). Results suggest that the offspring of non-PTSD participants exhibit implicit avoidance of displacement-related stimuli. This rather unexpected finding might either indicate resilience amongst offspring of PTSD participants or that offspring of non-PTSD participants are particularly affected. If these results were to replicate, they suggest that implicit avoidance tendencies amongst the offspring of trauma exposed participants might partially contribute to their heightened PTSD vulnerability. Longitudinal studies are needed to elucidate whether implicit avoidance tendencies are associated with increased stress vulnerability. Copyright © 2017 Elsevier Ltd. All rights reserved.

Maternal Obesity: Lifelong Metabolic Outcomes for Offspring from Poor Developmental Trajectories During the Perinatal Period.

PubMed

Zambrano, Elena; Ibáñez, Carlos; Martínez-Samayoa, Paola M; Lomas-Soria, Consuelo; Durand-Carbajal, Marta; Rodríguez-González, Guadalupe L

2016-01-01

The prevalence of obesity in women of reproductive age is increasing in developed and developing countries around the world. Human and animal studies indicate that maternal obesity adversely impacts both maternal health and offspring phenotype, predisposing them to chronic diseases later in life including obesity, dyslipidemia, type 2 diabetes mellitus, and hypertension. Several mechanisms act together to produce these adverse health effects including programming of hypothalamic appetite-regulating centers, increasing maternal, fetal and offspring glucocorticoid production, changes in maternal metabolism and increasing maternal oxidative stress. Effective interventions during human pregnancy are needed to prevent both maternal and offspring metabolic dysfunction due to maternal obesity. This review addresses the relationship between maternal obesity and its negative impact on offspring development and presents some maternal intervention studies that propose strategies to prevent adverse offspring metabolic outcomes. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

Neck/upper back and low back pain in parents and their adult offspring: Family linkage data from the Norwegian HUNT Study.

PubMed

Lier, R; Nilsen, T I L; Vasseljen, O; Mork, P J

2015-07-01

Chronic pain in the neck and low back is highly prevalent. Although heritable components have been identified, knowledge about generational transmission of spinal pain between parents and their adult offspring is sparse. This study examined the intergenerational association of spinal pain using data from 11,081 parent-offspring trios participating in the population-based HUNT Study in Norway. Logistic regression was used to calculate adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for offspring spinal pain associated with parental spinal pain. In total, 3654 (33%) offspring reported spinal pain at participation. Maternal and paternal spinal pain was consistently associated with higher ORs for offspring spinal pain. The results suggest a slightly stronger association for parental multilevel spinal pain (i.e., both neck/upper back pain and low back pain) than for pain localized to the neck/upper back or low back. Multilevel spinal pain in both parents was associated with ORs of 2.6 (95% CI, 2.1-3.3), 2.4 (95% CI, 1.9-3.1) and 3.1 (95% CI, 2.2-4.4) for offspring neck/upper back, low back and multilevel spinal pain, respectively. Parental chronic spinal pain was consistently associated with increased occurrence of chronic spinal pain in their adult offspring, and this association was particularly strong for multilevel spinal pain. © 2014 European Pain Federation - EFIC®

Animal models of maternal high fat diet exposure and effects on metabolism in offspring: a meta-regression analysis.

PubMed

Ribaroff, G A; Wastnedge, E; Drake, A J; Sharpe, R M; Chambers, T J G

2017-06-01

Animal models of maternal high fat diet (HFD) demonstrate perturbed offspring metabolism although the effects differ markedly between models. We assessed studies investigating metabolic parameters in the offspring of HFD fed mothers to identify factors explaining these inter-study differences. A total of 171 papers were identified, which provided data from 6047 offspring. Data were extracted regarding body weight, adiposity, glucose homeostasis and lipidaemia. Information regarding the macronutrient content of diet, species, time point of exposure and gestational weight gain were collected and utilized in meta-regression models to explore predictive factors. Publication bias was assessed using Egger's regression test. Maternal HFD exposure did not affect offspring birthweight but increased weaning weight, final bodyweight, adiposity, triglyceridaemia, cholesterolaemia and insulinaemia in both female and male offspring. Hyperglycaemia was found in female offspring only. Meta-regression analysis identified lactational HFD exposure as a key moderator. The fat content of the diet did not correlate with any outcomes. There was evidence of significant publication bias for all outcomes except birthweight. Maternal HFD exposure was associated with perturbed metabolism in offspring but between studies was not accounted for by dietary constituents, species, strain or maternal gestational weight gain. Specific weaknesses in experimental design predispose many of the results to bias. © 2017 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.

Does Male Care, Provided to Immature Individuals, Influence Immature Fitness in Rhesus Macaques?

PubMed Central

Langos, Doreen; Kulik, Lars; Ruiz-Lambides, Angelina; Widdig, Anja

2015-01-01

Among many mammals, maternal care strongly impacts infant survival; however, less is known about whether adult males also affect infant fitness. Paternal care is expected when providing care enhances offspring survival and reproduction, which likewise increases fathers’ fitness. Males might also care for unrelated immature individuals to increase their mating probability with the immature individuals’ mothers. Studies in multimale primate groups showed that sires enhance food access for offspring and provide protection in conflicts. Furthermore, fathers’ presence during infancy has been suggested to accelerate offspring sexual maturation. However, no study has yet directly linked the degree of father-offspring bonds to offspring fitness in primates. We previously reported father-offspring affiliation in rhesus macaques, pronounced during early infancy and independent of mothers’ presence. The present study aims at investigating whether affiliation with fathers or other males affects proxies of immature fitness (body mass gain, body fat and testis size). First, we combined behavioral, genetic and morphometric data from 55 subjects of one group. Second, using demographic and genetic data, we investigated for 92 individuals of the population whether mother- and father-offspring co-residence during immaturity influenced offspring lifetime reproductive success (LRS). Our results show that focal rank and higher amounts of affiliation with high-ranking males during infancy tend to positively impact body mass gain of female, but not male focal animals. In contrast, body mass gain of male focal individuals, but not females’, appeared to be higher when affiliation of male immature individuals was evenly distributed across their adult male partners. Moreover, we found mothers’, but not fathers’, presence during immaturity to predict offspring LRS. Our results suggest that male-immature affiliation, but not father-offspring co-residence, potentially impacts proxies of immature fitness. However, future studies should investigate the underlying mechanisms of male-immature relationships and their impact on immature fitness in more detail. PMID:26367536

Developmental programming of lipid metabolism and aortic vascular function in C57BL/6 mice: a novel study suggesting an involvement of LDL-receptor.

PubMed

Chechi, Kanta; McGuire, John J; Cheema, Sukhinder K

2009-04-01

We have previously shown that a maternal high-fat diet, rich in saturated fatty acids (SFA), alters the lipid metabolism of their adult offspring. The present study was designed to investigate 1) whether alterations in hepatic LDL-receptor (LDL-r) expression may serve as a potential mechanism of developmental programming behind the altered lipid metabolism of the offspring, 2) whether altered lipid metabolism leads to aortic vascular dysfunction in the offspring, 3) whether deleterious effects of SFA exposure preweaning are influenced by postweaning diet, and 4) whether gender-specific programming effects are observed. Female C57Bl/6 mice were fed a high-SFA diet or regular chow during gestation and lactation while their pups, both male and female, received either SFA or a chow diet after weaning. Male offspring obtained from mothers fed an SFA diet and those who continued on chow postweaning had higher plasma triglycerides and total cholesterol, whereas female offspring had higher plasma total and LDL cholesterol levels, lower hepatic LDL-r mRNA expression, and reduced aortic contractile responses compared with the offspring that were fed chow throughout the study. A comparison of the postweaning diet revealed significantly lower hepatic LDL-r expression along with significantly higher plasma LDL-cholesterol concentration in the female offspring that were obtained from mothers fed an SFA diet and who continued on an SFA diet postweaning, compared with the female offspring that were obtained from mothers fed an SFA diet but who continued on chow postweaning. In conclusion, we report a novel observation of hepatic LDL-r-mediated programming of altered lipid metabolism, along with aortic vascular dysfunction, in the female offspring of mothers fed a high-SFA diet. Male offspring only exhibited dyslipidemia, suggesting gender-mediated programming. This study further highlighted the role of postweaning diets in overriding the effects of maternal programming.

Offspring from mothers fed a 'junk food' diet in pregnancy and lactation exhibit exacerbated adiposity that is more pronounced in females.

PubMed

Bayol, S A; Simbi, B H; Bertrand, J A; Stickland, N C

2008-07-01

We have shown previously that a maternal junk food diet during pregnancy and lactation plays a role in predisposing offspring to obesity. Here we show that rat offspring born to mothers fed the same junk food diet rich in fat, sugar and salt develop exacerbated adiposity accompanied by raised circulating glucose, insulin, triglyceride and/or cholesterol by the end of adolescence (10 weeks postpartum) compared with offspring also given free access to junk food from weaning but whose mothers were exclusively fed a balanced chow diet in pregnancy and lactation. Results also showed that offspring from mothers fed the junk food diet in pregnancy and lactation, and which were then switched to a balanced chow diet from weaning, exhibited increased perirenal fat pad mass relative to body weight and adipocyte hypertrophy compared with offspring which were never exposed to the junk food diet. This study shows that the increased adiposity was more enhanced in female than male offspring and gene expression analyses showed raised insulin-like growth factor-1 (IGF-1), insulin receptor substrate (IRS)-1, vascular endothelial growth factor (VEGF)-A, peroxisome proliferator-activated receptor-gamma (PPARgamma), leptin, adiponectin, adipsin, lipoprotein lipase (LPL), Glut 1, Glut 3, but not Glut 4 mRNA expression in females fed the junk food diet throughout the study compared with females never given access to junk food. Changes in gene expression were not as marked in male offspring with only IRS-1, VEGF-A, Glut 4 and LPL being up-regulated in those fed the junk food diet throughout the study compared with males never given access to junk food. This study therefore shows that a maternal junk food diet promotes adiposity in offspring and the earlier onset of hyperglycemia, hyperinsulinemia and/or hyperlipidemia. Male and female offspring also display a different metabolic, cellular and molecular response to junk-food-diet-induced adiposity.

Offspring from mothers fed a ‘junk food’ diet in pregnancy and lactation exhibit exacerbated adiposity that is more pronounced in females

PubMed Central

Bayol, S A; Simbi, B H; Bertrand, J A; Stickland, N C

2008-01-01

We have shown previously that a maternal junk food diet during pregnancy and lactation plays a role in predisposing offspring to obesity. Here we show that rat offspring born to mothers fed the same junk food diet rich in fat, sugar and salt develop exacerbated adiposity accompanied by raised circulating glucose, insulin, triglyceride and/or cholesterol by the end of adolescence (10 weeks postpartum) compared with offspring also given free access to junk food from weaning but whose mothers were exclusively fed a balanced chow diet in pregnancy and lactation. Results also showed that offspring from mothers fed the junk food diet in pregnancy and lactation, and which were then switched to a balanced chow diet from weaning, exhibited increased perirenal fat pad mass relative to body weight and adipocyte hypertrophy compared with offspring which were never exposed to the junk food diet. This study shows that the increased adiposity was more enhanced in female than male offspring and gene expression analyses showed raised insulin-like growth factor-1 (IGF-1), insulin receptor substrate (IRS)-1, vascular endothelial growth factor (VEGF)-A, peroxisome proliferator-activated receptor-γ (PPARγ), leptin, adiponectin, adipsin, lipoprotein lipase (LPL), Glut 1, Glut 3, but not Glut 4 mRNA expression in females fed the junk food diet throughout the study compared with females never given access to junk food. Changes in gene expression were not as marked in male offspring with only IRS-1, VEGF-A, Glut 4 and LPL being up-regulated in those fed the junk food diet throughout the study compared with males never given access to junk food. This study therefore shows that a maternal junk food diet promotes adiposity in offspring and the earlier onset of hyperglycemia, hyperinsulinemia and/or hyperlipidemia. Male and female offspring also display a different metabolic, cellular and molecular response to junk-food-diet-induced adiposity. PMID:18467362

Effects of bisphenol A treatment during pregnancy on kidney development in mice: a stereological and histopathological study.

PubMed

Nuñez, P; Fernandez, T; García-Arévalo, M; Alonso-Magdalena, P; Nadal, A; Perillan, C; Arguelles, J

2018-04-01

Bisphenol A (BPA) is a chemical found in plastics that resembles oestrogen in organisms. Developmental exposure to endocrine-disrupting chemicals, such as BPA, increases the susceptibility to type 2 diabetes (T2DM) and cardiovascular diseases. Animal studies have reported a nephron deficit in offspring exposed to maternal diabetes. The aim of this study was to investigate the prenatal BPA exposure effects on nephrogenesis in a mouse model that was predisposed to T2DM. This study quantitatively evaluated the renal structural changes using stereology and histomorphometry methods. The OF1 pregnant mice were treated with a vehicle or BPA (10 or 100 μg/kg/day) during days 9-16 of gestation (early nephrogenesis). The 30-day-old offspring were sacrificed, and tissue samples were collected and prepared for histopathological and stereology studies. Glomerular abnormalities and reduced glomerular formation were observed in the BPA offspring. The kidneys of the BPA10 and BPA100 female offspring had a significantly lower glomerular number and density than those of the CONTROL female offspring. The glomerular histomorphometry revealed a significant difference between the female and male CONTROL offspring for the analysed glomerular parameters that disappeared in the BPA10 and BPA100 offspring. In addition, the kidney histopathological examination showed typical male cuboidal epithelial cells of the Bowman capsule in the female BPA offspring. Exposure to environmentally relevant doses of BPA during embryonic development altered nephrogenesis. These structural changes could be associated with an increased risk of developing cardiometabolic diseases later in life.

Colorectal cancer knowledge, attitudes, screening, and intergenerational communication among Japanese American families: an exploratory, community-based participatory study.

PubMed

Lau, Denys T; Machizawa, Sayaka; Demonte, William; Cameron, Kenzie A; Muramatsu, Naoko; Henker, Raymond D; Chikahisa, Frances; Tanimura, Michael

2013-03-01

Adults of Japanese descent (Nikkei) in the United States have higher risk for colorectal cancer (CRC) than their white counterparts. Family norms toward CRC screening may influence screening behaviors of Nikkei adults. This community-based participatory research study explores if mailing educational pamphlets to Nikkei families can influence CRC knowledge, attitudes, and screening adherence; and trigger intergenerational communication about CRC. Among 56 parent-offspring dyads contacted, 24 were eligible (e.g., no prior CRC screening/diagnosis) and were randomized into 3 cohorts defined by the "target recipient(s)" of study pamphlets about CRC screening: parent only, offspring only, and both parent and offspring. Among the 19 completed dyads (79.2 % = 19/24), results showed that CRC knowledge of most pamphlet recipients increased in all cohorts; however, some misinformation and attitudinal barriers persisted. Although some parent-offspring communication about CRC increased after mailing pamphlets to offspring, only spousal communication occurred after mailing pamphlets to parents. Additional benefits were not observed in increasing parental screening intent/behavior after mailing pamphlets to both parent and offspring. At the end, among the 10 parents who reported developing CRC screening intent or having scheduled a CRC screening, 8 attributed to study pamphlets and 2 to communication with their offspring. Self-reported barriers preventing screening and parent-offspring communication about CRC were identified. This exploratory study describes preliminary findings that will inform future research aimed to promote CRC screening and reduce racial/ethnic disparities at the community level by enhancing intergenerational communication among Nikkei families.

Colorectal cancer knowledge, attitudes, screening, and intergenerational communication among Japanese American families: an exploratory, community-based participatory study

PubMed Central

Lau, Denys T.; Machizawa, Sayaka; Demonte, William; Cameron, Kenzie A.; Muramatsu, Naoko; Henker, Raymond D.; Chikahisa, Frances; Tanimura, Michael

2012-01-01

Adults of Japanese descent (Nikkei) in the United States have higher risk for colorectal cancer (CRC) than their white counterparts. Family norms toward CRC screening may influence screening behaviors of Nikkei adults. This community-based participatory research study explores if mailing educational pamphlets to Nikkei families can influence CRC knowledge, attitudes, and screening adherence; and trigger intergenerational communication about CRC. Among 56 parent-offspring dyads contacted, 24 were eligible (e.g., no prior CRC screening/diagnosis) and were randomized into 3 cohorts defined by the “target recipient(s)” of study pamphlets about CRC screening: parent only, offspring only, and both parent and offspring. Among the 19 completed dyads (79.2%=19/24), results showed that CRC knowledge of most pamphlet recipients increased in all cohorts; however, some misinformation and attitudinal barriers persisted. Although some parent-offspring communication about CRC increased after mailing pamphlets to offspring, only spousal communication occurred after mailing pamphlets to parents. Additional benefits were not observed in increasing parental screening intent/behavior after mailing pamphlets to both parent and offspring. At the end, among the 10 parents who reported developing CRC screening intent or having scheduled a CRC screening, 8 attributed to study pamphlets and 2 to communication with their offspring. Self-reported barriers preventing screening and parent-offspring communication about CRC were identified. This exploratory study describes preliminary findings that will inform future research aimed to promote CRC screening and reduce racial/ethnic disparities at the community level by enhancing intergenerational communication among Nikkei families. PMID:23263883

Maternal smoking during pregnancy and self-reported delinquency by offspring.

PubMed

Ellis, Lee; Widmayer, Alan; Das, Shyamal

2012-12-01

Several studies have reported significant positive correlations between smoking during pregnancy by mothers and the involvement of their offspring in criminal/delinquent behaviour later in life, but these findings have been described as modest and the criminality based on official conviction statistics. We sought to verify this relationship and probe for more details on the basis of self-reported offending among college students. Independently completed questionnaires were collected from 6332 students and their mothers. The students provided information about their delinquent acts, if any, according to eight categories. Their mothers provided retrospective reports of their smoking habits, if any, during pregnancy. Mothers who recalled having smoked during pregnancy were significantly more likely than non-smoking mothers to have offspring who self-reported engaging in some types of delinquency. This relationship was more evident for female offspring than for male offspring and was most pronounced for illegal drug use by the offspring. There was, however, no relationship between offspring offending and estimated number of cigarettes smoked by mothers, month of pregnancy when smoked or consistency of smoking throughout pregnancy. Overall, our study confirms that maternal smoking during pregnancy is associated with offspring involvement in delinquency, but the lack of critical timing or dose-response relationships between maternal smoking and later offspring delinquency cast doubt on the possibility that the associations are due to teratogenic effects of tobacco smoke. Copyright © 2012 John Wiley & Sons, Ltd.

The experiences of adolescents and adults conceived by sperm donation: comparisons by age of disclosure and family type.

PubMed

Jadva, Vasanti; Freeman, Tabitha; Kramer, Wendy; Golombok, Susan

2009-08-01

This study presents findings from a large sample of donor offspring who are aware of the nature of their conception. Importantly, this is one of the first studies to compare the views of offspring told of their origins during childhood to those who found out during adulthood. Online questionnaires were completed anonymously by donor offspring who were members of the Donor Sibling Registry, a US-based worldwide registry that helps donor-conceived individuals search for and contact their donor and donor siblings (i.e. half-siblings). Data were obtained on offspring's feelings about being donor conceived and their feelings towards their parents. Offspring of single mothers and lesbian couples learnt of their donor origins earlier than offspring of heterosexual couples. Those told later in life reported more negative feelings regarding their donor conception than those told earlier. Offspring's feelings towards their parents were less clear, with some of those told later reporting more positive feelings and others reporting more negative feelings. Offspring from heterosexual-couple families were more likely to feel angry at being lied to by their mothers than by their fathers. The most common feeling towards fathers was 'sympathetic'. Age of disclosure is important in determining donor offspring's feelings about their donor conception. It appears it is less detrimental for children to be told about their donor conception at an early age.

Parental history of lupus and rheumatoid arthritis and risk in offspring in a nationwide cohort study: does sex matter?

PubMed

Somers, Emily C; Antonsen, Sussie; Pedersen, Lars; Sørensen, Henrik Toft

2013-04-01

To examine the familial risk of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), including juvenile rheumatoid/idiopathic arthritis (JRA), in a population-based setting; and to determine whether patterns of transmission differ according to the sex of the parent or offspring, in order to provide insight into the potential impact of X-chromosomal factors on sex disparities in these autoimmune diseases. A population-based cohort of parent-offspring triads from Denmark (1977-2010) was established. SLE and RA incidence rates among offspring were calculated, and Cox regression was performed to assess the sex-specific risk of disease in offspring according to maternal or paternal disease history. Among 3 513 817 parent-offspring triads, there were 1258 SLE cases among offspring (1095 female, 163 male) and 9118 cases of RA/JRA (6086 female, 3032 male). Among female offspring, SLE risk was nearly the same according to maternal (HR 14.1) or paternal (HR 14.5) history (p=NS); likewise among male offspring, risk according to maternal (HR 5.5) and paternal (no cases) history were similar (p=NS). For RA, all risk estimates were similar, regardless of the sex of the offspring or parent (HR 2.6-2.9; p=NS). The authors quantified the familial risk of SLE and RA in a nationwide cohort study. For both diseases, transmission was comparable among both female and male offspring of maternal and paternal cases. These data provide evidence at the population level that X-chromosomal factors do not play a major role in sex disparities associated with the risk of SLE and RA.

The association between teenage motherhood and poor offspring outcomes: A national cohort study across 30 years

PubMed Central

Coyne, Claire A; Långström, Niklas; Rickert, Martin E; Lichtenstein, Paul; D’Onofrio, Brian M

2013-01-01

Teenage motherhood is associated with poor offspring outcomes but these associations may be influenced by offspring birth year because of substantial social changes in recent decades. Existing research also has not examined whether these associations are due to the specific effect of mother’s age at childbirth or factors shared by siblings in a family. We used a population-based cohort study in Sweden comprising all children born from 1960–1989 (N=3,162,239), and a subsample of siblings differentially exposed to maternal teenage childbearing (N=485,259) to address these limitations. We examined the effect of teenage childbearing on offspring violent and nonviolent criminal convictions, poor academic performance, and substance-related problems. Population-wide, teenage childbearing was associated with offspring criminal convictions, poor academic performance, and substance-related problems. The magnitude of these associations increased over time. Comparisons of differentially exposed siblings indicated no within-family association between teenage childbearing and offspring violent and nonviolent criminal convictions or poor academic performance, although offspring born to teenage mothers were more likely to experience substance-related problems than their later-born siblings. Being born to a teenage mother in Sweden has become increasingly associated with negative outcomes across time, but the nature of this association may differ by outcome. Teenage childbearing may be associated with offspring violent and nonviolent criminal convictions and poor academic performance because of shared familial risk factors but may be causally associated with offspring substance-related problems. The findings suggest that interventions to improve offspring outcomes should delay teenage childbearing and target risk factors influencing all offspring of teenage mothers. PMID:23632141

Time to hospitalization for suicide attempt by the timing of parental suicide during offspring early development

PubMed Central

Kuramoto, S. Janet; Runeson, Bo; Stuart, Elizabeth A.; Lichtenstein, Paul; Wilcox, Holly C.

2013-01-01

Context Previous studies have suggested that children who experience parental suicide at earlier ages are at higher risk of future hospitalization for suicide attempt. However, how the trajectories of risk differ by offspring age at the time of parental suicide is currently unknown. Objective To study time at risk to hospitalization for suicide attempt among offspring after experiencing parental suicide or accidental death by offspring developmental period at the time of parental death. Design Population-based retrospective cohort study Setting Sweden Participants 26,096 offspring who experienced parental suicide and 32,395 offspring of accident decedents prior to age 25 from 1973-2003. Main Outcome Measures Hospitalization for suicide attempt. Parametric survival analysis was used to model the time to hospitalization for suicide attempt across offspring who lost a parent during early childhood (0-5 years old), later childhood (6-12), adolescence (13-17) and young adulthood (18-24). Results The risk in offspring who lost a parent during early or late childhood surpassed the other two age groups’ hazards approximately 5 years after the origin and, for the youngest group, continued to rise over the course of decades. Offspring who lost a parent during adolescence or young adulthood were at greatest risk within 1 to 2 years after parental suicide, and risk declined over time. The shape of hospitalization risk was similar among those who experienced parental fatal accident. When the shape of hospitalization for suicide attempt at each developmental period was fixed to be the same between the two groups, offspring who lost a parent to suicide had earlier risk to hospitalization for suicide attempt hospitalization than offspring who lost a parent to an accident. Conclusion The hospitalization risk for suicide attempt in offspring who lost a parent during their childhood is different from those who lost a parent during adolescence or young adulthood. The results suggest critical windows for careful monitoring and intervention for suicide attempt risk, especially 1-2 years after parental death for the older age groups and over decades for childhood survivors of parental death. PMID:23229861

Cognitive-emotional hyperarousal in the offspring of parents vulnerable to insomnia: a nuclear family study.

PubMed

Fernandez-Mendoza, Julio; Shaffer, Michele L; Olavarrieta-Bernardino, Sara; Vgontzas, Alexandros N; Calhoun, Susan L; Bixler, Edward O; Vela-Bueno, Antonio

2014-10-01

Cognitive-emotional hyperarousal is believed to be a predisposing factor for insomnia; however, there is limited information on the association of familial vulnerability to insomnia and cognitive-emotional hyperarousal. The aim of this study was to estimate the heritability of stress-related insomnia and examine whether parental vulnerability to stress-related insomnia is associated with cognitive-emotional hyperarousal in their offspring. We studied a volunteer sample of 135 nuclear families comprised of 270 middle-aged (51.5 ± 5.4 years) fathers and mothers and one of their biological offspring (n = 135, 20.2 ± 1.1 years). We measured vulnerability to stress-related insomnia (i.e. Ford Insomnia Response to Stress Test: FIRST), perceived stress, depression and anxiety in all participants, and arousability, presleep cognitive and somatic arousal, coping and personality in the offspring. We found a heritability estimate of 29% for FIRST scores. High FIRST parents had three to seven times the odds of having offspring highly vulnerable to stress-related insomnia. Offspring of high FIRST parents showed higher arousability, presleep cognitive arousal and emotion-oriented coping. Furthermore, high FIRST mothers contributed to offspring's higher anxiety and lower task-oriented coping, while high FIRST fathers contributed to offspring's higher presleep somatic arousal and conscientiousness. Vulnerability to stress-related insomnia is significantly heritable. Parents vulnerable to stress-related insomnia have offspring with cognitive-emotional hyperarousal who rely upon emotion-oriented coping. These data give support to the notion that arousability and maladaptive coping are key factors in the aetiology of insomnia. © 2014 European Sleep Research Society.

Paternal and maternal alcohol abuse and offspring mental distress in the general population: the Nord-Trøndelag health study

PubMed Central

2012-01-01

Background The degree to which parental alcohol abuse is a risk factor for offspring mental distress is unclear, due to conflicting results of previous research. The inconsistencies in previous findings may be related to sample characteristics and lack of control of confounding or moderating factors. One such factor may be the gender of the abusing parent. Also, other factors, such as parental mental health, divorce, adolescent social network, school functioning or self-esteem, may impact the outcome. This study examines the impact of maternal and paternal alcohol abuse on adolescent mental distress, including potentially confounding, mediating or moderating effects of various variables. Methods Data from the Nord-Trøndelag Health Study (HUNT), a Norwegian population based health survey, from 4012 offspring and their parents were analyzed. Parental alcohol abuse was measured by numerical consumption indicators and CAGE, whereas offspring mental distress was measured by SCL-5, an abbreviated instrument tapping symptoms of anxiety and depression. Statistical method was analysis of variance. Results Maternal alcohol abuse was related to offspring mental distress, whereas no effect could be shown of paternal alcohol abuse. Effects of maternal alcohol abuse was partly mediated by parental mental distress, offspring social network and school functioning. However, all effects were relatively small. Conclusions The results indicate graver consequences for offspring of alcohol abusing mothers compared to offspring of alcohol abusing fathers. However, small effect sizes suggest that adolescent offspring of alcohol abusing parents in general manage quite well. PMID:22708789

A maternal "junk food" diet in pregnancy and lactation promotes nonalcoholic Fatty liver disease in rat offspring.

PubMed

Bayol, Stéphanie A; Simbi, Bigboy H; Fowkes, Robert C; Stickland, Neil C

2010-04-01

With rising obesity rates, nonalcoholic fatty liver disease is predicted to become the main cause of chronic liver disease in the next decades. Rising obesity prevalence is attributed to changes in dietary habits with increased consumption of palatable junk foods, but maternal malnutrition also contributes to obesity in progeny. This study examines whether a maternal junk food diet predisposes offspring to nonalcoholic fatty liver disease. The 144 rat offspring were fed either a balanced chow diet alone or with palatable junk foods rich in energy, fat, sugar, and/or salt during gestation, lactation, and/or after weaning up to the end of adolescence. Offspring fed junk food throughout the study exhibited exacerbated hepatic steatosis, hepatocyte ballooning, and oxidative stress response compared with offspring given free access to junk food after weaning only. These offspring also displayed sex differences in their hepatic molecular metabolic adaptation to diet-induced obesity with increased expression of genes associated with insulin sensitivity, de novo lipogenesis, lipid oxidation, and antiinflammatory properties in males, whereas the gene expression profile in females was indicative of hepatic insulin resistance. Hepatic inflammation and fibrosis were not detected indicating that offspring had not developed severe steatohepatitis by the end of adolescence. Hepatic steatosis and increased oxidative stress response also occurred in offspring born to junk food-fed mothers switched to a balanced chow diet from weaning, highlighting a degree of irreversibility. This study shows that a maternal junk food diet in pregnancy and lactation contributes to the development of nonalcoholic fatty liver disease in offspring.

Maternal Diet, Metabolic State, and Inflammatory Response Exert Unique and Long-Lasting Influences on Offspring Behavior in Non-Human Primates

PubMed Central

Thompson, Jacqueline R.; Gustafsson, Hanna C.; DeCapo, Madison; Takahashi, Diana L.; Bagley, Jennifer L.; Dean, Tyler A.; Kievit, Paul; Fair, Damien A.; Sullivan, Elinor L.

2018-01-01

Nutritional status influences brain health and gestational exposure to metabolic disorders (e.g. obesity and diabetes) increases the risk of neuropsychiatric disorders. The aim of the present study was to further investigate the role of maternal Western-style diet (WSD), metabolic state, and inflammatory factors in the programming of Japanese macaque offspring behavior. Utilizing structural equation modeling, we investigated the relationships between maternal diet, prepregnancy adiposity, third trimester insulin response, and plasma cytokine levels on 11-month-old offspring behavior. Maternal WSD was associated with greater reactive and ritualized anxiety in offspring. Maternal adiposity and third trimester macrophage-derived chemokine (MDC) exerted opposing effects on offspring high-energy outbursts. Elevated levels of this behavior were associated with low maternal MDC and increased prepregnancy adiposity. This is the first study to show that maternal MDC levels influence offspring behavior. We found no evidence suggesting maternal peripheral inflammatory response mediated the effect of maternal diet and metabolic state on aberrant offspring behavior. Additionally, the extent of maternal metabolic impairment differentially influenced chemokine response. Elevated prepregnancy adiposity suppressed third trimester chemokines, while obesity-induced insulin resistance augmented peripheral chemokine levels. WSD also directly increased maternal interleukin-12. This is the first non-human primate study to delineate the effects of maternal diet and metabolic state on gestational inflammatory environment and subsequent offspring behavior. Our findings give insight to the complex mechanisms by which diet, metabolic state, and inflammation during pregnancy exert unique influences on offspring behavioral regulation. PMID:29740395

A Maternal “Junk Food” Diet in Pregnancy and Lactation Promotes Nonalcoholic Fatty Liver Disease in Rat Offspring

PubMed Central

Bayol, Stéphanie A.; Simbi, Bigboy H.; Fowkes, Robert C.; Stickland, Neil C.

2010-01-01

With rising obesity rates, nonalcoholic fatty liver disease is predicted to become the main cause of chronic liver disease in the next decades. Rising obesity prevalence is attributed to changes in dietary habits with increased consumption of palatable junk foods, but maternal malnutrition also contributes to obesity in progeny. This study examines whether a maternal junk food diet predisposes offspring to nonalcoholic fatty liver disease. The 144 rat offspring were fed either a balanced chow diet alone or with palatable junk foods rich in energy, fat, sugar, and/or salt during gestation, lactation, and/or after weaning up to the end of adolescence. Offspring fed junk food throughout the study exhibited exacerbated hepatic steatosis, hepatocyte ballooning, and oxidative stress response compared with offspring given free access to junk food after weaning only. These offspring also displayed sex differences in their hepatic molecular metabolic adaptation to diet-induced obesity with increased expression of genes associated with insulin sensitivity, de novo lipogenesis, lipid oxidation, and antiinflammatory properties in males, whereas the gene expression profile in females was indicative of hepatic insulin resistance. Hepatic inflammation and fibrosis were not detected indicating that offspring had not developed severe steatohepatitis by the end of adolescence. Hepatic steatosis and increased oxidative stress response also occurred in offspring born to junk food-fed mothers switched to a balanced chow diet from weaning, highlighting a degree of irreversibility. This study shows that a maternal junk food diet in pregnancy and lactation contributes to the development of nonalcoholic fatty liver disease in offspring. PMID:20207831

Higher dietary anthocyanin and flavonol intakes are associated with anti-inflammatory effects in a population of US adults.

PubMed

Cassidy, Aedin; Rogers, Gail; Peterson, Julia J; Dwyer, Johanna T; Lin, Honghuang; Jacques, Paul F

2015-07-01

Although growing evidence from trials and population-based studies has supported a protective role for flavonoids in relation to risk of certain chronic diseases, the underlying mechanisms remain unclear. Several previous studies focused on individual inflammatory biomarkers, but because of the limited specificity of any individual marker, an assessment of a combination of biomarkers may be more informative. We used an inflammation score (IS) that integrated 12 individual inflammatory biomarkers for the examination of associations with intakes of different flavonoid classes. The study was a cross-sectional analysis of 2375 Framingham Heart Study Offspring Cohort participants. Intakes of total flavonoids and their classes (anthocyanins, flavonols, flavanones, flavan-3-ols, polymers, and flavones) were calculated from validated food-frequency questionnaires. Individual inflammatory biomarkers were ranked, standardized, and summed to derive an overall IS and subgroup scores of functionally related biomarkers. In multivariate analyses, an inverse association between higher anthocyanin and flavonol intakes and IS was observed with a mean ± SE difference between quintile categories 5 and 1 of -1.48 ± 0.32 (P-trend ≤ 0.001) and -0.72 ± 0.33 (P-trend = 0.01), respectively. Results remained significant after additional adjustment for physical activity and vitamin C and fruit and vegetable intakes. Higher anthocyanin intake was inversely associated with all biomarker subgroups, whereas higher flavonol intake was associated only with lower cytokine and oxidative stress biomarker concentrations. In food-based analyses, higher intakes of apples and pears, red wine, and strawberries were associated with a lower IS with differences between quintiles 5 and 1 of -1.02 ± 0.43 (P = 0.006), -1.73 ± 0.39 (P < 0.001), and -0.44 ± 0.88 (P = 0.02), respectively. Although intakes of other classes were not associated with a reduction in overall IS, higher intakes of flavan-3-ols and their polymers were associated with a significant reduction in oxidative stress biomarkers. These findings provide evidence to suggest that an anti-inflammatory effect may be a key component underlying the reduction in risk of certain chronic diseases associated with higher intakes of anthocyanins and flavonols. The Framingham Offspring Study was registered at clinicaltrials.gov as NCT00005121 (Framingham Heart Study). © 2015 American Society for Nutrition.

Like mother, like offspring: maternal and offspring wound healing correlate in snakes.

PubMed

Hopkins, Brittney C; Chin, Stephanie Y; Willson, John D; Hopkins, William A

2013-07-15

Immune function early in life can be influenced by parental effects and the environment, but it remains unclear how these two factors may interact to influence immunocompetence. We evaluated maternal and environmental contributions to offspring healing ability in a viviparous reptile, the northern watersnake (Nerodia sipedon). We measured wound healing rates, a highly integrative and biologically relevant measure of innate immunity, of females and their offspring collected from sites contaminated with a toxic heavy metal and compared them with those of individuals from reference sites. We found that female watersnakes that healed the fastest produced offspring that also exhibited faster healing rates. However, we detected no influence of environmental pollution on maternal or offspring healing rates. To our knowledge, our study is the first to correlate maternal and offspring wound healing ability in a wild vertebrate.

Helpers increase the reproductive potential of offspring in cooperative meerkats

PubMed Central

Russell, A.F; Young, A.J; Spong, G; Jordan, N.R; Clutton-Brock, T.H

2006-01-01

In both animal and human societies, individuals may forego personal reproduction and provide care to the offspring of others. Studies aimed at investigating the adaptive nature of such cooperative breeding systems in vertebrates typically calculate helper ‘fitness’ from relationships of helper numbers and offspring survival to independence. The aim of this study is to use observations and supplemental feeding experiments in cooperatively breeding meerkats, Suricata suricatta, to investigate whether helpers influence the long-term reproductive potential of offspring during adulthood. We show that helpers have a significant and positive influence on the probability that offspring gain direct reproductive success in their lifetimes. This effect arises because helpers both reduce the age at which offspring begin to reproduce as subordinates and increase the probability that they will compete successfully for alpha rank. Supplemental feeding experiments confirm the causality of these results. Our results suggest that one can neither discount the significance of helper effects when none is found nor necessarily estimate accurately the fitness benefit that helpers accrue, unless their effects on offspring are considered in the long term. PMID:17476771

Personality profile of the children of long-lived parents.

PubMed

Antoniou, Evangelia E; Dutta, Ambarish; Langa, Kenneth M; Melzer, David; Llewellyn, David

2013-09-01

Past research has shown that parental longevity is related to offspring physical health and longevity. Preliminary studies suggest that parental longevity may be linked to the offspring's personality traits. A comprehensive 5-factor personality model has been related to physical health, but the association with parental longevity has not yet been investigated. We used a 5-factor personality model to investigate the relationship between parental longevity and offspring personality. Data from the longitudinal Health and Retirement Study (HRS) was used in the analyses. Using the Midlife Development Inventory and the Life Orientation test, the relationship between parental attained age and offspring personality was assessed using regression models for both men and women. Male offspring of long-lived fathers and mothers were more likely to be open to new experiences (p < .01) and be more extroverted (p = .03) compared with male offspring of short-lived fathers or mothers. Maternal or paternal attained age had no effect on the female offspring personality traits. Personality is an important phenotype to consider when investigating genetic and environmental determinants of longevity. Further research is needed to investigate the potential of gender-specific mechanisms.

Maternal Blood Pressure During Pregnancy and Early Childhood Blood Pressures in the Offspring

PubMed Central

Lim, Wai-Yee; Lee, Yung-Seng; Yap, Fabian Kok-Peng; Aris, Izzudin Mohd; Ngee, Lek; Meaney, Michael; Gluckman, Peter D.; Godfrey, Keith M.; Kwek, Kenneth; Chong, Yap-Seng; Saw, Seang-Mei; Pan, An

2015-01-01

Abstract Although epidemiological studies suggest that offspring of women with preeclampsia are at increased risk to higher blood pressures and cardiovascular disease, little is known about the nature of blood pressures between the mother and her offspring. As blood pressures comprise of both pulsatile (systolic blood pressure [SBP] and pulse pressure [PP]) and stable (diastolic blood pressure [DBP]) components, and they differ between central and peripheral sites, we sought to examine maternal peripheral and central blood pressure components in relation to offspring early childhood blood pressures. A prospective birth cohort of 567 Chinese, Malay, and Indian mother–offspring with complete blood pressure information were studied. Maternal brachial artery SBP, DBP, and PP were measured at 26 to 28 weeks gestation; and central SBP and PP were estimated from radial artery waveforms. Offspring brachial artery SBP, DBP, and PP were measured at 3 years of age. Associations between continuous variables of maternal blood pressures (peripheral SBP, DBP, PP, central SBP, and PP) and offspring blood pressures (peripheral SBP, DBP, and PP) were examined using multiple linear regression with adjustment for maternal characteristics (age, education level, parity, smoking status, alcohol consumption and physical activity during pregnancy, and pre-pregnancy BMI) and offspring characteristics (sex, ethnicity, BMI, and height at 3 years of age). In the multivariate models, offspring peripheral SBP increased by 0.08 (95% confidence interval 0.00–0.17, P = 0.06) mmHg with every 1-mmHg increase in maternal central SBP, and offspring peripheral PP increased by 0.10 (0.01–0.18, P = 0.03) mmHg for every 1-mmHg increase in maternal central PP. The relations of maternal-offspring peripheral blood pressures (SBP, DBP, and PP) were positive but not statistically significant, and the corresponding values were 0.05 (−0.03 to 0.13; P = 0.21), 0.03 (−0.04 to 0.10; P = 0.35), and 0.05 (−0.02 to 0.13; P = 0.14), respectively. Maternal central pulsatile blood pressure components (SBP and PP) during pregnancy are associated with higher blood pressures in the offspring. This positive correlation is already evident at 3-years old. Studies are needed to further evaluate the effects of maternal central pulsatile blood pressure components during pregnancy and long-term cardiovascular health in the offspring. PMID:26559279

Prenatal stress accelerates offspring growth to compensate for reduced maternal investment across mammals

PubMed Central

Berghänel, Andreas; Heistermann, Michael; Schülke, Oliver; Ostner, Julia

2017-01-01

Across mammals, prenatal maternal stress (PREMS) affects many aspects of offspring development, including offspring growth. However, how PREMS translates to offspring growth is inconsistent, even within species. To explain the full range of reported effects of prenatal adversity on offspring growth, we propose an integrative hypothesis: developmental constraints and a counteracting adaptive growth plasticity work in opposition to drive PREMS effects on growth. Mothers experiencing adversity reduce maternal investment leading to stunted growth (developmental constraints). Concomitantly, the pace of offspring life history is recalibrated to partly compensate for these developmental constraints (adaptive growth plasticity). Moreover, the relative importance of each process changes across ontogeny with increasing offspring independence. Thus, offspring exposed to PREMS may grow at the same rate as controls during gestation and lactation, but faster after weaning when direct maternal investment has ceased. We tested these predictions with a comparative analysis on the outcomes of 719 studies across 21 mammal species. First, the observed growth changes in response to PREMS varied across offspring developmental periods as predicted. We argue that the observed growth acceleration after weaning is not “catch-up growth,” because offspring that were small for age grew slower. Second, only PREMS exposure early during gestation produced adaptive growth plasticity. Our results suggest that PREMS effects benefit the mother’s future reproduction and at the same time accelerate offspring growth and possibly maturation and reproductive rate. In this sense, PREMS effects on offspring growth allow mother and offspring to make the best of a bad start. PMID:29180423

Maternal BMI, parity, and pregnancy weight gain: influences on offspring adiposity in young adulthood.

PubMed

Reynolds, R M; Osmond, C; Phillips, D I W; Godfrey, K M

2010-12-01

The prevalence of obesity among women of childbearing age is increasing. Emerging evidence suggests that this has long-term adverse influences on offspring health. The aim was to examine whether maternal body composition and gestational weight gain have persisting effects on offspring adiposity in early adulthood. The Motherwell birth cohort study was conducted in a general community in Scotland, United Kingdom. We studied 276 men and women whose mothers' nutritional status had been characterized in pregnancy. Four-site skinfold thicknesses, waist circumference, and body mass index (BMI), were measured at age 30 yr; sex-adjusted percentage body fat and fat mass index were calculated. Indices of offspring adiposity at age 30 yr were measured. Percentage body fat was greater in offspring of mothers with a higher BMI at the first antenatal visit (rising by 0.35%/kg/m2; P<0.001) and in offspring whose mothers were primiparous (difference, 1.5% in primiparous vs. multiparous; P=0.03). Higher offspring percentage body fat was also independently associated with higher pregnancy weight gain (7.4%/kg/wk; P=0.002). There were similar significant associations of increased maternal BMI, greater pregnancy weight gain, and parity with greater offspring waist circumference, BMI, and fat mass index. Adiposity in early adulthood is influenced by prenatal influences independently of current lifestyle factors. Maternal adiposity, greater gestational weight, and parity all impact on offspring adiposity. Strategies to reduce the impact of maternal obesity and greater pregnancy weight gain on offspring future health are required.

Maternal high-fat diet and offspring expression levels of vitamin K-dependent proteins.

PubMed

Lanham, S A; Cagampang, F R; Oreffo, R O C

2014-12-01

Studies suggest that bone growth and development and susceptibility to vascular disease in later life are influenced by maternal nutrition during intrauterine and early postnatal life. There is evidence for a role of vitamin K-dependent proteins (VKDPs) including osteocalcin, matrix Gla protein, periostin, and growth-arrest specific- protein 6, in both bone and vascular development. We have examined whether there are alterations in these VKDPs in bone and vascular tissue from offspring of mothers subjected to a nutritional challenge: a high-fat diet during pregnancy and postnatally, using 6-week-old mouse offspring. Bone site-specific and sex-specific differences across femoral and vertebral bone in male and female offspring were observed. Overall a high-fat maternal diet and offspring diet exacerbated the bone changes observed. Sex-specific differences and tissue-specific differences were observed in VKDP levels in aorta tissue from high-fat diet-fed female offspring from high-fat diet-fed mothers displaying increased levels of Gas6 and Ggcx compared with those of female controls. In contrast, differences were seen in VKDP levels in femoral bone of female offspring with lower expression levels of Mgp in offspring of mothers fed a high-fat diet compared with those of controls. We observed a significant correlation in Mgp expression levels within the femur to measures of bone structure of the femur and vertebra, particularly in the male offspring cohort. In summary, the current study has highlighted the importance of maternal nutrition on offspring bone development and the correlation of VKDPs to bone structure.

Micro RNAs from DNA Viruses are Found Widely in Plasma in a Large Observational Human Population.

PubMed

Koupenova, Milka; Mick, Eric; Corkrey, Heather A; Huan, Tianxiao; Clancy, Lauren; Shah, Ravi; Benjamin, Emelia J; Levy, Daniel; Kurt-Jones, Evelyn A; Tanriverdi, Kahraman; Freedman, Jane E

2018-04-23

Viral infections associate with disease risk and select families of viruses encode miRNAs that control an efficient viral cycle. The association of viral miRNA expression with disease in a large human population has not been previously explored. We sequenced plasma RNA from 40 participants of the Framingham Heart Study (FHS, Offspring Cohort, Visit 8) and identified 3 viral miRNAs from 3 different human Herpesviridae. These miRNAs were mostly related to viral latency and have not been previously detected in human plasma. Viral miRNA expression was then screened in the plasma of 2763 participants of the remaining cohort utilizing high-throughput RT-qPCR. All 3 viral miRNAs associated with combinations of inflammatory or prothrombotic circulating biomarkers (sTNFRII, IL-6, sICAM1, OPG, P-selectin) but did not associate with hypertension, coronary heart disease or cancer. Using a large observational population, we demonstrate that the presence of select viral miRNAs in the human circulation associate with inflammatory biomarkers and possibly immune response, but fail to associate with overt disease. This study greatly extends smaller singular observations of viral miRNAs in the human circulation and suggests that select viral miRNAs, such as those for latency, may not impact disease manifestation.

Assessing bottled water nitrate concentrations to evaluate total drinking water nitrate exposure and risk of birth defects.

PubMed

Weyer, Peter J; Brender, Jean D; Romitti, Paul A; Kantamneni, Jiji R; Crawford, David; Sharkey, Joseph R; Shinde, Mayura; Horel, Scott A; Vuong, Ann M; Langlois, Peter H

2014-12-01

Previous epidemiologic studies of maternal exposure to drinking water nitrate did not account for bottled water consumption. The objective of this National Birth Defects Prevention Study (NBDPS) (USA) analysis was to assess the impact of bottled water use on the relation between maternal exposure to drinking water nitrate and selected birth defects in infants born during 1997-2005. Prenatal residences of 1,410 mothers reporting exclusive bottled water use were geocoded and mapped; 326 bottled water samples were collected and analyzed using Environmental Protection Agency Method 300.0. Median bottled water nitrate concentrations were assigned by community; mothers' overall intake of nitrate in mg/day from drinking water was calculated. Odds ratios for neural tube defects, limb deficiencies, oral cleft defects, and heart defects were estimated using mixed-effects models for logistic regression. Odds ratios (95% CIs) for the highest exposure group in offspring of mothers reporting exclusive use of bottled water were: neural tube defects [1.42 (0.51, 3.99)], limb deficiencies [1.86 (0.51, 6.80)], oral clefts [1.43 (0.61, 3.31)], and heart defects [2.13, (0.87, 5.17)]. Bottled water nitrate had no appreciable impact on risk for birth defects in the NBDPS.

Assessing bottled water nitrate concentrations to evaluate total drinking water nitrate exposure and risk of birth defects

PubMed Central

Weyer, Peter J.; Brender, Jean D.; Romitti, Paul A.; Kantamneni, Jiji R.; Crawford, David; Sharkey, Joseph R.; Shinde, Mayura; Horel, Scott A.; Vuong, Ann M.; Langlois, Peter H.

2016-01-01

Previous epidemiologic studies of maternal exposure to drinking water nitrate did not account for bottled water consumption. The objective of this National Birth Defects Prevention Study (NBDPS) (USA) analysis was to assess the impact of bottled water use on the relation between maternal exposure to drinking water nitrate and selected birth defects in infants born during 1997–2005. Prenatal residences of 1,410 mothers reporting exclusive bottled water use were geocoded and mapped; 326 bottled water samples were collected and analyzed using Environmental Protection Agency Method 300.0. Median bottled water nitrate concentrations were assigned by community; mothers’ overall intake of nitrate in mg/day from drinking water was calculated. Odds ratios for neural tube defects, limb deficiencies, oral cleft defects, and heart defects were estimated using mixed-effects models for logistic regression. Odds ratios (95% CIs) for the highest exposure group in offspring of mothers reporting exclusive use of bottled water were: neural tube defects [1.42 (0.51, 3.99)], limb deficiencies [1.86 (0.51, 6.80)], oral clefts [1.43 (0.61, 3.31)], and heart defects [2.13, (0.87, 5.17)]. Bottled water nitrate had no appreciable impact on risk for birth defects in the NBDPS. PMID:25473985

Longitudinal Pathways between Maternal Mental Health in Infancy and Offspring Romantic Relationships in Adulthood: A 30-Year Prospective Study

ERIC Educational Resources Information Center

Slominski, Lisa; Sameroff, Arnold; Rosenblum, Katherine; Kasser, Tim

2011-01-01

Longitudinal pathways between maternal mental health in infancy and offspring romantic relationship outcomes in adulthood were examined using a 30-year prospective longitudinal study of 196 mothers and their children. Structural equation modeling revealed that maternal mental health at 30 months was related to offspring relationship status and…

Maternal caloric restriction partially rescues the deleterious effects of advanced maternal age on offspring.

PubMed

Gribble, Kristin E; Jarvis, George; Bock, Martha; Mark Welch, David B

2014-08-01

While many studies have focused on the detrimental effects of advanced maternal age and harmful prenatal environments on progeny, little is known about the role of beneficial non-Mendelian maternal inheritance on aging. Here, we report the effects of maternal age and maternal caloric restriction (CR) on the life span and health span of offspring for a clonal culture of the monogonont rotifer Brachionus manjavacas. Mothers on regimens of chronic CR (CCR) or intermittent fasting (IF) had increased life span compared with mothers fed ad libitum (AL). With increasing maternal age, life span and fecundity of female offspring of AL-fed mothers decreased significantly and life span of male offspring was unchanged, whereas body size of both male and female offspring increased. Maternal CR partially rescued these effects, increasing the mean life span of AL-fed female offspring but not male offspring and increasing the fecundity of AL-fed female offspring compared with offspring of mothers of the same age. Both maternal CR regimens decreased male offspring body size, but only maternal IF decreased body size of female offspring, whereas maternal CCR caused a slight increase. Understanding the genetic and biochemical basis of these different maternal effects on aging may guide effective interventions to improve health span and life span. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Paternal alcoholism and offspring conduct disorder: evidence for the 'common genes' hypothesis.

PubMed

Haber, Jon R; Jacob, Theodore; Heath, Andrew C

2005-04-01

Not only are alcoholism and externalizing disorders frequently comorbid, they often co-occur in families across generations; for example, paternal alcoholism predicts offspring conduct disorder just as it does offspring alcoholism. To clarify this relationship, the current study examined the 'common genes' hypothesis utilizing a children-of-twins research design. Participants were male monozygotic (MZ) and dizygotic (DZ) twins from the Vietnam Era Twin Registry who were concordant or discordant for alcohol dependence together with their offspring and the mothers of those offspring. All participants were conducted through a structured psychiatric interview. Offspring risk of conduct disorder was examined as a function of alcoholism genetic risk (due to paternal and co-twin alcohol dependence) and alcoholism environmental risk (due to being reared by a father with an alcohol dependence diagnosis). After controlling for potentially confounding variables, the offspring of alcohol-dependent fathers were significantly more likely to exhibit conduct disorder diagnoses than were offspring of nonalcohol-dependent fathers, thus indicating diagnostic crossover in generational family transmission. Comparing offspring at high genetic and high environmental risk with offspring at high genetic and low environmental risk indicated that genetic factors were most likely responsible for the alcoholism-conduct disorder association. The observed diagnostic crossover (from paternal alcoholism to offspring conduct disorder) across generations in the context of both high and low environmental risk (while genetic risk remained high) supported the common genes hypothesis.

Parental Smoking and Adult Offspring's Smoking Behaviors in Ethnic Minority Groups: An Intergenerational Analysis in the HELIUS Study.

PubMed

Ikram, Umar Z; Snijder, Marieke B; Derks, Eske M; Peters, Ron J G; Kunst, Anton E; Stronks, Karien

2018-05-03

To understand smoking behaviors among ethnic minority groups, studies have largely focused on societal factors, with little attention to family influences. Yet studies among majority groups have identified parental smoking as an important risk factor. It is unknown whether this applies to ethnic minority groups. We investigated the association between parental smoking and adult offspring's smoking behaviors among ethnic minority groups with an immigrant background. We used data from the Healthy Life in an Urban Setting study from Amsterdam (the Netherlands) from January 2011 to December 2015. The sample consisted of 2184 parent-offspring pairs from South-Asian Surinamese, African Surinamese, Turkish, Moroccan, and Ghanaian origin. We collected self-reported smoking data: current status, duration of exposure to parental smoking, number of daily cigarettes, heavy smoking ( > 10 cigarettes/day), and nicotine dependency (using the Fagerström Test). Analyses were stratified by offspring's age, cohabitation with parent, education (parent/offspring), offspring's cultural orientation, and gender concordance within pairs. Logistic regression was used. Overall, parental smoking was associated with offspring's smoking behaviors (eg, current smoking: odds ratio 2.33; 95% confidence interval 1.79-3.03), with little ethnic variation. We found dose-response associations between exposure to parental smoking and offspring's smoking. The associations were similar across different strata but stronger in gender-concordant pairs (3.16; 2.12-4.51 vs. 1.73; 1.15-2.59 in gender-discordant pairs; p-value for interaction .017). Parental smoking is associated with offspring's smoking behaviors in ethnic minority groups across different strata but particularly in gender-concordant pairs. Similar to majority groups, family influences matter to smoking behaviors in ethnic minority groups. Our findings have deepened our understanding of smoking behaviors among ethnic minority groups. Future studies should simultaneously consider societal factors and parental influences, to comprehensively understand their impact on smoking among ethnic minority groups. Also, smoking patterns among family members should be addressed in individual counselling, irrespective of ethnicity.

Left Ventricular Structure and Risk of Cardiovascular Events: A Framingham Heart Study Cardiac Magnetic Resonance Study.

PubMed

Tsao, Connie W; Gona, Philimon N; Salton, Carol J; Chuang, Michael L; Levy, Daniel; Manning, Warren J; O'Donnell, Christopher J

2015-09-15

Elevated left ventricular mass index (LVMI) and concentric left ventricular (LV) remodeling are related to adverse cardiovascular disease (CVD) events. The predictive utility of LV concentric remodeling and LV mass in the prediction of CVD events is not well characterized. Framingham Heart Study Offspring Cohort members without prevalent CVD (n=1715, 50% men, aged 65±9 years) underwent cardiovascular magnetic resonance for LVMI and geometry (2002-2006) and were prospectively followed for incident CVD (myocardial infarction, coronary insufficiency, heart failure, stroke) or CVD death. Over 13 808 person-years of follow-up (median 8.4, range 0.0 to 10.5 years), 85 CVD events occurred. In multivariable-adjusted proportional hazards regression models, each 10-g/m(2) increment in LVMI and each 0.1 unit in relative wall thickness was associated with 33% and 59% increased risk for CVD, respectively (P=0.004 and P=0.009, respectively). The association between LV mass/LV end-diastolic volume and incident CVD was borderline significant (P=0.053). Multivariable-adjusted risk reclassification models showed a modest improvement in CVD risk prediction with the incorporation of cardiovascular magnetic resonance LVMI and measures of LV concentricity (C-statistic 0.71 [95% CI 0.65 to 0.78] for the model with traditional risk factors only, improved to 0.74 [95% CI 0.68 to 0.80] for the risk factor model additionally including LVMI and relative wall thickness). Among adults free of prevalent CVD in the community, greater LVMI and LV concentric hypertrophy are associated with a marked increase in adverse incident CVD events. The potential benefit of aggressive primary prevention to modify LV mass and geometry in these adults requires further investigation. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Trends in dietary carbohydrate consumption from 1991 to 2008 in the Framingham Heart Study Offspring Cohort

PubMed Central

Makarem, Nour; Scott, Marc; Quatromoni, Paula; Jacques, Paul; Parekh, Niyati

2014-01-01

The intake of carbohydrates has been evaluated cross-sectionally, but not longitudinally in an ageing American adult population. The aim of the present study was to examine trends in the intake of dietary carbohydrates and their major food sources among the Framingham Heart Study Offspring (FOS) cohort, which had been uniquely tracked for 17 years in the study. The FOS cohort was recruited in 1971–1975. Follow-up examinations were conducted, on average, every 4 years. Dietary data collection began in 1991 (examination 5) using a validated semi-quantitative FFQ. The study included 2894 adults aged ≥25 years with complete dietary data in at least three examinations from 1991 to 2008. Descriptive statistics were generated using SAS version 9.3, and a repeated-measures model was used to examine trends in the intake of carbohydrates and their food sources in the whole sample, and by sex and BMI category. Over 17 years of follow-up, the percentage of energy from total carbohydrates (51·0–46·8 %; P for trend<0·001) and total sugars (18·2–16·6 %; P for trend<0·001) decreased. There was a decrease in the percentage of energy from fructose (5·4–4·7 %; P for trend<0·001) and sucrose (9·8–8·8 %; P for trend<0·001). Dietary fibre intake increased (18·0–19·2 g/d; P for trend<0·001). The number of weekly servings of yeast bread, soft drinks/soda, cakes/cookies/quick breads/doughnuts, potatoes, milk, pasta, rice and cooked grains, fruit juice/drinks, potato chips/maize chips/popcorn, and lunch foods (e.g. pizzas and burgers) decreased significantly (P for trend<0·001), while the intake of ready-to-eat cereals, legumes, fruits, dairy products, candy and ice cream/sherbet/frozen yogurt increased significantly (P for trend<0·04). Similar trends were observed when the analyses were stratified by sex and BMI. The present results suggest favourable trends in dietary carbohydrate consumption, but dietary guidelines for fruits, vegetables and fibre were not met in this cohort. PMID:24661608

MTHFR deficiency or reduced intake of folate or choline in pregnant mice results in impaired short-term memory and increased apoptosis in the hippocampus of wild-type offspring.

PubMed

Jadavji, N M; Deng, L; Malysheva, O; Caudill, M A; Rozen, R

2015-08-06

Genetic or nutritional disturbances in one-carbon metabolism, with associated hyperhomocysteinemia, can result in complex disorders including pregnancy complications and neuropsychiatric diseases. In earlier work, we showed that mice with a complete deficiency of methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate and homocysteine metabolism, had cognitive impairment with disturbances in choline metabolism. Maternal demands for folate and choline are increased during pregnancy and deficiencies of these nutrients result in several negative outcomes including increased resorption and delayed development. The goal of this study was to investigate the behavioral and neurobiological impact of a maternal genetic deficiency in MTHFR or maternal nutritional deficiency of folate or choline during pregnancy on 3-week-old Mthfr(+/+) offspring. Mthfr(+/+) and Mthfr(+/-) females were placed on control diets (CD); and Mthfr(+/+) females were placed on folate-deficient diets (FD) or choline-deficient diets (ChDD) throughout pregnancy and lactation until their offspring were 3weeks of age. Short-term memory was assessed in offspring, and hippocampal tissue was evaluated for morphological changes, apoptosis, proliferation and choline metabolism. Maternal MTHFR deficiency resulted in short-term memory impairment in offspring. These dams had elevated levels of plasma homocysteine when compared with wild-type dams. There were no differences in plasma homocysteine in offspring. Increased apoptosis and proliferation was observed in the hippocampus of offspring from Mthfr(+/-) mothers. In the maternal FD and ChDD study, offspring also showed short-term memory impairment with increased apoptosis in the hippocampus; increased neurogenesis was observed in ChDD offspring. Choline acetyltransferase protein was increased in the offspring hippocampus of both dietary groups and betaine was decreased in the hippocampus of FD offspring. Our results reveal short-term memory deficits in the offspring of dams with MTHFR deficiency or dietary deficiencies of critical methyl donors. We suggest that deficiencies in maternal one-carbon metabolism during pregnancy can contribute to hippocampal dysfunction in offspring through apoptosis or altered choline metabolism. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

A systematic review of the parenting and outcomes experienced by offspring of mothers with borderline personality pathology: Potential mechanisms and clinical implications.

PubMed

Eyden, Julie; Winsper, Catherine; Wolke, Dieter; Broome, Matthew R; MacCallum, Fiona

2016-07-01

There is growing interest in whether the parenting strategies and offspring outcomes of mothers with borderline personality disorder (BPD) differ from those of mothers without BPD. We searched PsychINFO, PubMed, EMBASE, Web of Science, Scopus and ASSIA databases for studies examining parenting skills and attitudes among mothers with BPD/BPD symptoms and/or offspring outcomes. PRISMA reporting guidelines were followed. Of 10,067 abstracts screened, 101 full-text articles were retrieved and 33 met pre-determined criteria for qualitative synthesis. Overall, studies suggest that mothers with BPD/BPD symptoms are more likely to engage in maladaptive interactions with their offspring characterised by insensitive, overprotective, and hostile parenting compared to mothers without BPD/BPD symptoms. Adverse offspring outcomes include BPD symptoms, internalising (including depression) and externalising problems, insecure attachment patterns, and emotional dysregulation. Findings suggest that vulnerability from mother to offspring may be partly transmitted via maladaptive parenting and maternal emotional dysfunction. Conclusions were limited by study heterogeneity in methodology and construct definitions, as well as a paucity of clinical comparison groups. Prospective studies of mothers with BPD and their offspring from pregnancy onwards may further elucidate mechanisms of transmission and identify resilience factors across development. Parenting behaviour awareness, improving attachment behaviours and emotional regulation strategies may be important intervention targets. Copyright © 2016 Elsevier Ltd. All rights reserved.

Selective organ specific inflammation in offspring harbouring microchimerism from strongly alloreactive mothers.

PubMed

Leveque, Lucie; Hodgson, Samantha; Peyton, Stephen; Koyama, Motoko; MacDonald, Kelli P A; Khosrotehrani, Kiarash

2014-05-01

The origins of autoimmunity are not yet understood despite significant advances in immunology. The trafficking of maternal cells to the offspring represents the very first immunological event in foetal life and is reinforced during lactation. The persistence of maternal cells in offspring's tissues and circulation has been associated with several autoimmune disorders. However a direct causal effect has never been demonstrated. Maternal T cells specifically targeting foetal insulin producing cells have been shown to generate islet inflammation without directly participating in this process. Our objective was to evaluate if alloreactive maternal cells could directly trigger a graft-versus host like reaction or indirectly influence the development of the offspring's regulatory T cells favouring autoimmunity. We adopted a breeding strategy comparing genetically identical offspring from either strongly alloreactive transgenic mothers compared to immunodeficient mothers. We detected maternal alloreactive T cells in the offspring and early signs of inflammation in small intestine of 6 weeks old offspring. Interestingly, CD4(+) Foxp3(+) regulatory T cell frequency was diminished in mesenteric lymph nodes from eight months old offspring born of alloreactive mothers compared to offspring of immunodeficient mothers. Our study favours a hypothesis where highly alloreactive maternal cell microchimerism indirectly predisposes offspring to autoimmunity. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Pregestational type 2 diabetes mellitus induces cardiac hypertrophy in the murine embryo through cardiac remodeling and fibrosis.

PubMed

Lin, Xue; Yang, Penghua; Reece, E Albert; Yang, Peixin

2017-08-01

Cardiac hypertrophy is highly prevalent in patients with type 2 diabetes mellitus. Experimental evidence has implied that pregnant women with type 2 diabetes mellitus and their children are at an increased risk of cardiovascular diseases. Our previous mouse model study revealed that maternal type 2 diabetes mellitus induces structural heart defects in their offspring. This study aims to determine whether maternal type 2 diabetes mellitus induces embryonic heart hypertrophy in a murine model of diabetic embryopathy. The type 2 diabetes mellitus embryopathy model was established by feeding 4-week-old female C57BL/6J mice with a high-fat diet for 15 weeks. Cardiac hypertrophy in embryos at embryonic day 17.5 was characterized by measuring heart size and thickness of the right and left ventricle walls and the interventricular septum, as well as the expression of β-myosin heavy chain, atrial natriuretic peptide, insulin-like growth factor-1, desmin, and adrenomedullin. Cardiac remodeling was determined by collagen synthesis and fibronectin synthesis. Fibrosis was evaluated by Masson staining and determining the expression of connective tissue growth factor, osteopontin, and galectin-3 genes. Cell apoptosis also was measured in the developing heart. The thicknesses of the left ventricle walls and the interventricular septum of embryonic hearts exposed to maternal diabetes were significantly thicker than those in the nondiabetic group. Maternal diabetes significantly increased β-myosin heavy chain, atrial natriuretic peptide, insulin-like growth factor-1, and desmin expression, but decreased expression of adrenomedullin. Moreover, collagen synthesis was significantly elevated, whereas fibronectin synthesis was suppressed, in embryonic hearts from diabetic dams, suggesting that cardiac remodeling is a contributing factor to cardiac hypertrophy. The cardiac fibrosis marker, galectin-3, was induced by maternal diabetes. Furthermore, maternal type 2 diabetes mellitus activated the proapoptotic c-Jun-N-terminal kinase 1/2 stress signaling and triggered cell apoptosis by increasing the number of terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick end labeling-positive cells (10.4 ± 2.2% of the type 2 diabetes mellitus group vs 3.8 ± 0.7% of the nondiabetic group, P < .05). Maternal type 2 diabetes mellitus induces cardiac hypertrophy in embryonic hearts. Adverse cardiac remodeling, including elevated collagen synthesis, suppressed fibronectin synthesis, profibrosis, and apoptosis, is implicated as the etiology of cardiac hypertrophy. Copyright © 2017 Elsevier Inc. All rights reserved.

Brain Structural and Vascular Anatomy Is Altered in Offspring of Pre-Eclamptic Pregnancies: A Pilot Study.

PubMed

Rätsep, M T; Paolozza, A; Hickman, A F; Maser, B; Kay, V R; Mohammad, S; Pudwell, J; Smith, G N; Brien, D; Stroman, P W; Adams, M A; Reynolds, J N; Croy, B A; Forkert, N D

2016-05-01

Pre-eclampsia is a serious clinical gestational disorder occurring in 3%-5% of all human pregnancies and characterized by endothelial dysfunction and vascular complications. Offspring born of pre-eclamptic pregnancies are reported to exhibit deficits in cognitive function, higher incidence of depression, and increased susceptibility to stroke. However, no brain imaging reports exist on these offspring. We aimed to assess brain structural and vascular anatomy in 7- to 10-year-old offspring of pre-eclamptic pregnancies compared with matched controls. Offspring of pre-eclamptic pregnancies and matched controls (n = 10 per group) were recruited from an established longitudinal cohort examining the effects of pre-eclampsia. Children underwent MR imaging to identify brain structural and vascular anatomic differences. Maternal plasma samples collected at birth were assayed for angiogenic factors by enzyme-linked immunosorbent assay. Offspring of pre-eclamptic pregnancies exhibited enlarged brain regional volumes of the cerebellum, temporal lobe, brain stem, and right and left amygdalae. These offspring displayed reduced cerebral vessel radii in the occipital and parietal lobes. Enzyme-linked immunosorbent assay analysis revealed underexpression of the placental growth factor among the maternal plasma samples from women who experienced pre-eclampsia. This study is the first to report brain structural and vascular anatomic alterations in the population of offspring of pre-eclamptic pregnancies. Brain structural alterations shared similarities with those seen in autism. Vascular alterations may have preceded these structural alterations. This pilot study requires further validation with a larger population to provide stronger estimates of brain structural and vascular outcomes among the offspring of pre-eclamptic pregnancies. © 2016 by American Journal of Neuroradiology.

Effect of Gestational Weight Gain and Prepregnancy Body Mass Index in Adolescent Mothers on Weight and Body Mass Index of Adolescent Offspring.

PubMed

Groth, Susan W; Holland, Margaret L; Smith, Joyce A; Meng, Ying; Kitzman, Harriet

2017-11-01

The purpose of the study was to examine the association of the gestational weight gain and prepregnancy body mass index (BMI) of low-income adolescent mothers with the risk of their children being overweight and/or obese in late adolescence. Study subjects were low-income, primiparous adolescents (n = 360) who self-identified as black and participated in the New Mothers Study in Memphis, Tennessee, and their children. Gestational weight gain was examined as a continuous variable and also categorized into overgain, recommended gain, and undergain following the 2009 Institute of Medicine guidelines. The effects of maternal prepregnancy BMI percentiles and calculated BMI were also considered. Multivariable logistic and linear regression models were used. The main outcome measures were offspring overweight, obesity, and BMI. Thirty-nine percent of offspring were overweight or obese. Higher maternal gestational weight gain increased the risk for offspring overweight and obesity. There was an interaction between gestational weight gain and prepregnancy BMI: offspring of mothers with a BMI percentile ≤76 were at greater risk of obesity with higher maternal weight gain. If mothers with a BMI percentile between the 29th and 83rd percentiles overgained, offspring were at greater risk for overweight. Using calculated BMIs, if a mother's BMI was ≤26 kg/m 2 , offspring risk for obesity was greater with higher gestational weight gain. High gestational weight gain had a larger effect on offspring overweight and obesity if maternal prepregnancy BMI percentile was ≤76. The gestational weight gain of primiparous adolescents who self-identified as black had an effect on offspring weight. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Maternal Postnatal Depression and the Development of Depression in Offspring up to 16 Years of Age

ERIC Educational Resources Information Center

Murray, Lynne; Arteche, Adriane; Fearon, Pasco; Halligan, Sarah; Goodyer, Ian; Cooper, Peter

2011-01-01

Objective: The aim of this study was to determine the developmental risk pathway to depression by 16 years in offspring of postnatally depressed mothers. Method: This was a prospective longitudinal study of offspring of postnatally depressed and nondepressed mothers; child and family assessments were made from infancy to 16 years. A total of 702…

A Genetically Informed Study of the Processes Underlying the Association between Parental Marital Instability and Offspring Adjustment

ERIC Educational Resources Information Center

D'Onofrio, Brian M.; Turkheimer, Eric; Emery, Robert E.; Slutske, Wendy S.; Heath, Andrew C.; Madden, Pamela A.; Martin, Nicholas G.

2006-01-01

Parental divorce is associated with problematic offspring adjustment, but the relation may be due to shared genetic or environmental factors. One way to test for these confounds is to study offspring of twins discordant for divorce. The current analyses used this design to separate the mechanisms responsible for the association between parental…

Transgenerational effects of caloric restriction on appetite: a meta-analysis.

PubMed

Lagisz, M; Blair, H; Kenyon, P; Uller, T; Raubenheimer, D; Nakagawa, S

2014-04-01

Maternal undernutrition can result in significant alterations to the post-natal offspring phenotype, including body size and behaviour. For example, maternal food restriction has been implicated in offspring hyperphagia, potentially causing increased weight gain and fat accumulation. This could result in obesity and other adverse long-term health effects in offspring. We investigated the link between maternal caloric restriction during gestation and offspring appetite by conducting the first meta-analysis on this topic using experimental data from mammalian laboratory models (i.e. rats and mice). We collected 89 effect sizes from 35 studies, together with relevant moderators. Our analysis revealed weak and statistically non-significant overall effect on offspring's appetite. However, we found that lower protein content of restricted diets is associated with higher food intake in female offspring. Importantly, we show that a main source of variation among studies arises from whether, and how, food intake was adjusted for body mass. This probably explains many of the contradictory results in the field. Based on our results, we recommend using allometric scaling of food intake to body mass in future studies. © 2014 The Authors. obesity reviews © 2014 International Association for the Study of Obesity.

Clinical study report on milk production in the offspring of a somatic cell cloned Holstein cow.

PubMed

Takahashi, Masahiro; Tsuchiya, Hideki; Hamano, Seizo; Inaba, Toshio; Kawate, Noritoshi; Tamada, Hiromichi

2013-12-17

This study examined two female offspring of a somatic cell cloned Holstein cow that had reproduction problems and milk production performance issues. The two offspring heifers, which showed healthy appearances and normal reproductive characteristics, calved on two separate occasions. The mean milk yields of the heifers in the first lactation period were 9,037 kg and 7,228 kg. The relative mean milk yields of these cows were 111.2% and 88.9%, respectively, when compared with that of the control group. No particular clinical abnormalities were revealed in milk yields and milk composition rate [e.g., fat, protein and solids-not-fat (SNF)], and reproductive characteristics of the offspring of the somatic cell cloned Holstein cow suggested that the cloned offspring had normal milk production.

Maternal inflammatory bowel disease has short and long-term effects on the health of their offspring: a multicenter study in Israel.

PubMed

Dotan, Iris; Alper, Arik; Rachmilewitz, Daniel; Israeli, Eran; Odes, Shmuel; Chermesh, Irit; Naftali, Timna; Fraser, Gerald; Shitrit, Ariella Bar-Gil; Peles, Vardit; Reif, Shimon

2013-08-01

There are concerns about the effect of inflammatory bowel diseases (IBD) on fertility, pregnancy and pregnancy outcomes, but no long-term data on the health of offspring born to IBD mothers. The aims were to assess the short- and long-term effects of maternal IBD on the morbidity and development of their offspring. Female IBD patients and controls completed questionnaires on their pregnancy outcome, and their offspring's short- and long-term health and development. IBD and control mothers (159 and 175, respectively) were recruited. Medical data of 412 IBD and 417 control offspring were recorded. IBD mothers had significantly more singleton pregnancies, their offspring's birth weight was significantly lower, and they breastfed significantly less compared to controls (P=0.028, 0.007, and <0.0001, respectively). There were significantly more congenital anomalies (mainly limb deformities) among the IBD offspring (P<0.035). Offspring born post-maternal IBD diagnosis, compared to pre-diagnosis, tended to have more neurodevelopmental problems (e.g., gross motor delay, P=0.03). IBD was significantly more prevalent in the offspring of IBD mothers, while allergies and atopic dermatitis were more frequent in offspring of control mothers. More offspring of IBD mothers taking medications during pregnancy were born preterm and had lower birth weights compared to offspring of IBD mothers not taking medications during pregnancy. Children of mothers taking steroids had the lowest birth weights, compared to those of IBD mothers taking 5ASAs or immunomodulators. Maternal IBD affects pregnancy and the offspring's immediate and long-term morbidity, specifically, congenital anomalies and neurodevelopmental problems. Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

A Maternal Low-Fiber Diet Predisposes Offspring to Improved Metabolic Phenotypes in Adulthood in an Herbivorous Rodent.

PubMed

Zhang, Xue-Ying; Lou, Mei-Fang; Shen, Wei; Fu, Rong-Shu; Wang, De-Hua

The maternal or paternal dietary composition can have important effects on various aspects of their offspring's physiology. Studies from animal models and humans showed that a maternal high-fiber diet protected offspring against fat accumulation. However, little is known about how a maternal low-fiber diet modifies the metabolism of offspring in herbivorous rodents. We hypothesized that a maternal low-fiber diet would confer long-lasting beneficial effects on offspring metabolic phenotypes in herbivorous Brandt's vole (Lasiopodomys brandtii). Female voles were fed either a control (12.4% fiber) or a low-fiber (3.5% fiber) diet throughout pregnancy and lactation, and all offspring were fed the control diet after weaning till 14 wk old. Offspring were sampled from each litter at 18 d and 14 wk of age. Another subset of adult offspring at 15 wk of age was fed a high-fat diet for 8 wk. We found that there was no difference in litter size, litter mass, or pup mass before weaning between the two maternal diet groups. Offspring from the maternal low-fiber diet increased energy intake, body mass, and lean mass; suppressed fat accumulation; and improved glucose tolerance compared with those from the control diet. Moreover, the maternal low-fiber diet alleviated high-fat diet-induced obesity in the adult offspring. Serum leptin concentration and uncoupling protein 1 content in brown adipose tissue of offspring were not affected by a maternal low-fiber diet. We demonstrate that herbivorous females fed a low-fiber diet during pregnancy and lactation may predispose their offspring to accelerated growth of lean tissue, which may increase the opportunity for survival and reproduction in offspring.

Administration of Non-Absorbable Antibiotics to Pregnant Mice to Perturb the Maternal Gut Microbiota Is Associated with Alterations in Offspring Behavior.

PubMed

Tochitani, Shiro; Ikeno, Takahiro; Ito, Tatsuhito; Sakurai, Asuka; Yamauchi, Tomoki; Matsuzaki, Hideo

2016-01-01

There is increasing evidence that the gut microbiota plays a major role in host health and disease. In this study, we examined whether perturbation of the maternal gut microbiota during pregnancy, induced by administration of non-absorbable antibiotics to pregnant dams, influences the behavior of offspring. Terminal restriction fragment length polymorphism analyses of fecal bacterial composition showed that the relative abundance of the bacterial order Lactobacillales was lower in offspring born from antibiotic-treated dams (20.7 ± 3.4%) than in control offspring (42.1 ± 6.2%) at P24, while the relative abundance of the bacterial family Clostridium subcluster XIVa was higher in offspring born from antibiotic-treated dams (34.2 ± 5.0%) than in control offspring (16.4 ± 3.3%). Offspring born from antibiotic-treated dams exhibited low locomotor activity in both familiar and novel environments, and preferred to explore in the peripheral area of an unfamiliar field at postnatal week 4. At postnatal weeks 7-8, no difference was observed in the level of locomotor activity between control offspring and offspring from antibiotic-treated dams, while the tendency for the offspring from antibiotic-treated dams to be less engaged in exploring the inside area was still observed. The behavioral phenotypes of the offspring from antibiotic-treated dams at postnatal week 4 could be rescued to a considerable extent through fostering of these offspring by normal dams from postnatal day 1. Although the detailed underlying mechanisms are not fully elucidated, the present results suggest that administration of non-absorbable antibiotics to pregnant dams to perturb the maternal gut microbiota during pregnancy leads to alterations in the behavior of their offspring.

Parental longevity and offspring's home blood pressure: the Ohasama study.

PubMed

Watanabe, Yumiko; Metoki, Hirohito; Ohkubo, Takayoshi; Hirose, Takuo; Kikuya, Masahiro; Asayama, Kei; Inoue, Ryusuke; Hara, Azusa; Obara, Taku; Hoshi, Haruhisa; Totsune, Kazuhito; Imai, Yutaka

2010-02-01

Longevity is clustered in particular families. Some studies using conventional blood pressure (BP) reported an association between parental longevity and offspring's BP. No study has used self-measurement of BP at home (home BP). We examined the association between parental longevity and home BP values of adult Japanese offspring. Home and conventional BPs were measured in 1961 residents aged 40 years and over in the general population of Ohasama, Japan. Information about the ages of offspring's parents (age at death or current age) was obtained from a standardized questionnaire. The mean +/- SD values of systolic/diastolic home BP in offspring whose mothers died at less than 69 years of age, at 69-84 years of age, and in offspring whose mothers were alive at age 84 years were 127.4 +/- 13.2/76.2 +/- 9.1, 124.8 +/- 15.0/74.4 +/- 10.0, and 123.4 +/- 15.2/74.4 +/- 10.3 mmHg (P = 0.0002/0.009), respectively. Corresponding values in offspring whose fathers died at less than 66 years of age, at 66-80 years of age, and in offspring whose fathers were alive at age 80 years were 125.7 +/- 15.2/75.6 +/- 10.6, 124.7 +/- 14.1/75.0 +/- 9.2 and 122.4 +/- 14.6/73.6 +/- 9.5 mmHg (P = 0.001/0.003), respectively. Multivariate analysis demonstrated associations that were only weakly observed for conventional BP values (conventional BP: P = 0.3/0.4 for maternal and P = 0.3/0.3 for paternal longevity; home BP: P = 0.05/0.2 for maternal and P = 0.0004/0.007 for paternal longevity). Parental premature death was significantly associated with higher home BP levels in adult offspring, suggesting that parental longevity might be a useful additional marker for screening adult offspring at higher risk of hypertension.

The association between parental history of diagnosed mood/anxiety disorders and psychiatric symptoms and disorders in young adult offspring

PubMed Central

2012-01-01

Background Parental history of mood or anxiety disorders is one of the strongest and most consistent risk factors for the development of these disorders in offspring. Gaps remain however in our knowledge of whether maternal or paternal disorders are more strongly associated with offspring disorders, and whether the association exists in non-clinical samples. This study uses a large population-based sample to test if maternal or paternal history of mood and/or anxiety disorders increases the risk of mood and/or anxiety disorders, or symptoms of specific anxiety disorders, in offspring. Methods Data were drawn from the Nicotine Dependence in Teens Study, a prospective cohort investigation of 1293 grade 7 students. Data on mental health outcomes were collected in mailed self-report questionnaires when participants were aged 20.4 (0.7) years on average. Parental data were collected in mailed self-report questionnaires. This current analysis pertains to 564 participants with maternal and/or paternal data. The association between maternal and paternal history and each of diagnosed anxiety disorder, diagnosed mood disorder, and symptoms of specific anxiety disorders in offspring was studied in multivariate logistic regression. Results A higher proportion of mothers than fathers had a diagnosed mood/anxiety disorder (23% versus 12%). Similarly, 14% of female offspring had a diagnosed mood/anxiety disorder, compared to 6% of male offspring. The adjusted odds ratio (95% confidence interval) for maternal history was 2.2 (1.1, 4.5) for diagnosed mood disorders, 4.0 (2.1, 7.8) for diagnosed anxiety disorders, and 2.2 (1.2, 4.0) for social phobia symptoms. Paternal history was not associated with any of the mental health outcomes in offspring. Conclusion Maternal, but not paternal mood/anxiety disorders were associated with diagnosed psychiatric disorders, as well as symptoms of specific anxiety disorders, in offspring. Efforts to detect mood and anxiety disorders in offspring with a maternal history should be encouraged. PMID:23126640

Aerobic exercise training performed by parents reduces mice offspring adiposity.

PubMed

Romero, Paulo Vitor da Silva; Guariglia, Débora Alves; Da Rocha, Francielli Ferreira; Picoli, Caroline de Carvalho; Gilio, Gustavo Renan; Fabricio, Gabriel Sergio; Mathias, Paulo Cesar de Freitas; Moraes, Solange Marta Franzói de; Peres, Sidney Barnabé

2018-07-01

The present study aimed to determine the effects of physical training performed by parents on mice offspring adiposity. Male and female parents underwent an aerobic training protocol for 7 weeks. The trained and sedentary parents were allowed to mate and the resultant offspring divided in: S (Offspring from Sedentary Parents), T (Offspring from Trained Parents), ST (Offspring from Sedentary Father and Trained Mother) and TS (Offspring from Trained Father and Sedentary Mother). After weaning, offspring was euthanized, blood collected and samples of mesenteric and inguinal fat pads used to isolate adipocytes for morphologic and histological analyses. Lee index, mesenteric fat pad, sum of visceral fat and total fat weight of female T was reduced in comparison to the other groups (p < 0.05). Periepididymal and sum of visceral fat in male T group was also reduced when compared to the other groups (p < 0.05). The diameter of mesenteric and inguinal adipocytes of T group was smaller compared to all groups comparisons for both sexes (p < 0.05). In summary, exercise training performed by parents reduced visceral offspring adiposity, the diameter of subcutaneous adipocytes and improved metabolic parameters associated to metabolic syndrome.

Developmental cigarette smoke exposure II: Hepatic proteome profiles in 6 month old adult offspring.

PubMed

Neal, Rachel E; Chen, Jing; Webb, Cindy; Stocke, Kendall; Gambrell, Caitlin; Greene, Robert M; Pisano, M Michele

2016-10-01

Utilizing a mouse model of 'active' developmental cigarette smoke exposure (CSE) [gestational day (GD) 1 through postnatal day (PD) 21] characterized by offspring low birth weight, the impact of developmental CSE on liver proteome profiles of adult offspring at 6 months of age was determined. Liver tissue was collected from Sham- and CSE-offspring for 2D-SDS-PAGE based proteome analysis with Partial Least Squares-Discriminant Analysis (PLS-DA). A similar study conducted at the cessation of exposure to cigarette smoke documented decreased gluconeogenesis coupled to oxidative stress in weanling offspring. In the current study, exposure throughout development to cigarette smoke resulted in impaired hepatic carbohydrate metabolism, decreased serum glucose levels, and increased gluconeogenic regulatory enzyme abundances during the fed-state coupled to decreased expression of SIRT1 as well as increased PEPCK and PGC1α expression. Together these findings indicate inappropriately timed gluconeogenesis that may reflect impaired insulin signaling in mature offspring exposed to 'active' developmental CSE. Copyright © 2016 Elsevier Inc. All rights reserved.

Motorboat noise impacts parental behaviour and offspring survival in a reef fish.

PubMed

Nedelec, Sophie L; Radford, Andrew N; Pearl, Leanne; Nedelec, Brendan; McCormick, Mark I; Meekan, Mark G; Simpson, Stephen D

2017-06-14

Anthropogenic noise is a pollutant of international concern, with mounting evidence of disturbance and impacts on animal behaviour and physiology. However, empirical studies measuring survival consequences are rare. We use a field experiment to investigate how repeated motorboat-noise playback affects parental behaviour and offspring survival in the spiny chromis ( Acanthochromis polyacanthus ), a brooding coral reef fish. Repeated observations were made for 12 days at 38 natural nests with broods of young. Exposure to motorboat-noise playback compared to ambient-sound playback increased defensive acts, and reduced both feeding and offspring interactions by brood-guarding males. Anthropogenic noise did not affect the growth of developing offspring, but reduced the likelihood of offspring survival; while offspring survived at all 19 nests exposed to ambient-sound playback, six of the 19 nests exposed to motorboat-noise playback suffered complete brood mortality. Our study, providing field-based experimental evidence of the consequences of anthropogenic noise, suggests potential fitness consequences of this global pollutant. © 2017 The Authors.

Giving offspring a head start in life: field and experimental evidence for selection on maternal basking behaviour in lizards.

PubMed

Wapstra, E; Uller, T; While, G M; Olsson, M; Shine, R

2010-03-01

The timing of birth is often correlated with offspring fitness in animals, but experimental studies that disentangle direct effects of parturition date and indirect effects mediated via variation in female traits are rare. In viviparous ectotherms, parturition date is largely driven by female thermal conditions, particularly maternal basking strategies. Our field and laboratory studies of a viviparous lizard (Niveoscincus ocellatus) show that earlier-born offspring are more likely to survive through their first winter and are larger following that winter, than are later-born conspecifics. Thus, the association between parturition date and offspring fitness is causal, rather than reflecting an underlying correlation between parturition date and maternal attributes. Survival selection on offspring confers a significant advantage for increased maternal basking in this species, mediated through fitness advantages of earlier parturition. We discuss the roles of environmentally imposed constraints and parent-offspring conflict in the evolution of maternal effects on parturition date.

Maternal handling during pregnancy reduces DMBA-induced mammary tumorigenesis among female offspring.

PubMed Central

Hilakivi-Clarke, L.

1997-01-01

The present study investigated whether handling of pregnant rats would affect mammary tumorigenesis in their female offspring. Pregnant Sprague-Dawley rats were injected daily with 0.05 ml of vehicle between days 14 and 20 of gestation or were left undisturbed. Handling did not have any effects on pregnancy or early development of the offspring. The female offspring were administered 10 mg of 7,12-dimethylbenz(a)anthracene (DMBA) at the age of 55 days. The rats whose mothers were handled during pregnancy had a significantly reduced mammary tumour incidence when compared with the offspring of non-handled mothers. Thus, on week 18 after DMBA exposure, 15% of the handled offspring had developed mammary tumours, whereas 44% of the non-handled offspring had tumours. No significant differences in the latency to tumour appearance, in the size of the tumours or in their growth rates were noted. Daily handling performed during post-natal days 5 and 20 produced similar data to that obtained for prenatal handling; on week 18 after DMBA exposure, the mammary tumour incidence among the post-natally handled rats was 22% and among the non-handled rats 44%. Possible deviations in hormonal parameters were also studied in adult female rats exposed in utero to handling. The onset of puberty tended to occur later among the handled offspring, but no differences in the uterine wet weights or serum oestradiol levels between the groups were noted. In conclusion, maternal handling reduced the offspring's risk to develop mammary tumours, and this effect was independent of the oestrogenic environment at adulthood. We propose that handling of a pregnant rat reduces mammary tumorigenesis in her offspring by means of changing the morphology of the mammary gland, the pattern of expression of specific genes and/or immune functions. PMID:9231913

Maternal high-sodium intake alters the responsiveness of the renin-angiotensin system in adult offspring.

PubMed

Ramos, Débora R; Costa, Nauilo L; Jang, Karen L L; Oliveira, Ivone B; da Silva, Alexandre A; Heimann, Joel C; Furukawa, Luzia N S

2012-05-22

The goal of the current study was to evaluate the impact of maternal sodium intake during gestation on the systemic and renal renin-angiotensin-aldosterone-system (RAAS) of the adult offspring. Female Wistar rats were fed high- (HSD-8.0% NaCl) or normal-sodium diets (NSD-1.3% NaCl) from 8 weeks of age until the delivery of their first litter. After birth, the offspring received NSD. Tail-cuff blood pressure (TcBP) was measured in the offspring between 6 and 12 weeks of age. At 12 weeks of age, the offspring were subjected to either one week of HSD or low sodium diet (LSD-0.16% NaCl) feeding to evaluate RAAS responsiveness or to acute saline overload to examine sodium excretory function. Plasma (PRA) and renal renin content (RRC), serum aldosterone (ALDO) levels, and renal cortical and medullary renin mRNA expression levels were evaluated at the end of the study. TcBP was higher among dams fed HSD, but no TcBP differences were observed among the offspring. Male offspring, however, exhibited increased TcBP after one week of HSD feeding, and this effect was independent of maternal diet. Increased RAAS responsiveness to the HSD and LSD was also observed in male offspring. The baseline levels of PRA, ALDO, and cortical and medullary renin gene expression were lower but the RRC levels were higher among HSD-fed male offspring (HSDoff). Conversely, female HSDoff showed reduced sodium excretion 4 h after saline overload compared with female NSDoff. High maternal sodium intake is associated with gender-specific changes in RAAS responsiveness among adult offspring. Copyright © 2012 Elsevier Inc. All rights reserved.

Maternal depression in childhood and aggression in young adulthood: evidence for mediation by offspring amygdala-hippocampal volume ratio.

PubMed

Gilliam, Mary; Forbes, Erika E; Gianaros, Peter J; Erickson, Kirk I; Brennan, Lauretta M; Shaw, Daniel S

2015-10-01

There is abundant evidence that offspring of depressed mothers are at increased risk for persistent behavior problems related to emotion regulation, but the mechanisms by which offspring incur this risk are not entirely clear. Early adverse caregiving experiences have been associated with structural alterations in the amygdala and hippocampus, which parallel findings of cortical regions altered in adults with behavior problems related to emotion regulation. This study examined whether exposure to maternal depression during childhood might predict increased aggression and/or depression in early adulthood, and whether offspring amygdala:hippocampal volume ratio might mediate this relationship. Participants were 258 mothers and sons at socioeconomic risk for behavior problems. Sons' trajectories of exposure to maternal depression were generated from eight reports collected prospectively from offspring ages 18 months to 10 years. Offspring brain structure, aggression, and depression were assessed at age 20 (n = 170). Persistent, moderately high trajectories of maternal depression during childhood predicted increased aggression in adult offspring. In contrast, stable and very elevated trajectories of maternal depression during childhood predicted depression in adult offspring. Increased amygdala: hippocampal volume ratios at age 20 were significantly associated with concurrently increased aggression, but not depression, in adult offspring. Offspring amygdala: hippocampal volume ratio mediated the relationship found between trajectories of moderately elevated maternal depression during childhood and aggression in adult offspring. Alterations in the relative size of brain structures implicated in emotion regulation may be one mechanism by which offspring of depressed mothers incur increased risk for the development of aggression. © 2014 Association for Child and Adolescent Mental Health.

Explaining risk for suicidal ideation in adolescent offspring of mothers with depression.

PubMed

Hammerton, G; Zammit, S; Thapar, A; Collishaw, S

2016-01-01

It is well-established that offspring of depressed mothers are at increased risk for suicidal ideation. However, pathways involved in the transmission of risk for suicidal ideation from depressed mothers to offspring are poorly understood. The aim of this study was to examine the contribution of potential mediators of this association, including maternal suicide attempt, offspring psychiatric disorder and the parent-child relationship. Data were utilized from a population-based birth cohort (ALSPAC). Three distinct classes of maternal depression symptoms across the first 11 years of the child's life had already been identified (minimal, moderate, chronic-severe). Offspring suicidal ideation was assessed at age 16 years. Data were analysed using structural equation modelling. There was evidence for increased risk of suicidal ideation in offspring of mothers with chronic-severe depression symptoms compared to offspring of mothers with minimal symptoms (odds ratio 3.04, 95% confidence interval 2.19-4.21). The majority of this association was explained through maternal suicide attempt and offspring psychiatric disorder. There was also evidence for an independent indirect effect via the parent-child relationship in middle childhood. There was no longer evidence of a direct effect of maternal depression on offspring suicidal ideation after accounting for all three mediators. The pattern of results was similar when examining mechanisms for maternal moderate depression symptoms. Findings highlight that suicide prevention efforts in offspring of depressed mothers should be particularly targeted at both offspring with a psychiatric disorder and offspring whose mothers have made a suicide attempt. Interventions aimed at improving the parent-child relationship may also be beneficial.

Prenatal and early postnatal dietary sodium restriction sensitizes the adult rat to amphetamines.

PubMed

McBride, Shawna M; Culver, Bruce; Flynn, Francis W

2006-10-01

Acute sodium deficiency sensitizes adult rats to psychomotor effects of amphetamine. This study determined whether prenatal and early life manipulation of dietary sodium sensitized adult offspring to psychomotor effects of amphetamine (1 or 3 mg/kg ip) in two strains of rats. Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) dams were fed chow containing low NaCl (0.12%; LN), normal NaCl (1%; NN), or high NaCl (4%; HN) throughout breeding, gestation, and lactation. Male offspring were maintained on the test diet for an additional 3 wk postweaning and then fed standard chow thereafter until testing began. Overall, blood pressure (BP), total fluid intake, salt preference, and adrenal gland weight were greater in SHR than in WKY. WKY LN offspring had greater water intake and adrenal gland weight than did WKY NN and HN offspring, whereas WKY HN offspring had increased BP, salt intake, and salt preference compared with other WKY offspring. SHR HN offspring also had increased BP compared with other SHR offspring; all other measures were similar for SHR offspring. The low-dose amphetamine increased locomotor and stereotypical behavior compared with baseline and saline injection in both WKY and SHR offspring. Dietary sodium history affected the rats' psychomotor response to the higher dose of amphetamine. Injections of 3 mg/kg amphetamine in both strains produced significantly more behavioral activity in the LN offspring than in NN and HN offspring. These results show that early life experience with low-sodium diets produce long-term changes in adult rats' behavioral responses to amphetamine.

Effects of maternal cortisol treatment on offspring size, responses to stress, and anxiety-related behavior in wild largemouth bass (Micropterus salmoides).

PubMed

Redfern, Julia C; Cooke, Steven J; Lennox, Robert J; Nannini, Michael A; Wahl, David H; Gilmour, Kathleen M

2017-10-15

Cortisol, the main glucocorticoid stress hormone in teleost fish, is of interest as a mediator of maternal stress on offspring characteristics because it plays an organizational role during early development. The present study tested the hypothesis that maternal exposure to cortisol treatment prior to spawn affects offspring phenotype using wild largemouth bass (Micropterus salmoides). Baseline and stress-induced cortisol concentrations, body size (i.e. length and mass), and behavior (i.e. anxiety, exploration, boldness, and aggression) were assessed at different offspring life-stages and compared between offspring of control and cortisol-treated females. Cortisol administration did not affect spawning success or timing, nor were whole-body cortisol concentrations different between embryos from cortisol-treated and control females. However, maternal cortisol treatment had significant effects on offspring stress responsiveness, mass, and behavior. Compared to offspring of control females, offspring of cortisol-treated females exhibited larger mass right after hatch, and young-of-the-year mounted an attenuated cortisol response to an acute stressor, and exhibited less thigmotaxic anxiety, exploratory behavior, boldness and aggression. Thus, offspring phenotype was affected by elevated maternal cortisol levels despite the absence of a significant increase in embryo cortisol concentrations, suggesting that a mechanism other than the direct deposition of cortisol into eggs mediates effects on offspring. The results of the present raise questions about the mechanisms through which maternal stress influences offspring behavior and physiology, as well as the impacts of such phenotypic changes on offspring fitness. Copyright © 2017 Elsevier Inc. All rights reserved.

Subclinical and clinical correlates of left ventricular wall motion abnormalities in the community.

PubMed

Tsao, Connie W; Gona, Philimon; Salton, Carol; Danias, Peter G; Blease, Susan; Hoffmann, Udo; Fox, Caroline S; Albert, Mark; Levy, Daniel; O'Donnell, Christopher J; Manning, Warren J; Yeon, Susan B

2011-03-15

The prevalence and clinical correlates of left ventricular (LV) wall motion abnormalities (WMAs), associated with morbidity and mortality, have not been well-characterized in the population. Framingham Heart Study Offspring Cohort participants (n = 1,794, 844 men, age 65 ± 9 years) underwent cine cardiovascular magnetic resonance for evaluation of LV function. A subset (n = 1,009, 460 men) underwent cardiac multidetector computed tomography for analysis of coronary artery calcium. The presence of coronary heart disease and heart failure (CHD-HF) were assessed in relation to the presence of WMAs. WMAs were present in 117 participants (6.5%) and were associated with male gender, elevated hemoglobin A1c, LV mass, LV end-diastolic volume, and lower LV ejection fraction. Of the 1,637 participants without CHD-HF, 68 (4.2%) had WMAs. In this group, WMAs were associated with obesity, hypertension, and Framingham coronary heart disease risk score in the age- and gender-adjusted analyses and were associated with male gender and hypertension on multivariate analysis. Most subjects with WMAs were in the greatest coronary artery calcium groups. The presence of coronary artery calcium greater than the seventy-fifth percentile and Agatston score >100 were associated with a greater than twofold risk of WMAs in the age- and gender-adjusted analysis but were no longer significant when additionally adjusted for CHD-HF. Previous Q-wave myocardial infarction was present in 29% of the 117 participants with WMAs. In conclusion, in the present longitudinally followed free-living population, 4.2% of the participants without CHD-HF had WMAs. WMAs were associated with the clinical parameters associated with cardiovascular disease risk. Aggressive risk factor modification may be prudent for subjects with WMAs, particularly those free of clinical CHD-HF. Copyright © 2011 Elsevier Inc. All rights reserved.

Hair Mercury Concentrations in Western Hudson Bay Polar Bear Family Groups.

PubMed

Bechshoft, Thea; Derocher, Andrew E; Richardson, Evan; Lunn, Nicholas J; St Louis, Vincent L

2016-05-17

Methylmercury is one of the more toxic forms of mercury (Hg), the biomagnification of which is prevalent in the Arctic where apex predators such as polar bears (Ursus maritimus) can carry high loads. The maternal transfer of contaminants to offspring is a concern, as offspring may be particularly sensitive to the effects of environmental pollutants during early development. However, few studies of polar bears report on Hg in dependent young. We examined hair total Hg (THg) concentrations in 24 polar bear family groups in western Hudson Bay: mother, cub-of-the-year (COY), yearling, and 2 year old. THg concentrations increased with bear age, with COYs having lower concentrations than other offspring groups (p ≤ 0.008). Using AICc-based regression models, we found maternal THg to be positively related to body condition and litter size, while overall offspring THg was positively related to maternal body condition in addition to being dependent on the sex and age of the offspring. COY THg concentrations were positively related to maternal THg while also depending on the sex of the offspring. Considering our results, future studies in polar bear ecotoxicology are encouraged to include offspring of different ages and sexes.

Risk factor differences in calcified and noncalcified aortic plaque: the Framingham Heart Study.

PubMed

Chuang, Michael L; Gona, Philimon; Oyama-Manabe, Noriko; Manders, Emily S; Salton, Carol J; Hoffmann, Udo; Manning, Warren J; O'Donnell, Christopher J

2014-07-01

The objective of this study was to determine the prevalence and risk factor (RF) correlates of aortic plaque (AP) detected by cardiovascular magnetic resonance (CMR), which mainly shows noncalcified plaques, and by noncontrast computed tomography (CT), which best depicts calcified plaques, in community-dwelling adults. A total of 1016 Framingham Heart Study Offspring cohort members (64 ± 9 years; 474 men) underwent CMR and CT of the aorta. Potential RFs for AP (age; sex; body mass index; blood pressure; low-density lipoprotein and high-density lipoprotein cholesterol; fasting glucose; C-reactive protein; prevalent hypertension, diabetes mellitus, smoking; use of antihypertensive, diabetes mellitus, or lipid-lowering drugs) were compared between participants, with zero versus nonzero AP by CMR and by CT. Candidate RFs attaining P<0.05 for difference with either imaging modality were entered into multivariable logistic regression models adjusting for age, sex, and other RFs. Odds ratios were calculated for modality-specific prevalence of AP. Associations between RFs and continuous measures of AP were assessed using Tobit regression. Prevalence of CMR and CT AP was 49% and 82%, respectively. AP burdens by CMR and CT were correlated, r=0.28, P<0.0001. Increasing age and smoking were associated with prevalent AP by both CMR and CT. Additionally, prevalent AP by CMR was associated with female sex and fasting glucose and prevalent AP by CT with hypertension treatment and adverse lipid profile. AP by CMR and CT are both associated with smoking and increasing age, but other RFs differ between calcified and noncalcified AP. The relative predictive value of AP detected by CMR versus by CT for incident cardiovascular events remains to be determined. © 2014 American Heart Association, Inc.

Left Ventricular Structure and Risk of Cardiovascular Events: A Framingham Heart Study Cardiac Magnetic Resonance Study

PubMed Central

Tsao, Connie W; Gona, Philimon N; Salton, Carol J; Chuang, Michael L; Levy, Daniel; Manning, Warren J; O’Donnell, Christopher J

2015-01-01

Background Elevated left ventricular mass index (LVMI) and concentric left ventricular (LV) remodeling are related to adverse cardiovascular disease (CVD) events. The predictive utility of LV concentric remodeling and LV mass in the prediction of CVD events is not well characterized. Methods and Results Framingham Heart Study Offspring Cohort members without prevalent CVD (n=1715, 50% men, aged 65±9 years) underwent cardiovascular magnetic resonance for LVMI and geometry (2002–2006) and were prospectively followed for incident CVD (myocardial infarction, coronary insufficiency, heart failure, stroke) or CVD death. Over 13 808 person-years of follow-up (median 8.4, range 0.0 to 10.5 years), 85 CVD events occurred. In multivariable-adjusted proportional hazards regression models, each 10-g/m2 increment in LVMI and each 0.1 unit in relative wall thickness was associated with 33% and 59% increased risk for CVD, respectively (P=0.004 and P=0.009, respectively). The association between LV mass/LV end-diastolic volume and incident CVD was borderline significant (P=0.053). Multivariable-adjusted risk reclassification models showed a modest improvement in CVD risk prediction with the incorporation of cardiovascular magnetic resonance LVMI and measures of LV concentricity (C-statistic 0.71 [95% CI 0.65 to 0.78] for the model with traditional risk factors only, improved to 0.74 [95% CI 0.68 to 0.80] for the risk factor model additionally including LVMI and relative wall thickness). Conclusions Among adults free of prevalent CVD in the community, greater LVMI and LV concentric hypertrophy are associated with a marked increase in adverse incident CVD events. The potential benefit of aggressive primary prevention to modify LV mass and geometry in these adults requires further investigation. PMID:26374295

Cross-Sectional Associations of Flow Reversal, Vascular Function, and Arterial Stiffness in the Framingham Heart Study.

PubMed

Bretón-Romero, Rosa; Wang, Na; Palmisano, Joseph; Larson, Martin G; Vasan, Ramachandran S; Mitchell, Gary F; Benjamin, Emelia J; Vita, Joseph A; Hamburg, Naomi M

2016-12-01

Experimental studies link oscillatory flow accompanied by flow reversal to impaired endothelial cell function. The relation of flow reversal with vascular function and arterial stiffness remains incompletely defined. We measured brachial diastolic flow patterns along with vasodilator function in addition to tonometry-based central and peripheral arterial stiffness in 5708 participants (age 47±13 years, 53% women) in the Framingham Heart Study Offspring and Third Generation cohorts. Brachial artery diastolic flow reversal was present in 35% of the participants. In multivariable regression models, the presence of flow reversal was associated with lower flow-mediated dilation (3.9±0.2 versus 5.0±0.2%; P<0.0001) and reactive hyperemic flow velocity (50±0.99 versus 57±0.93 cm/s; P<0.0001). The presence of flow reversal (compared with absence) was associated with higher central aortic stiffness (carotid-femoral pulse wave velocity 9.3±0.1 versus 8.9±0.1 m/s), lower muscular artery stiffness (carotid-radial pulse wave velocity 9.6±0.1 versus 9.8±0.1 m/s), and higher forearm vascular resistance (5.32±0.03 versus 4.66±0.02 log dyne/s/cm 5 ; P<0.0001). The relations of diastolic flow velocity with flow-mediated dilation, aortic stiffness, and forearm vascular resistance were nonlinear, with a steeper decline in vascular function associated with increasing magnitude of flow reversal. In our large, community-based sample, brachial artery flow reversal was common and associated with impaired vasodilator function and higher aortic stiffness. Our findings are consistent with the concept that flow reversal may contribute to vascular dysfunction. © 2016 American Heart Association, Inc.

Relations of Arterial Stiffness and Brachial Flow-Mediated Dilation With New-Onset Atrial Fibrillation: The Framingham Heart Study.

PubMed

Shaikh, Amir Y; Wang, Na; Yin, Xiaoyan; Larson, Martin G; Vasan, Ramachandran S; Hamburg, Naomi M; Magnani, Jared W; Ellinor, Patrick T; Lubitz, Steven A; Mitchell, Gary F; Benjamin, Emelia J; McManus, David D

2016-09-01

The relations of measures of arterial stiffness, pulsatile hemodynamic load, and endothelial dysfunction to atrial fibrillation (AF) remain poorly understood. To better understand the pathophysiology of AF, we examined associations between noninvasive measures of vascular function and new-onset AF. The study sample included participants aged ≥45 years from the Framingham Heart Study offspring and third-generation cohorts. Using Cox proportional hazards regression models, we examined relations between incident AF and tonometry measures of arterial stiffness (carotid-femoral pulse wave velocity), wave reflection (augmentation index), pressure pulsatility (central pulse pressure), endothelial function (flow-mediated dilation), resting brachial arterial diameter, and hyperemic flow. AF developed in 407/5797 participants in the tonometry sample and 270/3921 participants in the endothelial function sample during follow-up (median 7.1 years, maximum 10 years). Higher augmentation index (hazard ratio, 1.16; 95% confidence interval, 1.02-1.32; P=0.02), baseline brachial artery diameter (hazard ratio, 1.20; 95% confidence interval, 1.01-1.43; P=0.04), and lower flow-mediated dilation (hazard ratio, 0.79; 95% confidence interval, 0.63-0.99; P=0.04) were associated with increased risk of incident AF. Central pulse pressure, when adjusted for age, sex, and hypertension (hazard ratio, 1.14; 95% confidence interval, 1.02-1.28; P=0.02) was associated with incident AF. Higher pulsatile load assessed by central pulse pressure and greater apparent wave reflection measured by augmentation index were associated with increased risk of incident AF. Vascular endothelial dysfunction may precede development of AF. These measures may be additional risk factors or markers of subclinical cardiovascular disease associated with increased risk of incident AF. © 2016 American Heart Association, Inc.

Relationship Between Central and Peripheral Atherosclerosis and Left Ventricular Dysfunction in a Community Population

PubMed Central

Tsao, Connie W.; Gona, Philimon; Salton, Carol; Murabito, Joanne M.; Oyama, Noriko; Danias, Peter G.; O’Donnell, Christopher J.; Manning, Warren J.; Yeon, Susan B.

2011-01-01

We aimed to determine the relationships between resting left ventricular (LV) wall motion abnormalities (WMAs), aortic plaque, and PAD in a community cohort. 1726 Framingham Heart Study Offspring Cohort participants (806 males, 65±9 years) underwent cardiovascular magnetic resonance with quantification of aortic plaque volume and assessment of regional LV systolic function. Claudication, lower extremity revascularization, and ankle-brachial index (ABI) were recorded at Examination 7. WMAs were associated with greater aortic plaque burden, decreased ABI, and claudication in age- and sex-adjusted analyses (all p<0.001), which were not significant after adjustment for cardiovascular risk factors. In age- and sex-adjusted analyses, both the presence (p<0.001) and volume of aortic plaque were associated with decreased ABI (p<0.001). After multivariable adjustment, ABI≤0.9 or prior revascularization was associated with a three-fold odds of aortic plaque (p=0.0083). Plaque volume significantly increased with decreasing ABI in multivariable-adjusted analyses (p<0.0001). In this free-living population, associations of WMAs with aortic plaque burden and clinical measures of PAD were attenuated after adjustment for coronary heart disease risk factors. Aortic plaque volume and ABI remained strongly negatively correlated after multivariable adjustment. Our findings suggest that the association between coronary heart disease and non-coronary atherosclerosis is explained by cardiovascular risk factors. Aortic atherosclerosis and PAD remain strongly associated after multivariable adjustment suggesting shared mechanisms beyond those captured by traditional risk factors. PMID:21708875

Sexual conflict and consistency of offspring desertion in Eurasian penduline tit Remiz pendulinus.

PubMed

Pogány, Akos; Szentirmai, István; Komdeur, Jan; Székely, Tamás

2008-09-01

The trade-off between current and future parental investment is often different between males and females. This difference may lead to sexual conflict between parents over care provisioning in animals that breed with multiple mates. One of the most obvious manifestations of sexual conflict over care is offspring desertion whereby one parent deserts the young to increase its reproductive success at the expense of its mate. Offspring desertion is a wide-spread behavior, and its frequency often varies within populations. We studied the consistency of offspring desertion in a small passerine bird, the Eurasian penduline tit Remiz pendulinus, that has an extremely variable breeding system. Both males and females are sequentially polygamous, and a single parent (either the male or the female) incubates the eggs and rears the young. About 28-40% of offspring are abandoned by both parents, and these offspring perish. Here we investigate whether the variation in offspring desertion in a population emerges either by each individual behaving consistently between different broods, or it is driven by the environment. Using a three-year dataset from Southern Hungary we show that offspring desertion by females is consistent between nests. Male desertion, however, depends on ambient environment, because all males desert their nests early in the season and some of them care late in the season. Therefore, within-population variation in parental care emerges by sexually different mechanisms; between-individual variation was responsible for the observed pattern of offspring desertion in females, whereas within-individual variation was responsible for the observed pattern in males. To our knowledge, our study is the first that investigates repeatability of offspring desertion behavior in nature. The contrasting strategies of the sexes imply complex evolutionary trajectories in breeding behavior of penduline tits. Our results raise an intriguing question whether the sexual difference in caring/deserting decisions explain the extreme intensity of sexual conflict in penduline tits that produces a high frequency of biparentally deserted (and thus wasted) offspring.

Maternal lipopolysaccharide exposure results in glucose metabolism disorders and sex hormone imbalance in male offspring.

PubMed

Zhao, Mei; Yuan, Li; Yuan, Man-Man; Huang, Li-Li; Su, Chang; Chen, Yuan-Hua; Yang, Yu-Ying; Hu, Yan; Xu, De-Xiang

2018-04-01

An adverse intrauterine environment may be an important factor contributing to the development of type 2 diabetes in later life. The present study investigated the longitudinal effects of maternal lipopolysaccharide (LPS) exposure during the third trimester on glucose metabolism and sex hormone balance in the offspring. Pregnant mice were intraperitoneally injected with LPS (50 μg/kg) daily from gestational day (GD) 15 to GD17. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were assessed at postnatal day (PND) 60 and PND120. Sex hormones, their receptors, and metabolic enzymes (aromatase) were measured in male offspring at different phases of development (PND14: juvenile; PND35: adolescence; PND60: adulthood; and PND120: middle age). LPS-exposed male offspring exhibited glucose intolerance and insulin resistance by GTT and ITT at middle age, accompanied by an increase in fasting blood glucose and reductions in serum insulin levels and hepatic phosphorylated (p) -AKT/AKT ratio. However, glucose intolerance and insulin resistance were not observed in LPS-exposed female offspring. Maternal LPS exposure upregulated hepatic aromatase proteins and mRNA levels in male offspring at all time points. At adolescence, the testosterone/estradiol ratio (T/E2) was markedly reduced in LPS-exposed male offspring. Moreover, maternal LPS exposure significantly increased hepatic estrogen receptor (ER) α expressions and decreased hepatic androgen receptor (AR) expressions in male offspring. At adulthood, maternal LPS exposure increased serum estradiol levels, decreased serum testosterone levels and elevated hepatic ERβ expressions in male offspring. In conclusion, maternal LPS exposure upregulated aromatase expressions, followed by a reduction in the T/E2 ratio and an alteration in sex hormone receptor activity, which might be involved in the development of glucose metabolism disorders in middle-aged male offspring. This study provides a novel clue and direction to clarify the pathogenesis of maternal infection-related diabetes in male offspring. Copyright © 2018 Elsevier B.V. All rights reserved.

Sexual conflict and consistency of offspring desertion in Eurasian penduline tit Remiz pendulinus

PubMed Central

2008-01-01

Background The trade-off between current and future parental investment is often different between males and females. This difference may lead to sexual conflict between parents over care provisioning in animals that breed with multiple mates. One of the most obvious manifestations of sexual conflict over care is offspring desertion whereby one parent deserts the young to increase its reproductive success at the expense of its mate. Offspring desertion is a wide-spread behavior, and its frequency often varies within populations. We studied the consistency of offspring desertion in a small passerine bird, the Eurasian penduline tit Remiz pendulinus, that has an extremely variable breeding system. Both males and females are sequentially polygamous, and a single parent (either the male or the female) incubates the eggs and rears the young. About 28–40% of offspring are abandoned by both parents, and these offspring perish. Here we investigate whether the variation in offspring desertion in a population emerges either by each individual behaving consistently between different broods, or it is driven by the environment. Results Using a three-year dataset from Southern Hungary we show that offspring desertion by females is consistent between nests. Male desertion, however, depends on ambient environment, because all males desert their nests early in the season and some of them care late in the season. Therefore, within-population variation in parental care emerges by sexually different mechanisms; between-individual variation was responsible for the observed pattern of offspring desertion in females, whereas within-individual variation was responsible for the observed pattern in males. Conclusion To our knowledge, our study is the first that investigates repeatability of offspring desertion behavior in nature. The contrasting strategies of the sexes imply complex evolutionary trajectories in breeding behavior of penduline tits. Our results raise an intriguing question whether the sexual difference in caring/deserting decisions explain the extreme intensity of sexual conflict in penduline tits that produces a high frequency of biparentally deserted (and thus wasted) offspring. PMID:18761745

Helpers benefit offspring in both the short and long-term in the cooperatively breeding banded mongoose.

PubMed

Hodge, Sarah J

2005-12-07

Helpers in cooperative and communal breeding species are thought to accrue fitness benefits through improving the condition and survival of the offspring that they care for, yet few studies have shown conclusively that helpers benefit the offspring they rear. Using a novel approach to control for potentially confounding group-specific variables, I compare banded mongoose (Mungos mungo) offspring within the same litter that differ in the amount of time they spend with a helper, and hence the amount of care they receive. I show that pups that spend more time in close proximity to a helper are fed more, grow faster and have a higher probability of survival to independence than their littermates. Moreover, high growth rates during development reduce the age at which females breed for the first time, suggesting that helpers can improve the future fecundity of the offspring for which they care. These results provide strong evidence that it is the amount of investment per se that benefits offspring, rather than some correlate such as territory quality, and validate the assumption that helpers improve the reproductive success of breeders, and hence may gain fitness benefits from their actions. Furthermore, the finding that helpers may benefit offspring in the long-term suggests that current studies underestimate the fitness benefits that helpers gain from rearing the offspring of others.

Maternal PTSD associates with greater glucocorticoid sensitivity in offspring of Holocaust survivors.

PubMed

Lehrner, Amy; Bierer, Linda M; Passarelli, Vincent; Pratchett, Laura C; Flory, Janine D; Bader, Heather N; Harris, Iris R; Bedi, Aarti; Daskalakis, Nikolaos P; Makotkine, Iouri; Yehuda, Rachel

2014-02-01

Intergenerational effects of trauma have been observed clinically in a wide range of populations, and parental PTSD has been associated with an increased risk for psychopathology in offspring. In studies of Holocaust survivor offspring, parental PTSD, and particularly maternal PTSD, has been associated with increased risk for PTSD, low basal urinary cortisol excretion and enhanced cortisol suppression in response to dexamethasone. Such findings implicate maternally derived glucocorticoid programming in the intergenerational transmission of trauma-related consequences, potentially resulting from in utero influences or early life experiences. This study investigated the relative influence of Holocaust exposure and PTSD in mothers and fathers on glucocorticoid sensitivity in offspring. Eighty Holocaust offspring and 15 offspring of non-exposed Jewish parents completed evaluations and provided blood and urine samples. Glucocorticoid sensitivity was evaluated using the lysozyme suppression test (LST), an in vitro measure of glucocorticoid receptor sensitivity in a peripheral tissue, the dexamethasone suppression test (DST), and 24-h urinary cortisol excretion. Maternal PTSD was associated with greater glucocorticoid sensitivity in offspring across all three measures of glucocorticoid function. An interaction of maternal and paternal PTSD on the DST and 24-h urinary cortisol showed an effect of decreased glucocorticoid sensitivity in offspring with paternal, but not maternal, PTSD. Although indirect, these findings are consistent with the hypothesis that epigenetic programming may be involved in the intergenerational transmission of trauma-related effects on glucocorticoid regulation. Published by Elsevier Ltd.

Maternal PTSD associates with greater glucocorticoid sensitivity in offspring of Holocaust survivors

PubMed Central

Lehrner, Amy; Bierer, Linda M.; Passarelli, Vincent; Pratchett, Laura C.; Flory, Janine D.; Bader, Heather; Harris, Iris R.; Bedi, Aarti; Daskalakis, Nikolaos P.; Makotkine, Iouri; Yehuda, Rachel

2014-01-01

Intergenerational effects of trauma have been observed clinically in a wide range of populations, and parental PTSD has been associated with an increased risk for psychopathology in offspring. In studies of Holocaust survivor offspring, parental PTSD, and particularly maternal PTSD, has been associated with increased risk for PTSD, low basal urinary cortisol excretion and enhanced cortisol suppression in response to dexamethasone. Such findings implicate maternally derived glucocorticoid programming in the intergenerational transmission of trauma-related consequences, potentially resulting from in utero influences or early life experiences. This study investigated the relative influence of Holocaust exposure and PTSD in mothers and fathers on glucocorticoid sensitivity in offspring. Eighty Holocaust offspring and 15 offspring of non-exposed Jewish parents completed evaluations and provided blood and urine samples. Glucocorticoid sensitivity was evaluated using the lysozyme suppression test (LST), an in vitro measure of glucocorticoid receptor sensitivity in a peripheral tissue, the dexamethasone suppression test (DST), and 24 hour urinary cortisol excretion. Maternal PTSD was associated with greater glucocorticoid sensitivity in offspring across all three measures of glucocorticoid function. An interaction of maternal and paternal PTSD on the DST and 24-hr urinary cortisol showed an effect of decreased glucocorticoid sensitivity in offspring with paternal, but not maternal, PTSD. Although indirect, these findings are consistent with the hypothesis that epigenetic programming may be involved in the intergenerational transmission of trauma-related effects on glucocorticoid regulation. PMID:24485493

Coping strategies and self-esteem in the high-risk offspring of bipolar parents.

PubMed

Goodday, Sarah M; Bentall, Richard; Jones, Steven; Weir, Arielle; Duffy, Anne

2018-03-01

This study investigated whether there were differences in coping strategies and self-esteem between offspring of parents with bipolar disorder (high-risk) and offspring of unaffected parents (control), and whether these psychological factors predicted the onset and recurrence of mood episodes. High-risk and control offspring were followed longitudinally as part of the Flourish Canadian high-risk bipolar offspring cohort study. Offspring were clinically assessed annually by a psychiatrist using semi-structured interviews and completed a measure of coping strategies and self-esteem. In high-risk offspring, avoidant coping strategies significantly increased the hazard of a new onset Diagnostic and Statistical Manual of Mental Disorders, 4th Edition twice revised mood episode or recurrence (hazard ratio: 1.89, p = 0.04), while higher self-esteem significantly decreased this hazard (hazard ratio: 2.50, p < 0.01). Self-esteem and avoidant coping significantly interacted with one another ( p < 0.05), where the risk of a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition twice revised new onset mood episode or recurrence was only significantly increased among high-risk offspring with both high avoidant coping and low self-esteem. A reduction of avoidant coping strategies in response to stress and improvement of self-esteem may be useful intervention targets for preventing the new onset or recurrence of a clinically significant mood disorder among individuals at high familial risk.

Altered amygdala-prefrontal response to facial emotion in offspring of parents with bipolar disorder.

PubMed

Manelis, Anna; Ladouceur, Cecile D; Graur, Simona; Monk, Kelly; Bonar, Lisa K; Hickey, Mary Beth; Dwojak, Amanda C; Axelson, David; Goldstein, Benjamin I; Goldstein, Tina R; Bebko, Genna; Bertocci, Michele A; Hafeman, Danella M; Gill, Mary Kay; Birmaher, Boris; Phillips, Mary L

2015-09-01

This study aimed to identify neuroimaging measures associated with risk for, or protection against, bipolar disorder by comparing youth offspring of parents with bipolar disorder versus youth offspring of non-bipolar parents versus offspring of healthy parents in (i) the magnitude of activation within emotional face processing circuitry; and (ii) functional connectivity between this circuitry and frontal emotion regulation regions. The study was conducted at the University of Pittsburgh Medical Centre. Participants included 29 offspring of parents with bipolar disorder (mean age = 13.8 years; 14 females), 29 offspring of non-bipolar parents (mean age = 13.8 years; 12 females) and 23 healthy controls (mean age = 13.7 years; 11 females). Participants were scanned during implicit processing of emerging happy, sad, fearful and angry faces and shapes. The activation analyses revealed greater right amygdala activation to emotional faces versus shapes in offspring of parents with bipolar disorder and offspring of non-bipolar parents than healthy controls. Given that abnormally increased amygdala activation during emotion processing characterized offspring of both patient groups, and that abnormally increased amygdala activation has often been reported in individuals with already developed bipolar disorder and those with major depressive disorder, these neuroimaging findings may represent markers of increased risk for affective disorders in general. The analysis of psychophysiological interaction revealed that offspring of parents with bipolar disorder showed significantly more negative right amygdala-anterior cingulate cortex functional connectivity to emotional faces versus shapes, but significantly more positive right amygdala-left ventrolateral prefrontal cortex functional connectivity to happy faces (all P-values corrected for multiple tests) than offspring of non-bipolar parents and healthy controls. Taken together with findings of increased amygdala-ventrolateral prefrontal cortex functional connectivity, and decreased amygdala-anterior cingulate cortex functional connectivity previously shown in individuals with bipolar disorder, these connectivity patterns in offspring of parents with bipolar disorder may be risk markers for, rather than markers conferring protection against, bipolar disorder in youth. The patterns of activation and functional connectivity remained unchanged after removing medicated participants and those with current psychopathology from analyses. This is the first study to demonstrate that abnormal functional connectivity patterns within face emotion processing circuitry distinguish offspring of parents with bipolar disorder from those of non-bipolar parents and healthy controls. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The relationship between offspring size and fitness: integrating theory and empiricism.

PubMed

Rollinson, Njal; Hutchings, Jeffrey A

2013-02-01

How parents divide the energy available for reproduction between size and number of offspring has a profound effect on parental reproductive success. Theory indicates that the relationship between offspring size and offspring fitness is of fundamental importance to the evolution of parental reproductive strategies: this relationship predicts the optimal division of resources between size and number of offspring, it describes the fitness consequences for parents that deviate from optimality, and its shape can predict the most viable type of investment strategy in a given environment (e.g., conservative vs. diversified bet-hedging). Many previous attempts to estimate this relationship and the corresponding value of optimal offspring size have been frustrated by a lack of integration between theory and empiricism. In the present study, we draw from C. Smith and S. Fretwell's classic model to explain how a sound estimate of the offspring size--fitness relationship can be derived with empirical data. We evaluate what measures of fitness can be used to model the offspring size--fitness curve and optimal size, as well as which statistical models should and should not be used to estimate offspring size--fitness relationships. To construct the fitness curve, we recommend that offspring fitness be measured as survival up to the age at which the instantaneous rate of offspring mortality becomes random with respect to initial investment. Parental fitness is then expressed in ecologically meaningful, theoretically defensible, and broadly comparable units: the number of offspring surviving to independence. Although logistic and asymptotic regression have been widely used to estimate offspring size-fitness relationships, the former provides relatively unreliable estimates of optimal size when offspring survival and sample sizes are low, and the latter is unreliable under all conditions. We recommend that the Weibull-1 model be used to estimate this curve because it provides modest improvements in prediction accuracy under experimentally relevant conditions.

Exercise in obese female rats has beneficial effects on maternal and male and female offspring metabolism

PubMed Central

Vega, Claudia C; Reyes-Castro, Luis A; Bautista, Claudia J; Larrea, Fernando; Nathanielsz, Peter W; Zambrano, Elena

2013-01-01

BACKGROUND Maternal obesity (MO) impairs maternal and offspring health. Mechanisms and interventions to prevent adverse maternal and offspring outcomes need to be determined. Human studies are confounded by socio-economic status providing the rationale for controlled animal data on effects of maternal exercise (MEx) intervention on maternal (F0) and offspring (F1) outcomes in MO. HYPOTHESIS MO produces metabolic and endocrine dysfunction, increases maternal and offspring glucocorticoid exposure, oxidative stress and adverse offspring outcomes by postnatal day (PND) 36. MEx prevents these outcomes. METHODS F0 female rats ate either control or obesogenic diet from weaning through lactation. Half of each group wheel ran (from day ninety of life through pregnancy beginning day 120) providing four groups (n=8/group) – i) controls, ii) obese, iii) exercised controls and iv) exercised obese. After weaning, PND 21, F1 offspring ate a control diet. Metabolic parameters of F0 prepregnancy and end of lactation and F1 offspring at PND 36 were analyzed. RESULTS Exercise did not change maternal weight. Before breeding, MO elevated F0 glucose, insulin, triglycerides, cholesterol, leptin, fat and oxidative stress. Exercise completely prevented the triglyceride rise and partially glucose, insulin, cholesterol and oxidative stress increases. MO decreased fertility, recovered by exercise. At the end of lactation, exercise returned all metabolic variables except leptin to control levels. Exercise partially prevented MO elevated corticosterone. F1 Offspring weights were similar at birth. At PND 36 MO increased F1 male but not female offspring leptin, triglycerides and fat mass. In controls exercise reduced male and female offspring glucose, prevented the offspring leptin increase and partially the triglyceride rise. CONCLUSIONS MEx before and during pregnancy has beneficial effects on maternal and offspring metabolism and endocrine function occurring with no weight change in mothers and offspring indicating the importance of body composition rather than weight in evaluations of metabolic status. PMID:23949616

Sugar-sweetened beverages and prevalence of the metabolically abnormal phenotype in the Framingham Heart Study.

PubMed

Green, Angela K; Jacques, Paul F; Rogers, Gail; Fox, Caroline S; Meigs, James B; McKeown, Nicola M

2014-05-01

The purpose of this study was to examine the relationship between usual sugar-sweetened beverage (SSB) consumption and prevalence of abnormal metabolic health across body mass index (BMI) categories. The metabolic health of 6,842 non-diabetic adults was classified using cross-sectional data from the Framingham Heart Study Offspring (1998-2001) and Third Generation (2002-2005) cohorts. Adults were classified as normal weight, overweight or obese and, within these categories, metabolic health was defined based on five criteria-hypertension, elevated fasting glucose, elevated triglycerides, low HDL cholesterol, and insulin resistance. Individuals without metabolic abnormalities were considered metabolically healthy. Logistic regression was used to examine the associations between categories of SSB consumption and risk of metabolic health after stratification by BMI. Comparing the highest category of SSB consumers (median of 7 SSB per week) to the lowest category (non-consumers), odds ratios (95% confidence intervals) for metabolically abnormal phenotypes, compared to the metabolically normal, were 1.9 (1.1-3.4) among the obese, 2.0 (1.4-2.9) among the overweight, and 1.9 (1.4-2.6) among the normal weight individuals. In this cross-sectional analysis, it is observed that, irrespective of weight status, consumers of SSB were more likely to display metabolic abnormalities compared to non-consumers in a dose-dependent manner. Copyright © 2014 The Obesity Society.

Embryonic caffeine exposure acts via A1 adenosine receptors to alter adult cardiac function and DNA methylation in mice.

PubMed

Buscariollo, Daniela L; Fang, Xiefan; Greenwood, Victoria; Xue, Huiling; Rivkees, Scott A; Wendler, Christopher C

2014-01-01

Evidence indicates that disruption of normal prenatal development influences an individual's risk of developing obesity and cardiovascular disease as an adult. Thus, understanding how in utero exposure to chemical agents leads to increased susceptibility to adult diseases is a critical health related issue. Our aim was to determine whether adenosine A1 receptors (A1ARs) mediate the long-term effects of in utero caffeine exposure on cardiac function and whether these long-term effects are the result of changes in DNA methylation patterns in adult hearts. Pregnant A1AR knockout mice were treated with caffeine (20 mg/kg) or vehicle (0.09% NaCl) i.p. at embryonic day 8.5. This caffeine treatment results in serum levels equivalent to the consumption of 2-4 cups of coffee in humans. After dams gave birth, offspring were examined at 8-10 weeks of age. A1AR+/+ offspring treated in utero with caffeine were 10% heavier than vehicle controls. Using echocardiography, we observed altered cardiac function and morphology in adult mice exposed to caffeine in utero. Caffeine treatment decreased cardiac output by 11% and increased left ventricular wall thickness by 29% during diastole. Using DNA methylation arrays, we identified altered DNA methylation patterns in A1AR+/+ caffeine treated hearts, including 7719 differentially methylated regions (DMRs) within the genome and an overall decrease in DNA methylation of 26%. Analysis of genes associated with DMRs revealed that many are associated with cardiac hypertrophy. These data demonstrate that A1ARs mediate in utero caffeine effects on cardiac function and growth and that caffeine exposure leads to changes in DNA methylation.

Parenting behaviours associated with the development of adaptive and maladaptive offspring personality traits.

PubMed

Johnson, Jeffrey G; Liu, Lydia; Cohen, Patricia

2011-08-01

To investigate the associations of beneficial parenting behaviours with adaptive and maladaptive offspring personality traits that persist into adulthood among individuals in the community. Families (n = 669) participating in the Children in the Community Study were interviewed during the childhood, adolescence, emerging adulthood, and adulthood of the offspring at the mean ages of 6, 14, 16, 22, and 33 years. Twelve types of beneficial maternal and paternal child-rearing behaviour, reported by offspring at the mean age of 16 years, were associated with elevated offspring personality resiliency, at the mean ages of 22 and 33 years, and with low offspring personality disorder trait levels. These longitudinal associations remained significant when histories of childhood behaviour problems and parental psychiatric disorder were controlled statistically. Similar linear (that is, dose-dependent) associations were observed between the number of beneficial parenting behaviours during childhood and adaptive and maladaptive offspring traits at the mean ages of 22 and 33 years. Maternal and paternal behaviours were independently associated with both adaptive and maladaptive offspring traits. Beneficial maternal and paternal child-rearing behaviours may promote the development of adaptive offspring personality traits that endure into adulthood, and they may be prospectively associated with reduced levels of maladaptive offspring traits. These associations may not be attributable to childhood behaviour problems or parental psychiatric disorders, and they may be equally evident during early and middle adulthood.

High dietary fat intake during lactation promotes development of diet-induced obesity in male offspring of mice.

PubMed

Tsuduki, Tsuyoshi; Kitano, Yasuna; Honma, Taro; Kijima, Ryo; Ikeda, Ikuo

2013-01-01

The maternal nutritional status during pregnancy and lactation influences the risk of obesity in offspring, but the details of this phenomenon are unclear. In particular, there is little information on the influence on the offspring of the maternal nutritional status during lactation only. Therefore, in this study, we examined the influence of high dietary fat intake in dams during lactation on the risk of obesity in offspring, using C57BL/6J mice. The mice were fed a control diet (CD) during pregnancy. After birth, dams were fed a CD or a high-fat diet (HD) during lactation (3 wk). Fat and energy were significantly increased in milk from dams fed a HD during lactation. Male offspring were weaned at 3 wk old and fed a CD for 4 wk, which resulted in no significant difference in their physique. Four weeks after weaning, the offspring (7 wk old) were fed a CD or HD for 4 wk to induce obesity. High dietary fat intake in dams and offspring promoted lipid accumulation in white adipose tissue and adipocyte hypertrophy in male offspring. The underlying mechanism may involve an increase in expression of Lpl and a decrease in expression of Hsl in white adipose tissue of offspring. In conclusion, our results show that high dietary fat intake during lactation promotes development of diet-induced obesity in male offspring.

Maternal exercise during pregnancy promotes physical activity in adult offspring

USDA-ARS?s Scientific Manuscript database

Previous rodent studies have shown that maternal voluntary exercise during pregnancy leads to metabolic changes in adult offspring. We set out to test whether maternal voluntary exercise during pregnancy also induces persistent changes in voluntary physical activity in the offspring. Adult C57BL/6J ...

Paternal Body Mass Index (BMI) Is Associated with Offspring Intrauterine Growth in a Gender Dependent Manner

PubMed Central

Chen, You-Peng; Xiao, Xiao-Min; Li, Jian; Reichetzeder, Christoph; Wang, Zi-Neng; Hocher, Berthold

2012-01-01

Background Environmental alternations leading to fetal programming of cardiovascular diseases in later life have been attributed to maternal factors. However, animal studies showed that paternal obesity may program cardio-metabolic diseases in the offspring. In the current study we tested the hypothesis that paternal BMI may be associated with fetal growth. Methods and Results We analyzed the relationship between paternal body mass index (BMI) and birth weight, ultrasound parameters describing the newborn's body shape as well as parameters describing the newborns endocrine system such as cortisol, aldosterone, renin activity and fetal glycated serum protein in a birth cohort of 899 father/mother/child triplets. Since fetal programming is an offspring sex specific process, male and female offspring were analyzed separately. Multivariable regression analyses considering maternal BMI, paternal and maternal age, hypertension during pregnancy, maternal total glycated serum protein, parity and either gestational age (for birth weight) or time of ultrasound investigation (for ultrasound parameters) as confounding showed that paternal BMI is associated with growth of the male but not female offspring. Paternal BMI correlated with birth parameters of male offspring only: birth weight; biparietal diameter, head circumference; abdominal diameter, abdominal circumference; and pectoral diameter. Cortisol was likewise significantly correlated with paternal BMI in male newborns only. Conclusions Paternal BMI affects growth of the male but not female offspring. Paternal BMI may thus represent a risk factor for cardiovascular diseases of male offspring in later life. It remains to be demonstrated whether this is linked to an offspring sex specific paternal programming of cortisol secretion. PMID:22570703

Gestational weight gain and the risk of offspring obesity at 10 and 16 years: a prospective cohort study in low-income women.

PubMed

Diesel, J C; Eckhardt, C L; Day, N L; Brooks, M M; Arslanian, S A; Bodnar, L M

2015-09-01

To study the association between gestational weight gain (GWG) and offspring obesity risk at ages chosen to approximate prepuberty (10 years) and postpuberty (16 years). Prospective pregnancy cohort. Pittsburgh, PA, USA. Low-income pregnant women (n = 514) receiving prenatal care at an obstetric residency clinic and their singleton offspring. Gestational weight gain was classified based on maternal GWG-for-gestational-age Z-score charts and was modelled using flexible spline terms in modified multivariable Poisson regression models. Obesity at 10 or 16 years, defined as body mass index (BMI) Z-scores ≥95th centile of the 2000 CDC references, based on measured height and weight. The prevalence of offspring obesity was 20% at 10 years and 22% at 16 years. In the overall sample, the risk of offspring obesity at 10 and 16 years increased when GWG exceeded a GWG Z-score of 0 SD (equivalent to 30 kg at 40 weeks); but for gains below a Z-score of 0 SD there was no relationship with child obesity risk. The association between GWG and offspring obesity varied by prepregnancy BMI. Among mothers with a pregravid BMI <25 kg/m(2) , the risk of offspring obesity increased when GWG Z-score exceeded 0 SD, yet among overweight women (BMI ≥25 kg/m(2) ), there was no association between GWG Z-scores and offspring obesity risk. Among lean women, higher GWG may have lasting effects on offspring obesity risk. © 2015 Royal College of Obstetricians and Gynaecologists.

Facial emotion labeling in unaffected offspring of adults with bipolar I disorder.

PubMed

Sharma, Aditya Narain; Barron, Evelyn; Le Couteur, James; Close, Andrew; Rushton, Steven; Grunze, Heinz; Kelly, Thomas; Nicol Ferrier, Ian; Le Couteur, Ann Simone

2017-01-15

Young people 'at risk' for developing Bipolar Disorder have been shown to have deficits in facial emotion labeling across emotions with some studies reporting deficits for one or more particular emotions. However, these have included a heterogeneous group of young people (siblings of adolescents and offspring of adults with bipolar disorder), who have themselves diagnosed psychopathology (mood disorders and neurodevelopmental disorders including ADHD). 24 offspring of adults with bipolar I disorder and 34 offspring of healthy controls were administered the Diagnostic Analysis of Non Verbal Accuracy 2 (DANVA 2) to investigate the ability of participants to correctly label 4 emotions: happy, sad, fear and anger using both child and adult faces as stimuli at low and high intensity. Mixed effects modelling revealed that the offspring of adults with bipolar I disorder made more errors in both the overall recognition of facial emotions and the specific recognition of fear compared with the offspring of healthy controls. Further more errors were made by offspring that were male, younger in age and also in recognition of emotions using 'child' stimuli. The sample size, lack of blinding of the study team and the absence of any stimuli that assess subjects' response to a neutral emotional stimulus are limitations of the study. Offspring (with no history of current or past psychopathology or psychotropic medication) of adults with bipolar I disorder displayed facial emotion labeling deficits (particularly fear) suggesting facial emotion labeling may be an endophenotype for bipolar disorder. Copyright © 2016 Elsevier B.V. All rights reserved.

Family dissolution and offspring depression and depressive symptoms: A systematic review of moderation effects.

PubMed

Di Manno, Laura; Macdonald, Jacqui A; Knight, Tess

2015-12-01

Parental separation is associated with increased risk for offspring depression; however, depression outcomes are divergent. Knowledge of moderators could assist in understanding idiosyncratic outcomes and developing appropriately targeted prevention programs for those at heightened risk of depression following parental separation. Therefore, the objective of the review was to identify and evaluate studies that examined moderators of the relationship between parental separation and offspring depression A search of scientific, medical and psychological databases was conducted in April 2015 for longitudinal research that had evaluated any moderator/s of the relationship between parental separation or divorce and offspring depression or depressive symptoms. Papers were assessed for quality by evaluating the study's sample, attrition rates, methodology and measurement characteristics. Fourteen quantitative studies from five countries assessed sixteen moderating factors of the relationship between parental separation and offspring depression or depressive symptoms. A number of factors were found to moderate this relationship, including offspring gender, age (at assessment and at depression onset), genotype, preadolescent temperament, IQ, emotional problems in childhood and maternal sensitivity. While robust longitudinal research was selected for inclusion, common issues with longitudinal studies such as low rates of participation and attrition were among the methodological concerns evident in some of the reviewed papers. The current review is the first to assess interaction effects of the relationship between parental separation and offspring depression or depressive symptoms. While further research is recommended, this assessment is critical in understanding variation in heterogeneous populations and can inform targeted policy and prevention.

Maternal infection during late pregnancy increases anxiety- and depression-like behaviors with increasing age in male offspring.

PubMed

Enayati, Mohsen; Solati, Jalal; Hosseini, Mohammad-Hassan; Shahi, Hamid-Reza; Saki, Golshid; Salari, Ali-Akbar

2012-02-10

Scientific reports suggest that the exposure to long-term stressors throughout or during late gestation increase anxiety- and depression-like behaviors of offspring in their later life. Moreover, several studies concluded that increasing age correlates with increased anxiety behaviors in humans and rodents. In the present study, we assessed the effects of prenatally administration of equal lipopolysaccharide (LPS) doses in various points of late gestation (days 15, 16, and 17) period, on neuroendocrine and immunological responses of pregnant mice, and subsequent long-lasting consequences of anxiety and depression with increasing age in male offspring at postnatal days (PD) 40 and 80. Four hours after the LPS injection, levels of corticosterone (COR) and pro-inflammatory cytokines (PIC) in pregnant mice, as compared to the control dams, were increased significantly. Furthermore, maternal inflammation raised the levels of COR, anxiety- and depression-like behaviors with increasing age in male offspring in comparison with saline male offspring. These data support other studies demonstrating that maternal stress increases the levels of anxiety and depression in offspring. Additionally, our data confirm other findings indicating that increasing age correlates with increased anxiety or depression behaviors in humans and rodents. Findings of this study suggest that time course of an inflammation response or stressor application during various stages of gestation and ages of offspring are important factors for assessing neuropsychiatric disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

[Study of genome instability using DNA fingerprinting of the offspring of male mice subjected to chronic low dose gamma irradiation].

PubMed

Bezlepkin, V G; Vasil'eva, G V; Lomaeva, M G; Sirota, N P; Gaziev, A I

2000-01-01

By a polymerase chain reaction with an arbitrary primer (AP-PCR), the possibility of transmission of genome instability to somatic cells of the offspring (F1 generation) from male parents of mice exposed to chronic low-level gamma-radiation was studied. Male BALB/c mice 15 days after exposure to 10-50 cGy were mated with unirradiated females. Biopsies were taken from tale tips of two month-old offspring mice and DNA was isolated. The primer in the AP-PCR was a 20-mer oligonucleotide flanking the microsatellite locus Atp1b2 on chromosome 11 of the mouse. A comparative analysis of individual fingerprints of AP-PCR products on DNA-templates from the offspring of irradiated and unirradiated male mice revealed an increased variability of microsatellite-associated sequences in the genome of the offspring of the males exposed to 25 and 50 cGy. The DNA-fingerprints of the offspring of male mice exposed to chronic irradiation with the doses 10 and 25 cGy 15 days before fertilization (at the post-meiotic stage of spermatogenesis) showed an increased frequency of "non-parent bands". The results of the study point to the possibility of transmission to the offspring somatic cells of changes increasing genome instability from male parents exposed to chronic low-level radiation prior to fertilization.

Quantifying inbreeding avoidance through extra-pair reproduction.

PubMed

Reid, Jane M; Arcese, Peter; Keller, Lukas F; Germain, Ryan R; Duthie, A Bradley; Losdat, Sylvain; Wolak, Matthew E; Nietlisbach, Pirmin

2015-01-01

Extra-pair reproduction is widely hypothesized to allow females to avoid inbreeding with related socially paired males. Consequently, numerous field studies have tested the key predictions that extra-pair offspring are less inbred than females' alternative within-pair offspring, and that the probability of extra-pair reproduction increases with a female's relatedness to her socially paired male. However, such studies rarely measure inbreeding or relatedness sufficiently precisely to detect subtle effects, or consider biases stemming from failure to observe inbred offspring that die during early development. Analyses of multigenerational song sparrow (Melospiza melodia) pedigree data showed that most females had opportunity to increase or decrease the coefficient of inbreeding of their offspring through extra-pair reproduction with neighboring males. In practice, observed extra-pair offspring had lower inbreeding coefficients than females' within-pair offspring on average, while the probability of extra-pair reproduction increased substantially with the coefficient of kinship between a female and her socially paired male. However, simulations showed that such effects could simply reflect bias stemming from inbreeding depression in early offspring survival. The null hypothesis that extra-pair reproduction is random with respect to kinship therefore cannot be definitively rejected in song sparrows, and existing general evidence that females avoid inbreeding through extra-pair reproduction requires reevaluation given such biases. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Maternal pre-pregnancy BMI and gestational weight gain, offspring DNA methylation and later offspring adiposity: findings from the Avon Longitudinal Study of Parents and Children

PubMed Central

Sharp, Gemma C; Lawlor, Debbie A; Richmond, Rebecca C; Fraser, Abigail; Simpkin, Andrew; Suderman, Matthew; Shihab, Hashem A; Lyttleton, Oliver; McArdle, Wendy; Ring, Susan M; Gaunt, Tom R; Davey Smith, George; Relton, Caroline L

2015-01-01

Background: Evidence suggests that in utero exposure to undernutrition and overnutrition might affect adiposity in later life. Epigenetic modification is suggested as a plausible mediating mechanism. Methods: We used multivariable linear regression and a negative control design to examine offspring epigenome-wide DNA methylation in relation to maternal and offspring adiposity in 1018 participants. Results: Compared with neonatal offspring of normal weight mothers, 28 and 1621 CpG sites were differentially methylated in offspring of obese and underweight mothers, respectively [false discovert rate (FDR)-corrected P-value < 0.05), with no overlap in the sites that maternal obesity and underweight relate to. A positive association, where higher methylation is associated with a body mass index (BMI) outside the normal range, was seen at 78.6% of the sites associated with obesity and 87.9% of the sites associated with underweight. Associations of maternal obesity with offspring methylation were stronger than associations of paternal obesity, supporting an intrauterine mechanism. There were no consistent associations of gestational weight gain with offspring DNA methylation. In general, sites that were hypermethylated in association with maternal obesity or hypomethylated in association with maternal underweight tended to be positively associated with offspring adiposity, and sites hypomethylated in association with maternal obesity or hypermethylated in association with maternal underweight tended to be inversely associated with offspring adiposity. Conclusions: Our data suggest that both maternal obesity and, to a larger degree, underweight affect the neonatal epigenome via an intrauterine mechanism, but weight gain during pregnancy has little effect. We found some evidence that associations of maternal underweight with lower offspring adiposity and maternal obesity with greater offspring adiposity may be mediated via increased DNA methylation. PMID:25855720

Maternal immunomodulation of the offspring's immunological system.

PubMed

Campos, Sylvia M N; de Oliveira, Vivian L; Lessa, Leonardo; Vita, Melissa; Conceição, Marcia; Andrade, Luiz Antonio Botelho; Teixeira, Gerlinde Agate Platais Brasil

2014-11-01

The mother's and the offspring's immunological system are closely related thus one can influence the other. This hypothesis drove our aim to study the impact of the mother's immunological status over the immunological response of their offspring. For this, female mice tolerant or allergic to peanuts were exposed or not to a challenge diet containing peanuts during the gestation-lactation period (TEP/AEP; TNEP/ANEP, respectively). After weaning the offspring was submitted to the peanut allergy or peanut tolerization protocol and then challenged with a peanut diet. Our results showed that when the offspring is submitted to the allergy induction protocol, they behave differently depending on their mother's immunological status. Offspring born to TEP mothers produced the lowest antibody titters while those born to AEP mothers produced the highest antibody titters compared to mice born to TNEP and ANEP. On the other hand when the offspring was submitted to the tolerization protocol all groups presented low antibody titers with no significant difference between groups, independent of the mothers immunological status and/or contact with peanuts during the gestation-lactation period. The analysis of the histological profile of the offspring correlates well to the serological response. In other words, offspring born to TEP mothers and submitted to the allergy induction protocol presented a normal histological profile, while the offspring born to AEP mothers produced the worst gut inflammation. These results indicate that mothers, exposed to the antigen (by the oral route) during gestation, actively influence the immune response of their offspring. This work sheds some light on the importance of the immunomodulation induced by dietary antigens during gestation and their influence on the immunological response of their offspring. However, more work is needed to elucidate the molecular and cellular components of this regulatory phenomenon. Copyright © 2014 Elsevier GmbH. All rights reserved.

Maternal smoking during pregnancy and the risk of pediatric cardiovascular diseases of the offspring: A population-based cohort study with up to 18-years of follow up.

PubMed

Leybovitz-Haleluya, Noa; Wainstock, Tamar; Landau, Daniella; Sheiner, Eyal

2018-06-01

Cigarette smoke is a well-known reproductive toxicant. We aimed to study the long-term effect of cigarette smoking during pregnancy on the risk for childhood cardiovascular morbidity of the offspring. A population-based cohort analysis was performed comparing total and subtypes of cardiovascular related pediatric hospitalizations among offspring of smoking mothers versus offspring of non-smoking mothers. The analysis included all singletons born between the years 1999-2014.A Kaplan-Meier survival curve was used to compare the cumulative cardiovascular morbidity, and a Cox proportional hazards model was constructed to adjust for confounders. The study population included 242,342 newborns which met inclusion criteria; among them 2861 were born to smoking mothers. Offspring of smoking mothers had higher rates of cardiovascular-related hospitalizations (1.3% vs. 0.6%, OR 2.1, 95% CI 1.5-2.9; p < 0.001; Kaplan-Meier log-rank test p < 0.001). Smoking exposure during pregnancy is associated with an increased risk for long-term pediatric cardiovascular morbidity of the offspring. Copyright © 2018 Elsevier Inc. All rights reserved.

Is there a link between biological parents' insight into their offspring's schizophrenia and their cognitive functioning, expressed emotion and knowledge about disorder?

PubMed

Macgregor, Alexandra; Norton, Joanna; Raffard, Stéphane; Capdevielle, Delphine

2017-07-01

Recent studies suggest that parents' awareness of their offspring's schizophrenia could influence their offspring's insight. Low patient insight is linked to impairment of specific cognitive abilities, and biological parents of schizophrenia patients have impaired capacities in these same domains. However, little is known about what specific socio-demographic, affective or cognitive factors may influence biological parents' awareness of their offspring's disease. Data were drawn from 41 patient-parent dyads. Insight was assessed with a modified version of Amador's Scale to assess Unawareness of Mental Disorders, exploring dimensions of parents' awareness and attribution of their offspring's illness and symptoms. Higher educational levels, better working memory and executive functioning of parents were associated with better attribution of their offspring's symptoms to schizophrenia. Parents' insight into their offspring's schizophrenia is associated with cognitive abilities. This must be taken into account when developing family interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

Does major depressive disorder in parents predict specific fears and phobias in offspring?

PubMed

Biel, Matthew G; Klein, Rachel G; Mannuzza, Salvatore; Roizen, Erica R; Truong, Nhan L; Roberson-Nay, Roxann; Pine, Daniel S

2008-01-01

Evidence suggests a relationship between parental depression and phobias in offspring as well as links between childhood fears and risk for major depression. This study examines the relationship between major depressive disorder (MDD) and anxiety disorders in parents and specific fears and phobias in offspring. Three hundred and eighteen children of parents with lifetime MDD, anxiety disorder, MDD+anxiety disorder, or neither were psychiatrically assessed via parent interview. Rates of specific phobias in offspring did not differ significantly across parental groups. Specific fears were significantly elevated in offspring of parents with MDD+anxiety disorder relative to the other groups (MDD, anxiety disorder, and controls, which did not differ). We failed to find increased phobias in offspring of parents with MDD without anxiety disorder. Elevated rates of specific fears in offspring of parents with MDD+anxiety disorder may be a function of more severe parental psychopathology, increased genetic loading, or unmeasured environmental influences. (c) 2007 Wiley-Liss, Inc.

Demographic analysis of arrhenotokous parthenogenesis and bisexual reproduction of Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae).

PubMed

Ding, Tianbo; Chi, Hsin; Gökçe, Ayhan; Gao, Yulin; Zhang, Bin

2018-02-20

Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae) is a serious pest that is capable of bisexual and arrhenotokous reproduction. In arrhenotokous reproduction, virgin females initially produce male offspring; later, when their sons are sexually mature, the mothers begin bisexual reproduction by carrying out oedipal mating with their sons. Because a virgin female produces many male offspring before oedipal mating occurs, multiple oedipal mating is common. In this study, we investigated the effect of multiple oedipal mating on the population growth of F. occidentalis by using the age-stage, two-sex life table theory. In the arrhenotokous cohorts, all unfertilized eggs developed into males. In the bisexual cohorts, the offspring sex ratio was significantly female biased with the mean number of female offspring and male offspring being 72.68 and 29.00, respectively. These were the same as the net reproductive rate of female offspring and male offspring. In arrhenotokous cohorts, the number of males available for oedipal mating significantly affected the production of female offspring. The number of female offspring increased as the number of sons available for oedipal mating increased. Correctly characterizing this unique type of reproduction will provide important information for predicting the timing of future outbreaks of F. occidentalis, as well as aiding in formulating successful management strategies against the species.

Paternal B Vitamin Intake Is a Determinant of Growth, Hepatic Lipid Metabolism and Intestinal Tumor Volume in Female Apc1638N Mouse Offspring

PubMed Central

Sabet, Julia A.; Park, Lara K.; Iyer, Lakshmanan K.; Tai, Albert K.; Koh, Gar Yee; Pfalzer, Anna C.; Parnell, Laurence D.; Mason, Joel B.; Liu, Zhenhua; Byun, Alexander J.; Crott, Jimmy W.

2016-01-01

Background The importance of maternal nutrition to offspring health and risk of disease is well established. Emerging evidence suggests paternal diet may affect offspring health as well. Objective In the current study we sought to determine whether modulating pre-conception paternal B vitamin intake alters intestinal tumor formation in offspring. Additionally, we sought to identify potential mechanisms for the observed weight differential among offspring by profiling hepatic gene expression and lipid content. Methods Male Apc1638N mice (prone to intestinal tumor formation) were fed diets containing replete (control, CTRL), mildly deficient (DEF), or supplemental (SUPP) quantities of vitamins B2, B6, B12, and folate for 8 weeks before mating with control-fed wild type females. Wild type offspring were euthanized at weaning and hepatic gene expression profiled. Apc1638N offspring were fed a replete diet and euthanized at 28 weeks of age to assess tumor burden. Results No differences in intestinal tumor incidence or burden were found between male Apc1638N offspring of different paternal diet groups. Although in female Apc1638N offspring there were no differences in tumor incidence or multiplicity, a stepwise increase in tumor volume with increasing paternal B vitamin intake was observed. Interestingly, female offspring of SUPP and DEF fathers had a significantly lower body weight than those of CTRL fed fathers. Moreover, hepatic trigylcerides and cholesterol were elevated 3-fold in adult female offspring of SUPP fathers. Weanling offspring of the same fathers displayed altered expression of several key lipid-metabolism genes. Hundreds of differentially methylated regions were identified in the paternal sperm in response to DEF and SUPP diets. Aside from a few genes including Igf2, there was a striking lack of overlap between these genes differentially methylated in sperm and differentially expressed in offspring. Conclusions In this animal model, modulation of paternal B vitamin intake prior to mating alters offspring weight gain, lipid metabolism and tumor growth in a sex-specific fashion. These results highlight the need to better define how paternal nutrition affects the health of offspring. PMID:26968002

Female fecundity and offspring survival are not increased through sexual cannibalism in the spider Larinioides sclopetarius.

PubMed

Deventer, S A; Herberstein, M E; Mayntz, D; O'Hanlon, J C; Schneider, J M

2017-12-01

Many hypotheses explaining the evolution and maintenance of sexual cannibalism incorporate the nutritional aspect of the consumption of males. Most studies have focused on a fecundity advantage through consumption of a male; however, recent studies have raised the intriguing possibility that consumption of a male may also affect offspring quality. In particular, recent studies suggest prolonged survival for offspring from sexually cannibalistic females. Here, we measured the protein and lipid content of males compared to insect prey (crickets), quantified female nutrient intake of both prey types and finally assessed how sexual cannibalism affects female fecundity and spiderling quality in the orb-web spider Larinioides sclopetarius. We found no evidence that sexual cannibalism increased fecundity when compared to a female control group fed a cricket. Contrary to previous studies, spiderlings from females fed a male showed reduced survival under food deprivation compared to spiderlings from the control group. Offspring from females fed a male also tended to begin web construction sooner. The low lipid content of males compared to crickets may have reduced offspring survival duration. Whether additional proteins obtained through consumption of a male translate to enhanced silk production in offspring requires further investigation. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

MATERNAL EXPERIENCE OF ABUSE IN CHILDHOOD AND DEPRESSIVE SYMPTOMS IN ADOLESCENT AND ADULT OFFSPRING: A 21-YEAR LONGITUDINAL STUDY

PubMed Central

Roberts, Andrea L.; Chen, Ying; Slopen, Natalie; McLaughlin, Katie A.; Koenen, Karestan C.; Austin, Sydney Bryn

2015-01-01

Background Intergenerational effects of child abuse have been documented, but it is unknown whether maternal childhood abuse influences offspring mental health in adolescence or adulthood. Methods To examine whether maternal experience of childhood abuse is associated with depressive symptoms in adolescent and young adult offspring, we linked data from two large longitudinal cohorts of women (N = 8,882) and their offspring (N = 11,402), and we examined three possible pathways by which maternal experience of abuse might be associated with offspring depressive symptoms: maternal mental health, family characteristics, and offspring’s own experience of abuse. Results Offspring of women who experienced severe versus no childhood abuse had greater likelihood of high depressive symptoms (RR = 1.78, 95% CI = 1.47, 2.16) and persistent high depressive symptoms (RR = 2.47, 95% CI = 1.37, 4.44). Maternal mental health accounted for 20.9% and offspring’s exposure to abuse accounted for 30.3% of the elevated risk of high depressive symptoms. Disparities in offspring depressive symptoms by maternal abuse exposure were evident at age 12 years and persisted through age 31 years. Conclusions Findings provide evidence that childhood abuse adversely affects the mental health of the victim’s offspring well into adulthood. As offspring exposure to abuse and maternal mental health accounted for more than 50% of the elevated risk of high depressive symptoms among offspring of women who experienced abuse, improving maternal mental health and parenting practices may reduce offspring risk for depressive symptoms in these families. PMID:26220852

Parental Depression as a Moderator of Secondary Deficits of Depression in Adult Offspring

ERIC Educational Resources Information Center

Timko, Christine; Cronkite, Ruth C.; Swindle, Ralph; Robinson, Rebecca L.; Sutkowi, Anne; Moos, Rudolf H.

2009-01-01

This study examined whether having a depressed parent intensifies the secondary deficits that often co-occur with offspring's depression symptoms. The sample was adult offspring of parents who had been diagnosed with depression 23 years earlier (N = 143) and demographically matched nondepressed parents (N = 197). Respondents completed mailed…

Psychopathology in the Adolescent Offspring of Parents with Panic Disorder and Depression

ERIC Educational Resources Information Center

Bhat, Amritha S.; Srinivasan, K.

2006-01-01

Aim: To study the prevalence of psychiatric diagnosis and psychopathology in adolescent offspring of parents with panic disorder, depression and normal controls. Methods: Adolescent offspring (11-16 years) of parents with a diagnosis of panic disorder and major depression, and normal controls were interviewed using Missouri Assessment of Genetics…

Postpartum maternal fat distribution and its association with offspring body fat through the first year of life

USDA-ARS?s Scientific Manuscript database

Maternal obesity is known to increase the risk of offspring obesity. Despite the evidence supporting the impact of maternal obesity on infant health, there are no studies examining the effects of maternal fat distribution on the programming of offspring obesity. We hypothesized that increased matern...

The cumulative burden borne by offspring whose mothers were sexually abused as children: descriptive results from a multigenerational study.

PubMed

Noll, Jennie G; Trickett, Penelope K; Harris, William W; Putnam, Frank W

2009-03-01

This multigenerational study empirically demonstrates the extent to which offspring whose parents experienced childhood abuse are at increased risk of being abused or neglected. Females with substantiated childhood sexual abuse and non abused comparison females were assessed at six points spanning 18 years in a prospective, longitudinal study. Non abusing parents or caregivers and offspring were also assessed. Descriptive results indicate that offspring born to mothers with histories of sexual abuse were more likely to be born preterm, have a teenage mother, and be involved in protective services. Abused mothers were more likely to be high-school dropouts, be obese, and have experienced psychiatric problems, substance dependence, and domestic violence. Results provide evidence for the advantages of intervention and prevention programs for victims of childhood maltreatment and their families. Primary prevention/intervention efforts extending throughout development and focusing on the cumulative risk to offspring will likely improve victim outcomes and curtail intergenerational transmission of adversity.

Quantifying inbreeding avoidance through extra-pair reproduction

PubMed Central

Reid, Jane M; Arcese, Peter; Keller, Lukas F; Germain, Ryan R; Duthie, A Bradley; Losdat, Sylvain; Wolak, Matthew E; Nietlisbach, Pirmin

2015-01-01

Extra-pair reproduction is widely hypothesized to allow females to avoid inbreeding with related socially paired males. Consequently, numerous field studies have tested the key predictions that extra-pair offspring are less inbred than females’ alternative within-pair offspring, and that the probability of extra-pair reproduction increases with a female's relatedness to her socially paired male. However, such studies rarely measure inbreeding or relatedness sufficiently precisely to detect subtle effects, or consider biases stemming from failure to observe inbred offspring that die during early development. Analyses of multigenerational song sparrow (Melospiza melodia) pedigree data showed that most females had opportunity to increase or decrease the coefficient of inbreeding of their offspring through extra-pair reproduction with neighboring males. In practice, observed extra-pair offspring had lower inbreeding coefficients than females’ within-pair offspring on average, while the probability of extra-pair reproduction increased substantially with the coefficient of kinship between a female and her socially paired male. However, simulations showed that such effects could simply reflect bias stemming from inbreeding depression in early offspring survival. The null hypothesis that extra-pair reproduction is random with respect to kinship therefore cannot be definitively rejected in song sparrows, and existing general evidence that females avoid inbreeding through extra-pair reproduction requires reevaluation given such biases. PMID:25346331

Cortical thickness in symptomatic and asymptomatic bipolar offspring.

PubMed

Hanford, Lindsay C; Sassi, Roberto B; Minuzzi, Luciano; Hall, Geoffrey B

2016-05-30

Children of parents diagnosed with bipolar disorder are at greater risk for developing a variety of psychiatric disorders, however, the reasons remain unknown. The present study aimed to investigate gray matter integrity in high-risk bipolar offspring (HRO) and healthy offspring (HCO) using cortical thickness techniques. Here we examined healthy control offspring (HCO; n=20) and HRO with (n=17) or without (n=13) psychiatric symptoms. T1-weighted images were collected from all offspring, and cortical thickness and age-cortical thickness correlations were compared. HRO showed cortical thinning in superior and inferior temporal regions, supramarginal, and caudal and rostral middle frontal regions compared to HCO. When comparing HRO with and without psychiatric symptoms, we found cortical thinning in symptomatic offspring in the superior frontal and somatosensory related cortices. Age-thickness correlations showed a relatively consistent negative relationship in most regions in HCO, while the reverse was true for the HRO. These regions included parahippocampal, lateral orbitofrontal, and inferior temporal regions. Our study provides evidence of cortical thickness reductions among symptomatic and asymptomatic high-risk offspring during youth. Some of these alterations, found in regions of emotion processing and regulation, are evident only when associated with the presence of psychiatric symptoms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Associations between postnatal maternal depression and psychological outcomes in adolescent offspring: a systematic review.

PubMed

Sanger, Camilla; Iles, Jane E; Andrew, Catharina S; Ramchandani, Paul G

2015-04-01

Postnatal depression (PND) affects approximately 10-20 % of new mothers in developed countries, with accumulating research documenting its adverse impact on not only the mother but also the wider family. Longitudinal studies assessing potential effects of maternal PND on offspring are mounting, and it is therefore timely to investigate the long-term psychological outcomes for adolescent offspring who were exposed to PND in infancy. PsycINFO, Medline, and Embase databases were searched with key terms for English language abstracts. Papers of 16 were identified that examined associations between PND and internalising problems, externalising problems, psychopathology, psychosocial, and cognitive outcomes of adolescent offspring. Impaired offspring cognitive outcomes reflected some of the most consistent findings. Conflicting evidence was found for an effect of PND on adolescent offspring internalising and externalising problems and overall psychopathology. Psychosocial outcomes in offspring adolescents indicated a specific adverse effect, although based on only two studies. Significant gender differences across outcomes were found. It was concluded that PND possibly increases risk vulnerability in the presence of recurrent, concurrent, and antenatal maternal depression but that these latter factors alone may be the stronger specific predictors. Limitations of the review are discussed as well as implications for future research and clinical practice.

Young Adults’ Provision of Support to Middle-Aged Parents

PubMed Central

Birditt, Kira S.; Zarit, Steven H.; Fingerman, Karen L.

2015-01-01

Objectives. Middle-aged adults often provide support to aging parents, but researchers know little about support that young adults provide middle-aged parents. This study examined support that young adults provide parents and explanations for that support from both offspring’s and parents’ perspectives. Method. Young adults (n = 515, mean age = 22.34) and their parents (n = 364, mean age = 50.09) from the Family Exchanges Study reported support that offspring provide parents. Participants also reported parental personal problems, parental disability status, relationship quality, and support that parents provide offspring. Results. Offspring provided parents with emotional support and listening more often than other forms of support. Offspring reported providing more frequent support than parents reported receiving. We examined factors associated with support using multilevel models. Both offspring and parents reported more frequent support provided to parents when they had higher quality relationships and when parents gave more frequent support to offspring. Offspring (but not parents) reported providing more frequent support to parents when parents were disabled. Discussion. Findings are consistent with solidarity theory, which suggests that high-quality relationships may explain support. The concept of self-enhancement and generativity in middle-aged parents may explain the intergenerational differences in the association between parental disability and support. PMID:24162441

Female offspring desertion and male-only care increase with natural and experimental increase in food abundance

PubMed Central

Eldegard, Katrine; Sonerud, Geir A.

2009-01-01

In species with biparental care, one parent may escape the costs of parental care by deserting and leaving the partner to care for the offspring alone. A number of theoretical papers have suggested a link between uniparental offspring desertion and ecological factors, but empirical evidence is scarce. We investigated the relationship between uniparental desertion and food abundance in a natural population of Tengmalm's owl Aegolius funereus, both by means of a 5-year observational study and a 1-year experimental study. Parents and offspring were fitted with radio-transmitters in order to reveal the parental care strategy (i.e. care or desert) of individual parents, and to keep track of the broods post-fledging. We found that 70 per cent of the females from non-experimental nests deserted, while their partner continued to care for their joint offspring alone. Desertion rate was positively related to natural prey population densities and body reserves of the male partner. In response to food supplementation, a larger proportion of the females deserted, and females deserted the offspring at an earlier age. Offspring survival during the post-fledging period tended to be lower in deserted than in non-deserted broods. We argue that the most important benefit of deserting may be remating (sequential polyandry). PMID:19324835

Female offspring desertion and male-only care increase with natural and experimental increase in food abundance.

PubMed

Eldegard, Katrine; Sonerud, Geir A

2009-05-07

In species with biparental care, one parent may escape the costs of parental care by deserting and leaving the partner to care for the offspring alone. A number of theoretical papers have suggested a link between uniparental offspring desertion and ecological factors, but empirical evidence is scarce. We investigated the relationship between uniparental desertion and food abundance in a natural population of Tengmalm's owl Aegolius funereus, both by means of a 5-year observational study and a 1-year experimental study. Parents and offspring were fitted with radio-transmitters in order to reveal the parental care strategy (i.e. care or desert) of individual parents, and to keep track of the broods post-fledging. We found that 70 per cent of the females from non-experimental nests deserted, while their partner continued to care for their joint offspring alone. Desertion rate was positively related to natural prey population densities and body reserves of the male partner. In response to food supplementation, a larger proportion of the females deserted, and females deserted the offspring at an earlier age. Offspring survival during the post-fledging period tended to be lower in deserted than in non-deserted broods. We argue that the most important benefit of deserting may be remating (sequential polyandry).

Chronic prenatal ethanol exposure increases adiposity and disrupts pancreatic morphology in adult guinea pig offspring.

PubMed

Dobson, C C; Mongillo, D L; Brien, D C; Stepita, R; Poklewska-Koziell, M; Winterborn, A; Holloway, A C; Brien, J F; Reynolds, J N

2012-12-17

Ethanol consumption during pregnancy can lead to a range of adverse developmental outcomes in children, termed fetal alcohol spectrum disorder (FASD). Central nervous system injury is a debilitating and widely studied manifestation of chronic prenatal ethanol exposure (CPEE). However, CPEE can also cause structural and functional deficits in metabolic pathways in offspring. This study tested the hypothesis that CPEE increases whole-body adiposity and disrupts pancreatic structure in guinea pig offspring. Pregnant guinea pigs received ethanol (4 g kg(-1) maternal body weight per day) or isocaloric-sucrose/pair-feeding (control) for 5 days per week throughout gestation. Male and female CPEE offspring demonstrated growth restriction at birth, followed by a rapid period of catch-up growth before weaning (postnatal day (PD) 1-7). Whole-body magnetic resonance imaging (MRI) in young adult offspring (PD100-140) revealed increased visceral and subcutaneous adiposity produced by CPEE. At the time of killing (PD150-200), CPEE offspring also had increased pancreatic adipocyte area and decreased β-cell insulin-like immunopositive area, suggesting reduced insulin production and/or secretion from pancreatic islets. CPEE causes increased adiposity and pancreatic dysmorphology in offspring, which may signify increased risk for the development of metabolic syndrome and type 2 diabetes mellitus.

Parenting behaviors associated with risk for offspring personality disorder during adulthood.

PubMed

Johnson, Jeffrey G; Cohen, Patricia; Chen, Henian; Kasen, Stephanie; Brook, Judith S

2006-05-01

Research has suggested that some types of parental child-rearing behavior may be associated with risk for offspring personality disorder (PD), but the association of parenting with offspring PD has not been investigated comprehensively with prospective longitudinal data. To investigate the association of parental child-rearing behavior with risk for offspring PD during adulthood. The Children in the Community study, a prospective longitudinal investigation. A community-based sample of 593 families interviewed during childhood (mean age, 6 years), adolescence (mean ages, 14 and 16 years), emerging adulthood (mean age, 22 years), and adulthood (mean age, 33 years) of the offspring. The Structured Clinical Interview for DSM-IV Personality Disorders. Ten types of parenting behavior that were evident during the child-rearing years were associated with elevated offspring risk for PD during adulthood when childhood behavioral or emotional problems and parental psychiatric disorders were controlled statistically. Parental behavior in the home during the child-rearing years was associated with elevated risk for offspring PD at mean ages of 22 and 33 years. Risk for offspring PD at both assessments increased steadily as a function of the number of problematic parenting behaviors that were evident. Low parental affection or nurturing was associated with elevated risk for offspring antisocial (P = .003), avoidant (P = .01), borderline (P = .002), depressive (P = .02), paranoid (P = .002), schizoid (P = .046), and schizotypal (P<.001) PDs. Aversive parental behavior (eg, harsh punishment) was associated with elevated risk for offspring borderline (P = .001), paranoid (P = .004), passive-aggressive (P = .046), and schizotypal (P = .02) PDs. Parental behavior during the child-rearing years may be associated with risk for offspring PD that endures into adulthood. This risk may not be attributable to offspring behavioral and emotional problems or parental psychiatric disorder, and it may not diminish over time. Low parental nurturing and aversive parental behavior during child rearing may both be associated with elevated risk for offspring PDs.

Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands.

PubMed

Jin, Sheng Chih; Homsy, Jason; Zaidi, Samir; Lu, Qiongshi; Morton, Sarah; DePalma, Steven R; Zeng, Xue; Qi, Hongjian; Chang, Weni; Sierant, Michael C; Hung, Wei-Chien; Haider, Shozeb; Zhang, Junhui; Knight, James; Bjornson, Robert D; Castaldi, Christopher; Tikhonoa, Irina R; Bilguvar, Kaya; Mane, Shrikant M; Sanders, Stephan J; Mital, Seema; Russell, Mark W; Gaynor, J William; Deanfield, John; Giardini, Alessandro; Porter, George A; Srivastava, Deepak; Lo, Cecelia W; Shen, Yufeng; Watkins, W Scott; Yandell, Mark; Yost, H Joseph; Tristani-Firouzi, Martin; Newburger, Jane W; Roberts, Amy E; Kim, Richard; Zhao, Hongyu; Kaltman, Jonathan R; Goldmuntz, Elizabeth; Chung, Wendy K; Seidman, Jonathan G; Gelb, Bruce D; Seidman, Christine E; Lifton, Richard P; Brueckner, Martina

2017-11-01

Congenital heart disease (CHD) is the leading cause of mortality from birth defects. Here, exome sequencing of a single cohort of 2,871 CHD probands, including 2,645 parent-offspring trios, implicated rare inherited mutations in 1.8%, including a recessive founder mutation in GDF1 accounting for ∼5% of severe CHD in Ashkenazim, recessive genotypes in MYH6 accounting for ∼11% of Shone complex, and dominant FLT4 mutations accounting for 2.3% of Tetralogy of Fallot. De novo mutations (DNMs) accounted for 8% of cases, including ∼3% of isolated CHD patients and ∼28% with both neurodevelopmental and extra-cardiac congenital anomalies. Seven genes surpassed thresholds for genome-wide significance, and 12 genes not previously implicated in CHD had >70% probability of being disease related. DNMs in ∼440 genes were inferred to contribute to CHD. Striking overlap between genes with damaging DNMs in probands with CHD and autism was also found.

A quasi-experimental study of maternal smoking during pregnancy and offspring academic achievement

PubMed Central

D'Onofrio, Brian M.; Singh, Amber L.; Iliadou, Anastasia; Lambe, Mats; Hultman, Christina M.; Neiderhiser, Jenae M.; Långström, Niklas; Lichtenstein, Paul

2013-01-01

Maternal smoking during pregnancy (SDP) is associated with lower academic achievement in offspring. The current study, which was based on all births in Sweden from 1983 through 1991, explored the possible causal processes underlying the association between SDP and offspring school grades and a standardized assessment of mathematic proficiency at age 15. The analyses compared relatives who varied in their exposure to SDP and who varied in their genetic relatedness. Although SDP was statistically associated with academic achievement when comparing unrelated individuals, the results suggest that SDP does not cause poorer academic performance, as full siblings differentially exposed to SDP did not differ in their academic scores. The pattern of results suggests that genetic factors shared by parents and their offspring explain significant variance in why offspring opposed to SDP have lower levels of academic achievement. Nevertheless, SDP impacts pregnancy-related outcomes. Reducing SDP, therefore, remains a major public health issue. PMID:20331655

Maternal diabetes mellitus and the origin of non-communicable diseases in offspring: the role of epigenetics.

PubMed

Ge, Zhao-Jia; Zhang, Cui-Lian; Schatten, Heide; Sun, Qing-Yuan

2014-06-01

Offspring of diabetic mothers are susceptible to the onset of metabolic syndromes, such as type 2 diabetes and obesity at adulthood, and this trend can be inherited between generations. Genetics cannot fully explain how the noncommunicable disease in offspring of diabetic mothers is caused and inherited by the next generations. Many studies have confirmed that epigenetics may be crucial for the detrimental effects on offspring exposed to the hyperglycemic environment. Although the adverse effects on epigenetics in offspring of diabetic mothers may be the result of the poor intrauterine environment, epigenetic modifications in oocytes of diabetic mothers are also affected. Therefore, the present review is focused on the epigenetic alterations in oocytes and embryos of diabetic mothers. Furthermore, we also discuss initial mechanistic insight on maternal diabetes mellitus causing alterations of epigenetic modifications. © 2014 by the Society for the Study of Reproduction, Inc.

Ephemeral clonal integration in Calathea marantifolia (Marantaceae): Evidence of diminished integration over time.

PubMed

Matlaga, David P; da S L Sternberg, Leonel

2009-02-01

A major advantage of clonal growth forms is the intergenerational transfer of resources through vascular connections (clonal integration). Connections linking ramets can be persistent or ephemeral. For species with ephemeral connections, whether the extent of clonal integration changes over time is unclear. To address this issue, we tracked water movement using an isotopic label and assessed the demographic performance of parent and offspring ramets over time in a severing experiment. Our study system was the understory herb Calathea marantifolia, which has parent ramets that produce vegetative bulbils (clonal offspring) that pass through distinct pre- and post-rooting stages. Little water was transported between parents and offspring, and the direction of movement was primarily from parent to pre-rooting offspring. Anatomical observations of inter-ramet connections showed that vascular bundles were twice as abundant in parent stems compared to inter-ramet connections. Severing inter-ramet connections reduced the growth of offspring ramets but not parents. Survival of pre-rooting offspring was reduced by 10% due to severing, but post-rooting offspring were not affected. Our results suggest that offspring ramets of C. marantifolia are weaned from their parent as they progress from pre- to post-rooting stages.

Male pregnancy and biparental immune priming.

PubMed

Roth, Olivia; Klein, Verena; Beemelmanns, Anne; Scharsack, Jörn P; Reusch, Thorsten B H

2012-12-01

In vertebrates, maternal transfer of immunity via the eggs or placenta provides offspring with crucial information on prevailing pathogens and parasites. Males contribute little to such transgenerational immune priming, either because they do not share the environment and parasite pressure of the offspring or because sperm are too small for transfer of immunity. In the teleost group of Syngnathids (pipefish, seahorses, and sea dragons), males brood female eggs in a placenta-like structure. Such sex-role-reversed species provide a unique opportunity to test for adaptive plasticity in immune transfer. Here, males and females should both influence offspring immunity. We experimentally tested paternal effects on offspring immunity by examining immune cell proliferation and immune gene expression. Maternal and paternal bacterial exposure induced offspring immune defense 5 weeks after hatching, and this effect persisted in 4-month-old offspring. For several offspring immune traits, double parental exposure (maternal and paternal) enhanced the response, whereas for another group of immune traits, the transgenerational induction already took place if only one parent was exposed. Our study shows that sex role reversal in connection with male pregnancy opens the door for biparental influences on offspring immunity and may represent an additional advantage for the evolution of male pregnancy.

Elevated paternal glucocorticoid exposure modifies memory retention in female offspring.

PubMed

Yeshurun, Shlomo; Rogers, Jake; Short, Annabel K; Renoir, Thibault; Pang, Terence Y; Hannan, Anthony J

2017-09-01

Recent studies have demonstrated that behavioral traits are subject to transgenerational modification by paternal environmental factors. We previously reported on the transgenerational influences of increased paternal stress hormone levels on offspring anxiety and depression-related behaviors. Here, we investigated whether offspring sociability and cognition are also influenced by paternal stress. Adult C57BL/6J male mice were treated with corticosterone (CORT; 25mg/L) for four weeks prior to paired-matings to generate F1 offspring. Paternal CORT treatment was associated with decreased body weights of female offspring and a marked reduction of the male offspring. There were no differences in social behavior of adult F1 offspring in the three-chamber social interaction test. Despite male offspring of CORT-treated fathers displaying hyperactivity in the Y-maze, there was no observable difference in short-term spatial working memory. Spatial learning and memory testing in the Morris water maze revealed that female, but not male, F1 offspring of CORT-treated fathers had impaired memory retention. We used our recently developed methodology to analyze the spatial search strategy of the mice during the learning trials and determined that the impairment could not be attributed to underlying differences in search strategy. These results provide evidence for the impact of paternal corticosterone administration on offspring cognition and complement the cumulative knowledge of transgenerational epigenetic inheritance of acquired traits in rodents and humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

Maternal programming of offspring hypothalamic-pituitary-interrenal axis in wild sockeye salmon (Oncorhynchus nerka).

PubMed

Sopinka, N M; Jeffrey, J D; Burnett, N J; Patterson, D A; Gilmour, K M; Hinch, S G

2017-02-01

In fishes, maternal exposure to a stressor can influence offspring size and behavior. However, less is known about how maternal stress influences physiological processes in offspring, such as function of the hypothalamic-pituitary-interrenal (HPI) axis. We examined the impact of chronic maternal exposure to an acute chase stressor on the stress response/HPI activity of progeny in wild sockeye salmon (Oncorhynchus nerka). Resting plasma cortisol and brain preoptic area (POA) corticotropin-releasing factor (CRF) mRNA levels did not vary between offspring reared from undisturbed, control females and offspring reared from females exposed to the stressor. However, resting levels of POA glucocorticoid receptors (GR1 and GR2), and head kidney melanocortin 2 receptor (MC2R), steroidogenic acute regulatory protein (StAR), and cytochrome P450 side chain cleavage enzyme (P450scc) were elevated in offspring reared from stressor-exposed females. Offspring reared from stressor-exposed females had lower plasma cortisol levels 1-h after an acute chase stressor compared to cortisol levels in offspring reared from control females. In offspring reared from chased females, mRNA levels of genes associated with cortisol biosynthesis were reduced in the head kidney post-chase. In offspring reared from control females, mRNA levels in the head kidney did not vary pre- to post-chase. Together, the results of the present study suggest maternal programming of progeny with respect to baseline and stressor-induced mediators of HPI axis activity. Copyright © 2015 Elsevier Inc. All rights reserved.

Disentangling prenatal and inherited influences in humans with an experimental design.

PubMed

Rice, Frances; Harold, Gordon T; Boivin, Jacky; Hay, Dale F; van den Bree, Marianne; Thapar, Anita

2009-02-17

Exposure to adversity in utero at a sensitive period of development can bring about physiological, structural, and metabolic changes in the fetus that affect later development and behavior. However, the link between prenatal environment and offspring outcomes could also arise and confound because of the relation between maternal and offspring genomes. As human studies cannot randomly assign offspring to prenatal conditions, it is difficult to test whether in utero events have true causal effects on offspring outcomes. We used an unusual approach to overcome this difficulty whereby pregnant mothers are either biologically unrelated or related to their child as a result of in vitro fertilization (IVF). In this sample, prenatal smoking reduces offspring birth weight in both unrelated and related offspring, consistent with effects arising through prenatal mechanisms independent of the relation between the maternal and offspring genomes. In contrast, the association between prenatal smoking and offspring antisocial behavior depended on inherited factors because association was only present in related mothers and offspring. The results demonstrate that this unusual prenatal cross-fostering design is feasible and informative for disentangling inherited and prenatal effects on human health and behavior. Disentangling these different effects is invaluable for pinpointing markers of prenatal adversity that have a causal effect on offspring outcomes. The origins of behavior and many common complex disorders may begin in early life, therefore this experimental design could pave the way for identifying prenatal factors that affect behavior in future generations.

Offspring of a parent with genetic disease: childhood experiences and adult psychological characteristics.

PubMed

van der Meer, Lucienne; van Duijn, Erik; Wolterbeek, Ron; Tibben, Aad

2014-12-01

To investigate childhood experiences and psychological characteristics in offspring of a parent with genetic disease. Self-report scales were used to assess adverse childhood experiences (ACEs), adult attachment style, mental health, and psychological symptomatology in offspring of a parent with a neurogenetic disorder (i.e. Huntington's Disease, HD; Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, CADASIL; and Hereditary Cerebral Hemorrhage With Amyloidosis-Dutch type, HCHWA-D), and in offspring of a parent affected with Hereditary Breast/Ovarian Cancer (HBOC). These groups were compared to persons who did not have a parent with one of these genetic diseases. Associations between childhood experiences and adult psychological characteristics were investigated. Compared with the reference group (n = 127), offspring of a parent with a neurogenetic disorder (n = 96) reported more parental dysfunction in childhood, and showed more adult attachment anxiety and poorer mental health. Offspring of a parent with HBOC (n = 70) reported more parental loss in childhood and showed poorer mental health. Offspring who experienced parental genetic disease in childhood had more attachment anxiety than offspring who experienced parental disease later in life. In the group of offspring, a higher number of ACEs was associated with poorer mental health and more psychological symptomatology. This cross-sectional study indicates that adult offspring of a parent with genetic disease may differ in attachment style and mental health from persons without one of these genetic diseases in their family, and that this may be related to adverse childhood experiences.

Cardiovascular and metabolic profiles of offspring conceived by assisted reproductive technologies: a systematic review and meta-analysis.

PubMed

Guo, Xiao-Yan; Liu, Xin-Mei; Jin, Li; Wang, Ting-Ting; Ullah, Kamran; Sheng, Jian-Zhong; Huang, He-Feng

2017-03-01

To evaluate cardiovascular and metabolic features of offspring conceived by in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI). Literature review and meta-analysis. Not applicable. Offspring from IVF-ICSI versus natural conception. None. Systolic and diastolic blood pressure (SBP and DBP), cardiovascular function, body mass index (BMI), and lipid and glucose profiles. We included 19 studies that had recruited 2,112 IVF-ICSI and 4,096 naturally conceived offspring, ranging from childhood to early adulthood. The blood pressure levels of IVF-ICSI offspring were statistically significantly higher than those of naturally conceived offspring (weighted mean differences and confidence intervals: 1.88 mm Hg [95% CI, 0.27, 3.49] for SBP and 1.51 mm Hg [95% CI, 0.33, 2.70] for DBP). In addition, cardiac diastolic function was suboptimal and vessel thickness was higher among IVF-ICSI offspring. Compared with the metabolism of naturally conceived offspring, IVF-ICSI offspring displayed comparable BMI, lower low-density lipoprotein cholesterol levels, and higher fasting insulin levels. Children conceived by IVF-ICSI manifested a minor yet statistically significant increase in blood pressure without the clustering of increased BMI or impaired lipid metabolism by early adulthood. Our findings indicate a risk of cardiovascular disease among IVF-ICSI offspring, which calls for longer-term follow-ups and further investigation. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Associations of Maternal Pre-Pregnancy Body Mass Index and Gestational Weight Gain with Adult Offspring Cardio-Metabolic Risk Factors: The Jerusalem Perinatal Family Follow-up Study

PubMed Central

Hochner, Hagit; Friedlander, Yechiel; Calderon-Margalit, Ronit; Meiner, Vardiella; Sagy, Yael; Avgil-Tsadok, Meytal; Burger, Ayala; Savitsky, Bella; Siscovick, David S.; Manor, Orly

2012-01-01

Background Accumulating evidence demonstrates that both maternal pre-pregnancy body mass index (mppBMI) and gestational weight gain (GWG) are associated with adult offspring adiposity. However, whether these maternal attributes are related to other cardio-metabolic risk factors in adulthood has not been comprehensively studied. Methods and Results We used a birth cohort of 1400 young adults born in Jerusalem, with extensive archival data as well as clinical information at age 32, to prospectively examine the associations of mppBMI and GWG with adiposity and related cardio-metabolic outcomes. Greater mppBMI, independent of GWG and confounders, was significantly associated with higher offspring BMI, waist circumference (WC), systolic and diastolic BP, insulin and triglycerides and with lower HDL-C. For example, the effect sizes were translated to nearly 5kg/m2 higher mean BMI, 8.4cm higher WC, 0.13mmol/L (11.4mg/dL) higher triglycerides and 0.10mmol/L (3.8mg/dL) lower HDL-C among offspring of mothers within the upper mppBMI quartile (BMI>26.4kg/m2) compared to the lower (BMI<21.0kg/m2). GWG, independent of mppBMI, was positively associated with offspring adiposity; differences of 1.6kg/m2 in BMI and 2.4cm in waist were observed when offspring of mothers in the upper (GWG>14kg) and lower (GWG<9kg) quartiles of GWG were compared. Further adjustment for offspring adiposity attenuated to null the observed associations. Conclusions Maternal size both before and during pregnancy are associated with cardio-metabolic risk factors in young adult offspring. The associations appear to be driven mainly by offspring adiposity. Future studies that explore mechanisms underlying the intergenerational cycle of obesity are warranted to identify potentially novel targets for cardio-metabolic risk-reduction interventions. PMID:22344037

Quantitative trait loci for maternal performance for offspring survival in mice.

PubMed Central

Peripato, Andréa C; De Brito, Reinaldo A; Vaughn, Ty T; Pletscher, L Susan; Matioli, Sergio R; Cheverud, James M

2002-01-01

Maternal performance refers to the effect that the environment provided by mothers has on their offspring's phenotypes, such as offspring survival and growth. Variations in maternal behavior and physiology are responsible for variations in maternal performance, which in turn affects offspring survival. In our study we found females that failed to nurture their offspring and showed abnormal maternal behaviors. The genetic architecture of maternal performance for offspring survival was investigated in 241 females of an F(2) intercross of the SM/J and LG/J inbred mouse strains. Using interval-mapping methods we found two quantitative trait loci (QTL) affecting maternal performance at D2Mit17 + 6 cM and D7Mit21 + 2 cM on chromosomes 2 and 7, respectively. In a two-way genome-wide epistasis scan we found 15 epistatic interactions involving 23 QTL distributed across all chromosomes except 12, 16, and 17. These loci form several small sets of interacting QTL, suggesting a complex set of mechanisms operating to determine maternal performance for offspring survival. Taken all together and correcting for the large number of significant factors, QTL and their interactions explain almost 35% of the phenotypic variation for maternal performance for offspring survival in this cross. This study allowed the identification of many possible candidate genes, as well as the relative size of gene effects and patterns of gene action affecting maternal performance in mice. Detailed behavior observation of mothers from later generations suggests that offspring survival in the first week is related to maternal success in building nests, grooming their pups, providing milk, and/or manifesting aggressive behavior against intruders. PMID:12454078

Prenatal Gender-Related Nicotine Exposure Increases Blood Pressure Response to Angiotensin II in Adult Offspring

PubMed Central

Xiao, DaLiao; Xu, Zhice; Huang, Xiaohui; Longo, Lawrence D.; Yang, Shumei; Zhang, Lubo

2008-01-01

Epidemiological studies suggest that maternal cigarette smoking is associated with an increased risk of elevated blood pressure (BP) in postnatal life. The present study tested the hypothesis that prenatal nicotine exposure causes an increase in BP response to angiotensin II (Ang II) in adult offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps throughout the gestation. BP and vascular responses to Ang II were measured in 5-month–old adult offspring. Prenatal nicotine had no effect on baseline BP but significantly increased Ang II–stimulated BP in male but not female offspring. The baroreflex sensitivity was significantly decreased in both male and female offspring. Prenatal nicotine significantly increased arterial media thickness in male but not female offspring. In male offspring, nicotine exposure significantly increased Ang II–induced contractions of aortas and mesenteric arteries. These responses were not affected by inhibition of endothelial NO synthase activity. Losartan blocked Ang II–induced contractions in both control and nicotine-treated animals. In contrast, PD123319 had no effect on Ang II–induced contractions in control but inhibited them in nicotine-treated animals. Nicotine significantly increased Ang II type 1 receptor but decreased Ang II type 2 receptor protein levels, resulting in a significant increase in the ratio of Ang II type 1 receptor/Ang II type 2 receptor in the aorta. Furthermore, the increased contractions of mesenteric arteries were mediated by increases in intracellular Ca2+ concentrations and Ca2+ sensitivity. These results suggest that prenatal nicotine exposure alters vascular function via changes in Ang II receptor–mediated signaling pathways in adult offspring in a gender-specific manner, which may lead to an increased risk of hypertension in male offspring. PMID:18259024

Developmental and neurobehavioral effects of perinatal exposure to diets with different omega-6:omega-3 ratios in mice.

PubMed

Santillán, María E; Vincenti, Laura M; Martini, Ana C; de Cuneo, Marta Fiol; Ruiz, Rubén D; Mangeaud, Arnaldo; Stutz, Graciela

2010-04-01

To investigate in mice the effect of diets enriched with soy or sunflower oil with different omega-6:omega-3 ratios on gestation, reproductive success, physical maturation, and the neurobiological development of the pups. Dams were assigned, throughout gestation and lactation, to different groups: a commercial diet (CD), a soy oil-enriched diet (SOD), or a sunflower oil-enriched diet (SFOD). Measurements during gestation were dams' body weights and daily food intakes. Measurements in the offspring were physical parameters (body weight, body length, body mass index, fur appearance, pinna detachment, incisor eruption, eye opening, and puberty onset) and behavioral preweaning tests (surface righting reflex, negative geotaxis, and cliff avoidance). The SOD and SFOD dams became significantly heavier than the CD dams from gestational days 14 and 19, respectively, to parturition. There were no significant differences in gestational length or food consumption during pregnancy or lactation or in maternal weight during lactation. Diets did not modify litter size, sex ratio, survival index at weaning, or body weight. The SFOD and SOD offspring were significantly shorter than the CD offspring at weaning. The mean offspring physical scores of SOD and SFOD offspring were higher than CD offspring and simple reflexes were earlier in the SOD and SFOD groups. In SFOD offspring, puberty onset was significantly delayed, at postnatal days 26 and 27 in male and female offspring, respectively. This study suggests that the maintenance of an adequate omega-6:omega-3 ratio is necessary for the optimal growth and development of murine offspring. In populations that do not have sufficient provision of polyunsaturated fatty acids in the diet, their consumption would be advisable during gestation and lactation because these improve most neurodevelopmental outcomes included in this study. Copyright 2010 Elsevier Inc. All rights reserved.

Trajectories of maternal leisure-time physical activity and sedentary behavior during adolescence to young adulthood and offspring birthweight.

PubMed

Badon, Sylvia E; Littman, Alyson J; Chan, Kwun Chuen Gary; Williams, Michelle A; Enquobahrie, Daniel A

2017-11-01

The objectives of the study were to determine the extent to which trajectories of maternal preconception leisure-time physical activity (LTPA) and leisure-time sedentary behavior (LTSB) during adolescence and young adulthood are associated with offspring birth weight (BW) and to test if these associations differ by offspring sex or maternal pre-pregnancy overweight-obese status. Participants with one or more birth (n = 1408) were identified from the National Longitudinal Study of Adolescent to Adult Health. Group-based trajectory modeling was used to characterize trajectories of LTPA (frequency/week) and LTSB (hours/week) which were measured, on average, over 7 years between age 15 and 22 years. Weighted regression and Wald tests were used to estimate and test mean differences and odds ratios for BW, small for gestational age, and large for gestational age (LGA). Three trajectories were identified for LTPA and five for LTSB. Associations differed by offspring sex for continuous BW and LGA (interaction P = .10 and .008, respectively). Among female offspring, participants with high followed by decreasing LTPA delivered offspring with 90 g greater BW (95% confidence interval [CI]: -4 to 184) and 72% greater risk of LGA (95% CI: 0.94-3.14), compared with participants with low LTPA. Among male offspring, LTPA patterns were not associated with BW. A pattern of high then decreasing LTPA among normal weight, but not overweight-obese women, was associated with 2.03 times greater risk of LGA (95% CI: 1.06-3.88). LTSB trajectories were not associated with BW. Associations of preconception trajectories of LTPA with offspring BW may differ by offspring sex and maternal pre-pregnancy overweight-obese status. Copyright © 2017 Elsevier Inc. All rights reserved.

Characteristics of depression among offspring at high and low familial risk of bipolar disorder.

PubMed

Diler, Rasim Somer; Goldstein, Tina R; Hafeman, Danella; Rooks, Brian Thomas; Sakolsky, Dara; Goldstein, Benjamin I; Monk, Kelly; Hickey, Mary Beth; Axelson, David; Iyengar, Satish; Birmaher, Boris

2017-08-01

Having a parent with bipolar disorder (BP) is a very strong risk factor for developing BP. Similarly, depression among youth is a clinical risk factor for subsequent BP. We evaluated whether mood symptomatology in depressed youth is different between those at high and low familial risk to develop BP. The most severe major depressive episode in BP offspring (N=61) and community control offspring (N=20) was evaluated using expanded depression and mania rating scales derived from the Schedule for Affective Disorders and Schizophrenia for Children Present Version. The results were adjusted for any between-group significant demographic differences and for multiple comparisons. The severity of depressive symptoms and the percentage of offspring with severe depressive symptoms, especially atypical depressive features, were significantly higher in the depressed offspring of BP parents compared to the depressed controls (P s <.05). The depressive symptoms were helpful to identify a high-risk group (e.g., odds ratio [OR] for hypersomnia: 22.4, 95% confidence interval [CI]: 1.3-404, P=.04). In addition, there were significantly more depressed offspring of BP parents with subsyndromal manic symptoms than controls (52.5% vs 20%, OR: 4.2, 95% CI: 1.2-14.7, P<.01). Depressed BP offspring had more severe depression including atypical depressive symptoms, and were more likely to have subsyndromal mixed manic symptoms than depressed control offspring. Prospective studies to evaluate whether these youth are at high risk to develop BP are warranted. If replicated, the results of this study have important clinical (e.g., treatment of depression in depressed offspring of BP parents) and research implications. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Risk of shoulder dystocia: associations with parity and offspring birthweight. A population study of 1 914 544 deliveries.

PubMed

Overland, Eva A; Vatten, Lars J; Eskild, Anne

2012-04-01

We estimated the associations of parity and offspring birthweight with the risk of shoulder dystocia, and studied whether the association of offspring birthweight differed by parity. Population-based register study. The Medical Birth Registry of Norway was used to identify all deliveries between 1967 and 2006. All vaginal deliveries of a singleton offspring in cephalic presentation during the period 1967-2006 (n=1,914,544). Shoulder dystocia at delivery. Shoulder dystocia occurred in 0.68% (13,109/1,914,544) of all deliveries. There was a strong positive association of birthweight with risk of shoulder dystocia, and 75% (9765/13,109) of all cases occurred in deliveries of offspring weighing 4000g or more. The association of birthweight displayed similar patterns across parities, but the association was slightly stronger in parous than in primiparous women. Among first-time mothers, 0.12% (320/276,614) with offspring weighing 3000-3499g (reference) experienced shoulder dystocia, compared with 13.30% (169/1244) with offspring birthweight higher than 5000g [odds ratio (OR) 135.7, 95%CI 111.6-165.1]. The corresponding results for women with one previous delivery were 0.08% (161/201,572) and 16.45% (501/3054) (OR 246.4, 95%CI 205.4-295.5). High offspring birthweight is the major risk factor for shoulder dystocia, constituting most cases. The positive association of birthweight with shoulder dystocia showed similar patterns across parities, but high birthweight parous women were at greater risk of shoulder dystocia compared with primiparous women. © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

The Association Between Maternal Early Life Forced Sexual Intercourse and Offspring Birth Weight: The Role of Socioeconomic Status.

PubMed

Gavin, Amelia R; Morris, Julia

2017-05-01

This study utilizes a life-course framework to investigate whether maternal early life forced sexual intercourse operates in conjunction with health behaviors during adolescence, young adulthood, and the prenatal period to influence offspring birth weight. Using data from the 1994-2009 National Longitudinal Study of Adolescent Health (Add Health), we examined whether early life forced sexual intercourse predicted offspring birth weight through a mediated pathway, including depressive symptoms, substance use, and prenatal cigarette smoking. We stratify our analysis by socioeconomic status (SES) to determine whether the proposed pathways operate similarly, or differently, according to SES. Our findings suggest that the pathways through which forced sexual intercourse affects offspring birth weight differ by SES. Among middle-to-high SES women, we found a mediated pathway linking forced sexual intercourse to offspring birth weight with prenatal cigarette smoking predicting lower offspring birth weight. Among low SES women, however, we did not find a mediated pathway linking forced sexual intercourse to birth weight. Findings suggest that prenatal cigarette smoking was not a mechanism of influence in the pathway between maternal early life forced sexual intercourse and offspring birth weight for low SES women. Our findings suggest that forced sexual intercourse may influence infant birth weight in the next generation. Infants born with a low birth weight are at increased risk for a myriad of adverse outcomes across the life-course. Study results suggest the importance of interventions designed to reduce behavioral risks and to support health promoting behaviors among survivors in the short term, in an effort to prevent long-term consequences among later-born offspring.

Major benefits of guarding behavior in subsocial bees: implications for social evolution.

PubMed

Mikát, Michael; Černá, Kateřina; Straka, Jakub

2016-10-01

Parental care is a behavior that increases the growth and survival of offspring, often at a cost to the parents' own survival and/or future reproduction. In this study, we focused on nest guarding, which is one of the most important types of extended parental care; we studied this behavior in two solitary bee species of the genus Ceratina with social ancestors. We performed the experiment of removing the laying female, who usually guards the nest after completing its provisioning, to test the effects of nest guarding on the offspring survival and nest fate. By dissecting natural nests, we found that Ceratina cucurbitina females always guarded their offspring until the offspring reached adulthood. In addition, the females of this species were able to crawl across the nest partitions and inspect the offspring in the brood cells. In contrast, several Ceratina chalybea females guarded their nests until the offspring reached adulthood, but others closed the nest entrance with a plug and deserted the nest. Nests with a low number of provisioned cells were more likely to be plugged and abandoned than nests with a higher number of cells. The female removal experiment had a significantly negative effect on offspring survival in both species. These nests frequently failed due to the attacks of natural enemies (e.g., ants, chalcidoid wasps, and other competing Ceratina bees). Increased offspring survival is the most important benefit of the guarding strategy. The abandonment of a potentially unsuccessful brood might constitute a benefit of the nest plugging behavior. The facultative nest desertion strategy is a derived behavior in the studied bees and constitutes an example of an evolutionary reduction in the extent of parental care.

Intraspecific Variation in and Environment-Dependent Resource Allocation to Embryonic Development Time in Common Terns.

PubMed

Vedder, Oscar; Kürten, Nathalie; Bouwhuis, Sandra

Embryonic development time is thought to impact life histories through trade-offs against life-history traits later in life, yet the inference is based on interspecific comparative analyses only. It is largely unclear whether intraspecific variation in embryonic development time that is not caused by environmental differences occurs, which would be required to detect life-history trade-offs. Here we performed a classical common-garden experiment by incubating fresh eggs of free-living common terns (Sterna hirundo) in a controlled incubation environment at two different temperatures. Hatching success was high but was slightly lower at the lower temperature. While correcting for effects of year, incubation temperature, and laying order, we found significant variation in the incubation time embryos required until hatching and in their heart rate. Embryonic heart rate was significantly positively correlated within clutches, and a similar tendency was found for incubation time, suggesting that intrinsic differences in embryonic development rate between offspring of different parents exist. Incubation time and embryonic heart rate were strongly correlated: embryos with faster heart rates required shorter incubation time. However, after correction for heart rate, embryos still required more time for development at the lower incubation temperature. This suggests that processes other than development require a greater share of resources in a suboptimal environment and that relative resource allocation to development is, therefore, environment dependent. We conclude that there is opportunity to detect intraspecific life-history trade-offs with embryonic development time and that the resolution of trade-offs may differ between embryonic environments.

Emotion Recognition Ability Test Using JACFEE Photos: A Validity/Reliability Study of a War Veterans' Sample and Their Offspring.

PubMed

Castro-Vale, Ivone; Severo, Milton; Carvalho, Davide; Mota-Cardoso, Rui

2015-01-01

Emotion recognition is very important for social interaction. Several mental disorders influence facial emotion recognition. War veterans and their offspring are subject to an increased risk of developing psychopathology. Emotion recognition is an important aspect that needs to be addressed in this population. To our knowledge, no test exists that is validated for use with war veterans and their offspring. The current study aimed to validate the JACFEE photo set to study facial emotion recognition in war veterans and their offspring. The JACFEE photo set was presented to 135 participants, comprised of 62 male war veterans and 73 war veterans' offspring. The participants identified the facial emotion presented from amongst the possible seven emotions that were tested for: anger, contempt, disgust, fear, happiness, sadness, and surprise. A loglinear model was used to evaluate whether the agreement between the intended and the chosen emotions was higher than the expected. Overall agreement between chosen and intended emotions was 76.3% (Cohen kappa = 0.72). The agreement ranged from 63% (sadness expressions) to 91% (happiness expressions). The reliability by emotion ranged from 0.617 to 0.843 and the overall JACFEE photo set Cronbach alpha was 0.911. The offspring showed higher agreement when compared with the veterans (RR: 41.52 vs 12.12, p < 0.001), which confirms the construct validity of the test. The JACFEE set of photos showed good validity and reliability indices, which makes it an adequate instrument for researching emotion recognition ability in the study sample of war veterans and their respective offspring.

Emotion Recognition Ability Test Using JACFEE Photos: A Validity/Reliability Study of a War Veterans' Sample and Their Offspring

PubMed Central

Castro-Vale, Ivone; Severo, Milton; Carvalho, Davide; Mota-Cardoso, Rui

2015-01-01

Emotion recognition is very important for social interaction. Several mental disorders influence facial emotion recognition. War veterans and their offspring are subject to an increased risk of developing psychopathology. Emotion recognition is an important aspect that needs to be addressed in this population. To our knowledge, no test exists that is validated for use with war veterans and their offspring. The current study aimed to validate the JACFEE photo set to study facial emotion recognition in war veterans and their offspring. The JACFEE photo set was presented to 135 participants, comprised of 62 male war veterans and 73 war veterans’ offspring. The participants identified the facial emotion presented from amongst the possible seven emotions that were tested for: anger, contempt, disgust, fear, happiness, sadness, and surprise. A loglinear model was used to evaluate whether the agreement between the intended and the chosen emotions was higher than the expected. Overall agreement between chosen and intended emotions was 76.3% (Cohen kappa = 0.72). The agreement ranged from 63% (sadness expressions) to 91% (happiness expressions). The reliability by emotion ranged from 0.617 to 0.843 and the overall JACFEE photo set Cronbach alpha was 0.911. The offspring showed higher agreement when compared with the veterans (RR: 41.52 vs 12.12, p < 0.001), which confirms the construct validity of the test. The JACFEE set of photos showed good validity and reliability indices, which makes it an adequate instrument for researching emotion recognition ability in the study sample of war veterans and their respective offspring. PMID:26147938

Correlation of trabeculae and papillary muscles with clinical and cardiac characteristics and impact on CMR measures of LV anatomy and function.

PubMed

Chuang, Michael L; Gona, Philimon; Hautvast, Gilion L T F; Salton, Carol J; Blease, Susan J; Yeon, Susan B; Breeuwer, Marcel; O'Donnell, Christopher J; Manning, Warren J

2012-11-01

The goal of this study was to assess the relationship of left ventricular (LV) trabeculae and papillary muscles (TPM) with clinical characteristics in a community-based, free-living adult cohort and to determine the effect of TPM on quantitative measures of LV volume, mass, and ejection fraction (EF). Hypertrabeculation has been associated with adverse cardiovascular events, but the distribution and clinical correlates of the volume and mass of the TPM in a normal left ventricle have not been well characterized. Short-axis cine cardiac magnetic resonance images, obtained using a steady-state free precession sequence from 1,494 members of the Framingham Heart Study Offspring cohort, were analyzed with software that automatically segments TPM. Absolute TPM volume, TPM as a fraction of end-diastolic volume (EDV) (TPM/EDV), and TPM mass as a fraction of LV mass were determined in all offspring and in a referent group of offspring free of clinical cardiovascular disease and hypertension. In the referent group (mean age 61 ± 9 years; 262 men and 423 women), mean TPM was 23 ± 3% of LV EDV in both sexes (p = 0.9). TPM/EDV decreased with age (p < 0.02) but was not associated with body mass index. TPM mass as a fraction of LV mass was inversely correlated with age (p < 0.0001), body mass index (p < 0.018), and systolic blood pressure (p < 0.0001). Among all 1,494 participants (699 men), LV volumes decreased 23%, LV mass increased 28%, and EF increased by 7.5 EF units (p < 0.0001) when TPM were considered myocardial mass rather than part of the LV blood pool. Global cardiac magnetic resonance LV parameters were significantly affected by whether TPM was considered as part of the LV blood pool or as part of LV mass. Our cross-sectional data from a healthy referent group of adults free of clinical cardiovascular disease demonstrated that TPM/EDV decreases with increasing age in both sexes but is not related to hypertension or obesity. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Parents' perceptions on offspring risk and prevention of anxiety and depression: a qualitative study.

PubMed

Festen, Helma; Schipper, Karen; de Vries, Sybolt O; Reichart, Catrien G; Abma, Tineke A; Nauta, Maaike H

2014-01-01

Offspring of patients with anxiety or depression are at high risk for developing anxiety or depression. Despite the positive findings regarding effectiveness of prevention programs, recruitment for prevention activities and trials is notoriously difficult. Our randomized controlled prevention trial was terminated due to lack of patient inclusion. Research on mentally-ill parents' perceptions of offspring's risk and need for preventive intervention may shed light on this issue, and may enhance family participation in prevention activities and trials. Qualitative data were collected through semi-structured interviews with 24 parents (patients with anxiety or depression, or their partners). An inductive content analysis of the data was performed. Five research questions were investigated regarding parents' perceptions of anxiety, depression, and offspring risk; anxiety, depression, and parenting; the need for offspring intervention and prevention; and barriers to and experiences with participation in preventive research. Parental perceptions of the impact of parental anxiety and depression on offspring greatly differed. Parents articulated concerns about children's symptomatology, however, most parents did not perceive a direct link between parent symptoms and offspring quality of life. They experienced an influence of parental symptoms on family quality of life, but chose not to discuss that with their children in order to protect them. Parents were not well aware of the possibilities regarding professional help for offspring and preferred parent-focused rather than offspring-focused interventions such as parent psycho-education. Important barriers to participation in preventive research included parental overburden, shame and stigma, and perceived lack of necessity for intervention. This study highlights the importance of educating parents in adult health care. Providing psycho-education regarding offspring risk, communication in the family, and parenting in order to increase parental knowledge and parent-child communication, and decrease guilt and shame are important first steps in motivating parents to participate in preventive treatment.

Sex-Differences in the Metabolic Health of Offspring of Parents with Diabetes: A Record-Linkage Study

PubMed Central

Aldhous, Marian C.; Reynolds, Rebecca M.; Campbell, Archie; Linksted, Pamela; Lindsay, Robert S.; Smith, Blair H.; Seckl, Jonathan R.; Porteous, David J.; Norman, Jane E.

2015-01-01

Maternal diabetes in pregnancy affects offspring health. The impact of parental diabetes on offspring health is unclear. We investigated the impact of parental diabetes on the metabolic-health of adult-offspring who did not themselves have diabetes. Data from the Generation Scotland: Scottish Family Health Study, a population-based family cohort, were record-linked to subjects’ own diabetes medical records. From F0-parents, we identified F1-offspring of: mothers with diabetes (OMD, n = 409), fathers with diabetes (OFD, n = 468), no parent with diabetes (ONoPD, n = 2489). Metabolic syndrome, body, biochemical measurements and blood-pressures were compared between F1-offspring groups by sex. A higher proportion of female OMD had metabolic syndrome than female OFD or ONoPD (P<0.0001). In female offspring, predictors of metabolic syndrome were: having a mother with diabetes (OR = 1.78, CI 1.03–3.07, [reference ONoPD]), body mass index (BMI, OR = 1.21, CI 1.13–1.30) and age (OR = 1.03, CI 1.01–1.06). In male offspring, predictors of metabolic syndrome were: BMI (OR = 1.18, CI 1.09–1.29) and percent body-fat (OR = 1.12, CI 1.05–1.19). In both sexes, OMD had higher blood-pressures than OFD (P<0.0001). In females, OMD had higher glucose (P<0.0001) and percent body-fat (P<0.0001) compared with OFD or ONoPD. OMD and OFD both had increased waist-measurements (P<0.0001), BMI (P<0.0001) and percent body-fat (P<0.0001) compared with ONoPD. Female OMD and OFD had lower HDL-cholesterol levels (P<0.0001) than female ONoPD. Parental diabetes is associated with higher offspring-BMI and body-fat. In female offspring, maternal diabetes increased the odds of metabolic syndrome, even after adjusting for BMI. Further investigations are required to determine the mechanisms involved. PMID:26308734

Association between Maternal Depression Symptoms across the First Eleven Years of Their Child’s Life and Subsequent Offspring Suicidal Ideation

PubMed Central

Hammerton, Gemma; Mahedy, Liam; Mars, Becky; Harold, Gordon T.; Thapar, Anita; Zammit, Stanley; Collishaw, Stephan

2015-01-01

Depression is common, especially in women of child-bearing age; prevalence estimates for this group range from 8% to 12%, and there is robust evidence that maternal depression is associated with mental health problems in offspring. Suicidal behaviour is a growing concern amongst young people and those exposed to maternal depression are likely to be especially at high risk. The aim of this study was to utilise a large, prospective population cohort to examine the relationship between depression symptom trajectories in mothers over the first eleven years of their child’s life and subsequent adolescent suicidal ideation. An additional aim was to test if associations were explained by maternal suicide attempt and offspring depressive disorder. Data were utilised from a population-based birth cohort: the Avon Longitudinal Study of Parents and Children. Maternal depression symptoms were assessed repeatedly from pregnancy to child age 11 years. Offspring suicidal ideation was assessed at age 16 years. Using multiple imputation, data for 10,559 families were analysed. Using latent class growth analysis, five distinct classes of maternal depression symptoms were identified (minimal, mild, increasing, sub-threshold, chronic-severe). The prevalence of past-year suicidal ideation at age 16 years was 15% (95% CI: 14-17%). Compared to offspring of mothers with minimal symptoms, the greatest risk of suicidal ideation was found for offspring of mothers with chronic-severe symptoms [OR 3.04 (95% CI 2.19, 4.21)], with evidence for smaller increases in risk of suicidal ideation in offspring of mothers with sub-threshold, increasing and mild symptoms. These associations were not fully accounted for by maternal suicide attempt or offspring depression diagnosis. Twenty-six percent of non-depressed offspring of mothers with chronic-severe depression symptoms reported suicidal ideation. Risk for suicidal ideation should be considered in young people whose mothers have a history of sustained high levels of depression symptoms, even when the offspring themselves do not have a depression diagnosis. PMID:26151929

Maternal substance use during pregnancy and offspring conduct problems: A meta-analysis.

PubMed

Ruisch, I Hyun; Dietrich, Andrea; Glennon, Jeffrey C; Buitelaar, Jan K; Hoekstra, Pieter J

2018-01-01

We conducted meta-analyses of relationships between highly prevalent substance use during pregnancy and offspring conduct disorder problems. In total 36 studies were included. Odds ratios (ORs) were 2.06 (1.67-2.54, 25 studies) for maternal smoking, 2.11 (1.42-3.15, 9 studies) for alcohol use, and 1.29 (0.93-1.81, 3 studies) for cannabis use, while a single study of caffeine use reported no effects. Our meta-analyses support an association between smoking and alcohol use during pregnancy, and offspring conduct problems, yet do not resolve causality issues given potential confounding by genetic factors, gene-environment interactions, and comorbidity such as with attention deficit hyperactivity disorders. Future studies should use genetically sensitive designs to investigate the role of pregnancy substance use in offspring conduct problems and may consider more broadly defined behavioral problems. Copyright © 2017 Elsevier Ltd. All rights reserved.

Intergenerational predictors of birth weight in the Philippines: correlations with mother's and father's birth weight and test of maternal constraint.

PubMed

Kuzawa, Christopher W; Eisenberg, Dan T A

2012-01-01

Birth weight (BW) predicts many health outcomes, but the relative contributions of genes and environmental factors to BW remain uncertain. Some studies report stronger mother-offspring than father-offspring BW correlations, with attenuated father-offspring BW correlations when the mother is stunted. These findings have been interpreted as evidence that maternal genetic or environmental factors play an important role in determining birth size, with small maternal size constraining paternal genetic contributions to offspring BW. Here we evaluate mother-offspring and father-offspring birth weight (BW) associations and evaluate whether maternal stunting constrains genetic contributions to offspring birth size. Data include BW of offspring (n = 1,101) born to female members (n = 382) and spouses of male members (n = 275) of a birth cohort (born 1983-84) in Metropolitan Cebu, Philippines. Regression was used to relate parental and offspring BW adjusting for confounders. Resampling testing was used to evaluate whether false paternity could explain any evidence for excess matrilineal inheritance. In a pooled model adjusting for maternal height and confounders, parental BW was a borderline-significantly stronger predictor of offspring BW in mothers compared to fathers (sex of parent interaction p = 0.068). In separate multivariate models, each kg in mother's and father's BW predicted a 271±53 g (p<0.00001) and 132±55 g (p = 0.017) increase in offspring BW, respectively. Resampling statistics suggested that false paternity rates of >25% and likely 50% would be needed to explain these differences. There was no interaction between maternal stature and maternal BW (interaction p = 0.520) or paternal BW (p = 0.545). Each kg change in mother's BW predicted twice the change in offspring BW as predicted by a change in father's BW, consistent with an intergenerational maternal effect on offspring BW. Evidence for excess matrilineal BW heritability at all levels of maternal stature points to indirect genetic, mitochondrial, or epigenetic maternal contributions to offspring fetal growth.

[SYNERGISM OF PRECONCEPTIVE RADIATION EXPOSURE AND PARENTS' ONCO-PATHOLOGY IN THE RISE OF CARCINOGENIC RISK IN THE OFFSPRINGS OF PROFESSIONAL EMPLOYEES].

PubMed

Telnov, V I; Kabirova, N R; Okatenko, P V

2015-01-01

The problem of carcinogenic risk in offsprings of individuals exposed to radiation is challenging and insufficiently studied. In that there are no evaluations of the interaction between radiation and non-radiation factors. The aim of the study was the analysis of interaction of preconceptive radiation exposure and parents' onco-pathology in cancer mortality in offsprings (F1) of workers (fathers) of the Mayak Production Association exposed to a wide range of doses of radiation over a year prior conception. The number of offspring is 8191 individuals (4180 men and 4011 women). The analysis was performed with the use of fourfold table and eightfold tables. The interaction offactors was estimated on the base of the additive and multiplicative models. The studied factors were independent. The odds ratio (OR) of cancer mortality in the offspring with parents' oncopathology (1.43) was insignificant. OR of cancer mortality in preconceptive radiation exposure in a dose over 110 mGy and without parents' onco-pathology was 2.61 (1.52-4.49), and in their combination--3.86 (1.93-7.71). Index of synergism of preconceptive radiation exposure and parents' onco-patholog in the rise of carcinogenic risk in the offspring was 1.34 and the character of their interaction was multiplicative. Thus, for the first time there was established the interaction between radiation and non-radiation factors in the synergism sort in the increase of carcinogenic risk in the offspring of people exposed to radiation.

The Effect of Neonatal Leptin Antagonism in Male Rat Offspring Is Dependent upon the Interaction between Prior Maternal Nutritional Status and Post-Weaning Diet

PubMed Central

Beltrand, J.; Sloboda, D. M.; Connor, K. L.; Truong, M.; Vickers, M. H.

2012-01-01

Epidemiological and experimental studies report associations between overweight mothers and increased obesity risk in offspring. It is unclear whether neonatal leptin regulation mediates this association between overweight mothers and offspring obesity. We investigated the effect of neonatal treatment with a leptin antagonist (LA) on growth and metabolism in offspring of mothers fed either a control or a high fat diet. Wistar rats were fed either a control (CON) or a high fat diet (MHF) during pregnancy and lactation. Male CON and MHF neonates received either saline (S) or a rat-specific pegylated LA on days 3, 5, and 7. Offspring were weaned onto either a control or a high fat (hf) diet. At day 100, body composition, blood glucose, β-hydroxybutyrate and plasma leptin and insulin were determined. In CON and MHF offspring, LA increased neonatal bodyweights compared to saline-treated offspring and was more pronounced in MHF offspring. In the post-weaning period, neonatal LA treatment decreased hf diet-induced weight gain but only in CON offspring. LA treatment induced changes in body length, fat mass, body temperature, and bone composition. Neonatal LA treatment can therefore exert effects on growth and metabolism in adulthood but is dependent upon interactions between maternal and post-weaning nutrition. PMID:22548153

The importance of calcium in improving resistance of Daphnia to Microcystis.

PubMed

Akbar, Siddiq; Du, Jingjing; Jia, Yong; Tian, Xingjun

2017-01-01

Changing environmental calcium (Ca) and rising cyanobacterial blooms in lake habitats could strongly reduce Daphnia growth and survival. Here, we assessed the effects of maternal Ca in Daphnia on transfer of resistance to their offspring against Microcystis aeruginosa PCC7806 (M. aeruginosa). Laboratory microcosm experiments were performed to examine effects in Daphnia carinata (D. carinata) and Daphnia pulex (D. pulex), and that how Ca induce responses in their offspring. The results showed that growth and survival were increased in offspring from exposed Daphnia as compared to unexposed, when raised in high Ca and increasing M. aeruginosa concentration. Among exposed Daphnia, offspring from high Ca mothers, produced more neonates with large size and higher survival as compared to offspring from low maternal Ca. Exposed D. carinata and D. pulex offspring, when reared in Ca deficient medium and increasing M. aeruginosa concentration, time to first brood increased, size become large and total offspring decreased subsequently in three alternative broods in offspring from low maternal Ca. In contrast, growth and reproduction in offspring from high Ca exposed mothers were consistent in three alternative broods. Despite species specific responses in growth, survival and variant life history traits in two Daphnia species, our results not only show maternal induction in Daphnia but also highlight that offspring response to M. aeruginosa varies with maternal Ca. This study demonstrates that Ca have role in Daphnia maternal induction against Microcystis, and recent Ca decline and increasing Microcystis concentration in lakes may decrease Daphnia growth and survival. Our data provide insights into the interactive effect of maternal Ca and Microcystis exposure on Daphnia and their outcome on offspring life history traits and survival.

Gestational and Lactational Exposure to Atrazine via the Drinking Water Causes Specific Behavioral Deficits and Selectively Alters Monoaminergic Systems in C57BL/6 Mouse Dams, Juvenile and Adult Offspring

PubMed Central

Krishna, Saritha; Ye, Xiaoqin; Filipov, Nikolay M.

2014-01-01

Atrazine (ATR) is one of the most frequently detected pesticides in the U.S. water supply. This study aimed to investigate neurobehavioral and neurochemical effects of ATR in C57BL/6 mouse offspring and dams exposed to a relatively low (3 mg/l, estimated intake 1.4 mg/kg/day) concentration of ATR via the drinking water (DW) from gestational day 6 to postnatal day (PND) 23. Behavioral tests included open field, pole, grip strength, novel object recognition (NOR), forced swim, and marble burying tests. Maternal weight gain and offspring (PND21, 35, and 70) body or brain weights were not affected by ATR. However, ATR-treated dams exhibited decreased NOR performance and a trend toward hyperactivity. Juvenile offspring (PND35) from ATR-exposed dams were hyperactive (both sexes), spent less time swimming (males), and buried more marbles (females). In adult offspring (PND70), the only behavioral change was a sex-specific (females) decreased NOR performance by ATR. Neurochemically, a trend toward increased striatal dopamine (DA) in dams and a significant increase in juvenile offspring (both sexes) was observed. Additionally, ATR exposure decreased perirhinal cortex serotonin in the adult female offspring. These results suggest that perinatal DW exposure to ATR targets the nigrostriatal DA pathway in dams and, especially, juvenile offspring, alters dams’ cognitive performance, induces sex-selective changes involving motor and emotional functions in juvenile offspring, and decreases cognitive ability of adult female offspring, with the latter possibly associated with altered perirhinal cortex serotonin homeostasis. Overall, ATR exposure during gestation and lactation may cause adverse nervous system effects to both offspring and dams. PMID:24913803

Effects of paternal obesity on growth and adiposity of male rat offspring.

PubMed

Lecomte, Virginie; Maloney, Christopher A; Wang, Kristy W; Morris, Margaret J

2017-02-01

Emerging evidence suggests that paternal obesity plays an important role in offspring health. Our previous work using a rodent model of diet-induced paternal obesity showed that female offspring from high-fat diet (HFD)-fed fathers develop glucose intolerance due to impairment of pancreatic insulin secretion. Here, we focused on the health outcomes of male offspring from HFD-fed fathers. Male Sprague-Dawley rats (3 wk old) were fed control (CD-F0) or HFD (HFD-F0) for 12 wk before mating with control-fed females. Male offspring were fed control diets for up to 8 wk or 6 mo. Although male offspring from HFD-F0 did not develop any obvious glucose metabolism defects in this study, surprisingly, a growth deficit phenotype was observed from birth to 6 mo of age. Male offspring from HFD-F0 had reduced birth weight compared with CD-F0, followed by reduced postweaning growth from 9 wk of age. This resulted in 10% reduction in body weight at 6 mo with significantly smaller fat pads and skeletal muscles. Reduced circulating levels of growth hormone (GH) and IGF-I were detected at 8 wk and 6 mo, respectively. Expression of adipogenesis markers was decreased in adipose tissue of HFD-F0 offspring at 8 wk and 6 mo, and expression of growth markers was decreased in muscle of HFD-F0 offspring at 8 wk. We propose that the reduced GH secretion at 8 wk of age altered the growth of male offspring from HFD-F0, resulting in smaller animals from 9 wk to 6 mo of age. Furthermore, increased muscle triglyceride content and expression of lipogenic genes were observed in HFD-F0 offspring, potentially increasing their metabolic risk. Copyright © 2017 the American Physiological Society.

Effect of maternal protein restriction during pregnancy and postweaning high-fat feeding on diet-induced thermogenesis in adult mouse offspring.

PubMed

Sellayah, Dyan; Dib, Lea; Anthony, Frederick W; Watkins, Adam J; Fleming, Tom P; Hanson, Mark A; Cagampang, Felino R

2014-10-01

Prenatal undernutrition followed by postweaning feeding of a high-fat diet results in obesity in the adult offspring. In this study, we investigated whether diet-induced thermogenesis is altered as a result of such nutritional mismatch. Female MF-1 mice were fed a normal protein (NP, 18% casein) or a protein-restricted (PR, 9% casein) diet throughout pregnancy and lactation. After weaning, male offspring of both groups were fed either a high-fat diet (HF; 45% kcal fat) or standard chow (C, 7% kcal fat) to generate the NP/C, NP/HF, PR/C and PR/HF adult offspring groups (n = 7-11 per group). PR/C and NP/C offspring have similar body weights at 30 weeks of age. Postweaning HF feeding resulted in significantly heavier NP/HF offspring (P < 0.01), but not in PR/HF offspring, compared with their chow-fed counterparts. However, the PR/HF offspring exhibited greater adiposity (P < 0.01) v the NP/HF group. The NP/HF offspring had increased energy expenditure and increased mRNA expression of uncoupling protein-1 and β-3 adrenergic receptor in the interscapular brown adipose tissue (iBAT) compared with the NP/C mice (both at P < 0.01). No such differences in energy expenditure and iBAT gene expression were observed between the PR/HF and PR/C offspring. These data suggest that a mismatch between maternal diet during pregnancy and lactation, and the postweaning diet of the offspring, can attenuate diet-induced thermogenesis in the iBAT, resulting in the development of obesity in adulthood.

Impact of maternal mild hyperglycemia on maternal care and offspring development and behavior of Wistar rats.

PubMed

Kiss, Ana Carolina Inhasz; Woodside, Barbara; Felício, Luciano Freitas; Anselmo-Franci, Janete; Damasceno, Débora Cristina

2012-10-10

The aim of the present study was to evaluate the effect of maternal mild hyperglycemia on maternal behavior, as well as the development, behavior, reproductive function, and glucose tolerance of the offspring. At birth, litters were assigned either to Control (subcutaneous (sc)-citrate buffer) or STZ groups (streptozotocin (STZ)-100mg/kg-sc.). On PND 90 both STZ-treated and Control female rats were mated. Glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were performed during pregnancy. Pregnancy duration, litter size and sex ratio were assessed. Newborns were classified according to birth weight as small (SPA), adequate (APA), or large for pregnancy age (LPA). Maternal behavior was analyzed on PND 5 and 10. Offspring body weight, length, and anogenital distance were measured and general activity was assessed in the open field. Sexual behavior was tested in both male and female offspring. Levels of reproductive hormones and estrous cycle duration were evaluated in female offspring. Female offspring were mated and both a GTT and ITT performed during pregnancy. Neonatal STZ administration caused mild hyperglycemia during pregnancy and changed some aspects of maternal care. The hyperglycemic intrauterine milieu impaired physical development and increased immobility in the open field in the offspring although the latter effect appeared at different ages for males (adulthood) and females (infancy). There was no impairment in the sexual behavior of either male or female offspring. As adults, female offspring of STZ-treated mothers did not show glucose intolerance during pregnancy. Thus, offspring of female rats that show mild hyperglycemia in pregnancy have fewer behavioral and developmental impairments than previously reported in the offspring of severely diabetic dams suggesting that the degree of impairment is directly related to the mother glycemic intensity. Copyright © 2012 Elsevier Inc. All rights reserved.

Association of Anxiety Symptoms in Offspring of Bipolar Parents with Serotonin Transporter-Linked Polymorphic Region (5-HTTLPR) Genotype

PubMed Central

Park, Min-Hyeon; Sanders, Erica; Howe, Meghan; Singh, Manpreet; Hallmayer, Joachim; Kim, Eunjoo

2015-01-01

Abstract Objective: Offspring of parents with bipolar disorder (BD) have been shown to be at high risk for BD. Anxiety symptoms, even at subclinical levels, have been associated with increased risk for BD in these youth. The s-allele of the serotonin transporter-linked polymorphic region (5-HTTLPR) has been implicated in the pathophysiology of both BD and anxiety disorders and has been associated with pharmacological treatment response and increased risk for antidepressant side effects. Therefore, we aimed to explore 1) whether anxiety symptoms in offspring of BD parents were associated with presence of the 5-HTTLPR s-allele and 2) whether anxiety symptoms in the offspring of BD parents according to the 5-HTTLPR genotypes are related to antianxiety medication status. Methods: A total of 64 offspring of BD parents (mean age: 13.7 years) and 51 healthy controls (HC) (mean age: 13.7 years) were compared genetically and on the Multidimensional Anxiety Scale for Children (MASC). Results: Offspring of BD parents showed higher levels of overall anxiety than did the HC group. Only antianxiety medication naïve offspring of BD parents were found to have an association between 5-HTTLPR genotypes and anxiety symptoms. The antianxiety medication naïve offspring of BD parents with the s-allele showed higher level of overall anxiety than offspring of BD parents with the l/l genotype. No significant differences in anxiety symptoms or their association with the 5-HTTLPR genotype were found in the HC group. Conclusions: This study indicated that there may be an association between 5-HTTLPR genotypes and anxiety symptoms in offspring of BD parents, and that antianxiety medication status may affect anxiety symptoms in the offspring of BD patients according to genotype. PMID:26218602

Paternal B vitamin intake is a determinant of growth, hepatic lipid metabolism and intestinal tumor volume in female Apc1638N mouse offspring

USDA-ARS?s Scientific Manuscript database

Background: The importance of maternal nutrition to offspring health and risk of disease is well established. Emerging evidence suggests paternal diet may affect offspring health as well. Objective: In the current study we sought to determine whether modulating pre-conception paternal B vitamin inta...

Subcortical Gray Matter Volume Abnormalities in Healthy Bipolar Offspring: Potential Neuroanatomical Risk Marker for Bipolar Disorder?

ERIC Educational Resources Information Center

Ladouceur, Cecile D.; Almeida, Jorge R. C.; Birmaher, Boris; Axelson, David A.; Nau, Sharon; Kalas, Catherine; Monk, Kelly; Kupfer, David J.; Phillips, Mary L.

2008-01-01

A study is conducted to examine the extent to which bipolar disorder (BD) is associated with gray matter volume abnormalities in brain regions in healthy bipolar offspring relative to age-matched controls. Results show increased gray matter volume in the parahippocampus/hippocampus in healthy offspring at genetic risk for BD.

Lower Maternal Folate Status in Early Pregnancy Is Associated with Childhood Hyperactivity and Peer Problems in Offspring

ERIC Educational Resources Information Center

Schlotz, Wolff; Jones, Alexander; Phillips, David I. W.; Gale, Catharine R.; Robinson, Sian M.; Godfrey, Keith M.

2010-01-01

Background: Maternal nutrition during pregnancy has been linked with fetal brain development and psychopathology in the offspring. We examined for associations of maternal folate status and dietary intake during pregnancy with brain growth and childhood behavioural difficulties in the offspring. Methods: In a prospective cohort study, maternal red…

Parental Involvement in Residential Care and Perceptions of their Offspring's Life Satisfaction in Residential Facilities for Adults with Intellectual Disability

ERIC Educational Resources Information Center

Schwartz, Chaya

2005-01-01

Background: This study examined parental involvement in relocation and post-placement care of offspring in residential facilities for adults with intellectual disability, as well as the characteristics of residents, parents, and residential institutions and the effect of those variables on parental perceptions of their offspring's life…

The Association of Maternal Socialization in Childhood and Adolescence with Adult Offsprings' Sympathy/Caring

ERIC Educational Resources Information Center

Eisenberg, Nancy; VanSchyndel, Sarah K.; Hofer, Claire

2015-01-01

The purpose of the study was to examine associations between mothers' socialization practices in childhood and adolescence and offsprings' (N = 32, 16 female) sympathy/concern in early adulthood. Mothers reported on their socialization practices and beliefs a total of 6 times using a Q-sort during their offsprings' childhood…

The Effect of Consanguineous Marriage on Reading Disability in the Arab Community

ERIC Educational Resources Information Center

Abu-Rabia, Salim; Maroun, Lateefeh

2005-01-01

The present study examined the effect of consanguineous marriage in the Arab community on reading disabilities of offspring. It examined whether the rate of reading disabilities was higher among offspring of first-cousin parents than offspring of unrelated parents; and whether reading-disabled children of first-cousin parents were more disabled in…

Effects of lifestyle intervention in pregnancy and anthropometrics at birth on offspring metabolic profile at 2.8 years: results from the Lifestyle in Pregnancy and Offspring (LiPO) study.

PubMed

Tanvig, Mette; Vinter, Christina A; Jørgensen, Jan S; Wehberg, Sonja; Ovesen, Per G; Beck-Nielsen, Henning; Christesen, Henrik T; Jensen, Dorte M

2015-01-01

Maternal obesity and gestational weight gain are linked to offspring adverse metabolic profiles, and lifestyle interventions during pregnancy in obese women may have long-term positive effects on their children. Furthermore, although the association between birth weight and later metabolic outcomes is well established, little is known about the predictive value of abdominal circumference at birth. The purpose of this study was to determine (1) the effects of lifestyle interventions during pregnancy in obese women on offspring metabolic risk factors and (2) predictive values of birth weight (BW) and birth abdominal circumference (BAC). This was a follow-up of a randomized controlled trial, the Lifestyle in Pregnancy (LiP) study. The study was conducted in Odense and Aarhus University Hospitals, Denmark. We studied the offspring of LiP study participants (n = 157) and offspring of normal-weight mothers (external reference group, n = 97). INTERVENTIONs included dietary advice, coaching, and exercise during pregnancy. The outcome measures were body mass index (BMI) Z-score, abdominal circumference, blood pressure, and fasting plasma glucose, insulin, high-density lipoprotein, and triglycerides at the age of 2.8 years. No differences were detected in BMI Z-scores or metabolic risk factors between the LiP intervention and control groups or between the LiP and external reference groups. BAC and BW were associated (all P < .05) with BMI Z-score (0.19-0.23), abdominal circumference (0.57-0.70), plasma glucose (0.11-0.09), insulin (4.33-3.13), and triglycerides (0.07-0.07) but not with blood pressure or high-density lipoprotein (regression coefficients per increase in BAC and BW of 1 SD score). Early childhood metabolic risk factors were unaffected by lifestyle interventions in obese pregnant women. Offspring of obese mothers who participated in the LiP study were comparable to offspring of normal-weight mothers, possibly indicating a general beneficial effect of trial participation. BAC and BW were both associated with later metabolic risk factors.

Psychological stress has a higher rate of developing addictive behaviors compared to physical stress in rat offspring

PubMed Central

Nazeri, Masoud; Ebrahimi, Arezoo; Aghaei, Iraj; Ghotbi Ravandi, Samaneh; Shabani, Mohammad

2017-01-01

Prenatal stress could have great influence on development of offspring and might alter cognitive function and other physiological processes of children. The current study was conducted to study the effect of physical or psychological prenatal stress on addictive and anxiety-like behavior of male and female offspring during their adolescence period (postnatal day (PND) 40). Adult female rats were exposed to physical (swimming) or psychological (observing another female rat swimming) stress from day six of gestation for 10 days. Male and female offspring were assayed for anxiety-like behavior, motor and balance function and morphine conditioned place preference using the open field, elevated plus maze (EPM), rotarod and wire grip assay and conditioned place preference. Offspring in both physical and psychological prenatal stress groups demonstrated significant increase in anxiety-like behavior in EPM paradigm, but no alterations were observed in motor and balance function of animals. Offspring in the psychological prenatal stress group had an increased preference for morphine in comparison to control and physical prenatal stress groups. Results of the current study demonstrated that animals exposed to psychological stress during fetal development are at a higher risk of developing addictive behaviors. Further research might elucidate the exact mechanisms involved to provide better preventive and therapeutic interventions. PMID:28900372

CMR reference values for left ventricular volumes, mass, and ejection fraction using computer-aided analysis: the Framingham Heart Study.

PubMed

Chuang, Michael L; Gona, Philimon; Hautvast, Gilion L T F; Salton, Carol J; Breeuwer, Marcel; O'Donnell, Christopher J; Manning, Warren J

2014-04-01

To determine sex-specific reference values for left ventricular (LV) volumes, mass, and ejection fraction (EF) in healthy adults using computer-aided analysis and to examine the effect of age on LV parameters. We examined data from 1494 members of the Framingham Heart Study Offspring cohort, obtained using short-axis stack cine SSFP CMR, identified a healthy reference group (without cardiovascular disease, hypertension, or LV wall motion abnormality) and determined sex-specific upper 95th percentile thresholds for LV volumes and mass, and lower 5th percentile thresholds for EF using computer-assisted border detection. In secondary analyses, we stratified participants by age-decade and tested for linear trend across age groups. The reference group comprised 685 adults (423F; 61 ± 9 years). Men had greater LV volumes and mass, before and after indexation to common measures of body size (all P = 0.001). Women had greater EF (73 ± 6 versus 71 ± 6%; P = 0.0002). LV volumes decreased with greater age in both sexes, even after indexation. Indexed LV mass did not vary with age. LV EF and concentricity increased with greater age in both sexes. We present CMR-derived LV reference values. There are significant age and sex differences in LV volumes, EF, and geometry, whereas mass differs between sexes but not age groups. Copyright © 2013 Wiley Periodicals, Inc.

CMR Reference Values for Left Ventricular Volumes, Mass and Ejection Fraction Using Computer-Aided Analysis: The Framingham Heart Study

PubMed Central

Chuang, Michael L.; Gona, Philimon; Hautvast, Gilion L.T.F.; Salton, Carol J.; Breeuwer, Marcel; O’Donnell, Christopher J.; Manning, Warren J.

2013-01-01

Purpose To determine sex-specific reference values for left ventricular (LV) volumes, mass and ejection fraction (EF) in healthy adults using computer-aided analysis and to examine the effect of age on LV parameters. Methods and Methods We examined data from 1494 members of the Framingham Heart Study Offspring cohort, obtained using short-axis stack cine SSFP CMR, identified a healthy reference group (without cardiovascular disease, hypertension, or LV wall motion abnormality) and determined sex-specific upper 95th percentile thresholds for LV volumes and mass, and lower 5th percentile thresholds for EF using computer-assisted border detection. In secondary analyses we stratified participants by age-decade and tested for linear trend across age groups. Results The reference group comprised 685 adults (423F; 61±9 years). Men had greater LV volumes and mass, before and after indexation to common measures of body size (all p<0.001). Women had greater EF (73±6 vs. 71±6%, p=0.0002). LV volumes decreased with greater age in both sexes, even after indexation. Indexed LV mass did not vary with age. LV EF and concentricity increased with greater age in both sexes. Conclusion We present CMR-derived LV reference values. There are significant age and sex differences in LV volumes, EF and geometry, while mass differs between sexes but not age groups. PMID:24123369

Risk comparison for prenatal use of analgesics and selected birth defects, National Birth Defects Prevention Study 1997-2011.

PubMed

Interrante, Julia D; Ailes, Elizabeth C; Lind, Jennifer N; Anderka, Marlene; Feldkamp, Marcia L; Werler, Martha M; Taylor, Lockwood G; Trinidad, James; Gilboa, Suzanne M; Broussard, Cheryl S

2017-10-01

To compare the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and/or opioids to the use of acetaminophen without NSAIDs or opioids with respect to associations with birth defects. We used data from the National Birth Defects Prevention Study (1997-2011). Exposure was self-reported maternal analgesic use from the month before through the third month of pregnancy (periconceptional). Adjusted odds ratios (aORs) were calculated to examine associations with 16 birth defects. Compared to acetaminophen, mothers reporting NSAIDs were significantly more likely to have offspring with gastroschisis, hypospadias, cleft palate, cleft lip with cleft palate, cleft lip without cleft palate, anencephaly, spina bifida, hypoplastic left heart syndrome, pulmonary valve stenosis, and tetralogy of Fallot (aOR range, 1.2-1.6). Opioids were associated with tetralogy of Fallot, perimembranous ventricular septal defect, and ventricular septal defect with atrial septal defect (aOR range, 1.8-2.3), whereas use of both opioids and NSAIDs was associated with gastroschisis, cleft palate, spina bifida, hypoplastic left heart syndrome, and pulmonary valve stenosis (aOR range, 2.0-2.9). Compared to periconceptional use of acetaminophen, selected birth defects occurred more frequently among infants of women using NSAIDs and/or opioids. However, we could not definitely determine whether these risks relate to the drugs or to indications for treatment. Published by Elsevier Inc.

AGT M235T genotype/anxiety interaction and gender in the HyperGEN study.

PubMed

Knox, Sarah S; Guo, Xinxin; Zhang, Yuqing; Weidner, G; Williams, Scott; Ellison, R Curtis

2010-10-13

Both anxiety and elevated heart rate (HR) have been implicated in the development of hypertension. The HyperGen cohort, consisting of siblings with severe and mild hypertension, an age-matched random sample of persons from the same base populations, and unmedicated adult offspring of the hypertensive siblings (N = 1,002 men and 987 women), was analyzed for an association of the angiotenisinogen AGTM235T genotype (TT, MT, MM) with an endophenotype, heart rate (HR) in high and low anxious groups. The interaction of AGTM genotype with anxiety, which has been independently associated with hypertension, was investigated adjusting for age, hypertension status, smoking, alcohol consumption, beta blocker medication, body mass index, physical activity and hours of television viewing (sedentary life style). Although there was no main effect of genotype on HR in men or women, high anxious men with the TT genotype had high HR, whereas high anxious men with the MM genotype had low HR. In women, HR was inversely associated with anxiety but there was no interaction with genotype. The results suggest that high anxiety in men with the TT genotype may increase risk for hypertension whereas the MM genotype may be protective in high anxious men. This type of gene x environment interaction may be one reason why genome wide association studies sometimes fail to replicate. The locus may be important only in combination with certain environmental factors.

Maternal Smoking in Pregnancy and Offspring Depression: a cross cohort and negative control study.

PubMed

Taylor, Amy E; Carslake, David; de Mola, Christian Loret; Rydell, Mina; Nilsen, Tom I L; Bjørngaard, Johan H; Horta, Bernardo Lessa; Pearson, Rebecca; Rai, Dheeraj; Galanti, Maria Rosaria; Barros, Fernando C; Romundstad, Pål R; Davey Smith, George; Munafò, Marcus R

2017-10-03

Previous reports suggest that offspring of mothers who smoke during pregnancy have greater risk of developing depression. However, it is unclear whether this is due to intrauterine effects. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) from the UK (N = 2,869), the Nord-Trøndelag health study (HUNT) from Norway (N = 15,493), the Pelotas 1982 Birth Cohort Study from Brazil (N = 2,626), and the Swedish Sibling Health Cohort (N = 258 sibling pairs), we compared associations of maternal smoking during pregnancy and mother's partner's smoking during pregnancy with offspring depression and performed a discordant sibling analysis. In meta-analysis, maternal smoking during pregnancy was associated with higher odds of offspring depression (OR 1.20, 95% CI:1.08,1.34), but mother's partner's smoking during pregnancy was not (OR 1.05, 95% CI:0.94,1.17). However, there was only weak statistical evidence that the odds ratios for maternal and mother's partner's smoking differed from each other (p = 0.08). There was no clear evidence for an association between maternal smoking during pregnancy and offspring depression in the sibling analysis. Findings do not provide strong support for a causal role of maternal smoking during pregnancy in offspring depression, rather observed associations may reflect residual confounding relating to characteristics of parents who smoke.

Do children born to teenage parents have lower adult intelligence? A prospective birth cohort study.

PubMed

Khatun, Mohsina; Al Mamun, Abdullah; Scott, James; William, Gail M; Clavarino, Alexandra; Najman, Jake M

2017-01-01

Teenage motherhood has been associated with a wide variety of negative offspring outcomes including poorer cognitive development. In the context of limitations of previous research, this paper assesses the contemporary relevance of this finding. In this study we investigate the long-term cognitive status (IQ) among 21 year adult offspring born to teenage parents using the Mater University Study of Pregnancy- a prospective birth cohort study, which recruited all pregnant mothers attending a large obstetrical hospital in Brisbane, Australia, from 1981 to 1983. The analyses were restricted to a sub-sample of 2643 mother-offspring pair. Offspring IQ was measured using the Peabody Picture Vocabulary Test at 21 year. Parental age was reported at first clinic visit. Offspring born to teenage mothers (<20 years) have -3.0 (95% Confidence Interval (CI): -4.3, -1.8) points lower IQ compared to children born to mothers ≥20 years and were more likely to have a low IQ (Odds Ratio (OR) 1.7; 95% CI: 1.3, 2.3). Adjustment for a range of confounding and mediating factors including parental socioeconomic status, maternal IQ, maternal smoking and binge drinking in pregnancy, birthweight, breastfeeding and parenting style attenuates the association, though the effect remains statistically significant (-1.4 IQ points; 95% CI: -2.8,-0.1). Similarly the risk of offspring having low IQ remained marginally significantly higher in those born to teenage mothers (OR 1.3; 95% CI: 1.0, 1.9). In contrast, teenage fatherhood is not associated with adult offspring IQ, when adjusted for maternal age. Although the reduction in IQ is quantitatively small, it is indicative of neurodevelopmental disadvantage experienced by the young adult offspring of teenage mothers. Our results suggest that public policy initiatives should be targeted not only at delaying childbearing in the population but also at supporting early life condition of children born to teenage mothers to minimize the risk for disadvantageous outcomes of the next generation.

Family ties: maternal-offspring attachment and young adult nonmedical prescription opioid use.

PubMed

Cerdá, M; Bordelois, P; Keyes, K M; Roberts, A L; Martins, S S; Reisner, S L; Austin, S B; Corliss, H L; Koenen, K C

2014-09-01

Nonmedical prescription drug use is prevalent among young adults, yet little is known about modifiable determinants of use. We examined whether maternal-offspring attachment reported at mean age 21 was associated with nonmedical prescription opioid use at mean age 26, and investigated whether a history of depressive symptoms and substance use played a role in associations between maternal-offspring attachment and nonmedical prescription opioid use. We used data from the Growing Up Today Study, a longitudinal cohort of United States adolescents followed into young adulthood. Maternal-offspring attachment was reported by young adults and their mothers, and defined as mutual low, mutual medium or high, and dissonant. Analyses were carried out in the full sample using generalized estimating equation models, and in a sibling subsample, using conditional fixed effects models to control for stable aspects of the family environment. Analyses with the full sample and the sibling subsample both showed that mutual medium/high maternal-offspring attachment at age 21 was associated with lower odds of nonmedical prescription opioid use at age 26 (RR=0.74; 95% CI=0.57-0.97 in full sample). The association was partly mediated by mean age 23 offspring smoking, heavy episodic drinking, and illicit drug use. Promoting reciprocal attachment in the maternal-offspring dyad should be investigated as a strategy to prevent nonmedical prescription opioid use by young adulthood. Even in young adulthood, programs that target both parents and offspring may have greater impact on offspring substance use than programs that target offspring alone. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Maternal insulin resistance and transient hyperglycemia impact the metabolic and endocrine phenotypes of offspring

PubMed Central

Kahraman, Sevim; Dirice, Ercument; De Jesus, Dario F.; Hu, Jiang

2014-01-01

Studies in both humans and rodents suggest that maternal diabetes leads to a higher risk of the fetus developing impaired glucose tolerance and obesity during adulthood. However, the impact of hyperinsulinemia in the mother on glucose homeostasis in the offspring has not been fully explored. We aimed to determine the consequences of maternal insulin resistance on offspring metabolism and endocrine pancreas development using the LIRKO mouse model, which exhibits sustained hyperinsulinemia and transient increase in blood glucose concentrations during pregnancy. We examined control offspring born to either LIRKO or control mothers on embryonic days 13.5, 15.5, and 17.5 and postpartum days 0, 4, and 10. Control offspring born to LIRKO mothers displayed low birth weights and subsequently rapidly gained weight, and their blood glucose and plasma insulin concentrations were higher than offspring born to control mothers in early postnatal life. In addition, concentrations of plasma leptin, glucagon, and active GLP-1 were higher in control pups from LIRKO mothers. Analyses of the endocrine pancreas revealed significantly reduced β-cell area in control offspring of LIRKO mothers shortly after birth. β-Cell proliferation and total islet number were also lower in control offspring of LIRKO mothers during early postnatal days. Together, these data indicate that maternal hyperinsulinemia and the transient hyperglycemia impair endocrine pancreas development in the control offspring and induce multiple metabolic alterations in early postnatal life. The relatively smaller β-cell mass/area and β-cell proliferation in these control offspring suggest cell-autonomous epigenetic mechanisms in the regulation of islet growth and development. PMID:25249504

Family ties: maternal-offspring attachment and young adult nonmedical prescription opioid use

PubMed Central

Cerdá, M.; Bordelois, P.; Keyes, K.M.; Roberts, A.L.; Martins, S.S.; Reisner, S.L.; Austin, S.B.; Corliss, H.L.; Koenen, K.C.

2014-01-01

Background Nonmedical prescription drug use is prevalent among young adults, yet little is known about modifiable determinants of use. We examined whether maternal-offspring attachment reported at mean age 21 was associated with nonmedical prescription opioid use at mean age 26, and investigated whether a history of depressive symptoms and substance use played a role in associations between maternal-offspring attachment and nonmedical prescription opioid use. Methods We used data from the Growing Up Today Study, a longitudinal cohort of United States adolescents followed into young adulthood. Maternal-offspring attachment was reported by young adults and their mothers, and defined as mutual low, mutual medium or high, and dissonant. Analyses were carried out in the full sample using generalized estimating equation models, and in a sibling subsample, using conditional fixed effects models to control for stable aspects of the family environment. Results Analyses with the full sample and the sibling subsample both showed that mutual medium/high maternal-offspring attachment at age 21 was associated with lower odds of nonmedical prescription opioid use at age 26 (RR=0.74; 95% CI=0.57-0.97 in full sample). The association was partly mediated by mean age 23 offspring smoking, heavy episodic drinking, and illicit drug use. Conclusions Promoting reciprocal attachment in the maternal-offspring dyad should be investigated as a strategy to prevent nonmedical prescription opioid use by young adulthood. Even in young adulthood, programs that target both parents and offspring may have greater impact on offspring substance use than programs that target offspring alone. PMID:25024105

Mother knows best, even when stressed? Effects of maternal exposure to a stressor on offspring performance at different life stages in a wild semelparous fish.

PubMed

Sopinka, N M; Hinch, S G; Middleton, C T; Hills, J A; Patterson, D A

2014-06-01

The environment mothers are exposed to has resonating effects on offspring performance. In iteroparous species, maternal exposure to stressors generally results in offspring ill-equipped for survival. Still, opportunities for future fecundity can offset low quality offspring. Little is known, however, as to how intergenerational effects of stress manifest in semelparous species with only a single breeding episode. Such mothers would suffer a total loss of fitness if offspring cannot survive past multiple life stages. We evaluated whether chronic exposure of female sockeye salmon (Oncorhynchus nerka) to a chase stressor impaired offspring performance traits. Egg size and early offspring survival were not influenced by maternal exposure to the repeated acute stressor. Later in development, fry reared from stressed mothers swam for shorter periods of time but possessed a superior capacity to re-initiate bouts of burst swimming. In contrast to iteroparous species, the mechanisms driving the observed effects do not appear to be related to cortisol, as egg hormone concentrations did not vary between stressed and undisturbed mothers. Sockeye salmon appear to possess buffering strategies that protect offspring from deleterious effects of maternal stress that would otherwise compromise progeny during highly vulnerable stages of development. Whether stressed sockeye salmon mothers endow offspring with traits that are matched or mismatched for survival in the unpredictable environment they encountered is discussed. This study highlights the importance of examining intergenerational effects among species-specific reproductive strategies, and across offspring life history to fully determine the scope of impact of maternal stress.

Development of Anxiety-Like Behavior via Hippocampal IGF-2 Signaling in the Offspring of Parental Morphine Exposure: Effect of Enriched Environment

PubMed Central

Li, Chang-Qi; Luo, Yan-Wei; Bi, Fang-Fang; Cui, Tao-Tao; Song, Ling; Cao, Wen-Yu; Zhang, Jian-Yi; Li, Fang; Xu, Jun-Mei; Hao, Wei; Xing, Xiao-Wei; Zhou, Fiona H; Zhou, Xin-Fu; Dai, Ru-Ping

2014-01-01

Opioid addiction is a major social, economic, and medical problem worldwide. Long-term adverse consequences of chronic opiate exposure not only involve the individuals themselves but also their offspring. Adolescent maternal morphine exposure results in behavior and morphologic changes in the brain of their adult offspring. However, few studies investigate the effect of adult opiate exposure on their offspring. Furthermore, the underlying molecular signals regulating the intergenerational effects of morphine exposure are still elusive. We report here that morphine exposure of adult male and female rats resulted in anxiety-like behavior and dendritic retraction in the dentate gyrus (DG) region of the hippocampus in their adult offspring. The behavior and morphologic changes were concomitant with the downregulation of insulin-like growth factor (IGF)-2 signaling in the granular zone of DG. Overexpression of hippocampal IGF-2 by bilateral intra-DG injection of lentivirus encoding the IGF-2 gene prevented anxiety-like behaviors in the offspring. Furthermore, exposure to an enriched environment during adolescence corrected the reduction of hippocampal IGF-2 expression, normalized anxiety-like behavior and reversed dendritic retraction in the adult offspring. Thus, parental morphine exposure can lead to the downregulation of hippocampal IGF-2, which contributed to the anxiety and hippocampal dendritic retraction in their offspring. An adolescent-enriched environment experience prevented the behavior and morphologic changes in their offspring through hippocampal IGF-2 signaling. IGF-2 and an enriched environment may be a potential intervention to prevention of anxiety and brain atrophy in the offspring of parental opioid exposure. PMID:24889368

Oxidative Stress in Mouse Sperm Impairs Embryo Development, Fetal Growth and Alters Adiposity and Glucose Regulation in Female Offspring

PubMed Central

Lane, Michelle; McPherson, Nicole O.; Fullston, Tod; Spillane, Marni; Sandeman, Lauren; Kang, Wan Xian; Zander-Fox, Deirdre L.

2014-01-01

Paternal health cues are able to program the health of the next generation however the mechanism for this transmission is unknown. Reactive oxygen species (ROS) are increased in many paternal pathologies, some of which program offspring health, and are known to induce DNA damage and alter the methylation pattern of chromatin. We therefore investigated whether a chemically induced increase of ROS in sperm impairs embryo, pregnancy and offspring health. Mouse sperm was exposed to 1500 µM of hydrogen peroxide (H2O2), which induced oxidative damage, however did not affect sperm motility or the ability to bind and fertilize an oocyte. Sperm treated with H2O2 delayed on-time development of subsequent embryos, decreased the ratio of inner cell mass cells (ICM) in the resulting blastocyst and reduced implantation rates. Crown-rump length at day 18 of gestation was also reduced in offspring produced by H2O2 treated sperm. Female offspring from H2O2 treated sperm were smaller, became glucose intolerant and accumulated increased levels of adipose tissue compared to control female offspring. Interestingly male offspring phenotype was less severe with increases in fat depots only seen at 4 weeks of age, which was restored to that of control offspring later in life, demonstrating sex-specific impacts on offspring. This study implicates elevated sperm ROS concentrations, which are common to many paternal health pathologies, as a mediator of programming offspring for metabolic syndrome and obesity. PMID:25006800

Does maternal body mass index during pregnancy influence risk of schizophrenia in the adult offspring?

PubMed Central

Khandaker, G M; Dibben, C R M; Jones, P B

2012-01-01

Summary Maternal obesity in pregnancy has been linked with several adverse outcomes in offspring including schizophrenia. The rising prevalence of obesity may contribute to an increase in the number of schizophrenia cases in the near future; therefore, it warrants further exploration. We reviewed current evidence regarding maternal body mass index (BMI) in pregnancy and risk of schizophrenia in adult offspring. We searched PubMed and Embase databases and included studies that were based on large and representative population-based datasets. A qualitative review was undertaken due to heterogeneity between studies. Four studies with 305 cases of schizophrenia and 24,442 controls were included. Maternal obesity (pre-pregnant BMI over 29 or 30 compared with mothers with low or average BMI) was associated with two- to threefold increased risk of schizophrenia in the adult offspring in two birth cohorts. High maternal BMI at both early and late pregnancy also increased risk of schizophrenia in the offspring. Discrepant findings from one study could be attributable to sample characteristics and other factors. The area needs more research. Future studies should take into account obstetric complications, diabetes, maternal infections and immune responses that might potentially mediate this association. PMID:22188548

Multigenerational hybridisation and its consequences for maternal effects in Atlantic salmon

PubMed Central

Debes, P V; Fraser, D J; McBride, M C; Hutchings, J A

2013-01-01

Outbreeding between segregating populations can be important from an evolutionary, conservation and economical-agricultural perspective. Whether and how outbreeding influences maternal effects in wild populations has rarely been studied, despite both the prominent maternal influence on early offspring survival and the known presence of fitness effects resulting from outbreeding in many taxa. We studied several traits during the yolk-feeding stage in multigenerational crosses between a wild and a domesticated Atlantic salmon (Salmo salar) population up to their third-generation hybrid in a common laboratory environment. Using cross-means analysis, we inferred that maternal additive outbreeding effects underlie most offspring traits but that yolk mass also underlies maternal dominant effects. As a consequence of the interplay between additive and dominant maternally controlled traits, offspring from first-generation hybrid mothers expressed an excessive proportion of residual yolk mass, relative to total mass, at the time of first feeding. Their residual yolk mass was 23–97% greater than those of other crosses and 31% more than that predicted by a purely additive model. Offspring additive, epistatic and epistatic offspring-by-maternal outbreeding effects appeared to further modify this largely maternally controlled cross-means pattern, resulting in an increase in offspring size with the percentage of domesticated alleles. Fitness implications remain elusive because of unknown phenotype-by-environment interactions. However, these results suggest how mechanistically co-adapted genetic maternal control on early offspring development can be disrupted by the effects of combining alleles from divergent populations. Complex outbreeding effects at both the maternal and offspring levels make the prediction of hybrid phenotypes difficult. PMID:23652564

Maternal periodontal disease in rats decreases insulin sensitivity and insulin signaling in adult offspring.

PubMed

Shirakashi, Daisy J; Leal, Rosana P; Colombo, Natalia H; Chiba, Fernando Y; Garbin, Cléa A S; Jardim, Elerson G; Antoniali, Cristina; Sumida, Doris H

2013-03-01

Periodontal disease during pregnancy has been recognized as one of the causes of preterm and low-birth-weight (PLBW) babies. Several studies have demonstrated that PLBW babies are prone to developing insulin resistance as adults. Although there is controversy over the association between periodontal disease and PLBW, the phenomenon known as programming can translate any stimulus or aggression experienced during intrauterine growth into physiologic and metabolic alterations in adulthood. The purpose of the present study is to investigate whether the offspring of rats with periodontal disease develop insulin resistance in adulthood. Ten female Wistar rats were divided into periodontal disease (PED) and control (CN) groups. All rats were mated at 7 days after induction of periodontal disease. Male offspring were divided into two groups: 1) periodontal disease offspring (PEDO; n = 24); and 2) control offspring (CNO; n = 24). Offspring body weight was measured from birth until 75 days. When the offspring reached 75 days old, the following parameters were measured: 1) plasma concentrations of glucose, insulin, fructosamine, lipase, amylase, and tumor necrosis factor-α (TNF-α); 2) insulin sensitivity (IS); and 3) insulin signal transduction (IST) in insulin-sensitive tissues. Low birth weight was not detected in the PEDO group. However, plasma concentrations of glucose, insulin, fructosamine, lipase, amylase, and TNF-α were increased and IS and IST were reduced (P <0.05) in the PEDO group compared with the CNO group. Maternal periodontal disease may induce insulin resistance and reduce IST in adult offspring, but such alterations are not attributable to low birth weight.

Maternal obesity in the rat programs male offspring exploratory, learning and motivation behavior: prevention by dietary intervention pre-gestation or in gestation.

PubMed

Rodriguez, J S; Rodríguez-González, G L; Reyes-Castro, L A; Ibáñez, C; Ramírez, A; Chavira, R; Larrea, F; Nathanielsz, P W; Zambrano, E

2012-04-01

We studied the effects of maternal high fat diet (HFD, 25% calories from fat administered before and during pregnancy and lactation) and dietary intervention (switching dams from HFD to control diet) at different periconceptional periods on male offspring anxiety related behavior, exploration, learning, and motivation. From weaning at postnatal day (PND) 21, female subjects produced to be the mothers in the study received either control diet (CTR - 5% calories from fat), HFD through pregnancy and lactation (MO), HFD during PNDs 21-90 followed by CTR diet (pre-gestation (PG) intervention) or HFD from PND 21 to 120 followed by CTR diet (gestation and lactation (G) intervention) and bred at PND 120. At 19 days of gestation maternal serum corticosterone was increased in MO and the PG and G dams showed partial recovery with intermediate levels. In offspring, no effects were found in the elevated plus maze test. In the open field test, MO and G offspring showed increase zone entries, displaying less thigmotaxis; PG offspring showed partial recuperation of this behavior. During initial operant conditioning MO, PG and G offspring displayed decreased approach behavior with subsequent learning impairment during the acquisition of FR-1 and FR-5 operant conditioning for sucrose reinforcement. Motivation during the progressive ratio test increased in MO offspring; PG and G intervention recuperated this behavior. We conclude that dietary intervention can reverse negative effects of maternal HFD and offspring outcomes are potentially due to elevated maternal corticosterone. Copyright © 2012 ISDN. Published by Elsevier Ltd. All rights reserved.

Lifestyle and cancer: effect of parental divorce.

PubMed

Hemminki, Kari; Chen, Bowang

2006-12-01

According to previous studies, divorced individuals have increased risks of cancers related to alcohol and tobacco consumption and sexual habits, but the increases are balanced with decreased risks of many common cancers. In the present study, cancer risks were analyzed for 0-70-year-old offspring of divorced parents, on the basis the Swedish Family-Cancer Database with cancer data from the years 1958 to 2002. We calculated standardized incidence ratios for cancer among offspring of divorced parents (19,000 cancer patients) and compared them with offspring of stably married parents (121,000 cancer patients). Standardized incidence ratios were adjusted for many factors, including socio-economic status. Offspring of divorced parents were divided into groups depending on whether their mothers, fathers or both had had children with different partners. Offspring of divorced parents had an increased risk of upper aerodigestive tract, esophageal, anal, pancreatic, lung and cervical cancers. Decreased risks were noted for Hodgkin's disease and bone cancer. For Hodgkin's disease, the data suggest protective effects through early exposure to childhood pathogens but for bone cancer mechanisms remain to be established. The overall cancer risk for offspring of divorced parents was at or above unity. The results show that offspring of divorced parents have increased cancer risks at tobacco-related, alcohol-related and sex-related sites, in analogy to their parent, but they lack decreased risks at common sites, experienced by their parents. Divorce is becoming increasingly common in many countries and any deviant cancer patterns among offspring of divorced parents will have an impact on the population risk.

Exposure of mother rats to chronic unpredictable stress before pregnancy alters the metabolism of gamma-aminobutyric acid and glutamate in the right hippocampus of offspring in early adolescence in a sexually dimorphic manner.

PubMed

Huang, Yuejun; Shen, Zhiwei; Hu, Liu; Xia, Fang; Li, Yuewa; Zhuang, Jingwen; Chen, Peishan; Huang, Qingjun

2016-12-30

There is increasing evidence that mothers' exposure to stress before or during pregnancy is linked to an incidence of psychiatric disorders in offspring. However, a few studies have estimated the role of sex in the detrimental effects of pre-gestational stress on the offspring rats at early adolescence. Sex differences regarding the metabolism of gamma-aminobutyric acid and glutamate in the right hippocampus were investigated by MRS when the offspring rats reached 30 days. Additionally, the impact of pre-gestational stress exposed on an additional short-term acute stressor, such as forced swim, was examined in the male and female offspring rats. Our findings showed female offspring rats were more vulnerable to stressful conditions for either pre-gestational stress or acute stress in early adolescence, and had decreased GABA/Cr+PCr and Glu/Cr+PCr in the right hippocampus. Interestingly, in response to forced swim, male offspring rats whose mothers were exposed to pre-gestational stress were more affected by the short-term acute stressor and this was manifested by change of Glu/GABA and Glu/Gln in the right hippocampus. These data indicated that although female offspring rats were more vulnerable to pre-gestational stress from their mothers than males, in response to an additional acute stressor they showed better response. Therefore, both sexually dimorphic manner and combination of stressful procedures should be carefully considered in the study of stress-related psychiatric disorders in early adolescence. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Perceptions of aging among middle-aged offspring of traumatized parents: the effects of parental Holocaust-related communication and secondary traumatization.

PubMed

Shrira, Amit

2016-01-01

Traumatized parents may transmit anxieties of physical deterioration and demise to their offspring. These anxieties can amplify negative perceptions of the aging process when the offspring enter old age. The current study examined how middle-aged offspring of Holocaust survivors (OHS) recount trauma-related communication by their parents, and how these reports are related to offspring's perceptions of their aging process. The study included 450 respondents at the age range of 50-67 (mean age = 57.5, SD = 4.6): 300 OHS and 150 comparisons. Participants reported parental communication of the Holocaust, completed measures of subjective successful aging, aging and death anxieties, and reported secondary traumatization assessing symptoms, developed as a result of a close and continuous relationship with a traumatized parent. Latent profile analysis identified two profiles of parental Holocaust-related communication: intrusive and informative. Offspring who reported intrusive parental communication about the Holocaust perceived themselves as aging less successfully and were more anxious of aging and death than comparisons. Offspring who reported informative parental communication and comparisons did not differ in perceptions of aging. Secondary traumatization mediated these group differences, meaning, intrusive parental communication was related to higher secondary traumatization, which in turn was related to less favorable perceptions of aging. These findings allude to the possibility that secondary traumatization mold negative perceptions of the aging process among middle-aged offspring of traumatized parents. Mental health practitioners may help OHS process fragmented and intrusive remnants of parental trauma, thereby diminishing secondary traumatization, and promoting more adaptive perceptions of aging.

Parental care mitigates carry-over effects of poor early conditions on offspring growth

USGS Publications Warehouse

Auer, Sonya K.; Martin, Thomas E.

2017-01-01

Poor developmental conditions can have long-lasting negative effects on offspring phenotypes, but impacts often differ among species. Contrasting responses may reflect disparities in experimental protocols among single-species studies or inherent differences among species in their sensitivity to early conditions and/or ability to mitigate negative impacts. We used a common experimental protocol to assess and compare the role of parental care in mitigating effects of poor early conditions on offspring among 4 sympatric bird species in the wild. We experimentally induced low incubation temperatures and examined effects on embryonic developmental rates, hatching success, nestling growth rates, and parental responses. We examined the generality of these effects across 4 species that differ in their phylogenetic history, breeding ecology, and life histories. We found that cooling led to delayed hatching in all species, but carry-over effects on offspring differed among species. Parents of some but not all species increased their offspring provisioning rates in response to experimental cooling with critical benefits for offspring growth rates. Our study shows for the first time that species exhibit clear differences in the degree to which they are affected by poor early conditions. Observed differences among species demonstrate that parental care is a critical mechanism for mitigating potential negative effects on offspring and suggest that parental responses may be constrained to varying degrees by ecology and life histories.

Maternal Dietary Patterns during Pregnancy in Relation to Offspring Forearm Fractures: Prospective Study from the Danish National Birth Cohort

PubMed Central

Petersen, Sesilje B.; Rasmussen, Morten A.; Olsen, Sjurdur F.; Vestergaard, Peter; Mølgaard, Christian; Halldorsson, Thorhallur I.; Strøm, Marin

2015-01-01

Limited evidence exists for an association between maternal diet during pregnancy and offspring bone health. In a prospective study, we examined the association between dietary patterns in mid-pregnancy and offspring forearm fractures. In total, 101,042 pregnancies were recruited to the Danish National Birth Cohort (DNBC) during 1996–2002. Maternal diet was collected by a food frequency questionnaire. Associations were analyzed between seven dietary patterns extracted by principal component analysis and offspring first occurrence of any forearm fracture diagnosis, extracted from the Danish National Patient Register, between time of birth and end of follow-up (<16 year) (n = 53,922). In multivariable Cox regression models, offspring of mothers in the fourth vs. first quintile of the Western pattern had a significant increased risk (Hazard ratio, 95% confidence interval: 1.11, 1.01–1.23) of fractures, and there was a borderline significant positive trend (p = 0.06). The other dietary patterns showed no associations and neither did supplementary analyses of macro- and micronutrients or single food groups, except for the intake of artificially sweetened soft drinks, which was positively associated with offspring forearm fractures (p = 0.02). In the large prospective DNBC high mid-pregnancy consumption of Western diet and artificially sweetened soft drinks, respectively, indicated positive associations with offspring forearm fractures, which provides interesting hypotheses for future research. PMID:25849947

A common haplotype of the glucokinase gene alters fasting glucose and birth weight: association in six studies and population-genetics analyses.

PubMed

Weedon, Michael N; Clark, Vanessa J; Qian, Yudong; Ben-Shlomo, Yoav; Timpson, Nicholas; Ebrahim, Shah; Lawlor, Debbie A; Pembrey, Marcus E; Ring, Susan; Wilkin, Terry J; Voss, Linda D; Jeffery, Alison N; Metcalf, Brad; Ferrucci, Luigi; Corsi, Anna Maria; Murray, Anna; Melzer, David; Knight, Bridget; Shields, Bev; Smith, George Davey; Hattersley, Andrew T; Di Rienzo, Anna; Frayling, Tim M

2006-12-01

Fasting glucose is associated with future risk of type 2 diabetes and ischemic heart disease and is tightly regulated despite considerable variation in quantity, type, and timing of food intake. In pregnancy, maternal fasting glucose concentration is an important determinant of offspring birth weight. The key determinant of fasting glucose is the enzyme glucokinase (GCK). Rare mutations of GCK cause fasting hyperglycemia and alter birth weight. The extent to which common variation of GCK explains normal variation of fasting glucose and birth weight is not known. We aimed to comprehensively define the role of variation of GCK in determination of fasting glucose and birth weight, using a tagging SNP (tSNP) approach and studying 19,806 subjects from six population-based studies. Using 22 tSNPs, we showed that the variant rs1799884 is associated with fasting glucose at all ages in the normal population and exceeded genomewide levels of significance (P=10-9). rs3757840 was also highly significantly associated with fasting glucose (P=8x10-7), but haplotype analysis revealed that this is explained by linkage disequilibrium (r2=0.2) with rs1799884. A maternal A allele at rs1799884 was associated with a 32-g (95% confidence interval 11-53 g) increase in offspring birth weight (P=.002). Genetic variation influencing birth weight may have conferred a selective advantage in human populations. We performed extensive population-genetics analyses to look for evidence of recent positive natural selection on patterns of GCK variation. However, we found no strong signature of positive selection. In conclusion, a comprehensive analysis of common variation of the glucokinase gene shows that this is the first gene to be reproducibly associated with fasting glucose and fetal growth.

Protective role of taurine in developing offspring affected by maternal alcohol consumption

PubMed Central

Ananchaipatana-Auitragoon, Pilant; Ananchaipatana-Auitragoon, Yutthana; Siripornpanich, Vorasith; Kotchabhakdi, Naiphinich

2015-01-01

Maternal alcohol consumption is known to affect offspring growth and development, including growth deficits, physical anomalies, impaired brain functions and behavioral disturbances. Taurine, a sulfur-containing amino acid, is essential during development, and continually found to be protective against neurotoxicity and various tissue damages including those from alcohol exposure. However, it is still unknown whether taurine can exert its protection during development of central nervous system and whether it can reverse alcohol damages on developed brain later in life. This study aims to investigate protective roles of taurine against maternal alcohol consumption on growth and development of offspring. The experimental protocol was conducted using ICR-outbred pregnant mice given 10 % alcohol, with or without maternal taurine supplementation during gestation and lactation. Pregnancy outcomes, offspring mortality and successive bodyweight until adult were monitored. Adult offspring is supplemented taurine to verify its ability to reverse damages on learning and memory through a water maze task performance. Our results demonstrate that offspring of maternal alcohol exposure, together with maternal taurine supplementation show conserved learning and memory, while that of offspring treated taurine later in life are disturbed. Taurine provides neuroprotective effects and preserves learning and memory processes when given together with maternal alcohol consumption, but not shown such effects when given exclusively in offspring. PMID:26648819

Type 2 diabetic patients and their offspring show altered parameters of iron status, oxidative stress and genes related to mitochondrial activity.

PubMed

Le Blanc, Solange; Villarroel, Pia; Candia, Valeria; Gavilán, Natalia; Soto, Néstor; Pérez-Bravo, Francisco; Arredondo, Miguel

2012-08-01

Type 2 diabetes (T2D) is directly related to alterations in iron status, oxidative stress and decreased mitochondrial activity, but the possible interaction of these parameters among T2D patients and their offspring is unclear. The whole study included 301 subjects: 77 T2D patients and one of their offspring and 51 control subjects with one of their offspring. The offspring were older than 20 years old. We measured parameters of iron status (serum iron, ferritin and transferrin receptor), diabetes (pre and post-prandial glucose, insulin, lipids), oxidative stress (Heme oxygenase activity, TBARS, SOD, GSH, Vitamin E), as well as the expression of genes in blood leukocytes related to mitochondrial apopotosis (mitofusin and Bcl/Bax ratios). The offspring of T2D patients had increased levels of serum ferritin (P < 0.01) and lower transferrin receptor (P < 0.008); higher insulin (P < 0.03) and total and LDL cholesterol; higher heme oxygenase and SOD activities increased TBARS and lower GSH; decreased mitofusin and Bcl/Bax expression ratios compared to offspring of normal subjects. These results suggest that the offspring of T2D patients could have an increased metabolic risk of develop a cardiovascular disease mediated by oxidative stress and iron status.

Paternal levels of DNA damage in spermatozoa and maternal parity influence offspring mortality in an endangered ungulate.

PubMed

Ruiz-López, María José; Espeso, Gerardo; Evenson, Donald P; Roldan, Eduardo R S; Gomendio, Montserrat

2010-08-22

Understanding which factors influence offspring mortality rates is a major challenge since it influences population dynamics and may constrain the chances of recovery among endangered species. Most studies have focused on the effects of maternal and environmental factors, but little is known about paternal factors. Among most polygynous mammals, males only contribute the haploid genome to their offspring, but the possibility that sperm DNA integrity may influence offspring survival has not been explored. We examined several maternal, paternal and individual factors that may influence offspring survival in an endangered species (Gazella cuvieri). Levels of sperm DNA damage had the largest impact upon offspring mortality rates, followed by maternal parity. In addition, there was a significant interaction between these two variables, so that offspring born to primiparous mothers were more likely to die if their father had high levels of sperm DNA damage, but this was not the case among multiparous mothers. Thus, multiparous mothers seem to protect their offspring from the deleterious effects of sperm DNA damage. Since levels of sperm DNA damage seem to be higher among endangered species, more attention should be paid to the impact of this largely ignored factor among the viability of endangered species.

Experiences of offspring searching for and contacting their donor siblings and donor.

PubMed

Jadva, Vasanti; Freeman, Tabitha; Kramer, Wendy; Golombok, Susan

2010-04-01

This study investigates a new phenomenon whereby individuals conceived by donor insemination are searching for and contacting their donor and/or 'donor siblings' (i.e. donor offspring conceived by the same donor who are their genetic half siblings). On-line questionnaires were completed by members of the Donor Sibling Registry (DSR), a US-based registry that facilitates contact between donor conception families who share the same donor. Of the 165 donor offspring who completed the survey, 15% were searching for their donor siblings, 13% were searching for their donor, and 64% were searching for both. Differences were found according to family type and age of disclosure. Fewer offspring from heterosexual couple families had told their father about their search when compared with offspring from lesbian couple families who had told their co-parent. Offspring who had found out about their conception after age 18 were more likely to be searching for medical reasons, whereas those who had found out before age 18 tended to be searching out of curiosity. Some offspring had discovered large numbers of half siblings (maximum=13). The majority of offspring who had found their donor relations reported positive experiences and remained in regular contact with them. Copyright (c) 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Maternal High Fat Diet Alters Skeletal Muscle Mitochondrial Catalytic Activity in Adult Male Rat Offspring

PubMed Central

Pileggi, Chantal A.; Hedges, Christopher P.; Segovia, Stephanie A.; Markworth, James F.; Durainayagam, Brenan R.; Gray, Clint; Zhang, Xiaoyuan D.; Barnett, Matthew P. G.; Vickers, Mark H.; Hickey, Anthony J. R.; Reynolds, Clare M.; Cameron-Smith, David

2016-01-01

A maternal high-fat (HF) diet during pregnancy can lead to metabolic compromise, such as insulin resistance in adult offspring. Skeletal muscle mitochondrial dysfunction is one mechanism contributing to metabolic impairments in insulin resistant states. Therefore, the present study aimed to investigate whether mitochondrial dysfunction is evident in metabolically compromised offspring born to HF-fed dams. Sprague-Dawley dams were randomly assigned to receive a purified control diet (CD; 10% kcal from fat) or a high fat diet (HFD; 45% kcal from fat) for 10 days prior to mating, throughout pregnancy and during lactation. From weaning, all male offspring received a standard chow diet and soleus muscle was collected at day 150. Expression of the mitochondrial transcription factors nuclear respiratory factor-1 (NRF1) and mitochondrial transcription factor A (mtTFA) were downregulated in HF offspring. Furthermore, genes encoding the mitochondrial electron transport system (ETS) respiratory complex subunits were suppressed in HF offspring. Moreover, protein expression of the complex I subunit, NDUFB8, was downregulated in HF offspring (36%), which was paralleled by decreased maximal catalytic linked activity of complex I and III (40%). Together, these results indicate that exposure to a maternal HF diet during development may elicit lifelong mitochondrial alterations in offspring skeletal muscle. PMID:27917127

Maternal high-fat diet and obesity impact palatable food intake and dopamine signaling in nonhuman primate offspring.

PubMed

Rivera, Heidi M; Kievit, Paul; Kirigiti, Melissa A; Bauman, Leigh Ann; Baquero, Karalee; Blundell, Peter; Dean, Tyler A; Valleau, Jeanette C; Takahashi, Diana L; Frazee, Tim; Douville, Luke; Majer, Jordan; Smith, M Susan; Grove, Kevin L; Sullivan, Elinor L

2015-11-01

To utilize a nonhuman primate model to examine the impact of maternal high-fat diet (HFD) consumption and pre-pregnancy obesity on offspring intake of palatable food and to examine whether maternal HFD consumption impaired development of the dopamine system, critical for the regulation of hedonic feeding. The impact of exposure to maternal HFD and obesity on offspring consumption of diets of varying composition was assessed after weaning. The influence of maternal HFD consumption on the development of the prefrontal cortex-dopaminergic system at 13 months of age was also examined. During a preference test, offspring exposed to maternal HFD consumption and obesity displayed increased intake of food high in fat and sugar content relative to offspring from lean control mothers. Maternal HFD consumption suppressed offspring dopamine signaling (as assessed by immunohistochemistry) relative to control offspring. Specifically, there was decreased abundance of dopamine fibers and of dopamine receptor 1 and 2 proteins. This study reveals that offspring exposed to both maternal HFD consumption and maternal obesity during early development are at increased risk for obesity due to overconsumption of palatable energy-dense food, a behavior that may be related to reduced central dopamine signaling. © 2015 The Obesity Society.

Exposure to sorbitol during lactation causes metabolic alterations and genotoxic effects in rat offspring.

PubMed

Cardoso, Felipe S; Araujo-Lima, Carlos F; Aiub, Claudia A F; Felzenszwalb, Israel

2016-10-17

Sorbitol is a polyol used by the food industry as a sweetener. Women are consuming diet and light products containing sorbitol during pregnancy and in the postnatal period to prevent themselves from excessive weight gain and maintain a slim body. Although there is no evidence for the genotoxicity of sorbitol in the perinatal period, this study focused on evaluating the effects of the maternal intake of sorbitol on the biochemical and toxicological parameters of lactating Wistar rat offspring after 14days of mother-to-offspring exposure. A dose-dependent reduction of offspring length was observed. An increase in sorbitol levels determined in the milk was also observed. However, we detected an inverse relationship between the exposition dose in milk fructose and triacylglycerols concentrations. There was an increase in the plasmatic levels of ALT, AST and LDLc and a decrease in proteins, cholesterol and glucose levels in the offspring. Sorbitol exposure caused hepatocyte genotoxicity, including micronuclei induction. Maternal sorbitol intake induced myelotoxicity and myelosuppression in their offspring. The Comet assay of the blood cells detected a dose-dependent genotoxic response within the sorbitol-exposed offspring. According to our results, sorbitol is able to induce important metabolic alterations and genotoxic responses in the exposed offspring. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Fetal nicotine exposure produces postnatal up-regulation of adenylate cyclase activity in peripheral tissues

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slotkin, T.A.; Navarro, H.A.; McCook, E.C.

1990-01-01

Gestational exposure to nicotine has been shown to affect development of noradrenergic activity in both the central and peripheral nervous systems. In the current study, pregnant rats received nicotine infusions of 6 mg/kg/day throughout gestation, administered by osmotic minipump implants. After birth, offspring of the nicotine-infused dams exhibited marked increases in basal adenylate cyclase activity in membranes prepared from kidney and heart, as well as supersensitivity to stimulation by either a {beta}-adrenergic agonist, isoproterenol, or by forskolin. The altered responses were not accompanied by up-regulation of {beta}-adrenergic receptors: in fact, ({sup 125}I)pindolol binding was significantly decreased in the nicotine group.more » These results indicate that fetal nicotine exposure affects enzymes involved in membrane receptor signal transduction, leading to altered responsiveness independently of changes at the receptor level.« less

Overnutrition and maternal obesity in sheep pregnancy alter the JNK-IRS-1 signaling cascades and cardiac function in the fetal heart

PubMed Central

Wang, Jingying; Ma, Heng; Tong, Chao; Zhang, Hanying; Lawlis, Gavin B.; Li, Yuanda; Zang, Mengwei; Ren, Jun; Nijland, Mark J.; Ford, Stephen P.; Nathanielsz, Peter W.; Li, Ji

2010-01-01

Maternal obesity in pregnancy predisposes offspring to insulin resistance and associated cardiovascular disease. Here, we used a well-established sheep model to investigate the effects of maternal obesity on cardiac functions. Multiparous ewes were assigned to a control (CON) diet [100% of National Research Council (NRC) recommendations] or an obesogenic (OB) diet (150% of NRC recommendations) from 60 d before conception to necropsy on d 135 of pregnancy. Fetal blood glucose and insulin were increased (P<0.01, n=8) in OB (35.09±2.03 mg/dl and 3.40±1.43 μU/ml, respectively) vs. CON ewes (23.80±1.38 mg/dl and 0.769±0.256 μU/ml). Phosphorylation of AMP-activated protein kinase (AMPK), a cardioprotective signaling pathway, was reduced (P<0.05), while the stress signaling pathway, p38 MAPK, was up-regulated (P<0.05) in OB maternal and fetal hearts. Phosphorylation of c-Jun N-terminal kinase (JNK) and insulin receptor substrate-1 (IRS-1) at Ser-307 were increased (P<0.05) in OB fetal heart associated with lower downstream PI3K-Akt activity (P<0.05), indicating impaired cardiac insulin signaling. Although OB fetal hearts exhibited a normal contractile function vs. CON fetal hearts during basal perfusion, they developed an impaired heart-rate-left-ventricular-developed pressure product in response to high workload stress. Taken together, fetuses of OB mothers demonstrate alterations in cardiac PI3K-Akt, AMPK, and JNK-IRS-1 signaling pathways that would predispose them to insulin resistance and cardiac dysfunction.—Wang, J., Ma, H., Tong, C., Zhang, H., Lawlis, G. B., Li, Y., Zang, M., Ren, J., Nijland, M. J., Ford, S. P., Nathanielsz, P. W., Li, J. Overnutrition and maternal obesity in sheep pregnancy alter the JNK-IRS-1 signaling cascades and cardiac function in the fetal heart. PMID:20110268

The Effect of Parents' Attitudes toward Divorce on Offspring's Attitudes: Gender and Parental Divorce as Mediating Factors

ERIC Educational Resources Information Center

Kapinus, Carolyn A.

2004-01-01

This study addresses three questions: (a) What influence do parents' attitudes toward divorce have on offspring's attitudes? (b) How are offspring's attitudes toward divorce influenced by parental divorce, and do the effects vary depending on the gender of the child? and (c) How do conditions surrounding parental divorce influence young adults'…

Socialization of Emotion and Offspring Internalizing Symptoms in Mothers with Childhood-Onset Depression

ERIC Educational Resources Information Center

Silk, Jennifer S.; Shaw, Daniel S.; Prout, Joanna T.; O'Rourke, Flannery; Lane, Tonya J.; Kovacs, Maria

2011-01-01

This study examines how mothers with and without a history of childhood-onset depression respond to their 3-9 year-old children's emotions. Mother-child dyads included 55 offspring of mothers with a history of childhood-onset depressive disorders and 57 offspring of never-depressed mothers. Mothers with a history of childhood depression were less…

Familial Depressive Symptoms and Delinquency: Separate Self-Reports From Mothers and Their Offspring.

PubMed

Ellis, Lee; Hoskin, Anthony

2018-04-01

Research has documented that both unipolar and bipolar depression are positively correlated with involvement in delinquency and crime. The present study sought to broaden the understanding of these relationships by looking for links between offending and family histories of depressive symptoms in relationship to offspring delinquency. More than 6,000 college students and their mothers provided self-reported information regarding feelings of depression. Students provided self-reports of involvement in various categories of offending and drug use from ages 10 through 18. Numerous significant positive correlations were found between general feelings of depression and of manic depression and involvement in delinquency. The depression-delinquency relationships were strongest when considering offspring themselves, although maternal depression symptoms were also associated with various forms of offspring delinquency and drug use. To help assess the causal chains that might be involved, multiple regression and mediation analysis revealed that parental depression enhanced the probability of offspring feeling depressed and may have thereby contributed to offspring being delinquent, particularly in the case of manic depression. This study reconfirmed the well-established relationship between depression and involvement in delinquency and drug use, and suggests that it extends back to parental forms of depression, especially by the mother.

Does exposure to hyperglycaemia in utero increase the risk of obesity and diabetes in the offspring? A critical reappraisal.

PubMed

Donovan, L E; Cundy, T

2015-03-01

The idea that exposure to hyperglycaemia in utero is an important factor in the development of obesity and diabetes in the offspring has become entrenched as popular belief. To appraise the literature supporting this hypothesis in the light of recent studies that have clarified the main drivers of obesity in children and adolescents. A review of published evidence from animal studies, human observational studies, systematic reviews and experimental trials that address the impact of diabetes (Types 1 and 2, genetic or gestational) on the future risk of obesity and/or glucose intolerance in the offspring. Some animal studies support a relationship between exposure to hyperglycaemia in utero and future development of obesity and diabetes, but the results are inconsistent. Most of the human studies claiming to show a relationship have not taken into account important known confounders, such as maternal and paternal BMI. Evidence supporting a dose-response relationship between maternal hyperglycaemia exposure and obesity and diabetes in the offspring is weak, and there is no convincing evidence that treating gestational diabetes reduces the later risk of offspring obesity or glucose intolerance. Exposure to hyperglycaemia in utero has minimal direct effect on the later risk of obesity and Type 2 diabetes. The increased risk of obesity in the offspring of women with Type 2 or gestational diabetes can be explained by confounding factors, such as parental obesity. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

Maternal exposure to environmental DEHP exacerbated OVA-induced asthmatic responses in rat offspring.

PubMed

Wang, Bohan; Liu, Fangwei; Dong, Jing; You, Mingdan; Fu, Yuanyuan; Li, Chao; Lu, Yiping; Chen, Jie

2018-02-15

Di (ethylhexyl) phthalate (DEHP) is a commonly used phthalates (PAEs) compound as plasticizer and becomes a severe environmental pollutant worldwide. Studies show that DEHP, as an environmental endocrine disruptor, has potential adverse effects on human. Epidemiologic studies indicate that DEHP is positively correlated to allergic diseases. Maternal exposure to DEHP may contribute to the increasing incidence of allergic diseases in offspring. However, the role of DEHP and its detailed mechanism in allergic disease of the offspring are still unclear. The aim of our study is to investigate whether DEHP maternal exposure could aggravate the allergic responses in offspring and its mechanism. Pregnant Wistar rats were randomly divided into three groups and exposed to different doses of DEHP. Half of the offspring were challenged with OVA after birth. All the pups of each group were sacrificed at postnatal day (PND)14, PND21 and PND28. The number of inflammatory cells in bronchoalveolar lavage was counted, lung pathological changes were observed, Th2 type cytokines expressions were checked, and the expression of TSLP signaling pathway were examined. Our results showed that maternal exposure to DEHP during pregnancy and lactation aggravated the eosinophils accumulation and the pathological inflammatory changes in pups' lung after OVA challenge. And maternal exposure to DEHP during pregnancy and lactation also elevated the levels of typical Th2 cytokines in OVA-challenged rats. What's more, maternal exposure to DEHP during pregnancy and lactation increased the levels of TSLP, TSLPR and IL-7R in the offspring after OVA challenge. Our study suggested that DEHP maternal exposure could aggravate the OVA-induced asthmatic responses in offspring. And this adjuvant effect of DEHP was related with the TSLP/TSLPR/IL-7R and its downstream signal pathways. Copyright © 2017. Published by Elsevier B.V.

Parental and offspring associations of the metabolic syndrome in the Fels Longitudinal Study123

PubMed Central

Sabo, Roy T; Lu, Zheng; Deng, Xiaoyan; Ren, Chunfeng; Daniels, Stephen; Arslanian, Silva; Sun, Shumei S

2012-01-01

Background: Evidence shows that some causes of the metabolic syndrome (MS) begin in childhood, which could indicate a familial association, through either genetic inheritance or cohabitation. Objective: This study examined associations between parents and adult offspring diagnoses of the MS and its risk factors. Design: Measurements were obtained from adult participants and their adult offspring enrolled in the Fels Longitudinal Study, with simultaneous waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides, HDL, and glucose observations used for diagnosis. On the basis of repeated measurements (in some cases), adult participants were classified as having the MS at least once or as never having the MS. Chi-square tests, ORs, and mixed-effects models were used to study familial associations. Results: Maternal (OR: 2.5; 95% CI: 1.1, 5.5) and paternal (OR: 4.1; 95% CI: 1.4, 12.1) MS classifications were significantly associated with MS classification in sons. MS classification in mothers and daughters (OR: 2.7; 95% CI: 0.9, 8.7; P = 0.08) was similar to that in sons but was not significant, whereas fathers and daughters were not associated (OR: 1.1; 95% CI: 0.4, 3.5). Maternal MS diagnoses were significantly and positively associated with triglycerides in male offspring and were significantly associated with SBP, DBP, and triglycerides in females. Paternal diagnoses were significantly associated only with DBP and HDL in male offspring. Conclusions: Parental MS diagnosis is significantly associated with MS diagnosis in adult male offspring, and adverse levels of certain risk factors are associated between offspring and parents, although these associations vary across risk factors and child sex. PMID:22811445

How do demographic and social factors influence parent-offspring conflict? The case of wild black and gold howler monkeys (Alouatta caraya).

PubMed

Pavé, Romina; Kowalewski, Martín M; Zunino, Gabriel E; Giraudo, Alejandro R

2015-08-01

In this study, we examined the influence of demography and social context on mother-offspring conflict in wild black and gold howler monkeys (Alouatta caraya) inhabiting two nearby sites in northern Argentina, one comprising continuous forest and one fragmented forest. These sites differed in population density (3.25 vs. 1.04 individuals/ha), degree of home range overlap between neighboring groups (70 vs. 31%), and rate of intergroup encounters (2 vs. 0.02-1 encounters/day), though not in interbirth interval or rate of infant mortality. During a 27-month study (September 2008 through November 2010), we observed 37 mother-offspring dyads across the two sites. We found a very similar pattern of mother-offspring conflict in both populations; specifically, the sites did not differ in any of the variables used to characterize the mother-offspring relationship (the time spent in contact, the rate at which the mother makes and breaks contact, the rate at which the infant breaks contact, the rate of maternal rejection, and signs of infant distress) except one (the rate at which the infant makes contact). Although mother-offspring conflict is a dynamic process that varies over time, our results suggest that the different demographic and social contexts found at the two study sites did not have a marked effect on quantitative aspects of the mother-offspring relationship in these populations of black and gold howlers. Finally, this study suggests that the environmental variability (ecological, demographic, and social traits) leads to a set of strategies used both by infants and mothers with a main goal of conflict resolution, with mothers specifically aiming to cope with the tradeoff between current and future reproduction. © 2015 Wiley Periodicals, Inc.

Maternal choline supplementation: a nutritional approach for improving offspring health?

PubMed

Jiang, Xinyin; West, Allyson A; Caudill, Marie A

2014-05-01

The modulatory role of choline on the fetal epigenome and the impact of in utero choline supply on fetal programming and health are of great interest. Studies in animals and/or humans suggest that maternal choline supplementation during pregnancy benefits important physiologic systems such as offspring cognitive function, response to stress, and cerebral inhibition. Because alterations in offspring phenotype frequently coincide with epigenetic modifications and changes in gene expression, maternal choline supplementation may be a nutritional strategy to improve lifelong health of the child. Future studies are warranted to elucidate further the effect of choline on the fetal epigenome and to determine the level of maternal choline intake required for optimal offspring physiologic function. Copyright © 2014 Elsevier Ltd. All rights reserved.

Is Maternal Smoking During Pregnancy a Risk Factor for Cigarette Smoking in Offspring? A Longitudinal Controlled Study of ADHD Children Grown Up.

PubMed

Biederman, Joseph; Martelon, MaryKate; Woodworth, K Yvonne; Spencer, Thomas J; Faraone, Stephen V

2017-10-01

This study examined whether exposure to maternal smoking during pregnancy in children with and without ADHD is associated with smoking in offspring and whether this association is selective to ADHD children. Ninety-six exposed and 400 unexposed participants were derived from two longitudinal studies of boys and girls with and without ADHD. Maternal smoking during pregnancy was defined by interviews with participants' mothers. A significant association was observed between exposure to maternal smoking in pregnancy and cigarette smoking in offspring ( p = .02). Exposed offspring were also more likely to have higher rates of major depression ( p = .04), bipolar disorder ( p = .04), and conduct disorder ( p = .04), and lower IQ ( p = .01), lower Global Assessment of Functioning (GAF) score ( p = .02), and more impaired Social Adjustment Inventory for Children and Adolescents (SAICA) scores versus unexposed offspring, adjusting for social class. Maternal smoking during pregnancy was found to increase the risk for smoking and a wide range of adverse psychiatric, cognitive, and functional outcomes in youth.

Maternal smoking during pregnancy and offspring conduct problems: evidence from 3 independent genetically sensitive research designs.

PubMed

Gaysina, Darya; Fergusson, David M; Leve, Leslie D; Horwood, John; Reiss, David; Shaw, Daniel S; Elam, Kit K; Natsuaki, Misaki N; Neiderhiser, Jenae M; Harold, Gordon T

2013-09-01

Several studies report an association between maternal smoking during pregnancy and offspring conduct disorder. However, past research evidences difficulty in disaggregating prenatal environmental influences from genetic and postnatal environmental influences. To examine the relationship between maternal smoking during pregnancy and offspring conduct problems among children reared by genetically related mothers and genetically unrelated mothers. The following 3 studies using distinct but complementary research designs were used: The Christchurch Health and Development Study (a longitudinal cohort study that includes biological and adopted children), the Early Growth and Development Study (a longitudinal adoption-at-birth study), and the Cardiff IVF (In Vitro Fertilization) Study (an adoption-at-conception study among genetically related families and genetically unrelated families). Maternal smoking during pregnancy was measured as the mean number of cigarettes per day (0, 1-9, or 10) smoked during pregnancy. Possible covariates were controlled for in the analyses, including child sex, birth weight, race/ethnicity, placement age, and breastfeeding, as well as maternal education and maternal age at birth and family breakdown, parenting practices, and family socioeconomic status. Offspring conduct problems (age range, 4-10 years) reported by parents or teachers using the behavior rating scales by Rutter and Conners, the Child Behavior Checklist and the Children's Behavior Questionnaire Short Form, and the Strengths and Difficulties Questionnaire. A significant association between maternal smoking during pregnancy and offspring conduct problems was observed among children reared by genetically related mothers and genetically unrelated mothers. Results from a meta-analysis affirmed this pattern of findings across pooled study samples. Findings across 3 studies using a complement of genetically sensitive research designs suggest that smoking during pregnancy is a prenatal risk factor for offspring conduct problems when controlling for specific perinatal and postnatal confounding factors.

Mediators and moderators of parental alcoholism effects on offspring self-esteem.

PubMed

Rangarajan, Sripriya

2008-01-01

The goal of the proposed study was fourfold: (i) to examine the effects of parental alcoholism on adult offspring's self-esteem; (ii) to identify and test possible mediators and moderators of parental alcoholism effects on the self-esteem of adult offspring; (iii) to examine the utility and relevance of attachment theory (Bowlby J. (1969) Attachment and Loss: Vol. 1. Attachment. New York: Basic Books) in explaining parental alcoholism effects on self-esteem and (iv) to address some of the methodological limitations identified in past research on adult children of alcoholics (ACOA). Participants (N = 515) completed retrospective reports of parental alcoholism, family stressors, family communication patterns, parental attachment and a current measure of self-esteem. The results showed support for the detrimental effects of parental alcoholism on offspring self-esteem and offered partial support for family stressors as a mediator of parental alcoholism effects on parental attachment and parental attachment as a mediator of parental alcoholism effects on offspring self-esteem, respectively. Finally, support was found for family communication patterns as a moderator of the effects of family stressors on attachment. The study findings offer preliminary support for the utility of attachment theory in explicating parental alcoholism effects on the self-esteem of adult offspring. Findings from the present study make salient the need to consider factors beyond the identification of parental alcohol abuse when explicating individual differences in offspring self-esteem in adulthood. The identification of protective and risk factors can contribute to the development of optimal intervention strategies to help ACOAs better than simply the knowledge of family drinking patterns.

Implications of temporal variation in maternal care for the prediction of neurobiological and behavioral outcomes in offspring

PubMed Central

Peña, Catherine Jensen; Champagne, Frances A.

2014-01-01

Previous studies in Long-Evans rats demonstrated a significant relationship between variation in pup licking/grooming and arched-back nursing (LG-ABN) and offspring development. However, maternal care is dynamic and exhibits significant temporal variation. In the current study, we assessed temporal variation in LG and ABN in lactating rats across the circadian cycle and determined the impact of these behaviors for the prediction of offspring hypothalamic gene expression, anxiety-like behavior, and responsiveness to high fat diet (HFD). We find that distinguishing between dams that engage in stable individual differences in maternal behavior (Low, Mid, High) requires assessment across the light-dark phases of the light cycle and across multiple postpartum days. Amongst juvenile female offspring, we find a positive correlation between maternal LG and mRNA levels of estrogen receptor alpha and beta and the oxytocin receptor (when LG is assessed across the light-dark cycle or in the dark phase). In young adults, we find sex-specific effects, with female High LG offspring exhibiting increased exploration of a novel environment and increased latency to approach HFD and male High LG offspring displaying increased activity in a novel environment and reduced HFD consumption. Importantly, these effects on behavior were primarily evident when LG was assessed across the light-dark cycle and ABN was not associated with these measures. Overall, our findings illustrate the dissociation between the effects of LG and ABN on offspring development and provide critical insights into the temporal characteristics of maternal behavior that have methodological implications for the study of maternal effects. PMID:23398440

Exposure to Gestational Diabetes Mellitus: Impact on the Development of Early-Onset Type 2 Diabetes in Canadian First Nations and Non-First Nations Offspring.

PubMed

Sellers, Elizabeth A C; Dean, Heather J; Shafer, Leigh Anne; Martens, Patricia J; Phillips-Beck, Wanda; Heaman, Maureen; Prior, Heather J; Dart, Allison B; McGavock, Jonathan; Morris, Margaret; Torshizi, Ali A; Ludwig, Sora; Shen, Garry X

2016-12-01

Type 2 diabetes is increasing in children worldwide, with Canadian First Nations (FN) children disproportionally affected. The prevalence of gestational diabetes mellitus (GDM) also is increasing. The objective of this study was to evaluate the impact of GDM exposure in utero and FN status on the subsequent risk of type 2 diabetes in offspring in the first 30 years of life. In this population-based historical prospective cohort study, we used administrative databases linked to a clinical database to explore the independent association and interaction between GDM and FN status on the subsequent development of type 2 diabetes in offspring. Among 321,008 births with a median follow-up of 15.1 years, both maternal GDM and FN status were independently associated with subsequent risk of type 2 diabetes in offspring in the first 30 years of life (hazard ratio 3.03 [95% CI 2.44-3.76; P < 0.0001] vs. 4.86 [95% CI 4.08-5.79; P < 0.0001], respectively). No interaction between GDM and FN status on type 2 diabetes risk was observed. FN status had a stronger impact on the development of type 2 diabetes in offspring than GDM. GDM is an important modifiable risk factor for type 2 diabetes, and its prevention may reduce the prevalence of subsequent type 2 diabetes in offspring. This study adds unique and rigorous evidence to the global public health debate about the impact of GDM on the long-term health of offspring. © 2016 by the American Diabetes Association.

Relationship between central and peripheral atherosclerosis and left ventricular dysfunction in a community population.

PubMed

Tsao, Connie W; Gona, Philimon; Salton, Carol; Murabito, Joanne M; Oyama, Noriko; Danias, Peter G; O'Donnell, Christopher J; Manning, Warren J; Yeon, Susan B

2011-08-01

We aimed to determine the relationships between resting left ventricular (LV) wall motion abnormalities (WMAs), aortic plaque, and peripheral artery disease (PAD) in a community cohort. A total of 1726 Framingham Heart Study Offspring Cohort participants (806 males, 65 ± 9 years) underwent cardiovascular magnetic resonance with quantification of aortic plaque volume and assessment of regional left ventricular systolic function. Claudication, lower extremity revascularization, and ankle-brachial index (ABI) were recorded at the most contemporaneous examination visit. WMAs were associated with greater aortic plaque burden, decreased ABI, and claudication in age- and sex-adjusted analyses (all p < 0.001), which were not significant after adjustment for cardiovascular risk factors. In age- and sex-adjusted analyses, both the presence (p < 0.001) and volume of aortic plaque were associated with decreased ABI (p < 0.001). After multivariable adjustment, an ABI ≤ 0.9 or prior revascularization was associated with a threefold odds of aortic plaque (p = 0.0083). Plaque volume significantly increased with decreasing ABI in multivariable-adjusted analyses (p < 0.0001). In this free-living population, associations of WMAs with aortic plaque burden and clinical measures of PAD were attenuated after adjustment for coronary heart disease risk factors. Aortic plaque volume and ABI remained strongly negatively correlated after multivariable adjustment. Our findings suggest that the association between coronary heart disease and non-coronary atherosclerosis is explained by cardiovascular risk factors. Aortic atherosclerosis and PAD remain strongly associated after multivariable adjustment, suggesting shared mechanisms beyond those captured by traditional risk factors.

Effect of maternal predator exposure on the ability of stickleback offspring to generalize a learned colour–reward association

PubMed Central

Feng, Sally; McGhee, Katie E.; Bell, Alison M.

2017-01-01

Maternal stress can have long-term negative consequences for offspring learning performance. However, it is unknown whether these maternal effects extend to the ability of offspring to apply previously learned information to new situations. In this study, we first demonstrate that juvenile threespine sticklebacks, Gasterosteus aculeatus, are indeed capable of generalizing an association between a colour and a food reward learned in one foraging context to a new foraging context (i.e. they can apply previously learned knowledge to a new situation). Next, we examined whether this ability to generalize was affected by maternal predator stress. We manipulated whether mothers were repeatedly chased by a model predator while yolking eggs (i.e. before spawning) and then assessed the learning performance of their juvenile offspring in groups and pairs using a colour discrimination task that associated a colour with a food reward. We found that maternal predator exposure affected the tendency of offspring to use social cues: offspring of predator-exposed mothers were faster at copying a leader’s behaviour towards the rewarded colour than offspring of unexposed mothers. However, once the colour–reward association had been learned, offspring of predator-exposed and unexposed mothers were equally able to generalize their learned association to a new foraging task. These results suggest that offspring of predator-exposed mothers might be able to overcome learning deficits caused by maternal stress by relying more on social cues. PMID:29046591

Low folate and selenium in the mouse maternal diet alters liver gene expression patterns in the offspring after weaning.

PubMed

Barnett, Matthew P G; Bermingham, Emma N; Young, Wayne; Bassett, Shalome A; Hesketh, John E; Maciel-Dominguez, Anabel; McNabb, Warren C; Roy, Nicole C

2015-05-08

During pregnancy, selenium (Se) and folate requirements increase, with deficiencies linked to neural tube defects (folate) and DNA oxidation (Se). This study investigated the effect of a high-fat diet either supplemented with (diet H), or marginally deficient in (diet L), Se and folate. Pregnant female mice and their male offspring were assigned to one of four treatments: diet H during gestation, lactation and post-weaning; diet L during gestation, lactation and post-weaning; diet H during gestation and lactation but diet L fed to offspring post-weaning; or diet L during gestation and lactation followed by diet H fed to offspring post-weaning. Microarray and pathway analyses were performed using RNA from colon and liver of 12-week-old male offspring. Gene set enrichment analysis of liver gene expression showed that diet L affected several pathways including regulation of translation (protein biosynthesis), methyl group metabolism, and fatty acid metabolism; this effect was stronger when the diet was fed to mothers, rather than to offspring. No significant differences in individual gene expression were observed in colon but there were significant differences in cell cycle control pathways. In conclusion, a maternal low Se/folate diet during gestation and lactation has more effects on gene expression in offspring than the same diet fed to offspring post-weaning; low Se and folate in utero and during lactation thus has persistent metabolic effects in the offspring.

Sexual Risk Behaviors in the Adolescent Offspring of Parents with Bipolar Disorder: Prospective Associations with Parents' Personality and Externalizing Behavior in Childhood.

PubMed

Nijjar, Rami; Ellenbogen, Mark A; Hodgins, Sheilagh

2016-10-01

We recently reported that adolescent and young adult offspring of parents with bipolar disorder (OBD), relative to control offspring, were more likely to engage in sexual risk behaviors (SRBs). The present prospective study aimed to determine the contribution of parents' personality and offspring behaviour problems in middle childhood to offspring SRBs 10 years later. We hypothesized that offspring externalizing problems in childhood would mediate the relationship between parents' personality traits of neuroticism and agreeableness and adolescent SRBs. Furthermore, we expected these associations to be more robust among the OBD than controls. At baseline, 102 offspring (52 OBD and 50 controls) aged between 4 and 14 years were assessed along with their parents, who completed a self-report personality measure and child behavior rating. Behaviour ratings were also obtained from the children's teachers. Ten years later the offspring completed an interview assessing SRBs. Mediation analyses using bootstrapping revealed that, after controlling for age and presence of an affective disorder, externalizing behaviors served as a pathway through which high parental neuroticism, low parental agreeableness, and low parental extraversion were related to SRBs in offspring. Moderated mediation analyses revealed that the relationship between parental neuroticism and childhood externalizing problems was stronger for OBD than controls. These findings add to our previous results showing parents' personality contributes to intergenerational risk transfer through behavioral problems in middle childhood. These results carry implications for optimal timing of preventative interventions in the OBD.

De novo mutations in histone modifying genes in congenital heart disease

PubMed Central

Zaidi, Samir; Choi, Murim; Wakimoto, Hiroko; Ma, Lijiang; Jiang, Jianming; Overton, John D.; Romano-Adesman, Angela; Bjornson, Robert D.; Breitbart, Roger E.; Brown, Kerry K.; Carriero, Nicholas J.; Cheung, Yee Him; Deanfield, John; DePalma, Steve; Fakhro, Khalid A.; Glessner, Joseph; Hakonarson, Hakon; Italia, Michael; Kaltman, Jonathan R.; Kaski, Juan; Kim, Richard; Kline, Jennie K.; Lee, Teresa; Leipzig, Jeremy; Lopez, Alexander; Mane, Shrikant M.; Mitchell, Laura E.; Newburger, Jane W.; Parfenov, Michael; Pe'er, Itsik; Porter, George; Roberts, Amy; Sachidanandam, Ravi; Sanders, Stephan J.; Seiden, Howard S.; State, Mathew W.; Subramanian, Sailakshmi; Tikhonova, Irina R.; Wang, Wei; Warburton, Dorothy; White, Peter S.; Williams, Ismee A.; Zhao, Hongyu; Seidman, Jonathan G.; Brueckner, Martina; Chung, Wendy K.; Gelb, Bruce D.; Goldmuntz, Elizabeth; Seidman, Christine E.; Lifton, Richard P.

2013-01-01

Congenital heart disease (CHD) is the most frequent birth defect, affecting 0.8% of live births1. Many cases occur sporadically and impair reproductive fitness, suggesting a role for de novo mutations. By analysis of exome sequencing of parent-offspring trios, we compared the incidence of de novo mutations in 362 severe CHD cases and 264 controls. CHD cases showed a significant excess of protein-altering de novo mutations in genes expressed in the developing heart, with an odds ratio of 7.5 for damaging mutations. Similar odds ratios were seen across major classes of severe CHD. We found a marked excess of de novo mutations in genes involved in production, removal or reading of H3K4 methylation (H3K4me), or ubiquitination of H2BK120, which is required for H3K4 methylation2–4. There were also two de novo mutations in SMAD2; SMAD2 signaling in the embryonic left-right organizer induces demethylation of H3K27me5. H3K4me and H3K27me mark `poised' promoters and enhancers that regulate expression of key developmental genes6. These findings implicate de novo point mutations in several hundred genes that collectively contribute to ~10% of severe CHD. PMID:23665959

Maternal high-fat feeding leads to alterations of brain glucose metabolism in the offspring: positron emission tomography study in a porcine model.

PubMed

Sanguinetti, Elena; Liistro, Tiziana; Mainardi, Marco; Pardini, Silvia; Salvadori, Piero A; Vannucci, Alessandro; Burchielli, Silvia; Iozzo, Patricia

2016-04-01

Maternal obesity negatively affects fetal development. Abnormalities in brain glucose metabolism are predictive of metabolic-cognitive disorders. We studied the offspring (aged 0, 1, 6, 12 months) of minipigs fed a normal vs high-fat diet (HFD), by positron emission tomography (PET) to measure brain glucose metabolism, and ex vivo assessments of brain insulin receptors (IRβ) and GLUT4. At birth, brain glucose metabolism and IRβ were twice as high in the offspring of HFD-fed than control mothers. During infancy and youth, brain glucose uptake, GLUT4 and IRβ increased in the offspring of control mothers and decreased in those of HFD-fed mothers, leading to a 40-85% difference (p < 0.05), and severe glycogen depletion, lasting until adulthood. Maternal high-fat feeding leads to brain glucose overexposure during fetal development, followed by long-lasting depression in brain glucose metabolism in minipigs. These features may predispose the offspring to develop metabolic-neurodegenerative diseases.

Impact of prenatal hypoxia on fetal bone growth and osteoporosis in ovariectomized offspring rats.

PubMed

Yang, Yuxian; Fan, Xiaorong; Tao, Jianying; Xu, Ting; Zhang, Yingying; Zhang, Wenna; Li, Lingjun; Li, Xiang; Ding, Hongmei; Sun, Miao; Gao, Qinqin; Xu, Zhice

2018-03-07

Prenatal hypoxia causes intrauterine growth retardation. It is unclear whether/how hypoxia affects the bone in fetal and offspring life. This study showed that prenatal hypoxia retarded fetal skeletal growth in rats, inhibited extracellular matrix (ECM) synthesis and down-regulated of insulin-like growth factor 1 (IGF1) signaling in fetal growth plate chondrocytes in vivo and in vitro. In addition, ovariectomized (OVX) was used for study of postmenopausal osteoporosis. Compared with the control, OVX offspring in prenatal hypoxic group showed an enhanced osteoporosis in the femurs, associated with reduced proteoglycan and IGF1 signaling. The results indicated prenatal hypoxia not only delayed fetal skeletal growth, but also increased OVX-induced osteoporosis in the elder offspring probably through down-regulated IGF1 signaling and inhibition of ECM synthesis, providing important information of prenatal hypoxia on functional and molecular bone growth and metabolism in fetal and offspring. Copyright © 2018 Elsevier Inc. All rights reserved.

The Role of Maternal Dietary Proteins in Development of Metabolic Syndrome in Offspring

PubMed Central

Jahan-Mihan, Alireza; Rodriguez, Judith; Christie, Catherine; Sadeghi, Marjan; Zerbe, Tara

2015-01-01

The prevalence of metabolic syndrome and obesity has been increasing. Pre-natal environment has been suggested as a factor influencing the risk of metabolic syndrome in adulthood. Both observational and experimental studies showed that maternal diet is a major modifier of the development of regulatory systems in the offspring in utero and post-natally. Both protein content and source in maternal diet influence pre- and early post-natal development. High and low protein dams’ diets have detrimental effect on body weight, blood pressure191 and metabolic and intake regulatory systems in the offspring. Moreover, the role of the source of protein in a nutritionally adequate maternal diet in programming of food intake regulatory system, body weight, glucose metabolism and blood pressure in offspring is studied. However, underlying mechanisms are still elusive. The purpose of this review is to examine the current literature related to the role of proteins in maternal diets in development of characteristics of the metabolic syndrome in offspring. PMID:26561832

Producing offspring in Armadillidium vulgare: Effects of genetic diversity and inbreeding.

PubMed

Durand, Sylvine; Loiseau, Vincent; Prigot, Cybèle; Braquart-Varnier, Christine; Beltran-Bech, Sophie

2018-03-01

Genetic diversity is known to be correlated to fitness traits, and inbred individuals often display lower values for life history traits. In this study, we attempt to quantify how inbreeding affects such traits in the terrestrial isopod Armadillidium vulgare by performing inbred and non-inbred crosses under laboratory conditions. We estimated genetic characteristics of parents and offspring, and related them to fecundity and fertility measures, as well as offspring growth and survival. Our study shows that a decrease in offspring number might result from mortality around birth, but not to changes in fecundity, fertilization rate, or developmental failure between inbred and non-inbred crosses. More heterozygous females tended to be bigger and had a higher fecundity, which could have implications in mate choice. No effect of inbreeding was detected on offspring growth and survival. These results can be related to previously observed effects of genetic characteristics on mating strategies in A. vulgare, and could shed light on mechanisms of inbreeding avoidance in this species. © 2018 Wiley Periodicals, Inc.

The influence of parents' religious practices on young adults' divorce attitudes.

PubMed

Kapinus, Carolyn A; Pellerin, Lisa A

2008-09-01

This study investigates the intergenerational transmission of parents' religious views and divorce attitudes, paying particular attention to the effect of parent-child closeness. We use structural equation modeling to examine a national longitudinal data set containing information from 455 married individuals and their adult offspring. We find that parent religiosity influences young adults' views of divorce via two pathways: by affecting offspring's religiosity and parents' views of divorce. More religious offspring are less tolerant of divorce, but offspring who do not share their parents' religious practices are nonetheless influenced by their parents' religiously-influenced divorce attitudes. While parent religiosity has no effect on parent-child closeness, religious offspring report having been closer to their parents, suggesting that their current religious practices may affect their perceptions of the parent-child relationship.

Transgenerational aspects of former Swiss child laborers: do second generations suffer from their parents’ adverse early-life experiences?

PubMed Central

Küffer, Andreas L.; Thoma, Myriam V.; Maercker, Andreas

2016-01-01

Background Recent research suggests that childhood adversity exerts a lasting impact not only on the affected individuals but also on their offspring. Little is known about the role of parental rearing behavior in the transgenerational conveyance of parental childhood adversity and filial psychological health. Objective Hence, it was the aim of the current study to investigate the relationship between parental rearing behavior of former Swiss indentured child laborers (“Verdingkinder”) and psychological health of their adult offspring. Methods We applied a two-generation control-group design with two parental samples (n=16, former “Verdingkinder,” Mage=76.13, SD=6.81 and n=19, parental controls, Mage=72.63, SD=5.96) and their offspring (n=21, former “Verdingkinder” offspring, Mage=52.91, SD=5.90, and n=29 offspring controls, Mage=44.55, SD=7.71). Parental rearing behavior, childhood trauma, and psychological health were assessed with questionnaires. Data were analyzed using Bayesian analyses, where Bayes factors (BF) of 3 or higher were considered as substantial evidence for the tested hypotheses. Results We found that “Verdingkinder” offspring reported more physical abuse (BF10=5.197) and higher total childhood trauma exposure (BF10=2.476). They described both their fathers (BF10=14.246) and mothers (BF10=24.153) as less emotional and their mothers as more punitive (BF10=18.725). An increased sense of reflection, for instance, one's ability to take different perspectives, was found in the offspring controls (BF10=5.245). Furthermore, exploratory analyses revealed that lower perceived familial emotionality was associated with higher psychopathology (all BF10=10.471) and higher pessimism (all BF10=5.396). Discussion Our data provide cross-sectional evidence of a meaningful transgenerational relationship between parental childhood adversity, dysfunctional rearing behavior, and psychological health of offspring. Prospective studies are needed to investigate these findings in a longitudinal setting. Highlights of the article The study showed elevated levels of aversive childhood events in the adult offspring of former indentured childhood laborers.The offspring of former indentured childhood laborers did not exhibit increased general psychopathology (as assessed by the Symptom-Checklist: SCL).However, the recalled childhood rearing behavior was more problematic (higher punishment, less emotional warmth) in the offspring of former indentured childhood laborers as compared to a 2nd generation control group.Second generation group differences for world view variables (optimism, pessimism) were not substantial or in favor of the control participants (reflection facet of sense of coherence-revised). PMID:27784510

Evidence relevant to untargeted and transgenerational effects in the offspring of irradiated parents

PubMed Central

Little, Mark P.; Goodhead, Dudley T.; Bridges, Bryn A.; Bouffler, Simon D.

2013-01-01

In this article we review health effects in offspring of human populations exposed as a result of radiotherapy and some groups exposed to chemotherapy. We also assess risks in offspring of other radiation-exposed groups, in particular those of the Japanese atomic bomb survivors and occupationally and environmentally exposed groups. Experimental findings are also briefly surveyed. Animal and cellular studies tend to suggest that the irradiation of males, at least at high doses (mostly 1 Gy and above), can lead to observable effects (including both genetic and epigenetic) in the somatic cells of their offspring over several generations that are not attributable to the inheritance of a simple mutation through the parental germ line. However, studies of disease in the offspring of irradiated humans have not identified any effects on health. The available evidence therefore suggests that human health has not been significantly affected by transgenerational effects of radiation. It is possible that transgenerational effects are restricted to relatively short times post-exposure and in humans conception at short times after exposure is likely to be rare. Further research that may help resolve the apparent discrepancies between cellular/animal studies and studies of human health are outlined. PMID:23648355

Mothers' Own Recollections Of Being Parented And Risk Of Offspring Depression 18 Years Later: A Prospective Cohort Study

PubMed Central

Mahedy, Liam; Heron, Jon; Stapinski, Lexine A; Pearson, Rebecca M; Evans, Jonathan; Joinson, Carol; Bowes, Lucy; Lewis, Glyn

2014-01-01

Background Although the relationship between maternal bonding and risk of offspring depression has been demonstrated, it is unclear whether this risk exists for subsequent generations. This study examines the association between maternal reports of her own mother's parenting and later risk of depression in offspring at age 18. Method This study is based on data from the Avon Longitudinal Study of Parents and Children. Mothers enrolled in the study, completed the Parental Bonding Instrument to provide an assessment of how they were parented by their own mothers up to the age of 16. Offspring depression was assessed at age of 18 using the Clinical Interview Schedule-Revised. The sample comprised 10,405 respondents who had completed the Parental Bonding Instrument during the antenatal period. Results were adjusted for grandmother's history of depression, maternal depression, and a range of socioeconomic variables. Results A one standard deviation increase in mothers’ perceived lack of care in their own childhood was associated with a 16% increase in the odds of offspring depression at age 18 (odds ratios = 1.16, 95% confidence intervals = [1.04, 1.30]). This effect remained following adjustment for potential confounders (odds ratios = 1.14, 95% confidence intervals = [1.02, 1.27]). There was no evidence for an association between overprotection and offspring depression. Conclusions This study is consistent with the hypothesis that sensitive caregiving is important to future risk of depression across generations. Preventative interventions could be aimed at promoting positive parenting practices, which may help to reduce the risk of depression in subsequent generations. PMID:24105778

Parent-offspring conflict and the genetic trade-offs shaping parental investment.

PubMed

Kölliker, Mathias; Boos, Stefan; Wong, Janine W Y; Röllin, Lilian; Stucki, Dimitri; Raveh, Shirley; Wu, Min; Meunier, Joël

2015-04-16

The genetic conflict between parents and their offspring is a cornerstone of kin selection theory and the gene-centred view of evolution, but whether it actually occurs in natural systems remains an open question. Conflict operates only if parenting is driven by genetic trade-offs between offspring performance and the parent's ability to raise additional offspring, and its expression critically depends on the shape of these trade-offs. Here we investigate the occurrence and nature of genetic conflict in an insect with maternal care, the earwig Forficula auricularia. Specifically, we test for a direct response to experimental selection on female future reproduction and correlated responses in current offspring survival, developmental rate and growth. The results demonstrate genetic trade-offs that differ in shape before and after hatching. Our study not only provides direct evidence for parent-offspring conflict but also highlights that conflict is not inevitable and critically depends on the genetic trade-offs shaping parental investment.

Accurate computer-aided quantification of left ventricular parameters: experience in 1555 cardiac magnetic resonance studies from the Framingham Heart Study.

PubMed

Hautvast, Gilion L T F; Salton, Carol J; Chuang, Michael L; Breeuwer, Marcel; O'Donnell, Christopher J; Manning, Warren J

2012-05-01

Quantitative analysis of short-axis functional cardiac magnetic resonance images can be performed using automatic contour detection methods. The resulting myocardial contours must be reviewed and possibly corrected, which can be time-consuming, particularly when performed across all cardiac phases. We quantified the impact of manual contour corrections on both analysis time and quantitative measurements obtained from left ventricular short-axis cine images acquired from 1555 participants of the Framingham Heart Study Offspring cohort using computer-aided contour detection methods. The total analysis time for a single case was 7.6 ± 1.7 min for an average of 221 ± 36 myocardial contours per participant. This included 4.8 ± 1.6 min for manual contour correction of 2% of all automatically detected endocardial contours and 8% of all automatically detected epicardial contours. However, the impact of these corrections on global left ventricular parameters was limited, introducing differences of 0.4 ± 4.1 mL for end-diastolic volume, -0.3 ± 2.9 mL for end-systolic volume, 0.7 ± 3.1 mL for stroke volume, and 0.3 ± 1.8% for ejection fraction. We conclude that left ventricular functional parameters can be obtained under 5 min from short-axis functional cardiac magnetic resonance images using automatic contour detection methods. Manual correction more than doubles analysis time, with minimal impact on left ventricular volumes and ejection fraction. Copyright © 2011 Wiley Periodicals, Inc.

High Dietary Fat Intake during Lactation Promotes the Development of Social Stress-Induced Obesity in the Offspring of Mice.

PubMed

Tsuduki, Tsuyoshi; Yamamoto, Kazushi; E, Shuang; Hatakeyama, Yu; Sakamoto, Yu

2015-07-17

This study examined how a maternal high-fat diet (HD) during lactation and exposure of offspring to isolation stress influence the susceptibility of offspring to the development of obesity. C57BL/6J mice were fed a commercial diet (CD) during pregnancy and a CD or HD during lactation. Male offspring were weaned at three weeks of age, fed a CD until seven weeks of age, and fed a CD or HD until 11 weeks of age. Offspring were housed alone (isolation stress) or at six per cage (ordinary circumstances). Thus, offspring were assigned to one of eight groups: dams fed a CD or HD during lactation and offspring fed a CD or HD and housed under ordinary circumstances or isolation stress. Serum corticosterone level was significantly elevated by isolation stress. High-fat feeding of offspring reduced their serum corticosterone level, which was significantly elevated by a maternal HD. A maternal HD and isolation stress had combined effects in elevating the serum corticosterone level. These findings suggest that a maternal HD during lactation enhances the stress sensitivity of offspring. White adipose tissue weights were significantly increased by a maternal HD and isolation stress and by their combination. In addition, significant adipocyte hypertrophy was induced by a maternal HD and isolation stress and exacerbated by their combination. Thus, a maternal HD and isolation stress promote visceral fat accumulation and adipocyte hypertrophy, accelerating the progression of obesity through their combined effects. The mechanism may involve enhanced fatty acid synthesis and lipid influx from blood into adipose tissue. These findings demonstrate that a maternal HD during lactation may increase the susceptibility of offspring to the development of stress-induced obesity.

Obesity and type 2 diabetes mellitus in a birth cohort of First Nation children born to mothers with pediatric-onset type 2 diabetes.

PubMed

Mendelson, Michael; Cloutier, Justin; Spence, Louise; Sellers, Elizabeth; Taback, Shayne; Dean, Heather

2011-05-01

Children who are born to mothers with pediatric-onset type 2 diabetes mellitus are exposed to a hyperglycemic intra-uterine environment throughout pregnancy. The growth patterns and risk of type 2 diabetes in these offspring may be influenced by unique gene-environment interactions during intra-uterine and postnatal life. We established a cohort of offspring of First Nation mothers with onset of type 2 diabetes before age 18 years in Manitoba, Canada. We measured height or length and weight at study entry and annually thereafter with fasting blood glucose in offspring aged ≥ 7 years. We collected birth and breastfeeding history and determined the population-specific hepatic nuclear factor-1α (HNF-1α) G319S genotype of offspring at age 7 years. From July 2003 to April 2008, we enrolled 76 offspring of 37 mothers. Sixty-four percent (23/36) of the offspring aged 2-19 years were obese at initial assessment. The rates of obesity remained constant throughout the 5 years. As of April 2008, 7/28 (25%) of the offspring aged 7-19 years have diabetes including 6/14 (43%) aged 10-19 years. Most offspring with diabetes (5/7, 71%) were obese at diagnosis. All of the 7 offspring with diabetes have 1 or 2 copies of the G319S polymorphism. The prevalence of type 2 diabetes in this cohort of offspring of First Nation women with pediatric-onset type 2 diabetes is the highest ever reported. Obesity is an important postnatal risk factor for type 2 diabetes in this population and may result from a unique gene-environment interaction. © 2011 John Wiley & Sons A/S.

Paternal occupational lead exposure and offspring risks for schizophrenia.

PubMed

Sallmén, Markku; Suvisaari, Jaana; Lindbohm, Marja-Liisa; Malaspina, Dolores; Opler, Mark G

2016-10-01

This register-based cohort study investigated whether paternal occupational exposure to inorganic lead was related to offspring risk for schizophrenia spectrum disorder (SSD). Exposed men (n=11,863) were identified from blood lead measurements taken at the Finnish Institute of Occupational Health in 1973-1983. Data on mothers and their offspring born from 1972-1984 were obtained from the national Population Information System. Two population comparison offspring for each exposed offspring were matched on date of birth, sex and area (n=23,720). SSD cases were identified from The Finnish Hospital Discharge Register. Hazard ratios of SSD between exposed groups were analyzed using conditional proportional hazards regression, adjusted for parental history of psychoses, parental ages, language of offspring, father's employment, and father's self-employment. After 26-38years of follow up, there were no significant differences in the incidence of schizophrenia, either between the offspring of exposed (188/11,863; 1.6%) and unexposed fathers (347/23,720; 1.5%) or based on blood lead levels (adjusted hazard ratios (aHR): 0.97, CI 0.52-1.83, 1.25, CI 0.85-1.82, 0.90, CI 0.54-1.49, and 1.38, CI 0.65-2.92 for lead categories <0.5, 0.5-0.9, 1.0-1.4, and ≥1.5μmol/L, respectively, as compared to population comparison). Parental psychosis, paternal age and offspring language were associated with offspring risk. The findings suggest that paternal exposure to lead is not a risk factor for schizophrenia in offspring. However, the majority of exposed fathers had low-level exposure, and we cannot exclude the possibility of an effect for higher exposures to lead. Copyright © 2016 Elsevier B.V. All rights reserved.

Maternal antibodies protect offspring from severe influenza infection and do not lead to detectable interference with subsequent offspring immunization.

PubMed

van der Lubbe, Joan E M; Vreugdenhil, Jessica; Damman, Sarra; Vaneman, Joost; Klap, Jaco; Goudsmit, Jaap; Radošević, Katarina; Roozendaal, Ramon

2017-06-26

Various studies have shown that infants under the age of 6 months are especially vulnerable for complications due to influenza. Currently there are no vaccines licensed for use in this age group. Vaccination of pregnant women during the last trimester, recommended by the WHO as protective measure for this vulnerable female population, may provide protection of newborns at this early age. Although it has been observed that maternal vaccination can passively transfer protection, maternal antibodies could possibly also interfere with subsequent active vaccination of the offspring. Using a mouse model, we evaluated in depth the ability of maternal influenza vaccination to protect offspring and the effect of maternal immunization on the subsequent influenza vaccination of the offspring. By varying the regimen of maternal immunization we explored the impact of different levels of maternal antibodies on the longevity of these antibodies in their progeny. We subsequently assessed to what extent maternal antibodies can mediate direct protection against influenza in their offspring, and whether these antibodies interfere with protection induced by active vaccination of the offspring. The number of immunizations of pregnant mice correlates to the level and longevity of maternal antibodies in the offspring. When these antibodies are present at time of influenza challenge they protect offspring against lethal influenza challenge, even in the absence of detectable HAI titers. Moreover, no detectable interference of passively-transferred maternal antibodies on the subsequent vaccination of the offspring was observed. In the absence of a licensed influenza vaccine for young children, vaccination of pregnant women is a promising measure to provide protection of young infants against severe influenza infection.

Maternal postpartum corticosterone and fluoxetine differentially affect adult male and female offspring on anxiety-like behavior, stress reactivity, and hippocampal neurogenesis.

PubMed

Gobinath, Aarthi R; Workman, Joanna L; Chow, Carmen; Lieblich, Stephanie E; Galea, Liisa A M

2016-02-01

Postpartum depression (PPD) affects approximately 15% of mothers, disrupts maternal care, and can represent a form of early life adversity for the developing offspring. Intriguingly, male and female offspring are differentially vulnerable to the effects of PPD. Antidepressants, such as fluoxetine, are commonly prescribed for treating PPD. However, fluoxetine can reach offspring via breast milk, raising serious concerns regarding the long-term consequences of infant exposure to fluoxetine. The goal of this study was to examine the long-term effects of maternal postpartum corticosterone (CORT, a model of postpartum stress/depression) and concurrent maternal postpartum fluoxetine on behavioral, endocrine, and neural measures in adult male and female offspring. Female Sprague-Dawley dams were treated daily with either CORT or oil and fluoxetine or saline from postnatal days 2-23, and offspring were weaned and left undisturbed until adulthood. Here we show that maternal postpartum fluoxetine increased anxiety-like behavior and impaired hypothalamic-pituitary-adrenal (HPA) axis negative feedback in adult male, but not female, offspring. Furthermore, maternal postpartum fluoxetine increased the density of immature neurons (doublecortin-expressing) in the hippocampus of adult male offspring but decreased the density of immature neurons in adult female offspring. Maternal postpartum CORT blunted HPA axis negative feedback in males and tended to increase density of immature neurons in males but decreased it in females. These results indicate that maternal postpartum CORT and fluoxetine can have long-lasting effects on anxiety-like behavior, HPA axis negative feedback, and adult hippocampal neurogenesis and that adult male and female offspring are differentially affected by these maternal manipulations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Maternal high-fat diet acts on the brain to induce baroreflex dysfunction and sensitization of angiotensin II-induced hypertension in adult offspring.

PubMed

Zhang, Yu-Ping; Huo, Yan-Li; Fang, Zhi-Qin; Wang, Xue-Fang; Li, Jian-Dong; Wang, Hai-Ping; Peng, Wei; Johnson, Alan Kim; Xue, Baojian

2018-05-01

Accumulating evidence indicates that maternal high-fat diet (HFD) is associated with metabolic syndrome and cardiovascular disease in adult offspring. The present study tested the hypothesis that maternal HFD modulates the brain renin-angiotensin system (RAS), oxidative stress, and proinflammatory cytokines that alter angiotensin II (ANG II) and TNF-α actions and sensitize the ANG II-elicited hypertensive response in adult offspring. All offspring were cross fostered by dams on the same or opposite diet to yield the following four groups: offspring from normal-fat control diet-fed dams suckled by control diet-fed dams (OCC group) or by HFD-fed dams (OCH group) and offspring from HFD-fed dams fed a HFD suckled by control diet-fed dams (OHC group) or by HFD-fed dams (OHH group). RT-PCR analyses of the lamina terminalis and paraventricular nucleus indicated upregulation of mRNA expression of several RAS components, NADPH oxidase, and proinflammatory cytokines in 10-wk-old male offspring of dams fed a HFD during either pregnancy, lactation, or both (OHC, OCH, and OHH groups). These offspring also showed decreased cardiac baroreflex sensitivity and increased pressor responses to intracerebroventricular microinjection of either ANG II or TNF-α. Furthermore, chronic systemic infusion of ANG II resulted in enhanced upregulation of mRNA expression of RAS components, NADPH oxidase, and proinflammatory cytokines in the lamina terminalis and paraventricular nucleus and an augmented hypertensive response in the OHC, OCH, and OHH groups compared with the OCC group. The results suggest that maternal HFD blunts cardiac baroreflex function and enhances pressor responses to ANG II or proinflammatory cytokines through upregulation of the brain RAS, oxidative stress, and inflammation. NEW & NOTEWORTHY The results of our study indicate that a maternal high-fat diet during either pregnancy or lactation is sufficient for perinatal programming of sensitization for hypertension, which is associated with hyperreactivity of central cardiovascular nuclei that, in all likelihood, involves elevated expression of the renin-angiotensin system, NADPH oxidase, and proinflammatory cytokines. The present study demonstrates, for the first time, the central mechanism underlying maternal high-fat diet sensitization of the hypertensive response in adult offspring.

What are the benefits of parental care? The importance of parental effects on developmental rate

PubMed Central

Klug, Hope; Bonsall, Michael B

2014-01-01

The evolution of parental care is beneficial if it facilitates offspring performance traits that are ultimately tied to offspring fitness. While this may seem self-evident, the benefits of parental care have received relatively little theoretical exploration. Here, we develop a theoretical model that elucidates how parental care can affect offspring performance and which aspects of offspring performance (e.g., survival, development) are likely to be influenced by care. We begin by summarizing four general types of parental care benefits. Care can be beneficial if parents (1) increase offspring survival during the stage in which parents and offspring are associated, (2) improve offspring quality in a way that leads to increased offspring survival and/or reproduction in the future when parents are no longer associated with offspring, and/or (3) directly increase offspring reproductive success when parents and offspring remain associated into adulthood. We additionally suggest that parental control over offspring developmental rate might represent a substantial, yet underappreciated, benefit of care. We hypothesize that parents adjust the amount of time offspring spend in life-history stages in response to expected offspring mortality, which in turn might increase overall offspring survival, and ultimately, fitness of parents and offspring. Using a theoretical evolutionary framework, we show that parental control over offspring developmental rate can represent a significant, or even the sole, benefit of care. Considering this benefit influences our general understanding of the evolution of care, as parental control over offspring developmental rate can increase the range of life-history conditions (e.g., egg and juvenile mortalities) under which care can evolve. PMID:25360271

Metabolomics reveals an involvement of pantothenate for male production responding to the short-day stimulus in the water flea, Daphnia pulex

PubMed Central

Toyota, Kenji; Gavin, Alex; Miyagawa, Shinichi; Viant, Mark R.; Iguchi, Taisen

2016-01-01

Under favorable conditions, the micro-crustacean Daphnia pulex produces female offspring by parthenogenesis, whereas under unfavorable conditions, they produce male offspring to induce sexual reproduction (environmental sex determination: ESD). We recently established a suitable system for ESD studies using D. pulex WTN6 strain, in which the sex of the offspring can be regulated by alterations in day-length; long-day and short-day conditions can induce female and male offspring, respectively. Taking advantage of this system, we have already demonstrated that methyl farnesoate (MF) synthesis is necessary for male offspring production, and identified ionotropic glutamate receptors as an upstream regulator of MF signaling. Despite these findings, the molecular mechanisms associated with MF signaling have not yet been well elucidated. In this study, we analyzed the whole metabolic profiles of mother daphnids reared under long-day (female-producing) and short-day (male-producing) conditions, and discovered that pantothenate (vitamin B5), a known precursor to coenzyme A, was significantly accumulated in response to the short-day condition. To confirm the innate role of pantothenate in D. pulex, this metabolite was administered to mother daphnids resulting in a significantly increased proportion of male offspring producing mothers. This study provides novel insights of the metabolic mechanisms of the ESD system in D. pulex. PMID:27113113

A Children of Twins Study of parental divorce and offspring psychopathology.

PubMed

D'Onofrio, Brian M; Turkheimer, Eric; Emery, Robert E; Maes, Hermine H; Silberg, Judy; Eaves, Lindon J

2007-07-01

Although parental divorce is associated with increased substance use and internalizing problems, experiencing the separation of one's parents may not cause these outcomes. The relations may be due to genetic or environmental selection factors, characteristics that lead to both marital separation and offspring functioning. We used the Children of Twins (CoT) Design to explore whether unmeasured genetic or environmental factors related to the twin parent, and measured characteristics of both parents, account for the association between parental divorce and offspring substance use and internalizing problems. The association between parental divorce and offspring substance use problems remained robust when controlling for genetic and environmental risk from the twin parent associated with parental divorce, and measured characteristics of both parents. The results do not prove, but are consistent with, a causal connection. In contrast, the analyses suggest that shared genetic liability in parents and their offspring accounts for the increased risk of internalizing problems in adult offspring from divorced families. The study illustrates that unmeasured genetic and environmental selection factors must be considered when studying parental divorce. In explaining associations between parental divorce and young-adult adjustment, our evidence suggests that selection versus causal mechanisms may operate differently for substance abuse (a causal relation) and internalizing problems (an artifact of selection). The CoT design only controls for the genetic and environmental characteristics of one parent; thus, additional genetically informed analyses are needed.

Metabolomics reveals an involvement of pantothenate for male production responding to the short-day stimulus in the water flea, Daphnia pulex.

PubMed

Toyota, Kenji; Gavin, Alex; Miyagawa, Shinichi; Viant, Mark R; Iguchi, Taisen

2016-04-26

Under favorable conditions, the micro-crustacean Daphnia pulex produces female offspring by parthenogenesis, whereas under unfavorable conditions, they produce male offspring to induce sexual reproduction (environmental sex determination: ESD). We recently established a suitable system for ESD studies using D. pulex WTN6 strain, in which the sex of the offspring can be regulated by alterations in day-length; long-day and short-day conditions can induce female and male offspring, respectively. Taking advantage of this system, we have already demonstrated that methyl farnesoate (MF) synthesis is necessary for male offspring production, and identified ionotropic glutamate receptors as an upstream regulator of MF signaling. Despite these findings, the molecular mechanisms associated with MF signaling have not yet been well elucidated. In this study, we analyzed the whole metabolic profiles of mother daphnids reared under long-day (female-producing) and short-day (male-producing) conditions, and discovered that pantothenate (vitamin B5), a known precursor to coenzyme A, was significantly accumulated in response to the short-day condition. To confirm the innate role of pantothenate in D. pulex, this metabolite was administered to mother daphnids resulting in a significantly increased proportion of male offspring producing mothers. This study provides novel insights of the metabolic mechanisms of the ESD system in D. pulex.

Fetal betamethasone exposure attenuates angiotensin-(1-7)-Mas receptor expression in the dorsal medulla of adult sheep.

PubMed

Marshall, Allyson C; Shaltout, Hossam A; Nautiyal, Manisha; Rose, James C; Chappell, Mark C; Diz, Debra I

2013-06-01

Glucocorticoids including betamethasone (BM) are routinely administered to women entering into early preterm labor to facilitate fetal lung development and decrease infant mortality; however, fetal steroid exposure may lead to deleterious long term consequences. In a sheep model of fetal programming, BM-exposed (BMX) offspring exhibit elevated mean arterial pressure (MAP) and decreased baroreflex sensitivity (BRS) for control of heart rate by 0.5-years of age associated with changes in the circulating and renal renin-angiotensin systems (RAS). In the brain solitary tract nucleus, angiotensin (Ang) II actions through the AT1 receptor oppose the beneficial actions of Ang-(1-7) at the Mas receptor for BRS regulation. Therefore, we examined Ang peptides, angiotensinogen (Aogen), and receptor expression in this brain region of exposed and control offspring of 0.5- and 1.8-years of age. Mas protein expression was significantly lower (>40%) in the dorsal medulla of BMX animals at both ages; however, AT1 receptor expression was not changed. BMX offspring exhibited a higher ratio of Ang II to Ang-(1-7) (2.30±0.36 versus 0.99±0.28; p<0.01) and Ang II to Ang I at 0.5-years. Although total Aogen was unchanged, Ang I-intact Aogen was lower in 0.5-year BMX animals (0.78±0.06 vs. 1.94±0.41; p<0.05) suggesting a greater degree of enzymatic processing of the precursor protein in exposed animals. We conclude that in utero BM exposure promotes an imbalance in the central RAS pathways of Ang II and Ang-(1-7) that may contribute to the elevated MAP and lower BRS in this model. Copyright © 2013 Elsevier Inc. All rights reserved.

FETAL BETAMETHASONE EXPOSURE ATTENUATES ANGIOTENSIN-(1-7)-MAS RECEPTOR EXPRESSION IN THE DORSAL MEDULLA OF ADULT SHEEP

PubMed Central

Marshall, Allyson C.; Shaltout, Hossam A.; Nautiyal, Manisha; Rose, James C.; Chappell, Mark C.; Diz, Debra I.

2013-01-01

Glucocorticoids including betamethasone (BM) are routinely administered to women entering into early preterm labor to facilitate fetal lung development and decrease infant mortality; however, fetal steroid exposure may lead to deleterious long term consequences. In a sheep model of fetal programming, BM-exposed (BMX) offspring exhibit elevated mean arterial pressure (MAP) and decreased baroreflex sensitivity (BRS) for control of heart rate by 0.5-years of age associated with changes in the circulating and renal renin-angiotensin systems (RAS). In the brain solitary tract nucleus, angiotensin (Ang) II actions through the AT1 receptor oppose the beneficial actions of Ang-(1-7) at the Mas receptor for BRS regulation. Therefore, we examined Ang peptides, angiotensinogen (Aogen), and receptor expression in this brain region of exposed and control offspring of 0.5- and 1.8-years of age. Mas protein expression was significantly lower (>40%) in the dorsal medulla of BMX animals at both ages; however, AT1 receptor expression was not changed. BMX offspring exhibited a higher ratio of Ang II to Ang-(1-7) (2.30 ± 0.36 versus 0.99 ± 0.28; p<0.01) and Ang II to Ang I at 0.5-years. Although total Aogen was unchanged, Ang I-intact Aogen was lower in 0.5-year BMX animals (0.78 ± 0.06 vs. 1.94 ± 0.41; p<0.05) suggesting a greater degree of enzymatic processing of the precursor protein in exposed animals. We conclude that in utero BM exposure promotes an imbalance in the central RAS pathways of Ang II and Ang-(1-7) that may contribute to the elevated MAP and lower BRS in this model. PMID:23538211

Can domestic helpers moderate distress of offspring caregivers of cognitively impaired older adults?

PubMed

Chong, Alice M L; Kwan, Chi Wai; Lou, Vivian W Q; Chi, Iris

2017-10-01

This study examined the moderating effect of domestic helpers on distress of offspring caring for parents with cognitive impairments and with or without behavioural problems. This secondary analysis of data involved 5086 Hong Kong Chinese adults aged 60 or older applying for public long-term care services from 2010 to 2012. All variables were measured using the mandatory Hong Kong version of the Minimum Data Set-Home Care 2.0. Regarding taking care of parents with cognitive impairments, 10.7% of offspring primary caregivers were aided by domestic helpers, 55.54% reported distress, and 75.70% lived with their parents. Assistance from domestic helpers reduced offspring caregiver distress if the offspring provided psychological support to parents (ratio of OR = 0.655, p < .05) and were not living with parents (ratio of OR = 1.183, p < .01). These findings might suggest: a) the positive effects of audience on psychological responses to stress; b) caregiving is usually less stressful for informal caregivers not residing with care recipients. Conversely, having a domestic helper could add to caregiving distress if offspring caregivers live with their parents, most likely because offspring may witness difficulties that domestic helpers face in providing dementia care.

Immune imbalance of global gene expression, and cytokine, chemokine and selectin levels in the brains of offspring with social deficits via maternal immune activation.

PubMed

Hsueh, P-T; Lin, H-H; Wang, H-H; Liu, C-L; Ni, W-F; Liu, J-K; Chang, H-H; Sun, D-S; Chen, Y-S; Chen, Y-L

2018-04-15

The murine maternal immune activation (MIA) offspring model enables longitudinal studies to explore aberrant social behaviors similar to those observed in humans. High levels of cytokines, chemokines and cell adhesion molecules (CAM) have been found in the plasma and/or brains of psychiatric patients. We hypothesized that upregulation of the systemic or brain immune response has an augmenting effect by potentially increasing the interplay between the neuronal and immune systems during the growth of the MIA offspring. In this study, a C57BL/6j MIA female offspring model exhibiting social deficits was established. The expression of fetal interferon (IFN)-stimulated (gbp3, irgm1, ifi44), adolescent immunodevelopmental transcription factor (eg, r2, tfap2b), hormone (pomc, hcrt), adult selectin (sell, selp) and neuroligin (nlgn2) genes was altered. Systemic upregulation of endogenous IL-10 occurred at the adult stage, while both IL-1β and IL-6 were increased and persisted in the sera throughout the growth of the MIA offspring. The cerebral IL-6 levels were endogenously upregulated, but both MCP-1 (macrophage inflammatory protein-1) and L-selectin levels were downregulated at the adolescent and/or adult stages. However, the MIA offspring were susceptible to lipopolysaccharide (LPS) stimulation. After reinjecting the MIA offspring with LPS in adulthood, a variety of sera and cerebral cytokines, chemokines and CAMs were increased. Particularly, both MCP-1 and L-selectin showed relatively high expression in the brain compared with the expression levels in phosphate-buffered saline (PBS)-treated offspring injected with LPS. Potentially, MCP-1 was attracted to the L-selectin-mediated immune cells due to augmentation of the immune response following stimulation in MIA female offspring. © 2018 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Gestational flu exposure induces changes in neurochemicals, affiliative hormones and brainstem inflammation, in addition to autism-like behaviors in mice.

PubMed

Miller, V M; Zhu, Y; Bucher, C; McGinnis, W; Ryan, L K; Siegel, A; Zalcman, S

2013-10-01

The prevalence of neurodevelopmental disorders such as autism is increasing, however the etiology of these disorders is unclear and thought to involve a combination of genetic, environmental and immune factors. A recent epidemiological study found that gestational viral exposure during the first trimester increases risk of autism in offspring by twofold. In mice gestational viral exposures alter behavior of offspring, but the biological mechanisms which underpin these behavioral changes are unclear. We hypothesized that gestational viral exposure induces changes in affiliative hormones, brainstem autonomic nuclei and neurotransmitters which are associated with behavioral alterations in offspring. To address this hypothesis, we exposed pregnant mice to influenza A virus (H3N2) on gestational day 9 and determined behavioral, hormonal and brainstem changes in male and female offspring. We found that gestational flu exposure induced dose-dependent alterations in social and aggressive behaviors (p≤0.05) in male and female offspring and increases in locomotor behaviors particularly in male offspring (p≤0.05). We found that flu exposure was also associated with reductions in oxytocin and serotonin (p≤0.05) levels in male and female offspring and sex-specific changes in dopamine metabolism. In addition we found changes in catecholaminergic and microglia density in brainstem tissues of male flu exposed offspring only (p≤0.05). This study demonstrates that gestational viral exposure induces behavioral changes in mice, which are associated with alterations in affiliative hormones. In addition we found sex-specific changes in locomotor behavior, which may be associated with sex-specific alterations in dopamine metabolism and brainstem inflammation. Further investigations into maternal immune responses are necessary to unravel the molecular mechanisms which underpin abnormal hormonal, immune and behavioral responses in offspring after gestational viral exposure. Copyright © 2013 Elsevier Inc. All rights reserved.

Antenatal exposure to the selective serotonin reuptake inhibitor fluoxetine leads to postnatal metabolic and endocrine changes associated with type 2 diabetes in Wistar rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Long, Nicole E.; Barry, Eric J.; Pinelli, Christopher

Hypothesis: 10–15% of women take antidepressant medications during pregnancy. A recent clinical study reported that the use of selective serotonin reuptake inhibitor antidepressants during pregnancy is linked with an increased risk of postnatal obesity. While obesity is often associated with fatty liver, dyslipidemia and inflammation, to date, the effects of perinatal exposure to SSRIs on these outcomes are unknown. Methods: Female nulliparous Wistar rats were given vehicle (N = 15) or fluoxetine hydrochloride (FLX 10 mg/kg/d; N = 15) orally for 2 weeks prior to mating until weaning. We assessed glucometabolic changes and hepatic pathophysiology in the offspring. Results: Fluoxetinemore » exposed offspring demonstrated altered glucose homeostasis without any alterations to beta cell mass. FLX-exposed offspring had a significant increase in the number of offspring with mild to moderate NASH and dyslipidemia. There was also increased inflammation of the liver in FLX-exposed offspring; males had significant elevations in TNFα, IL6 and monocyte chemoattractant protein 1 (MCP1), while female offspring had higher expression of TNFα, and increased macrophage infiltration (MCP1). Limitations: This is an animal study. Further research examining the metabolic outcomes of children exposed to antidepressants in utero are required, given the increase in childhood obesity and psychiatric medication use during pregnancy. Conclusion: These data demonstrate that fetal and neonatal exposure to FLX results in evidence of increased adiposity, fatty liver and abnormal glycemic control. Since these are all hallmarks of the metabolic syndrome, this raises concerns regarding the long term metabolic sequelae of fetal exposure to SSRIs in human populations. - Highlights: • Antenatal exposure to fluoxetine results in postnatal adiposity in the offspring. • Offspring exposed to fluoxetine have abnormal glycemic control in adulthood. • Maternal exposure to fluoxetine causes fatty liver in the offspring.« less

Gestational Protein Restriction Impairs Insulin-Regulated Glucose Transport Mechanisms in Gastrocnemius Muscles of Adult Male Offspring

PubMed Central

Blesson, Chellakkan S.; Sathishkumar, Kunju; Chinnathambi, Vijayakumar

2014-01-01

Type II diabetes originates from various genetic and environmental factors. Recent studies showed that an adverse uterine environment such as that caused by a gestational low-protein (LP) diet can cause insulin resistance in adult offspring. The mechanism of insulin resistance induced by gestational protein restriction is not clearly understood. Our aim was to investigate the role of insulin signaling molecules in gastrocnemius muscles of gestational LP diet–exposed male offspring to understand their role in LP-induced insulin resistance. Pregnant Wistar rats were fed a control (20% protein) or isocaloric LP (6%) diet from gestational day 4 until delivery and a normal diet after weaning. Only male offspring were used in this study. Glucose and insulin responses were assessed after a glucose tolerance test. mRNA and protein levels of molecules involved in insulin signaling were assessed at 4 months in gastrocnemius muscles. Muscles were incubated ex vivo with insulin to evaluate insulin-induced phosphorylation of insulin receptor (IR), Insulin receptor substrate-1, Akt, and AS160. LP diet-fed rats gained less weight than controls during pregnancy. Male pups from LP diet–fed mothers were smaller but exhibited catch-up growth. Plasma glucose and insulin levels were elevated in LP offspring when subjected to a glucose tolerance test; however, fasting levels were comparable. LP offspring showed increased expression of IR and AS160 in gastrocnemius muscles. Ex vivo treatment of muscles with insulin showed increased phosphorylation of IR (Tyr972) in controls, but LP rats showed higher basal phosphorylation. Phosphorylation of Insulin receptor substrate-1 (Tyr608, Tyr895, Ser307, and Ser318) and AS160 (Thr642) were defective in LP offspring. Further, glucose transporter type 4 translocation in LP offspring was also impaired. A gestational LP diet leads to insulin resistance in adult offspring by a mechanism involving inefficient insulin-induced IR, Insulin receptor substrate-1, and AS160 phosphorylation and impaired glucose transporter type 4 translocation. PMID:24797633

Influence of Pre-reproductive Maternal Enrichment on Coping Response to Stress and Expression of c-Fos and Glucocorticoid Receptors in Adolescent Offspring

PubMed Central

Cutuli, Debora; Berretta, Erica; Pasqualini, Greta; De Bartolo, Paola; Caporali, Paola; Laricchiuta, Daniela; Sampedro-Piquero, Patricia; Gelfo, Francesca; Pesoli, Matteo; Foti, Francesca; Begega, Azucena; Petrosini, Laura

2017-01-01

Environmental enrichment (EE) is an experimental setting broadly used for investigating the effects of complex social, cognitive, and sensorimotor stimulations on brain structure and function. Recent studies point out that parental EE experience, even occurring in the pre-reproductive phase, affects neural development and behavioral trajectories of the offspring. In the present study we investigated the influences of pre-reproductive EE of female rats on maternal behavior and adolescent male offspring's coping response to an inescapable stressful situation after chronic social isolation. For this purpose female Wistar rats were housed from weaning to breeding age in enriched or standard environments. Subsequently, all females were mated and housed in standard conditions until offspring weaning. On the first post partum day (ppd 1), mother-pup interactions in undisturbed conditions were recorded. Further, after weaning the male pups were reared for 2 weeks under social isolation or in standard conditions, and then submitted or not to a single-session Forced Swim Test (FST). Offspring's neuronal activation and plastic changes were identified by immunohistochemistry for c-Fos and glucocorticoid receptors (GRs), and assessed by using stereological analysis. The biochemical correlates were measured in the hippocampus, amygdala and cingulate cortex, structures involved in hypothalamic-pituitary-adrenocortical axis regulation. Enriched dams exhibited increased Crouching levels in comparison to standard reared dams. In the offspring of both kinds of dams, social isolation reduced body weight, decreased Immobility, and increased Swimming during FST. Moreover, isolated offspring of enriched dams exhibited higher levels of Climbing in comparison to controls. Interestingly, in the amygdala of both isolated and control offspring of enriched dams we found a lower number of c-Fos immunopositive cells in response to FST and a higher number of GRs in comparison to the offspring of standard dams. These results highlight the profound influence of a stressful condition, such as the social isolation, on the brain of adolescent rats, and underline intergenerational effects of maternal experiences in regulating the offspring response to stress. PMID:28536510

Does adolescent's exposure to parental intimate partner conflict and violence predict psychological distress and substance use in young adulthood? A longitudinal study.

PubMed

Schiff, Miriam; Plotnikova, Maria; Dingle, Kaeleen; Williams, Gail M; Najman, Jake; Clavarino, Alexandra

2014-12-01

Little is known about the extent to which parental conflict and violence differentially impact on offspring mental health and substance use. Using data from a longitudinal birth cohort study this paper examines: whether offspring exposure to parental intimate partner violence (involving physical violence which may include conflicts and/or disagreements) or parental intimate partner conflict (conflicting interactions and disagreements only) are associated with offspring depression, anxiety and substance use in early adulthood (at age 21); and whether these associations are independent of maternal background, depression and anxiety and substance use. Data (n=2,126 women and children) were taken from a large-scale Australian birth-cohort study, the Mater University of Queensland Study of Pregnancy (MUSP). IPC and IPV were measured at the 14-year follow-up. Offspring mental health outcomes--depression, anxiety and substance use--were assessed at the 21-year follow-up using the Composite International Diagnostic Interview (CIDI). Offspring of women experiencing IPV at the 14-year follow-up were more likely to manifest anxiety, nicotine, alcohol and cannabis disorders by the 21-year follow-up. These associations remained after adjustment for maternal anxiety, depression, and other potential confounders. Unlike males who experience anxiety disorders after exposure to IPV, females experience depressive and alcohol use disorders. IPV predicts offspring increased levels of substance abuse and dependence in young adulthood. Gender differences suggest differential impact. Copyright © 2014 Elsevier Ltd. All rights reserved.

Outcomes in the offspring of mothers with pre-diabetes during pregnancy: a protocol for a systematic review.

PubMed

Swaleh, Rukia; Zeng, Ling; Mbuagbaw, Lawrence; Morrison, Katherine M

2015-05-10

Despite the increasing prevalence of pre-diabetes worldwide, there is insufficient literature on the impact of gestational pre-diabetes on offspring outcomes. The objective of this systematic review is to determine the risk of developing adverse outcomes for the offspring in women with pre-diabetes compared to women with normal glucose levels and women with gestational diabetes mellitus. A systematic search of the published literature will be conducted for experimental and observational studies that report outcomes in the offspring of mothers with pre-diabetes during pregnancy. Databases including EMBASE, PsycINFO, and PubMed will be searched from 1979 (the year when the terms impaired glucose tolerance and pre-diabetes were coined) to December 2014. Screening of identified articles and data extraction will be conducted in duplicate and independently. Methodological quality of the included studies will be assessed using the Newcastle-Ottawa scale. Discrepancies will be resolved by consensus or by consulting a third author. Meta-analyses will be performed, and findings will be reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) and the meta-analysis of observational studies in epidemiology (MOOSE) guidelines. Determining the effect of pre-diabetes on offspring outcome will be important for clinicians providing care to pregnant women and their offspring. This review will also identify any gaps in the current literature on this topic and provide direction for future research in this area of study. PROSPERO CRD42015015536.

Happiness and depression in adolescence after maternal smoking during pregnancy: birth cohort study.

PubMed

Menezes, Ana Maria Baptista; Murray, Joseph; László, Mitzi; Wehrmeister, Fernando C; Hallal, Pedro C; Gonçalves, Helen; Assunção, Maria Cecilia F; Menezes, Carolina Baptista; Barros, Fernando C

2013-01-01

Prenatal cigarette smoke exposure may have adverse psychological effects on offspring. The objective was to assess the association between parental smoking during pregnancy and offspring happiness at age 18, as well as depression. Participants were part of a birth cohort study in Pelotas, Brazil (5,249 participants). Happiness was measured by the Subjective Happiness Scale, a Likert-like scale with four questions generating a score from 1 to 7, with ≥ 6 indicating "happiness". Depression was measured using the Mini International Psychiatric Interview. About one third of mothers reported having smoked during pregnancy and 4.6% reported smoking 20 or more cigarettes a day. The prevalence of happiness was 32.2% (95% CI 30.8; 33.7), depression 6.8% (95% CI 6.1; 7.6), and simultaneous happiness and depression less than 1%. The prevalence of offspring happiness decreased as smoking in pregnancy increased, even after control for confounding variables, showing an OR = 0.79 [95% CI 0.55; 1.13]. The opposite happened to depression; the prevalence of offspring depression increased as smoking in pregnancy increased (<20 cigarettes/day OR = 1.38 [95% CI 1.03; 1.84] and ≥ 20 cigarettes/day OR = 2.11[95% CI 1.31; 3.40]. Smoking by the partner was associated with decreased offspring happiness after adjustment for confounders, but did no show association with offspring depression. Offspring were less likely to be happy and more likely to be depressed if their mother smoked during pregnancy, and less likely to be happy if their father smoked during mother's pregnancy. Although we can not affirm that this is a "causal pathway", public policies to reduce smoking in pregnancy could improve the health of the offspring in the short and long term.

Offspring psychopathology following preconception, prenatal, and postnatal maternal bereavement stress

PubMed Central

Class, Quetzal A.; Abel, Kathryn M.; Khashan, Ali S.; Rickert, Martin E.; Dalman, Christina; Larsson, Henrik; Hultman, Christina M.; Långström, Niklas; Lichtenstein, Paul; D’Onofrio, Brian M.

2013-01-01

Background Preconception, prenatal, and postnatal maternal stress are associated with increased offspring psychopathology, but findings are inconsistent and need replication. We estimated associations between maternal bereavement stress and offspring autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, schizophrenia, suicide attempt, and completed suicide. Methods Using Swedish registers, we conducted the largest population-based study to date examining associations between stress exposure in 738,144 offspring born 1992–2000 for childhood outcomes and 2,155,221 offspring born 1973–1997 for adult outcomes with follow-up through 2009. Maternal stress was defined as death of a first degree relative during 6 months before conception, across pregnancy, or the first two postnatal years. Cox proportional survival analyses were used to obtain hazard ratios (HR) in unadjusted and adjusted analyses. Results Marginal increased risk of bipolar disorder and schizophrenia following preconception bereavement stress was not significant. Third trimester prenatal stress increased risk of ASD (adjusted HR=1.58, 95% CI: 1.15–2.17) and ADHD (adjusted HR=1.31, 95% CI: 1.04–1.66). First postnatal year stress increased risk for offspring suicide attempt (adjusted HR=1.13, 95% CI: 1.02–1.25) and completed suicide (adjusted HR=1.51, 95% CI: 1.08–2.11). Bereavement stress during the second postnatal year increased risk of ASD (adjusted HR=1.30, 95% CI: 1.09–1.55). Conclusions Further research is needed on associations between preconception stress and psychopathological outcomes. Prenatal bereavement stress increases risk of offspring ASD and ADHD. Postnatal bereavement stress moderately increases risk of offspring suicide attempt, completed suicide, and ASD. Smaller previous studies may have overestimated associations between early stress and psychopathological outcomes. PMID:23591021

Preeclampsia and gestational hypertension are associated with childhood blood pressure independently of family adiposity measures: the Avon Longitudinal Study of Parents and Children.

PubMed

Geelhoed, J J Miranda; Fraser, Abigail; Tilling, Kate; Benfield, Li; Davey Smith, George; Sattar, Naveed; Nelson, Scott M; Lawlor, Debbie A

2010-09-21

Offspring of women with hypertensive disorders of pregnancy are at increased risk of cardiovascular complications later in life, but the mechanisms underlying these associations are unclear. Our aim was to examine whether adjusting for birth weight and familial adiposity changed the association of hypertensive disorders of pregnancy with offspring blood pressure. Using data from 6343 nine-year-old participants in the Avon Longitudinal Study of Parents and Children, we examined the association between hypertensive disorders of pregnancy (preeclampsia and gestational hypertension) and offspring blood pressure. Both preeclampsia and gestational hypertension were associated with systolic and diastolic blood pressures in the 9-year-old offspring; after adjustment for parental and own adiposity and for other potential confounders, the mean difference in systolic blood pressure was 2.05 mm Hg (95 confidence interval, 0.72 to 3.38) and 2.04 mm Hg (95 confidence interval, 1.42 to 2.67) for preeclampsia and gestational hypertension, respectively, compared with those with no hypertensive disorders of pregnancy. Equivalent results for diastolic blood pressure were 1.00 mm Hg (95 confidence interval, -0.01 to 2.10) and 1.07 mm Hg (95 confidence interval, 0.60 to 1.54). The association of preeclampsia with offspring systolic and diastolic blood pressures attenuated toward the null with further adjustment for birth weight and gestational age, whereas these adjustments did not attenuate the association of gestational hypertension with offspring blood pressure. The associations of hypertensive disorders of pregnancy with higher offspring blood pressure are not explained by familial adiposity. The mechanisms linking preeclampsia and gestational hypertension with offspring blood pressure may differ, with the former mediated at least in part by the effect of preeclampsia on intrauterine growth restriction.

The effect of offspring on depressive disorder among old adults: Evidence from the Korean Longitudinal Study of Aging from 2006 to 2012.

PubMed

Kim, Jae-Hyun; Lee, Sang Gyu; Shin, Jaeyong; Choi, Young; Park, Eun-Cheol

2015-01-01

To investigate whether having an offspring protects against or increases the risk of depressive disorders. Data from the Korean Longitudinal Study of Aging (KLoSA) from 2006 and 2012 was assessed using longitudinal data analysis. We have included 10,149 research subjects at baseline and estimated the prevalence of depressive disorders for those with children. The number of offspring was from zero to five or more, and the composition of offspring is from zero boys and zero girls to two or more boys and two or more girls. For parents with zero offspring, the estimate for depressive disorder was 0.464 higher (SE: 0.123, p-value: 0.000, OR: 1.389; 95% CI: 1.176-1.640) and for parents with five or more offspring, the estimate for depressive disorder was 0.1 higher (SE: 0.104, p-value: 0.013, OR: 1.315; 95% CI: 1.150-1.504) compared to parents with two offspring. For parents with zero boys and zero girls, the estimate for depressive disorder was 0.599 higher (SE: 4.750, p-value: <0.0001, OR: 1.539; 95% CI: 1.298-1.825), and for parents with two or more boys and two or more girls, the estimate for depressive disorder was 1.328 higher (SE: 3.820, p-value: 0.000, OR: 1.328; 95% CI: 1.189-1.482) compared to parents with one boy and one girl. Our results indicate that there is a large effect of offspring on the prevalence of depressive disorder, with significant positive effects for mothers. Fathers are at lower risk for depressive disorder than mothers, and the graph was U-shaped. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Maternal protein restriction during pregnancy and lactation alters central leptin signalling, increases food intake, and decreases bone mass in 1 year old rat offspring.

PubMed

Qasem, Rani J; Li, Jing; Tang, Hee Man; Pontiggia, Laura; D'mello, Anil P

2016-04-01

The effects of perinatal nutrition on offspring physiology have mostly been examined in young adult animals. Aging constitutes a risk factor for the progressive loss of metabolic flexibility and development of disease. Few studies have examined whether the phenotype programmed by perinatal nutrition persists in aging offspring. Persistence of detrimental phenotypes and their accumulative metabolic effects are important for disease causality. This study determined the effects of maternal protein restriction during pregnancy and lactation on food consumption, central leptin sensitivity, bone health, and susceptibility to high fat diet-induced adiposity in 1-year-old male offspring. Sprague-Dawley rats received either a control or a protein restricted diet throughout pregnancy and lactation and pups were weaned onto laboratory chow. One-year-old low protein (LP) offspring exhibited hyperphagia. The inability of an intraperitoneal (i.p.) leptin injection to reduce food intake indicated that the hyperphagia was mediated by decreased central leptin sensitivity. Hyperphagia was accompanied by lower body weight suggesting increased energy expenditure in LP offspring. Bone density and bone mineral content that are negatively regulated by leptin acting via the sympathetic nervous system (SNS), were decreased in LP offspring. LP offspring did not exhibit increased susceptibility to high fat diet induced metabolic effects or adiposity. The results presented here indicate that the programming effects of perinatal protein restriction are mediated by specific decreases in central leptin signalling to pathways involved in the regulation of food intake along with possible enhancement of different CNS leptin signalling pathways acting via the SNS to regulate bone mass and energy expenditure. © 2016 John Wiley & Sons Australia, Ltd.

Schizotypal and affective traits in the offspring of antenatally depressed mothers - Relationship to family history of psychosis in the Northern Finland 1966 Birth Cohort.

PubMed

Taka-Eilola Née Riekki, T; Miettunen, J; Mäki, P

2017-05-01

Maternal depression is relatively common during pregnancy. However, follow-ups of the adult offspring of antenatally depressed mothers are scarce. Previously we found the risk of schizophrenia to be higher in the adult offspring with antenatally depressed mothers and parents with psychosis than in subjects with only one or neither of these risk factors. The aim was to study whether the risk of schizotypal or affective traits differ among adult offspring with antenatally depressed mothers with or without a parental history of psychosis when compared with offspring without antenatally depressed mothers and without parental psychosis. In the general population-based Northern Finland 1966 Birth Cohort (NFBC 1966), the mothers of the cohort members were asked at mid-gestation whether they felt depressed. Parental psychosis (Familial Risk, FR) was detected using the Finnish Care Register for Health Care. In the 31-year field study, seven psychometric questionnaires surveyed schizotypal and affective traits in the offspring. The final sample included 4928 individuals (2203 males). There were no statistically significant differences in mean scores on the schizotypal and affective scales between offspring with and without antenatally depressed mothers, or between subjects with and without parental psychosis. The scores were not highest in the subjects with both maternal antenatal depressed mood and FR. Surprisingly, maternal depressed mood during pregnancy was unlikely to increase the risk of schizotypy or affective traits in adult offspring, and not even with parental psychosis (FR) in this general population-based birth cohort with about 5000 subjects. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The long-term effects of maternal depression: early childhood physical health as a pathway to offspring depression.

PubMed

Raposa, Elizabeth; Hammen, Constance; Brennan, Patricia; Najman, Jake

2014-01-01

Cross-sectional and retrospective studies have highlighted the long-term negative effects of maternal depression on offspring physical, social, and emotional development, but longitudinal research is needed to clarify the pathways by which maternal depression during pregnancy and early childhood affects offspring outcomes. The current study tested one developmental pathway by which maternal depression during pregnancy might negatively impact offspring mental health in young adulthood, via poor physical health in early childhood. The sample consisted of 815 Australian youth and their mothers who were followed for 20 years. Mothers reported on their own depressive symptoms during pregnancy and offspring early childhood. Youth completed interviews about health-related stress and social functioning at age 20 years, and completed a questionnaire about their own depressive symptoms 2 to 5 years later. Path analysis indicated that prenatal maternal depressive symptoms predicted worse physical health during early childhood for offspring, and this effect was partially explained by ongoing maternal depression in early childhood. Offspring poor physical health during childhood predicted increased health-related stress and poor social functioning at age 20. Finally, increased health-related stress and poor social functioning predicted increased levels of depressive symptoms later in young adulthood. Maternal depression had a significant total indirect effect on youth depression via early childhood health and its psychosocial consequences. Poor physical health in early childhood and its effects on young adults' social functioning and levels of health related stress is one important pathway by which maternal depression has long-term consequences for offspring mental health. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Parental body mass index and blood pressure are associated with higher body mass index and blood pressure in their adult offspring: a cross-sectional study in a resource-limited setting in northern Peru.

PubMed

Carrillo-Larco, Rodrigo M; Bernabé-Ortiz, Antonio; Sal Y Rosas, Víctor G; Sacksteder, Katherine A; Diez-Canseco, Francisco; Cárdenas, María K; Gilman, Robert H; Miranda, J Jaime

2018-05-01

High body mass index (BMI) and blood pressure (BP) are major contributors to the high burden of non-communicable diseases in adulthood. Individual high-risk and population approaches for prevention require newer strategies to target these risk factors and focusing on the family to introduce prevention initiatives appears as a promising scenario. Characterisation of the relationship between BMI and BP among the adult members of a given family merits evaluation. We conducted a secondary analysis of an implementation study in Tumbes, Peru, benefiting from data derived from families with at least one adult offspring. The exposures of interest were the BMI, systolic BP (SBP) and diastolic BP (DBP) of the mother and father. The outcomes were the BMI, SBP and DBP of the offspring. Mixed-effects linear regression models were conducted. The mean age of the offspring, mothers and fathers was 29 (SD: 9.5), 54 (SD: 11.8) and 59 (SD: 11.6) years, respectively. Father's BMI was associated with a quarter-point increase in offspring BMI, regardless of the sex of the offspring. Mother's BMI had a similar effect on the BMI of her sons, but had no significant effect on her daughters'. Mother's SBP was associated with almost one-tenth of mmHg increase in the SBP of the adult offspring. There was no evidence of an association for DBP. In families with adult members, the higher the parents' BMI and SBP, the higher their adult offspring's levels will be. © 2018 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

Offspring of depressed and anxious patients: Help-seeking after first onset of a mood and/or anxiety disorder.

PubMed

Havinga, Petra J; Hartman, Catharina A; Visser, Ellen; Nauta, Maaike H; Penninx, Brenda W J H; Boschloo, Lynn; Schoevers, Robert A

2018-02-01

Offspring of patients with depressive and/or anxiety disorders are at high risk of developing a similar disorder themselves. Early recognition and treatment may have substantial effects on prognosis. The main aim of this study was to examine the time to initial help-seeking and its determinants in offspring after the first onset of a mood and/or anxiety disorder. Data are presented of 215 offspring with a mood and/or anxiety disorder participating in a cohort study with 10 year follow-up. We determined age of disorder onset and age of initial help-seeking. Offspring characteristics (gender, IQ, age of onset, disorder type, suicidal ideation) and family characteristics (socioeconomic status, family functioning) were investigated as potential predictors of the time to initial help-seeking. The estimated overall proportion of offspring of depressed/anxious patients who eventually seek help after onset of a mood and/or anxiety disorder was 91.9%. The time to initial help-seeking was more than two years in 39.6% of the offspring. Being female, having a mood disorder or comorbid mood and anxiety disorder (relative to anxiety) and a disorder onset in adolescence or adulthood (relative to childhood) predicted a shorter time to initial help-seeking. Baseline information relied on retrospective reports. Age of onsets and age of initial help-seeking may therefore be subject to recall bias. Although most offspring eventually seek help after onset of a mood/anxiety disorder, delays in help-seeking were common, especially in specific subgroups of patients. This information may help to develop targeted strategies to reduce help-seeking delays. Copyright © 2017 Elsevier B.V. All rights reserved.

Maternal corticosterone exposure in the mouse programs sex-specific renal adaptations in the renin-angiotensin-aldosterone system in 6-month offspring.

PubMed

Cuffe, James S M; Burgess, Danielle J; O'Sullivan, Lee; Singh, Reetu R; Moritz, Karen M

2016-04-01

Short-term maternal corticosterone (Cort) administration at mid-gestation in the mouse reduces nephron number in both sexes while programming renal and cardiovascular dysfunction in 12-month male but not female offspring. The renal renin-angiotensin-aldosterone system (RAAS), functions in a sexually dimorphic manner to regulate both renal and cardiovascular physiology. This study aimed to identify if there are sex-specific differences in basal levels of the intrarenal RAAS and to determine the impact of maternal Cort exposure on the RAAS in male and female offspring at 6 months of age. While intrarenal renin concentrations were higher in untreated females compared to untreated males, renal angiotensin II concentrations were higher in males than females. Furthermore, basal plasma aldosterone concentrations were greater in females than males. Cort exposed male but not female offspring had reduced water intake and urine excretion. Cort exposure increased renal renin concentrations and elevated mRNA expression of Ren1, Ace2, and Mas1 in male but not female offspring. In addition, male Cort exposed offspring had increased expression of the aldosterone receptor, Nr3c2 and renal sodium transporters. In contrast, Cort exposure increased Agtr1a mRNA levels in female offspring only. This study demonstrates that maternal Cort exposure alters key regulators of renal function in a sex-specific manner at 6 months of life. These finding likely contribute to the disease outcomes in male but not female offspring in later life and highlights the importance of renal factors other than nephron number in the programming of renal and cardiovascular disease. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Early physical and motor development of mouse offspring exposed to valproic acid throughout intrauterine development.

PubMed

Podgorac, Jelena; Pešić, Vesna; Pavković, Željko; Martać, Ljiljana; Kanazir, Selma; Filipović, Ljupka; Sekulić, Slobodan

2016-09-15

Clinical research has identified developmental delay and physical malformations in children prenatally exposed to the antiepileptic drug (AED) valproic acid (VPA). However, the early signs of neurodevelopmental deficits, their evolution during postnatal development and growth, and the dose effects of VPA are not well understood. The present study aimed to examine the influence of maternal exposure to a wide dose range (50, 100, 200 and 400mg/kg/day) of VPA during breeding and gestation on early physical and neuromotor development in mice offspring. Body weight gain, eye opening, the surface righting reflex (SRR) and tail suspension test (TST) were examined in the offspring at postnatal days 5, 10 and 15. We observed that: (1) all tested doses of VPA reduced the body weight of the offspring and the timing of eye opening; (2) offspring exposed to VPA displayed immature forms of righting and required more time to complete the SRR; (3) latency for the first immobilization in the TST is shorter in offspring exposed to higher doses of VPA; however, mice in all groups exposed to VPA exhibited atypical changes in this parameter during the examined period of maturation; (4) irregularities in swinging and curling activities were observed in animals exposed to higher doses of VPA. This study points to delayed somatic development and postponed maturation of the motor system in all of the offspring prenatally exposed to VPA, with stronger effects observed at higher doses. The results implicate that the strategy of continuous monitoring of general health and achievements in motor milestones during the early postnatal development in prenatally VPA-exposed offspring, irrespectively of the dose applied, could help to recognize early developmental irregularities. Copyright © 2016 Elsevier B.V. All rights reserved.

Mediation of Family Alcoholism Risk by Religious Affiliation Types*

PubMed Central

Haber, Jon Randolph; Jacob, Theodore

2009-01-01

Objective: Religious affiliation is inversely associated with alcohol dependence (AD). Our previous findings indicated that when a religious affiliation differentiated itself from cultural norms, then high-risk adolescents (those having parents with alcoholism history) raised with these affiliations exhibited fewer AD symptoms compared with adolescents of other religious affiliations and nonreligious adolescents. The first of two studies reported here provides a needed replication of our previous findings for childhood religious affiliation using a different sample, and the second study extends examination to current religious affiliation. Method: A national sample of male and female adolescents/young adults (N = 1,329; mean age = 19.6 years) was selected who were the offspring of members of the Vietnam Era Twin Registry. Parental alcoholism, religious affiliation types, and their interactions were examined as predictors of offspring AD symptoms. Results: (1) Offspring reared with a differentiating religious affiliation during childhood exhibited significantly fewer AD symptoms as young adults; (2) offspring with current differentiating religious affiliation also exhibited fewer AD symptoms; this main effect was not weakened by adding other measures of religiousness to the model; (3) differentiating religious affiliation was correlated with both family alcoholism risk and offspring outcome, and removed the association between family alcoholism risk and offspring outcome, thus indicating that differentiating religious affiliation was at least a partial mediator of the association between family AD history risk and offspring AD outcome. Conclusions: Current results indicate that religious differentiation is an inverse mediator of alcoholism risk for offspring with or without parental AD history and regardless of the influence of other religion variables. Results replicated our previous report on religious upbringing between ages 6 and 13 years and indicated an even stronger effect when current differentiating affiliation was examined. PMID:19895764

The effects of maternal and post-weaning diet interaction on glucose metabolism and gut microbiota in male mice offspring

PubMed Central

Zheng, Jia; Xiao, Xinhua; Zhang, Qian; Yu, Miao; Xu, Jianping; Qi, Cuijuan; Wang, Tong

2016-01-01

Substantial studies demonstrated that maternal nutrition can significantly determine the susceptibility to developing some metabolic diseases in offspring. However, investigations into the later-life effects of these diets on gut microbiota in the offspring are limited. Our objective was to explore the effects of maternal and post-weaning diet interaction on offspring's gut microbiota and glucose metabolism in later life. The male offspring of dams fed on either a high-fat (HF) diet or control (C) diet and then weaned to either a HF or C diet, generating four groups: C–C, HF–C, C–HF and HF–HF (n=8 in each group). The C–C offspring had lower body weight than C–HF group at 16 weeks of age (P<0.01) and both C–HF and HF–HF offspring had higher body weight than C–C group at 24 and 32 weeks of age (P<0.001 respectively). The blood glucose (BG) levels of the male offspring from the C and HF dams weaned HF diet were significantly higher at 30 min, 60 min and 120 min (P<0.001) after intraperitoneal glucose administration compared with those of the C–C group. The C–HF group had higher BG at 30 min than HF–HF group (P<0.01). Furthermore, area under the curve (AUC) in C–HF and HF–HF groups was also significantly larger than C–C group (P<0.001). Fasting BG and homoeostasis model assessment of insulin resistance (HOMA-IR) of the offspring were significantly higher in C–HF and HF–HF groups than C–C group at 32 weeks of age (P<0.05). Operational taxonomic unit (OTU), Chao and Shannon indexes showed a significantly lower diversity in C–HF offspring compared with HF–C and C–C groups (P<0.05). The dominant phyla of all the groups were Bacteroidetes, Firmicutes and Proteobacteria, which also showed significantly different percentages in the group (P<0.05). Furthermore, it is indicated that Lactobacillus and Bacteroides were significantly associated with glucose response to a glucose load (P<0.05). In conclusion, maternal and post-weaning diet interaction predisposes the offspring to aberrant glucose metabolism and alterations of gut microbiota in later life. Our study is novel in focusing on the effects of maternal and post-weaning diet interaction on offspring gut microbiota and glucose metabolism in later life. PMID:27129301

Paternal alcohol exposure in mice alters brain NGF and BDNF and increases ethanol-elicited preference in male offspring.

PubMed

Ceccanti, Mauro; Coccurello, Roberto; Carito, Valentina; Ciafrè, Stefania; Ferraguti, Giampiero; Giacovazzo, Giacomo; Mancinelli, Rosanna; Tirassa, Paola; Chaldakov, George N; Pascale, Esterina; Ceccanti, Marco; Codazzo, Claudia; Fiore, Marco

2016-07-01

Ethanol (EtOH) exposure during pregnancy induces cognitive and physiological deficits in the offspring. However, the role of paternal alcohol exposure (PAE) on offspring EtOH sensitivity and neurotrophins has not received much attention. The present study examined whether PAE may disrupt nerve growth factor (NGF) and/or brain-derived neurotrophic factor (BDNF) and affect EtOH preference/rewarding properties in the male offspring. CD1 sire mice were chronically addicted for EtOH or administered with sucrose. Their male offsprings when adult were assessed for EtOH preference by a conditioned place preference paradigm. NGF and BDNF, their receptors (p75(NTR) , TrkA and TrkB), dopamine active transporter (DAT), dopamine receptors D1 and D2, pro-NGF and pro-BDNF were also evaluated in brain areas. PAE affected NGF levels in frontal cortex, striatum, olfactory lobes, hippocampus and hypothalamus. BDNF alterations in frontal cortex, striatum and olfactory lobes were found. PAE induced a higher susceptibility to the EtOH rewarding effects mostly evident at the lower concentration (0.5 g/kg) that was ineffective in non-PAE offsprings. Moreover, higher ethanol concentrations (1.5 g/kg) produced an aversive response in PAE animals and a significant preference in non-PAE offspring. PAE affected also TrkA in the hippocampus and p75(NTR) in the frontal cortex. DAT was affected in the olfactory lobes in PAE animals treated with 0.5 g/kg of ethanol while no differences were found on D1/D2 receptors and for pro-NGF or pro-BDNF. In conclusion, this study shows that: PAE affects NGF and BDNF expression in the mouse brain; PAE may induce ethanol intake preference in the male offspring. © 2015 Society for the Study of Addiction.

Gestational and lactational exposure to atrazine via the drinking water causes specific behavioral deficits and selectively alters monoaminergic systems in C57BL/6 mouse dams, juvenile and adult offspring.

PubMed

Lin, Zhoumeng; Dodd, Celia A; Xiao, Shuo; Krishna, Saritha; Ye, Xiaoqin; Filipov, Nikolay M

2014-09-01

Atrazine (ATR) is one of the most frequently detected pesticides in the U.S. water supply. This study aimed to investigate neurobehavioral and neurochemical effects of ATR in C57BL/6 mouse offspring and dams exposed to a relatively low (3 mg/l, estimated intake 1.4 mg/kg/day) concentration of ATR via the drinking water (DW) from gestational day 6 to postnatal day (PND) 23. Behavioral tests included open field, pole, grip strength, novel object recognition (NOR), forced swim, and marble burying tests. Maternal weight gain and offspring (PND21, 35, and 70) body or brain weights were not affected by ATR. However, ATR-treated dams exhibited decreased NOR performance and a trend toward hyperactivity. Juvenile offspring (PND35) from ATR-exposed dams were hyperactive (both sexes), spent less time swimming (males), and buried more marbles (females). In adult offspring (PND70), the only behavioral change was a sex-specific (females) decreased NOR performance by ATR. Neurochemically, a trend toward increased striatal dopamine (DA) in dams and a significant increase in juvenile offspring (both sexes) was observed. Additionally, ATR exposure decreased perirhinal cortex serotonin in the adult female offspring. These results suggest that perinatal DW exposure to ATR targets the nigrostriatal DA pathway in dams and, especially, juvenile offspring, alters dams' cognitive performance, induces sex-selective changes involving motor and emotional functions in juvenile offspring, and decreases cognitive ability of adult female offspring, with the latter possibly associated with altered perirhinal cortex serotonin homeostasis. Overall, ATR exposure during gestation and lactation may cause adverse nervous system effects to both offspring and dams. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Nutritional Programming of Bone Structure in Male Offspring by Maternal Consumption of Citrus Flavanones.

PubMed

Sacco, Sandra M; Saint, Caitlin; LeBlanc, Paul J; Ward, Wendy E

2018-06-01

Maternal exposure to hesperidin (HSP) and naringin (NAR) during pregnancy and lactation transiently compromised bone mineral density (BMD) and bone structure at the proximal tibia in female CD-1 offspring. We examined whether maternal consumption of HSP + NAR during pregnancy and lactation compromises BMD, bone structure, and bone strength in male CD-1 offspring. Male CD-1 offspring, from mothers fed a control diet (CON, n = 10) or a 0.5% HSP + 0.25% NAR diet (HSP + NAR, n = 8) for 5 weeks before mating and throughout pregnancy and lactation, were weaned and fed CON until 6 months of age. In vivo micro-computed tomography (µCT) measured tibia BMD and structure at 2, 4, and 6 months of age. Ex vivo µCT measured femur and lumbar vertebrae (LV) structure at age 6 months. Ex vivo BMD (femur, LV) and biomechanical strength (femur and tibia midpoint, femur neck) were assessed at age 6 months by dual energy x-ray absorptiometry and strength testing, respectively. At all ages, HSP + NAR offspring had greater (p < 0.05) proximal tibia cortical structure compared to CON offspring. At age 4 months, proximal tibia trabecular structure was greater (p < 0.05) than CON offspring. At age 6 months, femur neck and LV trabecular structure were greater (p < 0.05) than CON offspring. Our results demonstrate that unlike our previous study of female offspring, maternal consumption of HSP + NAR resulted in greater bone structure at the proximal tibia in male CD-1 offspring that persisted to 6 months of age. Thus, maternal programming of offspring BMD and bone structure from consumption of HSP + NAR occurred as a sex-specific response.

Evaluation of cognitive behaviors in young offspring of C57BL/6J mice after gestational nicotine exposure during different time-windows.

PubMed

Alkam, Tursun; Kim, Hyoung-Chun; Mamiya, Takayoshi; Yamada, Kiyofumi; Hiramatsu, Masayuki; Nabeshima, Toshitaka

2013-12-01

Gestational nicotine exposure is associated with cognitive abnormalities in young offspring. However, practical strategies for prevention or treatment of impaired cognitive behaviors of offspring are not available due to the lack of systematic investigation of underlying mechanism. Therefore, this study aimed at examining the effects of gestational and/or perinatal nicotine exposure (GPNE) on cognitive behaviors in offspring of C57BL/6J mice to provide systematic behavioral data. Pregnant mice were exposed to nicotine via sweetened drinking water during six time-windows, including gestational day 0 to day 13 (G0-G13), G14-postnatal day 0 (P0), G0-P0, G14-P7, G0-P7, and P0-P7. During P42-P56 days, both male and female offspring were given a battery of behavioral tests. Depending on the time of exposure, GPNE impaired working memory, object-based attention, and prepulse inhibition in male and female offspring to different extents. Nicotine exposure during G14-P0 also decreased norepinephrine turnover in the prefrontal cortex on P28 and P56. Overall results indicate that nicotine exposure during any time-windows of development impairs cognitive behaviors in offspring, and suggest that certain time-windows, e.g., G14-P0, should be selected for further studies on the underlying neurochemical or molecular mechanisms.

Dietary intervention prior to pregnancy reverses metabolic programming in male offspring of obese rats

PubMed Central

Zambrano, E; Martínez-Samayoa, P M; Rodríguez-González, G L; Nathanielsz, P W

2010-01-01

Obesity involving women of reproductive years is increasing dramatically in both developing and developed nations. Maternal obesity and accompanying high energy obesogenic dietary (MO) intake prior to and throughout pregnancy and lactation program offspring physiological systems predisposing to altered carbohydrate and lipid metabolism. Whether maternal obesity-induced programming outcomes are reversible by altered dietary intake commencing before conception remains an unanswered question of physiological and clinical importance. We induced pre-pregnancy maternal obesity by feeding female rats with a high fat diet from weaning to breeding 90 days later and through pregnancy and lactation. A dietary intervention group (DINT) of MO females was transferred to normal chow 1 month before mating. Controls received normal chow throughout. Male offspring were studied. Offspring birth weights were similar. At postnatal day 21 fat mass, serum triglycerides, leptin and insulin were elevated in MO offspring and were normalized by DINT. At postnatal day 120 serum glucose, insulin and homeostasis model assessment (HOMA) were increased in MO offspring; glucose was restored, and HOMA partially reversed to normal by DINT. At postnatal day 150 fat mass was increased in MO and partially reversed in DINT. At postnatal day 150, fat cell size was increased by MO. DINT partially reversed these differences in fat cell size. We believe this is the first study showing reversibility of adverse metabolic effects of maternal obesity on offspring metabolic phenotype, and that outcomes and reversibility vary by tissue affected. PMID:20351043

Maternal antioxidant supplementation prevents adiposity in the offspring of Western diet-fed rats.

PubMed

Sen, Sarbattama; Simmons, Rebecca A

2010-12-01

Obesity in pregnancy significantly increases the risk of the offspring developing obesity after birth. The aims of this study were to test the hypothesis that maternal obesity increases oxidative stress during fetal development, and to determine whether administration of an antioxidant supplement to pregnant Western diet-fed rats would prevent the development of adiposity in the offspring. Female Sprague Dawley rats were started on the designated diet at 4 weeks of age. Four groups of animals were studied: control chow (control); control + antioxidants (control+Aox); Western diet (Western); and Western diet + antioxidants (Western+Aox). The rats were mated at 12 to 14 weeks of age, and all pups were weaned onto control diet. Offspring from dams fed the Western diet had significantly increased adiposity as early as 2 weeks of age as well as impaired glucose tolerance compared with offspring of dams fed a control diet. Inflammation and oxidative stress were increased in preimplantation embryos, fetuses, and newborns of Western diet-fed rats. Gene expression of proadipogenic and lipogenic genes was altered in fat tissue of rats at 2 weeks and 2 months of age. The addition of an antioxidant supplement decreased adiposity and normalized glucose tolerance. CONCLUSIONS; Inflammation and oxidative stress appear to play a key role in the development of increased adiposity in the offspring of Western diet-fed pregnant dams. Restoration of the antioxidant balance during pregnancy in the Western diet-fed dam is associated with decreased adiposity in offspring.

[Description of Clinical and Neurocognitive Profiles in Offspring of Bipolar-Type-I Parents From a Multimodal Intervention Program: Prisma].

PubMed

Palacio-Ortíz, Juan David; Uribe-Villa, Esteban; Duque-Ríos, Paula; Gutiérrez-Briceño, Paola; Zapata-Henao, Violeta; Peña-Quintero, Cristian Esteban; López-Jaramillo, Carlos

2015-01-01

Offspring of bipolar parents are a high risk population for the develop of mental diseases, their study allow determining the genetic risk, early symptoms, prodromes and psychopathology of bipolar disorder. To describe the psychopathological characteristics and neurocognitives profiles of the offspring of bipolar type I parents. And to identify the presence of sub-syndromal symptoms in all the symptom domains. A descriptive and cross-sectional study was conducted on 110 offspring between 6 and 30 years old. Semi-structured diagnostic interviews were performed. The intelectual coeficient was determined and a neuropsychological assessment was performed on 89 offspring. The most prevalent disorder in the offspring was ADHD (27.6%), with major depression (15.5%) and separation anxiety (14.1%) also being prevalent. Seven patients of the sample were diagnosed with bipolar disorder. There was a statistically significant difference between the age groups for ADHD prevalence. The most frequent sub-syndromal symptoms were observed in the disruptive group. Alterations in the cognitive domains: attention, verbal fluency, work memory, and speed of information processing, were observed in the group younger than 18 years. The offspring of bipolar parents have an elevated rate of psychopathology and cognitive alterations. They are a high risk population for the development of mental disease. These subjects also require close longitudinal observation and early and preventive therapeuthic interventions. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.