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Sample records for fetal growth indicators

  1. Urinary phthalate metabolite and bisphenol A associations with ultrasound and delivery indices of fetal growth.

    PubMed

    Ferguson, Kelly K; Meeker, John D; Cantonwine, David E; Chen, Yin-Hsiu; Mukherjee, Bhramar; McElrath, Thomas F

    2016-09-01

    Growth of the fetus is highly sensitive to environmental perturbations, and disruption can lead to problems in pregnancy as well as later in life. This study investigates the relationship between maternal exposure to common plasticizers in pregnancy and fetal growth. Participants from a longitudinal birth cohort in Boston were recruited early in gestation and followed until delivery. Urine samples were collected at up to four time points and analyzed for concentrations of phthalate metabolites and bisphenol A (BPA). Ultrasound scans were performed at four time points during pregnancy for estimation of growth parameters, and birthweight was recorded at delivery. Growth measures were standardized to a larger population. For the present analysis we examined cross-sectional and repeated measures associations between exposure biomarkers and growth estimates in 482 non-anomalous singleton pregnancies. Cross-sectional associations between urinary phthalate metabolites or BPA and growth indices were imprecise. However, in repeated measures models, we observed significant inverse associations between di-2-ethylhexyl phthalate (DEHP) metabolites and estimated or actual fetal weight. An interquartile range increase in summed DEHP metabolites was associated with a 0.13 standard deviation decrease in estimated or actual fetal weight (95% confidence interval=-0.23, -0.03). Associations were consistent across different growth parameters (e.g., head circumference, femur length), and by fetal sex. No consistent associations were observed for other phthalate metabolites or BPA. Maternal exposure to DEHP during pregnancy was associated with decreased fetal growth, which could have repercussive effects. PMID:27320326

  2. Fetal Hemodynamics and Fetal Growth Indices by Ultrasound in Late Pregnancy and Birth Weight in Gestational Diabetes Mellitus

    PubMed Central

    Liu, Fang; Liu, Yong; Lai, Ya-Ping; Gu, Xiao-Ning; Liu, Dong-Mei; Yang, Min

    2016-01-01

    Background: The offspring of women with gestational diabetes mellitus (GDM) are prone to macrosomia. However, birth weight is difficult to be correctly estimated by ultrasound because of fetal asymmetric growth characteristics. This study aimed to investigate the correlations between fetal hemodynamics, fetal growth indices in late pregnancy, and birth weight in GDM. Methods: A total of 147 women with GDM and 124 normal controls (NC) were enrolled in this study. Fetal hemodynamic indices, including the systolic/diastolic ratio (S/D), resistance index (RI), pulsatility index (PI) of umbilical artery (UA), middle cerebral artery (MCA), and renal artery (RA), were collected. Fetal growth indices, including biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length, were also measured by ultrasound. Birth weight, newborn gender, and maternal clinical data were collected. Results: The independent samples t-test showed that BPD, HC, and AC were larger in GDM than in NC (P < 0.05). Fetal hemodynamic indices of the UA and MCA were lower (P < 0.05), but those of the RA were higher (P < 0.001) in GDM than in NC. Birth weight was higher in GDM than in NC (P < 0.001). Pearson's correlation analysis showed that hemodynamic indices of the UA were negatively correlated with birth weight, BPD, HC, and AC in both groups (P < 0.05). MCA (S/D, PI, and RI) was negatively correlated with birth weight, HC, and AC in GDM (r = −0.164, −0.206, −0.200, −0.226, −0.189, −0.179, −0.196, −0.177, and − 0.172, respectively, P < 0.05), but there were no correlations in NC (P > 0.05). RA (S/D, PI, and RI) was positively correlated with birth weight in GDM (r = 0.168, 0.207, and 0.184, respectively, P < 0.05), but there were no correlations in NC (P > 0.05). Conclusion: Fetal hemodynamic indices in late pregnancy might be helpful for estimating newborn birth weight in women with GDM. PMID:27569240

  3. The association of indicators of fetal growth with visual acuity and hearing among conscripts.

    PubMed

    Olsen, J; Sørensen, H T; Steffensen, F H; Sabroe, S; Gillman, M W; Fischer, P; Rothman, K J

    2001-03-01

    Impaired fetal growth is associated with increased susceptibility to several chronic diseases. We studied the association between birth weight, indicators of disproportional fetal growth, and impaired visual acuity and hearing in 4,300 conscripts from a well-defined region in Denmark from August 1, 1993, to July 31, 1994. From the standard health examination for conscripts, we obtained data on sight based on the Snellen's chart and data on hearing acuity based on audiometry. By means of record linkage, we obtained data on outcomes for the conscripts at birth from the Medical Birth Registry. From this registry, we have data on birth weight, gestational age, and birth length that were recorded from existing computerized registers based on the records of midwives. A birth weight of less than 3,000 gm and a body mass index at birth of less than 3.4 were associated with reduced visual acuity and impaired hearing. The results could be due to fetal brain programming or due to confounding, by early birth trauma or other factors. PMID:11246586

  4. Perfluoroalkyl Acids in Maternal Serum and Indices of Fetal Growth: The Aarhus Birth Cohort

    PubMed Central

    Bach, Cathrine Carlsen; Bech, Bodil Hammer; Nohr, Ellen Aagaard; Olsen, Jørn; Matthiesen, Niels Bjerregård; Bonefeld-Jørgensen, Eva Cecilie; Bossi, Rossana; Henriksen, Tine Brink

    2015-01-01

    Background: Previous studies indicated an association between intrauterine exposure to perfluorooctane sulfonate (PFOS) or perfluorooctanoate (PFOA) and lower birth weight. However, these perfluoroalkyl acids (PFAAs) have to some extent been substituted by other compounds on which little is known. Objectives: We investigated the association between specific PFAAs and birth weight, birth length, and head circumference at birth. Methods: We studied 1,507 mothers and their children from the Aarhus Birth Cohort (2008–2013). Nulliparous women were included during pregnancy, and serum levels of 16 PFAAs were measured between 9 and 20 completed gestational weeks (96% within 13 weeks). For compounds with quantifiable values in > 50% of samples (7 compounds), we report the associations with birth weight, birth length, and head circumference at birth determined by multivariable linear regression. Results: Estimated mean birth weights were lower among women with serum perfluorohexane sulfonate, perfluoroheptane sulfonate, and PFOS concentrations above the lowest exposure quartile, but we found no consistent monotonic dose–response patterns. These associations were stronger when the population was restricted to term births (n = 1,426). For PFOS, the birth weight estimates for the highest versus lowest quartile were –50 g (95% CI: –123, 23 g) in all births and –62 g (95% CI: –126, 3 g) in term births. For the other PFAAs, the direction of the associations was inconsistent, and no overall association with birth weight was apparent. No PFAAs were associated with birth length or head circumference at birth. Conclusions: Overall, we did not find strong or consistent associations between PFAAs and birth weight or other indices of fetal growth, though estimated mean birth weights were lower among those with exposures above the lowest quartile for some compounds. Citation: Bach CC, Bech BH, Nohr EA, Olsen J, Matthiesen NB, Bonefeld-Jørgensen EC, Bossi R, Henriksen TB

  5. Magnesium and fetal growth

    SciTech Connect

    Weaver, K.

    1988-01-01

    Fetal growth retardation and premature labor are major problems in perinatal medicine today and account for a great deal of the observed fetal morbidity. While the neonatal death rate has steadily declined over the past decade, there has been a lack of concommitant decrease in these two leading problems. Magnesium (Mg/sup ++/) plays a major role in both of these areas of concern. The fact that it is used as a treatment for premature labor has led investigators to look at low Mg/sup ++/ as a possible cause of this poorly understood phenomenon. The second major cause of small for gestational age infants is intrauterine growth retardation, a condition which may be of either fetal or maternal origin. In either case, Mg/sup ++/ may be implicated since it exerts a strong influence on the underlying pathophysiology of placental failure and maternal hypertension. Both of these conditions are mediated by vascular and platelet hyperactivity as well as by and increase in the ration of thromboxane to prostacyclin. Studies in both the human and animal species are beginning to show how Mg/sup ++/ interacts in these conditions to produce such a damaging fetal outcome. The recent use of Doppler velocimetry of the developing fetus has shown reduced fetal vascular and maternal uterine vascular compliance as early as 14 weeks of gestation in those who would be so affected.

  6. Birth Weight, Birth Length, and Gestational Age as Indicators of Favorable Fetal Growth Conditions in a US Sample

    PubMed Central

    Bollen, Kenneth A.

    2016-01-01

    The “fetal origins” hypothesis suggests that fetal conditions not only affect birth characteristics such as birth weight and gestational age, but also have lifelong health implications. Despite widespread interest in this hypothesis, few methodological advances have been proposed to improve the measurement and modeling of fetal conditions. A Statistics in Medicine paper by Bollen, Noble, and Adair examined favorable fetal growth conditions (FFGC) as a latent variable. Their study of Filipino children from Cebu provided evidence consistent with treating FFGC as a latent variable that largely mediates the effects of mother’s characteristics on birth weight, birth length, and gestational age. This innovative method may have widespread utility, but only if the model applies equally well across diverse settings. Our study assesses whether the FFGC model of Cebu replicates and generalizes to a very different population of children from North Carolina (N = 705) and Pennsylvania (N = 494). Using a series of structural equation models, we find that key features of the Cebu analysis replicate and generalize while we also highlight differences between these studies. Our results support treating fetal conditions as a latent variable when researchers test the fetal origins hypothesis. In addition to contributing to the substantive literature on measuring fetal conditions, we also discuss the meaning and challenges involved in replicating prior research. PMID:27097023

  7. Hormonal Control of Fetal Growth.

    ERIC Educational Resources Information Center

    Cooke, Paul S.; Nicoll, Charles S.

    1983-01-01

    Summarizes recent research on hormonal control of fetal growth, presenting data obtained using a new method for studying the area. Effects of endocrine ablations and congenital deficiencies, studies of hormone/receptor levels, in-vitro techniques, hormones implicated in promoting fetal growth, problems with existing methodologies, and growth of…

  8. Uterine artery blood flow, fetal hypoxia and fetal growth

    PubMed Central

    Browne, Vaughn A.; Julian, Colleen G.; Toledo-Jaldin, Lillian; Cioffi-Ragan, Darleen; Vargas, Enrique; Moore, Lorna G.

    2015-01-01

    Evolutionary trade-offs required for bipedalism and brain expansion influence the pregnancy rise in uterine artery (UtA) blood flow and, in turn, reproductive success. We consider the importance of UtA blood flow by reviewing its determinants and presenting data from 191 normotensive (normal, n = 125) or hypertensive (preeclampsia (PE) or gestational hypertension (GH), n = 29) Andean residents of very high (4100–4300 m) or low altitude (400 m, n = 37). Prior studies show that UtA blood flow is reduced in pregnancies with intrauterine growth restriction (IUGR) but whether the IUGR is due to resultant fetal hypoxia is unclear. We found higher UtA blood flow and Doppler indices of fetal hypoxia in normotensive women at high versus low altitude but similar fetal growth. UtA blood flow was markedly lower in early-onset PE versus normal high-altitude women, and their fetuses more hypoxic as indicated by lower fetal heart rate, Doppler indices and greater IUGR. We concluded that, despite greater fetal hypoxia, fetal growth was well defended by higher UtA blood flows in normal Andeans at high altitude but when compounded by lower UtA blood flow in early-onset PE, exaggerated fetal hypoxia caused the fetus to respond by decreasing cardiac output and redistributing blood flow to help maintain brain development at the expense of growth elsewhere. We speculate that UtA blood flow is not only an important supply line but also a trigger for stimulating the metabolic and other processes regulating feto-placental metabolism and growth. Studies using the natural laboratory of high altitude are valuable for identifying the physiological and genetic mechanisms involved in human reproductive success. PMID:25602072

  9. Uterine artery blood flow, fetal hypoxia and fetal growth.

    PubMed

    Browne, Vaughn A; Julian, Colleen G; Toledo-Jaldin, Lillian; Cioffi-Ragan, Darleen; Vargas, Enrique; Moore, Lorna G

    2015-03-01

    Evolutionary trade-offs required for bipedalism and brain expansion influence the pregnancy rise in uterine artery (UtA) blood flow and, in turn, reproductive success. We consider the importance of UtA blood flow by reviewing its determinants and presenting data from 191 normotensive (normal, n = 125) or hypertensive (preeclampsia (PE) or gestational hypertension (GH), n = 29) Andean residents of very high (4100-4300 m) or low altitude (400 m, n = 37). Prior studies show that UtA blood flow is reduced in pregnancies with intrauterine growth restriction (IUGR) but whether the IUGR is due to resultant fetal hypoxia is unclear. We found higher UtA blood flow and Doppler indices of fetal hypoxia in normotensive women at high versus low altitude but similar fetal growth. UtA blood flow was markedly lower in early-onset PE versus normal high-altitude women, and their fetuses more hypoxic as indicated by lower fetal heart rate, Doppler indices and greater IUGR. We concluded that, despite greater fetal hypoxia, fetal growth was well defended by higher UtA blood flows in normal Andeans at high altitude but when compounded by lower UtA blood flow in early-onset PE, exaggerated fetal hypoxia caused the fetus to respond by decreasing cardiac output and redistributing blood flow to help maintain brain development at the expense of growth elsewhere. We speculate that UtA blood flow is not only an important supply line but also a trigger for stimulating the metabolic and other processes regulating feto-placental metabolism and growth. Studies using the natural laboratory of high altitude are valuable for identifying the physiological and genetic mechanisms involved in human reproductive success. PMID:25602072

  10. Prenatal Depression Restricts Fetal Growth

    PubMed Central

    Diego, Miguel A.; Field, Tiffany; Hernandez-Reif, Maria; Schanberg, Saul; Kuhn, Cynthia; Gonzalez-Quintero, Victor Hugo

    2009-01-01

    Objective To identify whether prenatal depression is a risk factor for fetal growth restriction. Methods Midgestation (18-20 weeks GA) estimated fetal weight and urine cortisol and birth weight and gestational age at birth data were collected on a sample of 40 depressed and 40 non-depressed women. Estimated fetal weight and birthweight data were then used to compute fetal growth rates. Results Depressed women had a 13% greater incidence of premature delivery (Odds Ratio (OR) = 2.61) and 15% greater incidence of low birthweight (OR = 4.75) than non-depressed women. Depressed women also had elevated prenatal cortisol levels (p = .006) and fetuses who were smaller (p = .001) and who showed slower fetal growth rates (p = .011) and lower birthweights (p = .008). Mediation analyses further revealed that prenatal maternal cortisol levels were a potential mediator for the relationship between maternal symptoms of depression and both gestational age at birth and the rate of fetal growth. After controlling for maternal demographic variables, prenatal maternal cortisol levels were associated with 30% of the variance in gestational age at birth and 14% of the variance in the rate of fetal growth. Conclusion Prenatal depression was associated with adverse perinatal outcomes, including premature delivery and slower fetal growth rates. Prenatal maternal cortisol levels appear to play a role in mediating these outcomes. PMID:18723301

  11. Fetal sex and race modify the predictors of fetal growth.

    PubMed

    Reynolds, Simone A; Roberts, James M; Bodnar, Lisa M; Haggerty, Catherine L; Youk, Ada O; Catov, Janet M

    2015-04-01

    The objective of this study is unknown if fetal sex and race modify the impact of maternal pre-pregnancy body mass index (BMI), and smoking on fetal growth. The authors studied markers of fetal growth in singleton offspring of 8,801 primiparous, normotensive women, enrolled in the Collaborative Perinatal Project. The authors tested for departures from additivity between sex/race and each predictor. The head-to-chest circumference ratio (HCC) decreased more, while birthweight and ponderal index (PI) increased more for each 1 kg/m(2) increase in pre-pregnancy BMI among term females versus males (P = 0.07, P < 0.01 and P = 0.08, interaction respectively). For term offspring of White compared with Black women, smoking independent of "dose" was associated with larger reductions in growth (165 g vs. 68 g reduction in birthweight, P < 0.01, interaction), greater reduction in fetal placental ratio (P < 0.01, interaction), PI (P < 0.01, interaction), and greater increase in HCC (P = 0.02), respectively. The association of BMI and smoking with fetal size appeared to be reversed in term versus preterm infants. Our study provides evidence that the associations of pre-pregnancy BMI and smoking are not constant across sex and race. This finding may be relevant to sex and race differences in neonatal and long term health outcomes. PMID:25030701

  12. Indicated preterm birth for fetal anomalies.

    PubMed

    Craigo, Sabrina D

    2011-10-01

    Between 2% and 3% of pregnancies are complicated by fetal anomalies. For most anomalies, there is no advantage to late preterm or early-term delivery. The risks of maternal or fetal complication are specific for each anomaly. Very few anomalies pose potential maternal risk. Some anomalies carry ongoing risks to the fetus, such as an increased risk of fetal death, hemorrhage, or organ damage. In a limited number of select cases, the advantages of late preterm or early-term birth may include avoiding an ongoing risk of fetal death related to the anomaly, allowing delivery in a controlled setting with availability of subspecialists and allowing direct care for the neonate with organ injury. The optimal gestational age for delivery cannot be determined for all pregnancies complicated by fetal anomalies. For most pregnancies complicated by anomalies, there is no change to obstetrical management regarding timing of delivery. For those that may benefit from late preterm or early-term delivery, variability exists such that each management plan should be individualized. PMID:21962626

  13. Maternal HCV infection is associated with intrauterine fetal growth disturbance

    PubMed Central

    Huang, Qi-tao; Hang, Li-lin; Zhong, Mei; Gao, Yun-fei; Luo, Man-ling; Yu, Yan-hong

    2016-01-01

    Abstract Since the evidence regarding the association between maternal hepatitis C virus (HCV) infection and impaired intrauterine fetal growth had not been conclusive, the aim of the present study was to evaluate the risk of maternal HCV infection in association with intrauterine fetal growth restriction (IUGR) and/or low birth weight infants (LBW). We performed an extensive literature search of PubMed, MEDLINE, and EMBASE through December 1, 2015. The odds ratios (ORs) of HCV infection and IUGR/LBW were calculated and reported with 95% confidence intervals (95% CIs). Statistical analysis was performed using RevMen 5.3 and Stata 10.0. Seven studies involving 4,185,414 participants and 5094 HCV infection cases were included. Significant associations between HCV infection and IUGR (OR = 1.53, 95% CI: 1.40–1.68, fixed effect model) as well as LBW were observed (OR = 1.97, 95% CI: 1.43–2.71, random effect model). The results still indicated consistencies after adjusting for multiple risk factors which could affect fetal growth, including maternal age, parity, maternal smoking, alcohol abuse, drugs abuse, coinfected with HBV/HIV and preeclampsia. Our findings suggested that maternal HCV infection was significantly associated with an increased risk of impaired intrauterine fetal growth. In clinical practice, a closer monitoring of intrauterine fetal growth by a series of ultrasound might be necessary for HCV-infected pregnant population. PMID:27583932

  14. A review of contemporary modalities for identifying abnormal fetal growth.

    PubMed

    O'Connor, C; Stuart, B; Fitzpatrick, C; Turner, M J; Kennelly, M M

    2013-04-01

    Detecting aberrant fetal growth has long been an important goal of modern obstetrics. Failure to diagnose abnormal fetal growth results in perinatal morbidity or mortality. However, the erroneous diagnosis of abnormal growth may lead to increased maternal anxiety and unnecessary obstetric interventions. We review the aetiology of deviant fetal growth and its implications both for the neonatal period and later in adult life. We examine maternal factors that may influence fetal growth such as obesity, glycaemic control and body composition. We discuss novel ways to improve our detection of abnormal fetal growth with a view to optimising antenatal care and clinical outcomes. These include using customised centiles or individualised growth assessment methods to improve accuracy. The role of fetal subcutaneous measurements as a surrogate marker of the nutritional status of the baby is also discussed. Finally, we investigate the role of Doppler measurements in identifying growth-restricted babies. PMID:23550849

  15. Fetal growth: a review of terms, concepts and issues relevant to obstetrics.

    PubMed

    Mayer, C; Joseph, K S

    2013-02-01

    The perinatal literature includes several potentially confusing and controversial terms and concepts related to fetal size and growth. This article discusses fetal growth from an obstetric perspective and addresses various issues including the physiologic mechanisms that determine fetal growth trajectories, known risk factors for abnormal fetal growth, diagnostic and prognostic issues related to restricted and excessive growth and temporal trends in fetal growth. Also addressed are distinctions between fetal growth 'standards' and fetal growth 'references', and between fetal growth charts based on estimated fetal weight vs those based on birth weight. Other concepts discussed include the incidence of fetal growth restriction in pregnancy (does the frequency of fetal growth restriction increase or decrease with increasing gestation?), the obstetric implications of studies showing associations between fetal growth and adult chronic illnesses (such as coronary heart disease) and the need for customizing fetal growth standards. PMID:22648955

  16. Biopsychosocial determinants of pregnancy length and fetal growth.

    PubMed

    St-Laurent, Jennifer; De Wals, Philippe; Moutquin, Jean-Marie; Niyonsenga, Theophile; Noiseux, Manon; Czernis, Loretta

    2008-05-01

    The causes and mechanisms related to preterm delivery and intrauterine growth restriction are poorly understood. Our objective was to assess the direct and indirect effects of psychosocial and biomedical factors on the duration of pregnancy and fetal growth. A self-administered questionnaire was distributed to pregnant women attending prenatal ultrasound clinics in nine hospitals in the Montérégie region in the province of Quebec, Canada, from November 1997 to May 1998. Prenatal questionnaires were linked with birth certificates. Theoretical models explaining pregnancy length and fetal growth were developed and tested, using path analysis. In order to reduce the number of variables from the questionnaire, a principal component analysis was performed, and the three most important new dimensions were retained as explanatory variables in the final models. Data were available for 1602 singleton pregnancies. The biophysical score, covering both maternal age and the pre-pregnancy body mass index, was the only variable statistically associated with pregnancy length. Smoking, obstetric history, maternal health and biophysical indices were direct predictors of fetal growth. Perceived stress, social support and self-esteem were not directly related to pregnancy outcomes, but were determinants of smoking and the above-mentioned biomedical variables. More studies are needed to identify the mechanisms by which adverse psychosocial factors are translated into adverse biological effects. PMID:18426519

  17. Update: consequences of abnormal fetal growth.

    PubMed

    Chernausek, Steven D

    2012-03-01

    Intrauterine growth restriction (IUGR) is prevalent worldwide and affects children and adults in multiple ways. These include predisposition to type 2 diabetes mellitus, the metabolic syndrome, cardiovascular disease, persistent reduction in stature, and possibly changes in the pattern of puberty. A review of recent literature confirms that the metabolic effects of being born small for gestational age are evident in the very young, persist with age, and are amplified by adiposity. Furthermore, the pattern of growth in the first few years of life has a significant bearing on a person's later health, with those that show increasing weight gain being at the greatest risk for future metabolic dysfunction. Treatment with exogenous human GH is used to improve height in children who remain short after being small for gestational age at birth, but the response of individuals remains variable and difficult to predict. The mechanisms involved in the metabolic programming of IUGR children are just beginning to be explored. It appears that IUGR leads to widespread changes in DNA methylation and that specific "epigenetic signatures" for IUGR are likely to be found in various fetal tissues. The challenge is to link such alterations with modifications in gene expression and ultimately the metabolic abnormalities of adulthood, and it represents one of the frontiers for research in the field. PMID:22238390

  18. Activation of Nod1 Signaling Induces Fetal Growth Restriction and Death through Fetal and Maternal Vasculopathy

    PubMed Central

    Nishio, Hisanori; Takada, Hidetoshi; Sakai, Yasunari; Nanishi, Etsuro; Ochiai, Masayuki; Onimaru, Mitsuho; Chen, Si Jing; Matsui, Toshiro; Hara, Toshiro

    2016-01-01

    Intrauterine fetal growth restriction (IUGR) and death (IUFD) are both serious problems in the perinatal medicine. Fetal vasculopathy is currently considered to account for a pathogenic mechanism of IUGR and IUFD. We previously demonstrated that an innate immune receptor, the nucleotide-binding oligomerization domain-1 (Nod1), contributed to the development of vascular inflammations in mice at postnatal stages. However, little is known about the deleterious effects of activated Nod1 signaling on embryonic growth and development. We report that administration of FK565, one of the Nod1 ligands, to pregnant C57BL/6 mice induced IUGR and IUFD. Mass spectrometry analysis revealed that maternally injected FK565 was distributed to the fetal tissues across placenta. In addition, maternal injection of FK565 induced robust increases in the amounts of CCL2, IL-6, and TNF proteins as well as NO in maternal, placental and fetal tissues. Nod1 was highly expressed in fetal vascular tissues, where significantly higher levels of CCL2 and IL-6 mRNAs were induced with maternal injection of FK565 than those in other tissues. Using Nod1-knockout mice, we verified that both maternal and fetal tissues were involved in the development of IUGR and IUFD. Furthermore, FK565 induced upregulation of genes associated with immune response, inflammation, and apoptosis in fetal vascular tissues. Our data thus provided new evidence for the pathogenic role of Nod1 in the development of IUGR and IUFD at the maternal-fetal interface. PMID:26880761

  19. Third trimester fetal growth and umbilical venous blood concentrations of IGF-1, IGFBP-1, and growth hormone at term.

    PubMed Central

    Spencer, J. A.; Chang, T. C.; Jones, J.; Robson, S. C.; Preece, M. A.

    1995-01-01

    Insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-1 (IGFBP-1) and growth hormone (GH) concentrations were measured in umbilical venous blood after delivery of 78 term newborn infants. Three groups of pregnancies were prospectively identified during the third trimester, according to fetal size and subsequent fetal growth, assessed by repeated ultrasound scans. Fetal size was considered either appropriate for gestational age (AGA) or small for gestational age (SGA), according to whether the first ultrasound measurement of abdominal circumference was equal to or above, or below the tenth centile for gestational age, respectively. Subsequent fetal growth was quantified by the change in the standard deviation score of abdominal circumference measurements between the first and last scans before delivery. Fetal growth retardation (FGR) was defined as a (negative) change in SD score of greater than -1.5. Eighteen SGA fetuses with evidence of FGR had significantly lower IGF-1 (median 0.05 (range 0.0-0.24) U/ml) at delivery than 35 SGA fetuses with normal growth (median 0.13 (range 0.0-0.94) U/ml; P < 0.05) and 25 AGA fetuses with normal growth (median 0.31 (range 0.0-0.84) U/ml; P < 0.05). The median concentration in the SGA group with normal growth was also significantly lower than that of the AGA group with normal growth. There were no significant differences in IGFBP-1 or GH concentrations between the three groups. These observations indicate that umbilical blood concentrations at birth of IGF-1, but not IGFBP-1 or GH, relate to both fetal size and fetal growth during the third trimester of pregnancies reaching term. PMID:7583612

  20. Fetal growth and risk of childhood asthma and allergic disease

    PubMed Central

    Tedner, S G; Örtqvist, A K; Almqvist, C

    2012-01-01

    Introduction Early genetic and environmental factors have been discussed as potential causes for the high prevalence of asthma and allergic disease in the western world, and knowledge on fetal growth and its consequence on future health and disease development is emerging. Objective This review article is an attempt to summarize research on fetal growth and risk of asthma and allergic disease. Current knowledge and novel findings will be reviewed and open research questions identified, to give basic scientists, immunologists and clinicians an overview of an emerging research field. Methods PubMed-search on pre-defined terms and cross-references. Results Several studies have shown a correlation between low birth weight and/or gestational age and asthma and high birth weight and/or gestational age and atopy. The exact mechanism is not yet clear but both environmental and genetic factors seem to contribute to fetal growth. Some of these factors are confounders that can be adjusted for, and twin studies have been very helpful in this context. Suggested mechanisms behind fetal growth are often linked to the feto-maternal circulation, including the development of placenta and umbilical cord. However, the causal link between fetal growth restriction and subsequent asthma and allergic disease remains unexplained. New research regarding the catch-up growth following growth restriction has posited an alternative theory that diseases later on in life result from rapid catch-up growth rather than intrauterine growth restriction per se. Several studies have found a correlation between a rapid weight gain after birth and development of asthma or wheezing in childhood. Conclusion and clinical relevance Asthma and allergic disease are multifactorial. Several mechanisms seem to influence their development. Additional studies are needed before we fully understand the causal links between fetal growth and development of asthma and allergic diseases. PMID:22994341

  1. Prenatal diagnosis of a placental infarction hematoma associated with fetal growth restriction, preeclampsia and fetal death: clinicopathological correlation

    PubMed Central

    Aurioles-Garibay, Alma; Hernandez-Andrade, Edgar; Romero, Roberto; Qureshi, Faisal; Ahn, Hyunyoung; Jacques, Suzanne M.; Garcia, Maynor; Yeo, Lami; Hassan, Sonia S.

    2014-01-01

    The lesion termed “placental infarction hematoma” is associated with fetal death and adverse perinatal outcome. Such lesion has been associated with a high risk of fetal death and abruption placentae. The fetal and placental hemodynamic changes associated with placental infarction hematoma have not been reported. This communication describes a case of early and severe growth restriction with preeclampsia, and progressive deterioration of the fetal and placental Doppler parameters in the presence of a placental infarction hematoma. PMID:24852332

  2. Humans at high altitude: hypoxia and fetal growth

    PubMed Central

    Moore, Lorna G.; Charles, Shelton M.; Julian, Colleen G.

    2011-01-01

    High-altitude studies offer insight into the evolutionary processes and physiological mechanisms affecting the early phases of the human lifespan. Chronic hypoxia slows fetal growth and reduces the pregnancy-associated rise in uterine artery (UA) blood flow. Multigenerational vs. shorter-term high-altitude residents are protected from the altitude-associated reductions in UA flow and fetal growth. Presently unknown is whether this fetal-growth protection is due to the greater delivery or metabolism of oxygen, glucose or other substrates or to other considerations such as mechanical factors protecting fragile fetal villi, the creation of a reserve protecting against ischemia/reperfusion injury, or improved placental O2 transfer as the result of narrowing the A-V O2 difference and raising uterine PvO2. Placental growth and development appear to be normal or modified at high altitude in ways likely to benefit diffusion. Much remains to be learned concerning the effects of chronic hypoxia on embryonic development. Further research is required for identifying the fetoplacental and maternal mechanisms responsible for transforming the maternal vasculature and regulating UA blood flow and fetal growth. Genomic as well as epigenetic studies are opening new avenues of investigation that can yield insights into the basic pathways and evolutionary processes involved. PMID:21536153

  3. GLI3 Links Environmental Arsenic Exposure and Human Fetal Growth.

    PubMed

    Winterbottom, Emily F; Fei, Dennis L; Koestler, Devin C; Giambelli, Camilla; Wika, Eric; Capobianco, Anthony J; Lee, Ethan; Marsit, Carmen J; Karagas, Margaret R; Robbins, David J

    2015-06-01

    Although considerable evidence suggests that in utero arsenic exposure affects children's health, these data are mainly from areas of the world where groundwater arsenic levels far exceed the World Health Organization limit of 10 μg/L. We, and others, have found that more common levels of in utero arsenic exposure may also impact children's health. However, the underlying molecular mechanisms are poorly understood. To address this issue, we analyzed the expression of key developmental genes in fetal placenta in a birth cohort of women using unregulated water supplies in a US region with elevated groundwater arsenic. We identified several genes whose expression associated with maternal arsenic exposure in a fetal sex-specific manner. In particular, expression of the HEDGEHOG pathway component, GLI3, in female placentae was both negatively associated with arsenic exposure and positively associated with infant birth weight. This suggests that modulation of GLI3 in the fetal placenta, and perhaps in other fetal tissues, contributes to arsenic's detrimental effects on fetal growth. We showed previously that arsenic-exposed NIH3T3 cells have reduced GLI3 repressor protein. Together, these studies identify GLI3 as a key signaling node that is affected by arsenic, mediating a subset of its effects on developmental signaling and fetal health. PMID:26288817

  4. The neglected role of insulin-like growth factors in the maternal circulation regulating fetal growth

    PubMed Central

    Sferruzzi-Perri, A N; Owens, J A; Pringle, K G; Roberts, C T

    2011-01-01

    Maternal insulin-like growth factors (IGFs) play a pivotal role in modulating fetal growth via their actions on both the mother and the placenta. Circulating IGFs influence maternal tissue growth and metabolism, thereby regulating nutrient availability for the growth of the conceptus. Maternal IGFs also regulate placental morphogenesis, substrate transport and hormone secretion, all of which influence fetal growth either via indirect effects on maternal substrate availability, or through direct effects on the placenta and its capacity to supply nutrients to the fetus. The extent to which IGFs influence the mother and/or placenta are dependent on the species and maternal factors, including age and nutrition. As altered fetal growth is associated with increased perinatal morbidity and mortality and a greater risk of developing degenerative diseases in adult life, understanding the role of maternal IGFs during pregnancy is essential in order to identify mechanisms underlying altered fetal growth and offspring programming. PMID:20921199

  5. Heme oxygenase-1 modulates fetal growth in the rat.

    PubMed

    Kreiser, Doron; Nguyen, Xuandai; Wong, Ron; Seidman, Daniel; Stevenson, David; Quan, Shou; Abraham, Nader; Dennery, Phyllis A

    2002-06-01

    Intrauterine growth restriction is associated with increased perinatal morbidity and mortality as well as with lifelong cardiovascular and metabolic complications. Deficiency of heme oxygenase 1 (HO-1) is associated with growth restriction in mice and in humans, suggesting a role for HO-1 in fetal growth and maintenance of pregnancy. We hypothesized that modulation of HO-1 in the pregnant rat would alter fetal growth. In pregnant dams, placental HO activity was significantly inhibited with zinc deuteroporphyrin IX 2,4 bis glycol, and HO-1 protein was increased by transducing adenoviral human HO-1. Inhibition of HO-1 by zinc deuteroporphyrin IX 2,4 bis glycol resulted in a significant decrease in pup size, whereas transfection with hHO-1 resulted in increased pup size. Furthermore, the expression of IGF binding protein-1 and its receptor paralleled the expression of HO-1 in the placenta and were significantly modulated by modification of HO-1 along with the expression of vascular endothelial growth factor. These observations demonstrate that HO-1 modulates fetal growth by its effects on placental growth factors. PMID:12065678

  6. Alcohol use in pregnancy, craniofacial features, and fetal growth.

    PubMed Central

    Rostand, A; Kaminski, M; Lelong, N; Dehaene, P; Delestret, I; Klein-Bertrand, C; Querleu, D; Crepin, G

    1990-01-01

    STUDY OBJECTIVE--The aim was to study the relationship between the level of alcohol consumption in pregnancy and craniofacial characteristics of the neonate. DESIGN--This was a prospective survey of a sample of pregnant women, stratified on prepregnancy level of alcohol consumption. SETTING--The study was carried out at the public antenatal clinic of Roubaix maternity hospital. PARTICIPANTS--During an eight month period, 684 women (89% of those eligible) were interviewed in a standardised way at their first antenatal clinic visit. Of these, all who were suspected of being alcoholic or heavy drinkers (at least 21 drinks per week) were selected for follow up, as was a subsample of light (0-6 drinks per week) and moderate (7-20 drinks per week) drinkers. Of 347 women selected in this way, 202 had their infants assessed by a standardised morphological examination. MEASUREMENTS AND AND MAIN RESULTS--Suggestive craniofacial characteristics of the infants, present either in isolation or in association with growth retardation ("fetal alcohol effects"), were compared in relation to maternal alcohol consumption (alcoholic 12%; heavy drinking 24%; moderate drinking 28%; light drinking 36%). No differences were found between light and moderate drinkers. Infants born to alcoholics had a greater number of craniofacial characteristics and the proportion with features compatible with fetal alcohol effects was higher. There was a similar trend for infants of heavy drinkers. Infants of heavy drinkers who had decreased their alcohol consumption during pregnancy had fewer craniofacial features. Infants of heavy smokers were also found to have increased numbers of craniofacial characteristics. CONCLUSIONS--Craniofacial morphology could be a sensitive indicator of alcohol exposure in utero. Altered morphology is usually considered specific for alcohol exposure, but the relation observed with smoking needs further exploration. PMID:2277252

  7. Fetal Genotype for the Xenobiotic Metabolizing Enzyme "NQO1" Influences Intrauterine Growth among Infants Whose Mothers Smoked during Pregnancy

    ERIC Educational Resources Information Center

    Price, Thomas S.; Grosser, Tilo; Plomin, Robert; Jaffee, Sara R.

    2010-01-01

    Maternal smoking during pregnancy retards fetal growth and depresses infant birth weight. The magnitude of these effects may be moderated by fetal genotype. The current study investigated maternal smoking, fetal genotype, and fetal growth in a large population sample of dizygotic twins. Maternal smoking retarded fetal growth in a dose-dependent…

  8. Growth curve analysis of placental and fetal growth influenced by adjacent fetal sex status under crowded uterine conditions in pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Intrauterine position and sex of adjacent fetuses in litter bearing species have been implicated in physiological and behavioral differences in males and females. Our objective was to establish growth curves for fetal and placental weight gain as influenced by sex status of flanking fetuses under cr...

  9. Increased fetal myocardial sensitivity to insulin-stimulated glucose metabolism during ovine fetal growth restriction.

    PubMed

    Barry, James S; Rozance, Paul J; Brown, Laura D; Anthony, Russell V; Thornburg, Kent L; Hay, William W

    2016-04-01

    Unlike other visceral organs, myocardial weight is maintained in relation to fetal body weight in intrauterine growth restriction (IUGR) fetal sheep despite hypoinsulinemia and global nutrient restriction. We designed experiments in fetal sheep with placental insufficiency and restricted growth to determine basal and insulin-stimulated myocardial glucose and oxygen metabolism and test the hypothesis that myocardial insulin sensitivity would be increased in the IUGR heart. IUGR was induced by maternal hyperthermia during gestation. Control (C) and IUGR fetal myocardial metabolism were measured at baseline and under acute hyperinsulinemic/euglycemic clamp conditions at 128-132 days gestation using fluorescent microspheres to determine myocardial blood flow. Fetal body and heart weights were reduced by 33% (P = 0.008) and 30% (P = 0.027), respectively. Heart weight to body weight ratios were not different. Basal left ventricular (LV) myocardial blood flow per gram of LV tissue was maintained in IUGR fetuses compared to controls. Insulin increased LV myocardial blood flow by ∼38% (P < 0.01), but insulin-stimulated LV myocardial blood flow in IUGR fetuses was 73% greater than controls. Similar to previous reports testing acute hypoxia, LV blood flow was inversely related to arterial oxygen concentration (r(2 )= 0.71) in both control and IUGR animals. Basal LV myocardial glucose delivery and uptake rates were not different between IUGR and control fetuses. Insulin increased LV myocardial glucose delivery (by 40%) and uptake (by 78%) (P < 0.01), but to a greater extent in the IUGR fetuses compared to controls. During basal and hyperinsulinemic-euglycemic clamp conditions LV myocardial oxygen delivery, oxygen uptake, and oxygen extraction efficiency were not different between groups. These novel results demonstrate that the fetal heart exposed to nutrient and oxygen deprivation from placental insufficiency appears to maintain myocardial energy supply

  10. Extrinsic Factors Influencing Fetal Deformations and Intrauterine Growth Restriction

    PubMed Central

    Moh, Wendy; Graham, John M.; Wadhawan, Isha; Sanchez-Lara, Pedro A.

    2012-01-01

    The causes of intrauterine growth restriction (IUGR) are multifactorial with both intrinsic and extrinsic influences. While many studies focus on the intrinsic pathological causes, the possible long-term consequences resulting from extrinsic intrauterine physiological constraints merit additional consideration and further investigation. Infants with IUGR can exhibit early symmetric or late asymmetric growth abnormality patterns depending on the fetal stage of development, of which the latter is most common occurring in 70–80% of growth-restricted infants. Deformation is the consequence of extrinsic biomechanical factors interfering with normal growth, functioning, or positioning of the fetus in utero, typically arising during late gestation. Biomechanical forces play a critical role in the normal morphogenesis of most tissues. The magnitude and direction of force impact the form of the developing fetus, with a specific tissue response depending on its pliability and stage of development. Major uterine constraining factors include primigravida, small maternal size, uterine malformation, uterine fibromata, early pelvic engagement of the fetal head, aberrant fetal position, oligohydramnios, and multifetal gestation. Corrective mechanical forces similar to those that gave rise to the deformation to reshape the deformed structures are often used and should take advantage of the rapid postnatal growth to correct form. PMID:22888434

  11. Pravastatin ameliorates placental vascular defects, fetal growth, and cardiac function in a model of glucocorticoid excess.

    PubMed

    Wyrwoll, Caitlin S; Noble, June; Thomson, Adrian; Tesic, Dijana; Miller, Mark R; Rog-Zielinska, Eva A; Moran, Carmel M; Seckl, Jonathan R; Chapman, Karen E; Holmes, Megan C

    2016-05-31

    Fetoplacental glucocorticoid overexposure is a significant mechanism underlying fetal growth restriction and the programming of adverse health outcomes in the adult. Placental glucocorticoid inactivation by 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) plays a key role. We previously discovered that Hsd11b2(-/-) mice, lacking 11β-HSD2, show marked underdevelopment of the placental vasculature. We now explore the consequences for fetal cardiovascular development and whether this is reversible. We studied Hsd11b2(+/+), Hsd11b2(+/-), and Hsd11b2(-/-) littermates from heterozygous (Hsd11b(+/-)) matings at embryonic day (E)14.5 and E17.5, where all three genotypes were present to control for maternal effects. Using high-resolution ultrasound, we found that umbilical vein blood velocity in Hsd11b2(-/-) fetuses did not undergo the normal gestational increase seen in Hsd11b2(+/+) littermates. Similarly, the resistance index in the umbilical artery did not show the normal gestational decline. Surprisingly, given that 11β-HSD2 absence is predicted to initiate early maturation, the E/A wave ratio was reduced at E17.5 in Hsd11b2(-/-) fetuses, suggesting impaired cardiac function. Pravastatin administration from E6.5, which increases placental vascular endothelial growth factor A and, thus, vascularization, increased placental fetal capillary volume, ameliorated the aberrant umbilical cord velocity, normalized fetal weight, and improved the cardiac function of Hsd11b2(-/-) fetuses. This improved cardiac function occurred despite persisting indications of increased glucocorticoid exposure in the Hsd11b2(-/-) fetal heart. Thus, the pravastatin-induced enhancement of fetal capillaries within the placenta and the resultant hemodynamic changes correspond with restored fetal cardiac function. Statins may represent a useful therapeutic approach to intrauterine growth retardation due to placental vascular hypofunction. PMID:27185937

  12. WHO multicentre study for the development of growth standards from fetal life to childhood: the fetal component

    PubMed Central

    2014-01-01

    Background In 2006 WHO presented the infant and child growth charts suggested for universal application. However, major determinants for perinatal outcomes and postnatal growth are laid down during antenatal development. Accordingly, monitoring fetal growth in utero by ultrasonography is important both for clinical and scientific reasons. The currently used fetal growth references are derived mainly from North American and European population and may be inappropriate for international use, given possible variances in the growth rates of fetuses from different ethnic population groups. WHO has, therefore, made it a high priority to establish charts of optimal fetal growth that can be recommended worldwide. Methods This is a multi-national study for the development of fetal growth standards for international application by assessing fetal growth in populations of different ethnic and geographic backgrounds. The study will select pregnant women of high-middle socioeconomic status with no obvious environmental constraints on growth (adequate nutritional status, non-smoking), and normal pregnancy history with no complications likely to affect fetal growth. The study will be conducted in centres from ten developing and industrialized countries: Argentina, Brazil, Democratic Republic of Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand. At each centre, 140 pregnant women will be recruited between 8 + 0 and 12 + 6 weeks of gestation. Subsequently, visits for fetal biometry will be scheduled at 14, 18, 24, 28, 32, 36, and 40 weeks (+/− 1 week) to be performed by trained ultrasonographers. The main outcome of the proposed study will be the development of fetal growth standards (either global or population specific) for international applications. Discussion The data from this study will be incorporated into obstetric practice and national health policies at country level in coordination with the activities presently conducted by WHO to implement the use

  13. Is the diagnostic yield influenced by the indication for fetal autopsy?

    PubMed

    Puri, Ratna Dua; Kotecha, Udhaya; Lall, Meena; Dash, Pratima; Bijarnia-Mahay, Sunita; Verma, Ishwar Chander

    2016-08-01

    The utility of fetal autopsy to corroborate antenatal ultrasound findings and to aid genetic counseling is well known. However, the ability to identify an underlying cause for the common indications for which it is performed is not well studied. This study aimed to determine if the diagnostic yield of fetal autopsy in identifying the underlying cause is determined by the indication of the autopsy. Five groups of fetuses were defined based on the indication for the autopsy performed in 903 cases: (i) malformations, (ii) intrauterine death (IUD), (iii) cystic hygroma and hydrops fetalis, (iv) isolated abnormalities of amniotic fluid, and (v) intrauterine growth restriction (IUGR). The highest diagnostic yield was in fetuses with isolated abnormalities of amniotic fluid (77%), followed by those with IUGR (75%), with IUD (69.6%), those in group five (55.2%) and lowest (45%) in fetuses with malformations (P < 0.001). A cause was identified in 77.8% fetuses with multiple malformations compared to 37.5% with isolated malformations (P < 0.001), with chromosomal abnormalities in 31.8% versus 9.9% respectively (P < 0.001) and malformation syndromes in 42.5% versus 26.3% (P < 0.001). Placental examination provided the highest yield in IUD, IUGR, and oligohydramnios (43.1%; P < 0.003) whereas chromosomal analysis was most useful in cystic hygroma/NIHF (28.9%; P < 0.001). This information on the diagnostic yield in fetal autopsy related its common indications, can be utilized to counsel families of the utility of autopsy to establish cause and recurrence risks and thereby assist then to make an informed decision to consent for the procedure. © 2016 Wiley Periodicals, Inc. PMID:27197608

  14. Maternal parity, fetal and childhood growth, and cardiometabolic risk factors.

    PubMed

    Gaillard, Romy; Rurangirwa, Akashi A; Williams, Michelle A; Hofman, Albert; Mackenbach, Johan P; Franco, Oscar H; Steegers, Eric A P; Jaddoe, Vincent W V

    2014-08-01

    We examined the associations of maternal parity with fetal and childhood growth characteristics and childhood cardiometabolic risk factors in a population-based prospective cohort study among 9031 mothers and their children. Fetal and childhood growth were repeatedly measured. We measured childhood anthropometrics, body fat distribution, left ventricular mass, blood pressure, blood lipids, and insulin levels at the age of 6 years. Compared with nulliparous mothers, multiparous mothers had children with higher third trimester fetal head circumference, length and weight growth, and lower risks of preterm birth and small-size-for-gestational-age at birth but a higher risk of large-size-for-gestational-age at birth (P<0.05). Children from multiparous mothers had lower rates of accelerated infant growth and lower levels of childhood body mass index, total fat mass percentage, and total and low-density lipoprotein cholesterol than children of nulliparous mothers (P<0.05). They also had a lower risk of childhood overweight (odds ratio, 0.75 [95% confidence interval, 0.63–0.88]). The risk of childhood clustering of cardiometabolic risk factors was not statistically significantly different (odds ratio, 0.82; 95% confidence interval, 0.64–1.05). Among children from multiparous mothers only, we observed consistent trends toward a lower risk of childhood overweight and lower cholesterol levels with increasing parity (P<0.05). In conclusion, offspring from nulliparous mothers have lower fetal but higher infant growth rates and higher risks of childhood overweight and adverse metabolic profile. Maternal nulliparity may have persistent cardiometabolic consequences for the offspring. PMID:24866145

  15. From the α to the ω-3: Breaking the link between impaired fetal growth and adult cardiovascular disease.

    PubMed

    Skilton, Michael R; Phang, Melinda

    2016-01-01

    Atherosclerotic vascular disease is an important cause of premature morbidity and mortality. An extensive body of epidemiologic data links impaired fetal growth, evidenced by reductions in birth weight, with a higher risk for cardiovascular disease in adulthood. This association appears to be at least partially independent of established cardiovascular risk factors, such as hypertension and type 2 diabetes. There is currently no clinically established strategy to prevent cardiovascular events secondary to being born with poor fetal growth. This review summarizes recent evidence that suggests that ω-3 polyunsaturated fatty acids may be beneficial for this indication; in particular being associated with more marked reductions in blood pressure and subclinical atherosclerosis in people who were born with poor fetal growth, than in those with healthy birth weight. Possible mechanisms, and the evidence base required to support the implementation of dietary guidelines specific to people born with impaired fetal growth are also described. PMID:27025974

  16. NOTE: Trends of discordant fetal growth in monochorionic twin pregnancies

    NASA Astrophysics Data System (ADS)

    van Gemert, Martin J. C.; Umur, Asli

    2000-08-01

    We derived simple analytical relations representing trends of discordant fetal growth in monochorionic twins developing the twin-twin transfusion syndrome from an approximation of previously developed model equations. In severe twin-twin transfusion syndrome cases, the difference between the estimated fetal weights of both twins increases proportional to (t-5)5 (t denotes gestational age in weeks) and the sum of both weights increases proportional to t3. Hence, the ratio between the difference of estimated fetal weights and the average of the two weights (difference average ratio) increases in proportion to (t-5)5/t3. In mild cases, the difference between estimated fetal weights as well as the sum of the two weights increases proportional to t3. Therefore, the difference average ratio becomes a constant. Comparison with clinical data of severe and mild cases showed surprisingly good agreement except after laser coagulation of placental anastomoses. These relations may therefore enable us to distinguish between severe and mild developing twin-twin transfusion syndrome cases.

  17. Fetal diagnostic indications for second and third trimester outpatient pregnancy termination

    PubMed Central

    Hern, Warren M

    2014-01-01

    Objective To determine the frequency of diagnostic indications among women seeking to terminate pregnancies for reasons of fetal abnormality, spontaneous fetal demise, or a genetic disorder in a private outpatient clinic specializing in late outpatient abortion procedures. Method A total of 1005 women requested termination of pregnancy for reasons of genetic disorder, fetal anomaly, or fetal demise over 20 years (1992–2012). Gestational ages ranged from 12 to 39 weeks. In all cases, a documented diagnosis of fetal abnormality or fetal demise was made prior to referral. Records were reviewed to verify fetal diagnosis for all patients seeking termination of pregnancy for reasons of fetal disorder. Major complications included major unintended surgery, hemorrhage requiring transfusion, or pelvic infection. Results Preoperative diagnoses included the following: chromosomal abnormalities (n = 378), genetic syndromes and single gene disorders (n = 30), structural anomalies (n = 494), and other conditions (n = 103). These include 26 cases of spontaneous fetal demise and nine selective terminations of one abnormal twin. The major complication rate was 0.5%. Conclusions The majority of diagnoses were in the categories of genetic disorder and neurologic abnormality. © 2014 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd. PMID:24424620

  18. IGF2 DNA methylation is a modulator of newborn’s fetal growth and development

    PubMed Central

    St-Pierre, Julie; Hivert, Marie-France; Perron, Patrice; Poirier, Paul; Guay, Simon-Pierre; Brisson, Diane; Bouchard, Luigi

    2012-01-01

    The insulin-like growth factor 2 (IGF2) gene, located within a cluster of imprinted genes on chromosome 11p15, encodes a fetal and placental growth factor affecting birth weight. DNA methylation variability at the IGF2 gene locus has been previously reported but its consequences on fetal growth and development are still mostly unknown in normal pediatric population. We collected one hundred placenta biopsies from 50 women with corresponding maternal and cord blood samples and measured anthropometric indices, blood pressure and metabolic phenotypes using standardized procedures. IGF2/H19 DNA methylation and IGF2 circulating levels were assessed using sodium bisulfite pyrosequencing and ELISA, respectively. Placental IGF2 (DMR0 and DMR2) DNA methylation levels were correlated with newborn’s fetal growth indices, such as weight, and with maternal IGF2 circulating concentration at the third trimester of pregnancy, whereas H19 (DMR) DNA methylation levels were correlated with IGF2 levels in cord blood. The maternal genotype of a known IGF2/H19 polymorphism (rs2107425) was associated with birth weight. Taken together, we showed that IGF2/H19 epigenotype and genotypes independently account for 31% of the newborn’s weight variance. No association was observed with maternal diabetic status, glucose concentrations or prenatal maternal body mass index. This is the first study showing that DNA methylation at the IGF2/H19 genes locus may act as a modulator of IGF2 newborn’s fetal growth and development within normal range. IGF2/H19 DNA methylation could represent a cornerstone in linking birth weight and fetal metabolic programming of late onset obesity. PMID:22907587

  19. Dietary -carbamylglutamate and rumen-protected -arginine supplementation ameliorate fetal growth restriction in undernourished ewes.

    PubMed

    Zhang, H; Sun, L W; Wang, Z Y; Deng, M T; Zhang, G M; Guo, R H; Ma, T W; Wang, F

    2016-05-01

    This study was conducted with an ovine intrauterine growth restriction (IUGR) model to test the hypothesis that dietary -carbamylglutamate (NCG) and rumen-protected -Arg (RP-Arg) supplementation are effective in ameliorating fetal growth restriction in undernourished ewes. Beginning on d 35 of gestation, ewes were fed a diet providing 100% of NRC-recommended nutrient requirements, 50% of NRC recommendations (50% NRC), 50% of NRC recommendations supplemented with 20 g/d RP-Arg (providing 10 g/d of Arg), and 50% of NRC recommendations supplemented with 5 g/d NCG product (providing 2.5 g/d of NCG). On d 110, maternal, fetal, and placental tissues and fluids were collected and weighed. Ewe weights were lower ( < 0.05) in nutrient-restricted ewes compared with adequately fed ewes. Maternal RP-Arg or NCG supplementation did not alter ( = 0.26) maternal BW in nutrient-restricted ewes. Weights of most fetal organs were increased ( < 0.05) in RP-Arg-treated and NCG-treated underfed ewes compared with 50% NRC-fed ewes. Supplementation of RP-Arg or NCG reduced ( < 0.05) concentrations of β-hydroxybutyrate, triglycerides, and ammonia in serum of underfed ewes but had no effect on concentrations of lactate and GH. Maternal RP-Arg or NCG supplementation markedly improved ( < 0.05) concentrations of AA (particularly arginine-family AA and branched-chain AA) and polyamines in maternal and fetal plasma and in fetal allantoic and amniotic fluids within nutrient-restricted ewes. These novel results indicate that dietary NCG and RP-Arg supplementation to underfed ewes ameliorated fetal growth restriction, at least in part, by increasing the availability of AA in the conceptus and provide support for its clinical use to ameliorate IUGR in humans and sheep industry production. PMID:27285704

  20. Early rapid growth, early birth: Accelerated fetal growth and spontaneous late preterm birth

    PubMed Central

    Kusanovic, Juan Pedro; Erez, Offer; Espinoza, Jimmy; Gotsch, Francesca; Goncalves, Luis; Hassan, Sonia; Gomez, Ricardo; Nien, Jyh Kae; Frongillo, Edward A.; Romero, Roberto

    2011-01-01

    The past two decades in the United States have seen a 24 % rise in spontaneous late preterm delivery (34 to 36 weeks) of unknown etiology. This study tested the hypothesis that fetal growth was identical prior to spontaneous preterm (n=221, median gestational age at birth 35.6 weeks) and term (n=3706) birth among pregnancies followed longitudinally in Santiago, Chile. The hypothesis was not supported: Preterm-delivered fetuses were significantly larger than their term-delivered peers by mid-second trimester in estimated fetal weight, head, limb and abdominal dimensions, and they followed different growth trajectories. Piecewise regression assessed time-specific differences in growth rates at 4-week intervals from 16 weeks. Estimated fetal weight and abdominal circumference growth rates faltered at 20 weeks among the preterm-delivered, only to match and/or exceed their term-delivered peers at 24–28 weeks. After an abrupt decline at 28 weeks attenuating growth rates in all dimensions, fetuses delivered preterm did so at greater population-specific sex and age-adjusted weight than their peers from uncomplicated pregnancies (p<0.01). Growth rates predicted birth timing: one standard score of estimated fetal weight increased the odds ratio for preterm birth from 2.8 prior to 23 weeks, to 3.6 (95% confidence interval, 1.82–7.11, p<0.05) between 23 and 27 weeks. After 27 weeks, increasing size was protective (OR: 0.56, 95% confidence interval, 0.38–0.82, p=0.003). These data document, for the first time, a distinctive fetal growth pattern across gestation preceding spontaneous late preterm birth, identify the importance of mid-gestation for alterations in fetal growth, and add perspective on human fetal biological variability. PMID:18988282

  1. Normative biometrics for fetal ocular growth using volumetric MRI reconstruction

    PubMed Central

    Velasco-Annis, Clemente; Gholipour, Ali; Afacan, Onur; Prabhu, Sanjay P.; Estroff, Judy A.; Warfield, Simon K.

    2015-01-01

    Objective To determine normative ranges for fetal ocular biometrics between 19 and 38 weeks gestational age (GA) using volumetric MRI reconstruction. Method 3D images of 114 healthy fetuses between 19 and 38 weeks GA were created using super-resolution volume reconstructions from MRI slice acquisitions. These 3D images were semi-automatically segmented to measure fetal orbit volume, binocular distance (BOD), interocular distance (IOD), and ocular diameter (OD). Results All biometry correlated with GA (Volume, CC = 0.9680; BOD, CC = 0.9552; OD, CC = 0.9445; and IOD, CC = 0.8429), and growth curves were plotted against linear and quadratic growth models. Regression analysis showed quadratic models to best fit BOD, IOD and OD, and a linear model to best fit volume. Conclusion Orbital volume had the greatest correlation with GA, though BOD and OD also showed strong correlation. The normative data found in this study may be helpful for the detection of congenital fetal anomalies with more consistent measurements than are currently available. PMID:25601041

  2. Role of lung fluid volume in growth and maturation of the fetal sheep lung.

    PubMed Central

    Moessinger, A C; Harding, R; Adamson, T M; Singh, M; Kiu, G T

    1990-01-01

    We studied the effects of alterations in lung fluid volume on growth and maturation of the fetal lung. In a chronic fetal sheep preparation, right fetal lung volume was decreased by drainage of lung fluid while the volume of the left lung was expanded by mainstem bronchus ligation leading to lung fluid retention. After an experimental period of 25 d (from 105 to 129 d of gestation, term = 145 d), the right (deflated) lung was significantly hypoplastic and contained less DNA than the controls; 175.15 +/- 55.18 vs. 346.77 +/- 61.97 mg, respectively; P less than 0.001. In contrast, the left (expanded) lung was significantly hyperplastic and contained more DNA than the controls; 390.74 +/- 103.53 vs. 238.85 +/- 33.32 mg, respectively; P = 0.001. Biochemical indices of lung maturation, including total phospholipids, phosphatidylcholine, and disaturated phosphatidylcholine content expressed per unit of tissue DNA, were no different when comparing the hypoplastic, hyperplastic, and control lungs. These findings demonstrate that fetal lung cell multiplication is influenced by local distension with lung fluid, while the biochemical maturation of fetal lung surfactant is under systemic control. Images PMID:2212011

  3. Effect of placental factors on growth and function of the human fetal adrenal in vitro

    SciTech Connect

    Riopel, L.; Branchaud, C.L.; Goodyer, C.G.; Zweig, M.; Lipowski, L.; Adkar, V.; Lefebvre, Y. )

    1989-11-01

    Conditioned medium from human placental monolayer cultures (PM) had a marked stimulatory effect on proliferation (3H-thymidine uptake) of human fetal zone adrenal cells in primary monolayer culture, even in the absence of serum. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) also significantly stimulated fetal adrenal cell growth. However, the effects of PM differed from those of EGF and FGF in several respects: (1) maximal response to PM was 2-5 times greater; (2) mitogenic effects of EGF and FGF were suppressed by adrenocorticotropic hormone (ACTH), whereas that of 50% PM was not; (3) PM inhibited ACTH-stimulated steroidogenesis (dehydroepiandrosterone sulfate and cortisol), but EGF and FGF did not. Preliminary characterization studies have indicated that approximately half of the placental growth-promoting activity is heat resistant and sensitive to bacterial proteases, and that 50-60% of the activity is lost after dialysis with membranes having a molecular weight cutoff of 3500. These findings suggest a role for the placenta in the growth and differentiated function of the human fetal adrenal gland.

  4. Fetal growth and the ethnic origins of type 2 diabetes.

    PubMed

    Skilton, Michael R

    2015-03-01

    Birthweight is known to differ by ethnicity, with South Asian, black African and Caribbean, and Hispanic ethnic groups having lower birthweight on average, when compared with people of white European ethnicity. Birthweight is the most frequently used proxy of fetal growth, and represents the net effect of a host of genetic, physiological and pathophysiological factors. These same ethnic groups that have lower average birthweight also tend to have a higher prevalence of type 2 diabetes in adulthood. It is not unreasonable to propose that the well-established inverse association between birthweight and risk of type 2 diabetes may at least partially contribute to these differences in prevalence of type 2 diabetes between ethnic groups. This hypothesis would rely on the mechanisms that drive the ethnic differences in birthweight aligning with those that modify the risk of type 2 diabetes. In this issue of Diabetologia (DOI: 10.1007/s00125-014-3474-7), Nightingale et al have furthered this field by determining whether ethnic differences in markers of cardio-metabolic risk are consistent with the differences in birthweight in an ethnically diverse cohort of children. The likely contribution of fetal growth to ethnic differences in risk of type 2 diabetes and cardiovascular disease is discussed, particularly in light of the magnitude of the birthweight differences, as are implications for the prevention of type 2 diabetes. PMID:25567103

  5. Sexual dimorphism in epigenomicresponses of stem cells to extreme fetal growth

    PubMed Central

    Delahaye, Fabien; Wijetunga, N. Ari; Heo, Hye J.; Tozour, Jessica N.; Zhao, Yong Mei; Greally, John M.; Einstein, Francine H.

    2014-01-01

    Extreme fetal growth is associated with increased susceptibility to a range of adult diseases through an unknown mechanism of cellular memory. We tested whether heritable epigenetic processes in long-lived CD34+ hematopoietic stem/progenitor cells (HSPCs) showed evidence for re-programming associated with the extremes of fetal growth. Here we show that both fetal growth restriction and over-growth are associated with global shifts towards DNA hypermethylation, targeting cis-regulatory elements in proximity to genes involved in glucose homeostasis and stem cell function. We find a sexually dimorphic response; intrauterine growth restriction (IUGR) is associated with substantially greater epigenetic dysregulation in males, whereas large for gestational age (LGA) growth predominantly affects females. The findings are consistent with extreme fetal growth interacting with variable fetal susceptibility to influence cellular aging and metabolic characteristics through epigenetic mechanisms, potentially generating biomarkers that could identify infants at higher risk for chronic disease later in life. PMID:25300954

  6. Fetal growth patterns in Beckwith-Wiedemann syndrome.

    PubMed

    Mussa, A; Russo, S; de Crescenzo, A; Freschi, A; Calzari, L; Maitz, S; Macchiaiolo, M; Molinatto, C; Baldassarre, G; Mariani, M; Tarani, L; Bedeschi, M F; Milani, D; Melis, D; Bartuli, A; Cubellis, M V; Selicorni, A; Silengo, M C; Larizza, L; Riccio, A; Ferrero, G B

    2016-07-01

    We provide data on fetal growth pattern on the molecular subtypes of Beckwith-Wiedemann syndrome (BWS): IC1 gain of methylation (IC1-GoM), IC2 loss of methylation (IC2-LoM), 11p15.5 paternal uniparental disomy (UPD), and CDKN1C mutation. In this observational study, gestational ages and neonatal growth parameters of 247 BWS patients were compared by calculating gestational age-corrected standard deviation scores (SDS) and proportionality indexes to search for differences among IC1-GoM (n = 21), UPD (n = 87), IC2-LoM (n = 147), and CDKN1C mutation (n = 11) patients. In IC1-GoM subgroup, weight and length are higher than in other subgroups. Body proportionality indexes display the following pattern: highest in IC1-GoM patients, lowest in IC2-LoM/CDKN1C patients, intermediate in UPD ones. Prematurity was significantly more prevalent in the CDKN1C (64%) and IC2-LoM subgroups (37%). Fetal growth patterns are different in the four molecular subtypes of BWS and remarkably consistent with altered gene expression primed by the respective molecular mechanisms. IC1-GoM cases show extreme macrosomia and severe disproportion between weight and length excess. In IC2-LoM/CDKN1C patients, macrosomia is less common and associated with more proportionate weight/length ratios with excess of preterm birth. UPD patients show growth patterns closer to those of IC2-LoM, but manifest a body mass disproportion rather similar to that seen in IC1-GoM cases. PMID:26857110

  7. Maternal HCV infection is associated with intrauterine fetal growth disturbance: A meta-analysis of observational studies.

    PubMed

    Huang, Qi-Tao; Hang, Li-Lin; Zhong, Mei; Gao, Yun-Fei; Luo, Man-Ling; Yu, Yan-Hong

    2016-08-01

    Since the evidence regarding the association between maternal hepatitis C virus (HCV) infection and impaired intrauterine fetal growth had not been conclusive, the aim of the present study was to evaluate the risk of maternal HCV infection in association with intrauterine fetal growth restriction (IUGR) and/or low birth weight infants (LBW). We performed an extensive literature search of PubMed, MEDLINE, and EMBASE through December 1, 2015. The odds ratios (ORs) of HCV infection and IUGR/LBW were calculated and reported with 95% confidence intervals (95% CIs). Statistical analysis was performed using RevMen 5.3 and Stata 10.0. Seven studies involving 4,185,414 participants and 5094 HCV infection cases were included. Significant associations between HCV infection and IUGR (OR = 1.53, 95% CI: 1.40-1.68, fixed effect model) as well as LBW were observed (OR = 1.97, 95% CI: 1.43-2.71, random effect model). The results still indicated consistencies after adjusting for multiple risk factors which could affect fetal growth, including maternal age, parity, maternal smoking, alcohol abuse, drugs abuse, coinfected with HBV/HIV and preeclampsia. Our findings suggested that maternal HCV infection was significantly associated with an increased risk of impaired intrauterine fetal growth. In clinical practice, a closer monitoring of intrauterine fetal growth by a series of ultrasound might be necessary for HCV-infected pregnant population. PMID:27583932

  8. Brief Report: A Preliminary Study of Fetal Head Circumference Growth in Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Whitehouse, Andrew J. O.; Hickey, Martha; Stanley, Fiona J.; Newnham, John P.; Pennell, Craig E.

    2011-01-01

    Fetal head circumference (HC) growth was examined prospectively in children with autism spectrum disorder (ASD). ASD participants (N = 14) were each matched with four control participants (N = 56) on a range of parameters known to influence fetal growth. HC was measured using ultrasonography at approximately 18 weeks gestation and again at birth…

  9. Fetal PCB syndrome: clinical features, intrauterine growth retardation and possible alteration in calcium metabolism

    SciTech Connect

    Yamashita, F.; Hayashi, M.

    1985-02-01

    Pregnant mothers with Yusho in Fukuoka, Nagasaki and Kochi Prefectures delivered babies with a peculiar clinical manifestation which will be called fetal PCB syndrome (FPS). The birth rate incidences were 3.6% (Fukuoka Prefecture), 4% (Nagasaki Prefecture), 2.9% (Kochi Prefecture) and 3.9% (total). The manifestations consisted of dark brown pigmentation of the skin and the mucous membrane, gingival hyperplasia, exophthalmic edematous eye, dentition at birth, abnormal calcification of the skull as demonstrated by X-ray, rocker bottom heel and high incidence of light for date (low birth weight) babies. The authors suggest that there may be a possible alteration in calcium metabolism in these babies, related to the fragile egg shells observed in PCB-contaminated birds and to the female hormone-enhancing effect of PCB. The high incidence of low birth weight among these newborns and two other similar studies indicated that PCBs suppress fetal growth.

  10. Human fetal and adult chondrocytes. Effect of insulinlike growth factors I and II, insulin, and growth hormone on clonal growth.

    PubMed Central

    Vetter, U; Zapf, J; Heit, W; Helbing, G; Heinze, E; Froesch, E R; Teller, W M

    1986-01-01

    Clonal proliferation of freshly isolated human fetal chondrocytes and adult chondrocytes in response to human insulinlike growth factors I and II (IGF I, IGF II), human biosynthetic insulin, and human growth hormone (GH) was assessed. IGF I (25 ng/ml) stimulated clonal growth of fetal chondrocytes (54 +/- 12 colonies/1,000 inserted cells, mean +/- 1 SD), but IGF II (25 ng/ml) was significantly more effective (106 +/- 12 colonies/1,000 inserted cells, P less than 0.05, unstimulated control: 14 +/- 4 colonies/1,000 inserted cells). In contrast, IGF I (25 ng/ml) was more effective in adult chondrocytes (42 +/- 6 colonies/1,000 inserted cells) than IGF II (25 ng/ml) (21 +/- 6 colonies/1,000 inserted cells; P less than 0.05, unstimulated control: 6 +/- 3 colonies/1,000 inserted cells). GH and human biosynthetic insulin did not affect clonal growth of fetal or adult chondrocytes. The clonal growth pattern of IGF-stimulated fetal and adult chondrocytes was not significantly changed when chondrocytes were first grown in monolayer culture, harvested, and then inserted in the clonal culture system. However, the adult chondrocytes showed a time-dependent decrease of stimulation of clonal growth by IGF I and II. This was not true for fetal chondrocytes. The results are compatible with the concept that IGF II is a more potent stimulant of clonal growth of chondrocytes during fetal life, whereas IGF I is more effective in stimulating clonal growth of chondrocytes during postnatal life. Images PMID:3519682

  11. The impact of a human IGF-II analog ([Leu27]IGF-II) on fetal growth in a mouse model of fetal growth restriction.

    PubMed

    Charnock, Jayne C; Dilworth, Mark R; Aplin, John D; Sibley, Colin P; Westwood, Melissa; Crocker, Ian P

    2016-01-01

    Enhancing placental insulin-like growth factor (IGF) availability appears to be an attractive strategy for improving outcomes in fetal growth restriction (FGR). Our approach was the novel use of [Leu(27)]IGF-II, a human IGF-II analog that binds the IGF-II clearance receptor IGF-IIR in fetal growth-restricted (FGR) mice. We hypothesized that the impact of [Leu(27)]IGF-II infusion in C57BL/6J (wild-type) and endothelial nitric oxide synthase knockout (eNOS(-/-); FGR) mice would be to enhance fetal growth and investigated this from mid- to late gestation; 1 mg·kg(-1)·day(-1) [Leu(27)]IGF-II was delivered via a subcutaneous miniosmotic pump from E12.5 to E18.5. Fetal and placental weights recorded at E18.5 were used to generate frequency distribution curves; fetuses <5th centile were deemed growth restricted. Placentas were harvested for immunohistochemical analysis of the IGF system, and maternal serum was collected for measurement of exogenously administered IGF-II. In WT pregnancies, [Leu(27)]IGF-II treatment halved the number of FGR fetuses, reduced fetal(P = 0.028) and placental weight variations (P = 0.0032), and increased the numbers of pups close to the mean fetal weight (131 vs. 112 pups within 1 SD). Mixed-model analysis confirmed litter size to be negatively correlated with fetal and placental weight and showed that [Leu(27)]IGF-II preferentially improved fetal weight in the largest litters, as defined by number. Unidirectional (14C)MeAIB transfer per gram placenta (System A amino acid transporter activity) was inversely correlated with fetal weight in [Leu(27)]IGF-II-treated WT animals (P < 0.01). In eNOS(-/-) mice, [Leu(27)]IGF-II reduced the number of FGR fetuses(1 vs. 5 in the untreated group). The observed reduction in FGR pup numbers in both C57 and eNOS(-/-) litters suggests the use of this analog as a means of standardizing and rescuing fetal growth, preferentially in the smallest offspring. PMID:26530156

  12. The impact of a human IGF-II analog ([Leu27]IGF-II) on fetal growth in a mouse model of fetal growth restriction

    PubMed Central

    Charnock, Jayne C.; Dilworth, Mark R.; Aplin, John D.; Sibley, Colin P.; Westwood, Melissa

    2015-01-01

    Enhancing placental insulin-like growth factor (IGF) availability appears to be an attractive strategy for improving outcomes in fetal growth restriction (FGR). Our approach was the novel use of [Leu27]IGF-II, a human IGF-II analog that binds the IGF-II clearance receptor IGF-IIR in fetal growth-restricted (FGR) mice. We hypothesized that the impact of [Leu27]IGF-II infusion in C57BL/6J (wild-type) and endothelial nitric oxide synthase knockout (eNOS−/−; FGR) mice would be to enhance fetal growth and investigated this from mid- to late gestation; 1 mg·kg−1·day−1 [Leu27]IGF-II was delivered via a subcutaneous miniosmotic pump from E12.5 to E18.5. Fetal and placental weights recorded at E18.5 were used to generate frequency distribution curves; fetuses <5th centile were deemed growth restricted. Placentas were harvested for immunohistochemical analysis of the IGF system, and maternal serum was collected for measurement of exogenously administered IGF-II. In WT pregnancies, [Leu27]IGF-II treatment halved the number of FGR fetuses, reduced fetal(P = 0.028) and placental weight variations (P = 0.0032), and increased the numbers of pups close to the mean fetal weight (131 vs. 112 pups within 1 SD). Mixed-model analysis confirmed litter size to be negatively correlated with fetal and placental weight and showed that [Leu27]IGF-II preferentially improved fetal weight in the largest litters, as defined by number. Unidirectional 14CMeAIB transfer per gram placenta (System A amino acid transporter activity) was inversely correlated with fetal weight in [Leu27]IGF-II-treated WT animals (P < 0.01). In eNOS−/− mice, [Leu27]IGF-II reduced the number of FGR fetuses(1 vs. 5 in the untreated group). The observed reduction in FGR pup numbers in both C57 and eNOS−/− litters suggests the use of this analog as a means of standardizing and rescuing fetal growth, preferentially in the smallest offspring. PMID:26530156

  13. Perinatal programming of childhood asthma: early fetal size, growth trajectory during infancy, and childhood asthma outcomes.

    PubMed

    Turner, Steve

    2012-01-01

    The "fetal origins hypothesis" or concept of "developmental programming" suggests that faltering fetal growth and subsequent catch-up growth are implicated in the aetiology of cardiovascular disease. Associations between reduced birth weight, rapid postnatal weight gain, and asthma suggest that there are fetal origins to respiratory disease. The present paper first summarises the literature relating birth weight and post natal growth trajectories to asthma outcomes. Second, issues regarding the interpretation of antenatal fetal ultrasound measurements are discussed. Finally, recent reports linking antenatal measurement and growth trajectory to early childhood asthma outcomes are discussed. Understanding the nature and timing of factors which influence antenatal growth may give important insight into the antecedents of early-onset asthma with implications for interventions. PMID:22400043

  14. Growth and development symposium: Fetal programming in animal agriculture

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fetal programming is the ability to improve animal production and well-being by altering the maternal environment and holds enormous challenges and great opportunities for researchers and the animal industry. A symposium was held to provide an overview of current knowledge of fetal programming in re...

  15. Antenatal taurine supplementation increases taurine content in intrauterine growth restricted fetal rat brain tissue.

    PubMed

    Li, Fang; Teng, Hui-Yun; Liu, Jing; Wang, Hua-Wei; Zeng, Li; Zhao, Li-Fang

    2014-09-01

    This study aimed to determine the influence of antenatal taurine supplementation on taurine content in the brains of fetal rats with intrauterine growth restriction (IUGR). Experiments were performed at the Central Laboratory of Bayi Children's Hospital Affiliated to Beijing Military General Hospital in China from January to June 2013. Fifteen pregnant rats were randomly divided into three groups: normal controls, an IUGR group and an IUGR + antenatal taurine supplement group (Taurine group) (n = 5). The IUGR model was induced using a low-protein diet throughout gestation. Rats in the taurine group were fed a diet supplemented with 300 mg/kg/day taurine for 12 days after conception until natural delivery. Two fetal rats were randomly selected in every litter, and taurine levels in the brains of rats were detected using high-performance liquid chromatography-mass spectrometry. Results showed that (1) the mean body weight of the fetal rats in the normal control, IUGR and IUGR + antenatal taurine supplement groups was 6.619 ± 0.4132, 4.509 ± 0.454, and 5.176 ± 0.436 g (F = 429.818, P < 0.01), respectively, and (2) that taurine levels in the brains of the fetal rats in the normal control, IUGR and taurine groups were (2.399 ± 0.134) × 10(5), (1.881 ± 0.166) × 10(5) and (2.170 ± 0.191) × 10(5) μg/g (F = 24.828, P < 0.01), respectively. Overall, our results indicated that taurine levels in IUGR fetal rat brains were lower than in the control animals, and that antenatal taurine supplementation could significantly increase taurine levels in the brains of fetal rats with IUGR. PMID:24676564

  16. [The EXIT procedure: Indications, limitations, risks and progress to the fetal endoscopical tracheal intubation].

    PubMed

    Cruz-Martínez, Rogelio; Méndez, Antonio; Pineda-Alemán, Hugo; Rebolledo-Fernández, Carlos

    2015-01-01

    Congenital oral and neck masses are associated with a high perinatal mortality and morbidity secondary to airway obstruction due to a mass effect of the tumor with subsequent neonatal asphyxia and/or neonatal death. In 1997, the Ex Utero Intrapartum Treatment (EXIT) technique was designed to establish a secure neonatal airway. This procedure allows neonatal tracheal intubation while the uteroplacental circulation maintains fetal oxygenation in a partial fetal delivery during cesarean section. However, it must be emphasized that this technique requires a multidisciplinary team, maternal general anesthesia, high surgery times and potential maternal risks such as placental abruption and increased maternal blood loss due to uterine atony. In addition, the clinical algorithm to obtain a neonatal airway can be quite challenging and neonatal mortality has been reported due to the inability in obtaining an airway at birth. Recently, our Mexican group described a novel minimally invasive fetoscopical technique before cesarean delivery that allows prenatal airway control by means of a fetal endoscopic tracheal intubation (FETI) under maternal peridural anesthesia. This procedure attempted to avoid the need for an EXIT procedure and its potential risks. In this review we described the indications, risks and potential benefits of the EXIT technique and its possible replacement by the fetal endoscopic tracheal intubation technique. PMID:26016317

  17. Relation of FTO gene variants to fetal growth trajectories: Findings from the Southampton Women's survey

    PubMed Central

    Barton, S.J.; Mosquera, M.; Cleal, J.K.; Fuller, A.S.; Crozier, S.R.; Cooper, C.; Inskip, H.M.; Holloway, J.W.; Lewis, R.M.; Godfrey, K.M.

    2016-01-01

    Introduction Placental function is an important determinant of fetal growth, and fetal growth influences obesity risk in childhood and adult life. Here we investigated how FTO and MC4R gene variants linked with obesity relate to patterns of fetal growth and to placental FTO expression. Methods Southampton Women's Survey children (n = 1990) with measurements of fetal growth from 11 to 34 weeks gestation were genotyped for common gene variants in FTO (rs9939609, rs1421085) and MC4R (rs17782313). Linear mixed-effect models were used to analyse relations of gene variants with fetal growth. Results Fetuses with the rs9939609 A:A FTO genotype had faster biparietal diameter and head circumference growth velocities between 11 and 34 weeks gestation (by 0.012 (95% CI 0.005 to 0.019) and 0.008 (0.002–0.015) standard deviations per week, respectively) compared to fetuses with the T:T FTO genotype; abdominal circumference growth velocity did not differ between genotypes. FTO genotype was not associated with placental FTO expression, but higher placental FTO expression was independently associated with larger fetal size and higher placental ASCT2, EAAT2 and y + LAT2 amino acid transporter expression. Findings were similar for FTO rs1421085, and the MC4R gene variant was associated with the fetal growth velocity of head circumference. Discussion FTO gene variants are known to associate with obesity but this is the first time that the risk alleles and placental FTO expression have been linked with fetal growth trajectories. The lack of an association between FTO genotype and placental FTO expression adds to emerging evidence of complex biology underlying the association between FTO genotype and obesity. PMID:26907388

  18. Uteroplacental Adenovirus Vascular Endothelial Growth Factor Gene Therapy Increases Fetal Growth Velocity in Growth-Restricted Sheep Pregnancies

    PubMed Central

    Wallace, Jacqueline M.; Aitken, Raymond P.; Milne, John S.; Mehta, Vedanta; Martin, John F.; Zachary, Ian C.; Peebles, Donald M.; David, Anna L.

    2014-01-01

    Abstract Fetal growth restriction (FGR) occurs in ∼8% of pregnancies and is a major cause of perinatal mortality and morbidity. There is no effective treatment. FGR is characterized by reduced uterine blood flow (UBF). In normal sheep pregnancies, local uterine artery (UtA) adenovirus (Ad)-mediated overexpression of vascular endothelial growth factor (VEGF) increases UBF. Herein we evaluated Ad.VEGF therapy in the overnourished adolescent ewe, an experimental paradigm in which reduced UBF from midgestation correlates with reduced lamb birthweight near term. Singleton pregnancies were established using embryo transfer in adolescent ewes subsequently offered a high intake (n=45) or control intake (n=12) of a complete diet to generate FGR or normal fetoplacental growth, respectively. High-intake ewes were randomized midgestation to receive bilateral UtA injections of 5×1011 particles Ad.VEGF-A165 (n=18), control vector Ad.LacZ (n=14), or control saline (n=13). Fetal growth/well-being were evaluated using serial ultrasound. UBF was monitored using indwelling flowprobes until necropsy at 0.9 gestation. Vasorelaxation, neovascularization within the perivascular adventitia, and placental mRNA expression of angiogenic factors/receptors were examined using organ bath analysis, anti-vWF immunohistochemistry, and qRT-PCR, respectively. Ad.VEGF significantly increased ultrasonographic fetal growth velocity at 3–4 weeks postinjection (p=0.016–0.047). At 0.9 gestation fewer fetuses were markedly growth-restricted (birthweight >2SD below contemporaneous control-intake mean) after Ad.VEGF therapy. There was also evidence of mitigated fetal brain sparing (lower biparietal diameter-to-abdominal circumference and brain-to-liver weight ratios). No effects were observed on UBF or neovascularization; however, Ad.VEGF-transduced vessels demonstrated strikingly enhanced vasorelaxation. Placental efficiency (fetal-to-placental weight ratio) and FLT1/KDR mRNA expression were

  19. FETAL DEXAMETHASONE EXPOSURE ACCELERATES DEVELOPMENT OF RENAL FUNCTION: RELATIONSHIP TO DOSE, CELL DIFFERENTIATION AND GROWTH INHIBITION

    EPA Science Inventory

    Fetal exposure to high doses of glucocorticoids slows cellular development and impairs organ performance, in association with growth retardation. evertheless, low doses of glucocorticoids may enhance cell differentiation and accelerate specific functions. he current study examine...

  20. Disproportionate Fetal Growth and the Risk for Congenital Cerebral Palsy in Singleton Births

    PubMed Central

    Streja, Elani; Miller, Jessica E.; Wu, Chunsen; Bech, Bodil H.; Pedersen, Lars Henning; Schendel, Diana E.; Uldall, Peter; Olsen, Jørn

    2015-01-01

    Objective To investigate the association between proportionality of fetal and placental growth measured at birth and the risk for congenital cerebral palsy (CP). Study Design We identified all live-born singletons born in Denmark between 1995 and 2003 and followed them from 1 year of age until December 31st, 2008. Information on four indices of fetal growth: ponderal index, head circumference/ abdominal circumference ratio, cephalization index and birth weight/ placenta weight ratio was collected. Cox proportional hazards regression models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). All measurements were evaluated as gestational age and sex specific z-scores and in z-score percentile groups, adjusted for potential confounders, and stratified on gestational age groups (<32, 32-36, 37-38, 39, 40, ≥41 weeks). Results We identified 503,784 singleton births, of which 983 were confirmed cases of CP. Head/ abdominal circumference ratio (aHR:1.12; 95%CI:1.07-1.16) and cephalization index (aHR:1.14; 95%CI:1.11-1.16) were associated with the risk of CP irrespective of gestational age. Birth weight-placental weight ratio was also associated with CP in the entire cohort (aHR:0.90; 95%CI:0.83-0.97). Ponderal index had a u-shaped association with CP, where both children with low and high ponderal index were at higher risk of CP. Conclusions CP is associated with disproportions between birth weight, birth length, placental weight and head circumference suggesting pre and perinatal conditions contribute to fetal growth restriction in children with CP. PMID:25974407

  1. Fetal growth and maternal exposure to particulate matter during pregnancy.

    PubMed Central

    Dejmek, J; Selevan, S G; Benes, I; Solanský, I; Srám, R J

    1999-01-01

    Prior studies reported an association between ambient air concentrations of total suspended particles and SO2 during pregnancy and adverse pregnancy outcomes. We examined the possible impact of particulate matter up to 10 microm (PM10) and up to 2.5 microm (PM2. 5) in size on intrauterine growth retardation (IUGR) risk in a highly polluted area of Northern Bohemia (Teplice District). The study group includes all singleton full-term births of European origin over a 2-year period in the Teplice District. Information on reproductive history, health, and lifestyle was obtained from maternal questionnaires. The mean concentrations of pollutants for each month of gestation were calculated using continuous monitoring data. Three intervals (low, medium, and high) were constructed for each pollutant (tertiles). Odds ratios (ORs) for IUGR for PM10 and PM2.5 levels were generated using logistic regression for each month of gestation after adjustment for potential confounding factors. Adjusted ORs for IUGR related to ambient PM10 levels in the first gestational month increased along the concentration intervals: medium 1.62 [95% confidence interval (CI), 1.07-2.46], high 2.64 (CI, 1.48-4.71). ORs for PM2.5 were 1.26 (CI, 0.81-1.95) and 2.11 (CI, 1. 20-3.70), respectively. No other associations of IUGR risk with particulate matter were found. Influence of particles or other associated air pollutants on fetal growth in early gestation is one of several possible explanations of these results. Timing of this effect is compatible with a current hypothesis of IUGR pathogenesis. Seasonal factors, one of the other possible explanations, is less probable. More investigation is required to examine these findings and alternative explanations. Images Figure 1 PMID:10339448

  2. Phthalate levels in cord blood are associated with preterm delivery and fetal growth parameters in Chinese women.

    PubMed

    Huang, Yujing; Li, Junnan; Garcia, Jose M; Lin, Hui; Wang, Yanzhou; Yan, Ping; Wang, Lingqiao; Tan, Yao; Luo, Jiaohua; Qiu, Zhiqun; Chen, Ji-an; Shu, Weiqun

    2014-01-01

    Data concerning the effects of phthalate exposure on preterm delivery and fetal growth are limited in humans. In this paper, we assessed the relationship between 15 phthalate levels in cord blood and preterm delivery and fetal growth parameters in 207 Chinese women going into labor. Exposure to phthalates except DCHP was associated with gestational age reduction and preterm delivery (p<0.05). There were associations between phthalates and fetal growth parameters, many of which disappeared when analyses were adjusted for gestational age, especially in male infants (Only DEEP was associated with birth weight; DEP, DNHP, BBP, DNP with abdominal circumference; DEP, DBP, DCHP, DEHP with femur length in female infants. And DPP, DBEP was associated with birth length in male infants. p<0.05). This study indicates that prenatal exposure to phthalates is associated with younger gestational age and preterm delivery. Also, phthalate exposure may adversely affect fetal growth parameters via gestational age reduction and preterm delivery with a significant gender effect. PMID:24503621

  3. [Possibility of predicting intrauterine fetal growth retardation by a single ultrasonic examination (using varying standards)].

    PubMed

    Fedorova, M V; Kotov, Iu B; Lukashenko, S Iu; Alekseevskiĭ, A V; Dub, N V; Sichinava, L G; Novikova, S V; Klimenko, P A

    1991-05-01

    The paper deals with early prediction of fetal growth retardation and its severity in a newborn from single ultrasound fetal biometric findings (biparietal head size, chest and belly diameters) at week 20 of pregnancy. The prediction was made by employing the developed varying standards for these parameters as percentile curves and tables. A stepwise prediction of fetal growth retardation was proposed for obstetric in- and outpatient settings, which was presented as an IBM personal computer dialogue program. The positive diagnostic value of fetal growth retardation prediction was found to be 69.7%, its negative value was 86.9%. The paper discusses whether therapeutic measures and pregnancy length affect the efficiency of its prediction and stresses that the prediction is valuable for individual well-grounded tactics for pregnancy management. PMID:1897665

  4. Cadmium-induced fetal growth retardation: protective effect of excess dietary zinc

    SciTech Connect

    Ahokas, R.A.; Dilts, P.V. Jr.; LaHaye, E.B.

    1980-01-15

    Reproductive performance and fetal cellular growth and development were investigated in laboratory rats chronically fed low drinking water levels (0, 1.0, 10.0, and 100 ..mu..g/ml) of cadmium (Cd), a known embryotoxic trace element, through gestation. Maternal daily food and water consumption, total weight gain, maternal weight gain, and feed efficiency all decreased with increasing Cd consumption. Term fetal weight was significantly less than that of control subjects only in the group fed 100 ..mu..g Cd/ml drinking water. Total litter weight, however, gradually decreased with increasing Cd concentration due to reduced litter size. Fetal growth retardation was a result of decreased cell division (DNA) and cell growth (protein/DNA ratio). When dams were pair-fed the average daily amount of food consumed by those fed 100 ..mu..g Cd/ml drinking water, maternal weight gain and fetal weight, DNA, and protein/DNA ratio were increased, but not to control levels. Dietary zinc (Zn) supplementation (5.0 ..mu..g/ml drinking water) of Cd-fed dams increased maternal food consumption and fetal weight, DNA, and protein/DNA ratio to control levels. Fetal levels of Cd were extremely low (0.038 to 0.095 ..mu..g/gm fetus) and did not increase with increasing Cd consumption, while placental Cd increased more than 10-fold. Fetal Zn was decreased in Cd-fed dams, and Zn supplementation increased fetal Zn levels, but not to control levels.These results suggest that Cd-induced fetal growth retardation is an indirect rather than a direct effect, resulting from reduced maternal food consumption and metabolism. Since dietary Zn blocks these effects, Cd may be a result of induced Zn deficiency.

  5. Clustering and classical analysis of clinical and placental phenotypes in fetal growth restriction and constitutional fetal smallness.

    PubMed

    Stanek, Jerzy; Biesiada, Jacek

    2016-06-01

    This study aims to determine whether placental examination can be used to distinguish between pathologic fetal growth restriction (FGR) and constitutional fetal smallness. Data were extracted from a clinicoplacental database of high risk pregnancies during the period 1994-2013. These data were used to compare the 590 consecutive cases having birth weights below the 10th percentile with the 5201 remaining cases having gestational ages ≥20 weeks. The authors analyzed 20 clinical and 46 placental phenotypes using classical statistics, clustering analysis, and multidimensional scaling. Of the low-birth-weight babies, the following types of cases were compared: Four categories of placental phenotypes (those with features of poor uteroplacental perfusion, postuterine placental pathology, chronic inflammation, and a mixed category) better defined the presumably true FGR than did the clinical phenotypes. Maternal smoking and oligohydramnios were associated with fewer abnormal placental phenotypes than were maternal hypertensive diseases and abnormal Dopplers. Early-onset cases of fetal smallness clustered with placental features of poor uteroplacental perfusion, whereas late onset cases did not. Placental examination helps to retrospectively distinguish constitutionally small fetuses from those that are pathologically growth restricted. The latter correlate best with the clinical risk for FGR and with early-onset FGR. This correlation may have prognostic significance for the child and for future pregnancies, since hypoxic placental lesions can occur without clinical risk factors but with a tendency to recur in future pregnancies. PMID:27238719

  6. Placental Responses to Changes in the Maternal Environment Determine Fetal Growth

    PubMed Central

    Dimasuay, Kris Genelyn; Boeuf, Philippe; Powell, Theresa L.; Jansson, Thomas

    2016-01-01

    Placental responses to maternal perturbations are complex and remain poorly understood. Altered maternal environment during pregnancy such as hypoxia, stress, obesity, diabetes, toxins, altered nutrition, inflammation, and reduced utero-placental blood flow may influence fetal development, which can predispose to diseases later in life. The placenta being a metabolically active tissue responds to these perturbations by regulating the fetal supply of nutrients and oxygen and secretion of hormones into the maternal and fetal circulation. We have proposed that placental nutrient sensing integrates maternal and fetal nutritional cues with information from intrinsic nutrient sensing signaling pathways to balance fetal demand with the ability of the mother to support pregnancy by regulating maternal physiology, placental growth, and placental nutrient transport. Emerging evidence suggests that the nutrient-sensing signaling pathway mechanistic target of rapamycin (mTOR) plays a central role in this process. Thus, placental nutrient sensing plays a critical role in modulating maternal–fetal resource allocation, thereby affecting fetal growth and the life-long health of the fetus. PMID:26858656

  7. Prenatal maternal mental health and fetal growth restriction: a systematic review.

    PubMed

    Lewis, A J; Austin, E; Galbally, M

    2016-08-01

    Maternal mental disorders during pregnancy are associated with a range of adverse health outcomes for offspring. This systematic review examines studies reporting on the relationship between maternal depression, anxiety or stress during pregnancy and fetal growth measured during pregnancy using ultrasound biometry. A systematic search of PsycINFO, Medline, Scopus, Web of Science and Embase was conducted and 1575 records were identified, with nine studies meeting inclusion criteria gathering data from over 7000 participants. All studies measured depression, six examined anxiety and depression, and five examined all three exposures. The majority measured symptoms rather than clinically diagnosable disorder. Studies consistently reported significant associations between maternal mental health, particularly anxiety symptoms, and reduced fetal head growth. Other fetal growth parameters showed inconsistent findings. A number of studies suggest that cortisol dysregulation associated with maternal mental health may play a role in fetal growth restriction. However, heterogeneity in the timing of growth measurement, assessment measures used for mental health and inconsistencies in adjustment for confounders, limits the synthesis and interpretation of findings. Future studies should consider differences in the timing, intensity and duration of mental health symptoms over pregnancy and should employ diagnostic assessment of mental disorders. Fetal growth should be repeatedly measured and further work is needed to establish the biological mechanisms involved. PMID:26983652

  8. Fetal development

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/002398.htm Fetal development To use the sharing features on this page, ... Cunningham FG, Leveno KJ, Bloom SL, et al. Fetal growth and development. In: Cunningham FG, Leveno KL, Bloom SL, et ...

  9. Birth weight- and fetal weight-growth restriction: impact on neurodevelopment

    PubMed Central

    Streimish, Iris G.; Ehrenkranz, Richard A.; Allred, Elizabeth N.; O’Shea, T. Michael; Kuban, Karl C.K.; Paneth, Nigel; Leviton, Alan

    2013-01-01

    Background The newborn classified as growth-restricted on birth weight curves, but not on fetal weight curves, is classified prenatally as small for gestational age (SGA), but postnatally as appropriate for gestational age (AGA). Aims To see (1) to what extent the neurodevelopmental outcomes at 24 months corrected age differed among three groups of infants (those identified as SGA based on birth weight curves (B-SGA), those identified as SGA based on fetal weight curves only (F-SGA), and the referent group of infants considered AGA, (2) if girls and boys were equally affected by growth restriction, and (3) to what extent neurosensory limitations influenced what we found. Study design Observational cohort of births before the 28 week of gestation. Outcome measures: Mental Development Index (MDI) and Psychomotor Development Index (PDI) of the Bayley Scales of Infant Development II. Results B-SGA, but not F-SGA girls were at an increased risk of a PDI < 70 (OR=2.8; 95% CI: 1.5, 5.3) compared to AGA girls. B-SGA and F-SGA boys were not at greater risk of low developmental indices than AGA boys. Neurosensory limitations diminished associations among girls of B-SGA with low MDI, and among boys B-SGA and F-SGA with PDI < 70. Conclusions Only girls with the most severe growth restriction were at increased risk of neurodevelopmental impairment at 24 months corrected age in the total sample. Neurosensory limitations appear to interfere with assessing growth restriction effects in both girls and boys born preterm. PMID:22732241

  10. The role and interaction of imprinted genes in human fetal growth

    PubMed Central

    Moore, Gudrun E.; Ishida, Miho; Demetriou, Charalambos; Al-Olabi, Lara; Leon, Lydia J.; Thomas, Anna C.; Abu-Amero, Sayeda; Frost, Jennifer M.; Stafford, Jaime L.; Chaoqun, Yao; Duncan, Andrew J.; Baigel, Rachel; Brimioulle, Marina; Iglesias-Platas, Isabel; Apostolidou, Sophia; Aggarwal, Reena; Whittaker, John C.; Syngelaki, Argyro; Nicolaides, Kypros H.; Regan, Lesley; Monk, David; Stanier, Philip

    2015-01-01

    Identifying the genetic input for fetal growth will help to understand common, serious complications of pregnancy such as fetal growth restriction. Genomic imprinting is an epigenetic process that silences one parental allele, resulting in monoallelic expression. Imprinted genes are important in mammalian fetal growth and development. Evidence has emerged showing that genes that are paternally expressed promote fetal growth, whereas maternally expressed genes suppress growth. We have assessed whether the expression levels of key imprinted genes correlate with fetal growth parameters during pregnancy, either early in gestation, using chorionic villus samples (CVS), or in term placenta. We have found that the expression of paternally expressing insulin-like growth factor 2 (IGF2), its receptor IGF2R, and the IGF2/IGF1R ratio in CVS tissues significantly correlate with crown–rump length and birthweight, whereas term placenta expression shows no correlation. For the maternally expressing pleckstrin homology-like domain family A, member 2 (PHLDA2), there is no correlation early in pregnancy in CVS but a highly significant negative relationship in term placenta. Analysis of the control of imprinted expression of PHLDA2 gave rise to a maternally and compounded grand-maternally controlled genetic effect with a birthweight increase of 93/155 g, respectively, when one copy of the PHLDA2 promoter variant is inherited. Expression of the growth factor receptor-bound protein 10 (GRB10) in term placenta is significantly negatively correlated with head circumference. Analysis of the paternally expressing delta-like 1 homologue (DLK1) shows that the paternal transmission of type 1 diabetes protective G allele of rs941576 single nucleotide polymorphism (SNP) results in significantly reduced birth weight (−132 g). In conclusion, we have found that the expression of key imprinted genes show a strong correlation with fetal growth and that for both genetic and genomics data analyses

  11. Effect of maternal alcohol and nicotine intake, individually and in combination, on fetal growth in the rat

    SciTech Connect

    Leichter, J. )

    1991-03-15

    The effect of maternal ethanol and nicotine administration, separately and in combination, on fetal growth of rats was studied. Nicotine was administered by gavage for the entire gestational period. Alcohol was given in drinking water for 4 weeks prior to mating and 30% throughout gestation. Appropriate pair-fed and ad libitum control animals were included to separate the effect of ethanol and nicotine on the outcome of pregnancy from those produced by the confounding variables of malnutrition. Body weights of fetuses exposed to alcohol alone or in combination with nicotine were significantly lower than those of the pair-fed and ad libitum controls. However, the difference in fetal body weight between the alcohol plus nicotine and the alcohol alone group was not significant. Similarly, in the rats administered nicotine only, fetal weight was not significantly different compared to control animals. The results of this study indicate that maternal alcohol intake impairs fetal growth and nicotine does not, regardless whether it is administered separately or in combination with alcohol for the entire gestational period.

  12. Gestational Dietary Protein Is Associated with Sex Specific Decrease in Blood Flow, Fetal Heart Growth and Post-Natal Blood Pressure of Progeny

    PubMed Central

    2015-01-01

    Study Overview The incidence of adverse pregnancy outcomes is higher in pregnancies where the fetus is male. Sex specific differences in feto-placental perfusion indices identified by Doppler assessment have recently been associated with placental insufficiency and fetal growth restriction. This study aims to investigate sex specific differences in placental perfusion and to correlate these changes with fetal growth. It represents the largest comprehensive study under field conditions of uterine hemodynamics in a monotocous species, with a similar long gestation period to the human. Primiparous 14mo heifers in Australia (n=360) and UK (n=180) were either individually or group fed, respectively, diets with differing protein content (18, 14, 10 or 7% crude protein (CP)) from 60d prior to 98 days post conception (dpc). Fetuses and placentae were excised at 98dpc (n = 48). Fetal development an median uterine artery blood flow were assessed monthly from 36dpc until term using B-mode and Doppler ultrasonography. MUA blood flow to the male feto-placental unit increased in early pregnancy associated with increased fetal growth. Protein restriction before and shortly after conception (-60d up to 23dpc) increased MUA diameter and indices of velocity during late pregnancy, reduced fetal heart weight in the female fetus and increased heart rate at birth, but decreased systolic blood pressure at six months of age. Conclusion and Significance Sex specific differences both in feto-placental Doppler perfusion indices and response of these indices to dietary perturbations were observed. Further, maternal diet affected development of fetal cardiovascular system associated with altered fetal haemodynamics in utero, with such effects having a sex bias. The results from this study provide further insight into the gender specific circulatory differences present in the fetal period and developing cardiovascular system. PMID:25915506

  13. Syncytiotrophoblast Functions and Fetal Growth Restriction during Placental Malaria: Updates and Implication for Future Interventions

    PubMed Central

    Kidima, Winifrida B.

    2015-01-01

    Syncytiotrophoblast lines the intervillous space of the placenta and plays important roles in fetus growth throughout gestation. However, perturbations at the maternal-fetal interface during placental malaria may possibly alter the physiological functions of syncytiotrophoblast and therefore growth and development of the embryo in utero. An understanding of the influence of placental malaria on syncytiotrophoblast function is paramount in developing novel interventions for the control of placental pathology associated with placental malaria. In this review, we discuss how malaria changes syncytiotrophoblast function as evidenced from human, animal, and in vitro studies and, further, how dysregulation of syncytiotrophoblast function may impact fetal growth in utero. We also formulate a hypothesis, stemming from epidemiological observations, that nutrition may override pathogenesis of placental malaria-associated-fetal growth restriction. We therefore recommend studies on nutrition-based-interventional approaches for high placental malaria-risk women in endemic areas. More investigations on the role of nutrition on placental malaria pathogenesis are needed. PMID:26587536

  14. Thyroid hormone is required for growth adaptation to pressure load in the ovine fetal heart.

    PubMed

    Segar, Jeffrey L; Volk, Ken A; Lipman, Michael H B; Scholz, Thomas D

    2013-03-01

    Thyroid hormone exerts broad effects on the adult heart, but little is known regarding the role of thyroid hormone in the regulation of cardiac growth early in development and in response to pathophysiological conditions. To address this issue, we determined the effects of fetal thyroidectomy on cardiac growth and growth-related gene expression in control and pulmonary-artery-banded fetal sheep. Fetal thyroidectomy (THX) and/or placement of a restrictive pulmonary artery band (PAB) were performed at 126 ± 1 days of gestation (term, 145 days). Four groups of animals [n = 5-6 in each group; (i) control; (ii) fetal THX; (iii) fetal PAB; and (iv) fetal PAB + THX] were monitored for 1 week prior to being killed. Fetal heart rate was significantly lower in the two THX groups compared with the non-THX groups, while mean arterial blood pressure was similar among groups. Combined left and right ventricle free wall + septum weight, expressed per kilogram of fetal weight, was significantly increased in PAB (6.27 ± 0.85 g kg(-1)) compared with control animals (4.72 ± 0.12 g kg(-1)). Thyroidectomy significantly attenuated the increase in cardiac mass associated with PAB (4.94 ± 0.13 g kg(-1)), while THX alone had no detectable effect on heart mass (4.95 ± 0.27 g kg(-1)). The percentage of binucleated cardiomyocytes was significantly decreased in THX and PAB +THX groups (∼16%) compared with the non-THX groups (∼27%). No differences in levels of activated Akt, extracellular signal-regulated kinase or c-Jun N-terminal kinase were detected among the groups. Markers of cellular proliferation but not apoptosis or expression of growth-related genes were lower in the THX and THX+ PAB groups relative to thyroid-intact animals. These findings suggest that in the late-gestation fetal heart, thyroid hormone has important cellular growth functions in both physiological and pathophysiological states. Specifically, thyroid hormone is required for adaptive fetal cardiac growth in

  15. Parenteral Administration of l-Arginine Enhances Fetal Survival and Growth in Sheep Carrying Multiple Fetuses123

    PubMed Central

    Lassala, Arantzatzu; Bazer, Fuller W.; Cudd, Timothy A.; Datta, Sujay; Keisler, Duane H.; Satterfield, M. Carey; Spencer, Thomas E.; Wu, Guoyao

    2011-01-01

    The frequency of multiple fetuses has increased in human pregnancies due to assisted reproductive technologies. This translates into a greater proportion of premature and low-birth weight infants in the United States and worldwide. In addition, improvements in sheep breeding have resulted in new breeds with increased litter size but reduced fetal survival and birth weight. Currently, there are no treatments for preventing fetal growth restriction in humans or sheep (an established model for studying human fetal physiology) carrying multiple fetuses. In this work, Booroola Rambouillet ewes (FecB+/−) with 2–4 fetuses were fed a diet providing 100% of NRC-recommended nutrient requirements. Between d 100 and 121 of gestation, ewes received an i.v. bolus injection of either saline solution or 345 μmol arginine-HCl/kg body weight 3 times daily. The arginine treatment reduced (P < 0.05) the percentage of lambs born dead by 23% while increasing (P = 0.05) the percentage of lambs born alive by 59%. The i.v. administration of arginine enhanced (P < 0.05) the birth weights of quadruplets by 23% without affecting maternal body weight. The improved pregnancy outcome was associated with an increase in maternal plasma concentrations of arginine, ornithine, cysteine, and proline, as well as a decrease in circulating levels of ammonia and β-hydroxybutyrate. These novel results indicate that parenteral administration of arginine to prolific ewes ameliorated fetal mortality and growth retardation. Our findings provide support for experiments to assess the clinical use of arginine to enhance fetal growth and survival in women gestating multiple fetuses. PMID:21430253

  16. Effects of Atypical Patterns of Fetal Growth on Newborn (NBAS) Behavior.

    ERIC Educational Resources Information Center

    Lester, Barry M.; And Others

    1986-01-01

    Newborn infants showing anthropometric signs of atypical patterns of fetal growth were compared with infants of appropriate growth on the Neonatal Behavioral Assessment Scale and on recently developed supplementary items. The sample consisted of lower-socioeconomic-status families in San Juan, Puerto Rico, and included teenage and older mothers.…

  17. In utero glucocorticoid (GLC) exposure reduces fetal skeletal muscle growth in rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maternal undernutrition and stress expose the fetus to above normal levels of GLC and predispose to intrauterine growth restriction. The aim of this study was to determine if fetal GLC exposure impairs skeletal muscle growth independently of maternal undernutrition. Three groups (n=7/group) of timed...

  18. Sex differences in fetal growth responses to maternal height and weight

    PubMed Central

    Gotsch, Francesca; Kusanovic, Juan Pedro; Gomez, Ricardo; Nien, Jyh Kae; Frongillo, Edward A.; Romero, Roberto

    2012-01-01

    Sex differences in fetal growth have been reported, but how this happens remains to be described. It is unknown if fetal growth rates, a reflection of genetic and environmental factors, express sexually dimorphic sensitivity to the mother herself. This analysis investigated homogeneity of male and female growth responses to maternal height and weight. The study sample included 3495 uncomplicated singleton pregnancies followed longitudinally. Analytic models regressed fetal and neonatal weight on tertiles of maternal height and weight, and modification by sex was investigated (n=1814 males, n=1681 females) with birth gestational age, maternal parity and smoking as covariates. Sex modified the effects of maternal height and weight on fetal growth rates and birth weight. Among boys, tallest maternal height influenced fetal weight growth prior to 18 gestational weeks of age (p=0.006), pre-pregnancy maternal weight and BMI subsequently had influence (p<0.001); this was not found among girls. Additionally, interaction terms between sex, maternal height, and maternal weight identified that males were more sensitive to maternal weight among shorter mothers (p=0.003), and more responsive to maternal height among lighter mothers (p<=0.03), compared to females. Likewise, neonatal birth weight dimorphism varied by maternal phenotype. A male advantage of 60 grams occurred among neonates of the shortest and lightest mothers (p=0.08), compared to 150 and 191 grams among short and heavy mothers, and tall and light weight mothers, respectively (p=0.01). Sex differences in response to maternal size are underappreciated sources of variation in fetal growth studies and may reflect differential growth strategies. PMID:19950190

  19. The effects of maternal exercise on fetal oxygenation and feto-placental growth.

    PubMed

    Clapp, James F

    2003-09-22

    Sustained bouts of maternal exercise during pregnancy cause an acute reduction in oxygen and nutrient delivery to the placental site. The decreased flow also initiates a slight fall in intervillous and fetal pO2 which initiates a fetal sympathetic response. This, coupled with hemoconcentration and improved placental perfusion balance, maintains fetal tissue perfusion and oxygen uptake. Exercise training during pregnancy (regular bouts of sustained exercise) increases resting maternal (and perhaps fetal) plasma volume, intervillous space blood volume, cardiac output and placental function. These changes buffer the acute reductions in oxygen and nutrient delivery during exercise and probably increase 24 h nutrient delivery to the placental site. Thus, the effect of any given exercise regimen on fetal growth and size at birth is dependent on the type, frequency, intensity and duration of the exercise as well as the time point in the pregnancy when the exercise is performed. Maternal carbohydrate intake is yet another modifying factor. Beginning a moderate exercise regimen increases both anatomic markers of placental function and size at birth while maintaining a rigorous exercise regimen throughout pregnancy selectively reduces growth of the fetal fat organ and size at birth. Likewise, decreasing exercise performance in late-pregnancy increases size at birth while increasing exercise performance decreases it. Finally, the infants born of exercising women who eat carbohydrates which elevate 24 h blood glucose levels are large at birth irrespective of exercise performance. PMID:12965094

  20. Epidermal growth factor modulation of prostaglandins and nitrite biosynthesis in rat fetal membranes.

    PubMed

    Ribeiro, M L; Ogando, D; Farina, M; Franchi, A

    2004-01-01

    The production of prostaglandins (PGs) and nitric oxide (NO) by amnion tissue may play a significant role in parturition. It is thought that epidermal growth factor (EGF) may be one of the fetal signals that governs the initiation of labor. The aim of the present study was to investigate the effect of EGF in vivo on the PGs and nitrite production of rat fetal membranes. We have evaluated the regulation of PGs and nitrite production in rat fetal membranes ex vivo. The intra-uterine administration of EGF 500 ng in day 21 of pregnancy induced increases in PGE(2) (P<0.001) and PGF(2alpha) (P<0.01) compared to the control fetal membranes from pregnant rats on day 22. Also, this dose of EGF diminished nitrate production significantly (P<0.01). We found that fetal membranes at term (days 18-22 of gestation) expressed EGF-R. The NO donor, nitroprussiate 300 and 600 microM, elicited an inhibitory effect on the PGE(2) and PGF(2alpha) stimulated synthesis. On the other hand, indomethacin 10(-6) and 10(-7)M, a non-selective cyclooxygenase inhibitor, reverted the inhibitory effect exerted by EGF. Hence, rat fetal membranes were found to express epidermal growth factor receptors and, under the effect of EGF, PGs and nitrites production pathways interact probably to prevent a toxic effect caused by an exacerbated synthesis of these mediators. PMID:14643177

  1. Associations of Maternal Retinal Vasculature with Subsequent Fetal Growth and Birth Size

    PubMed Central

    Li, Ling-Jun; Aris, Izzuddin; Su, Lin Lin; Tint, Mya Thway; Cheung, Carol Yim-Lui; Ikram, M. Kamran; Gluckman, Peter; Godfrey, Keith M.; Tan, Kok Hian; Yeo, George; Yap, Fabian; Kwek, Kenneth; Saw, Seang-Mei; Chong, Yap-Seng; Wong, Tien-Yin; Lee, Yung Seng

    2015-01-01

    Objective We aimed to study the maternal retinal microvasculature at mid-trimester and its relationship with subsequent fetal growth and birth size. Methods We recruited 732 pregnant women aged 18-46 years in the first trimester with singleton pregnancies. All had retinal photography and fetal scan performed at 26-28 weeks gestation, and subsequent fetal scan at 32-34 weeks gestation. Infant anthropometric measurements were done at birth. Retinal microvasculature was measured using computer software from the retinal photographs. Results In multiple linear regression models, each 10 μm narrowing in maternal retinal arteriolar caliber was associated with decreases of 1.36 mm in fetal head circumference at 32-34 weeks gestation, as well as decreases of 1.50 mm and 2.30 mm in infant head circumference and birth length at delivery, respectively. Each standard deviation decrease in maternal retinal arteriolar fractal dimension was associated with decreases of 1.55 mm in fetal head circumference at 32-34 weeks gestation, as well as decreases of 1.08 mm and 46.42 g in infant head circumference and birth weight at delivery, respectively. Conclusions Narrower retinal arteriolar caliber and a sparser retinal vascular network in mothers, reflecting a suboptimal uteroplacental microvasculature during mid-pregnancy, were associated with poorer fetal growth and birth size. PMID:25909909

  2. A comparative analysis of prenatal care and fetal growth in eight South American countries.

    PubMed

    Woodhouse, Cristina; Lopez Camelo, Jorge; Wehby, George L

    2014-01-01

    There has been little work that comprehensively compared the relationship between prenatal care and infant health across multiple countries using similar data sources and analytical models. Such comparative analyses are useful for understanding the background of differences in infant health between populations. We evaluated the association between prenatal care visits and fetal growth measured by birth weight (BW) in grams or low birth weight (<2500 grams; LBW) adjusted for gestational age in eight South American countries using similarly collected data across countries and the same analytical models. OLS and logistic regressions were estimated adjusting for a large set of relevant infant, maternal, and household characteristics and birth year and hospital fixed effects. Birth data were acquired from 140 hospitals that are part of the Latin American Collaborative Study of Congenital Malformations (ECLAMC) network. The analytical sample included 56,014 live-born infants (∼69% of total sample) with complete data born without congenital anomalies in the years 1996-2011 in Brazil, Argentina, Chile, Venezuela, Ecuador, Colombia, Bolivia, and Uruguay. Prenatal care visits were significantly (at p<.05) and positively associated with BW and negatively associated with LBW for all countries. The OLS coefficients ranged from 9 grams per visit in Bolivia to 36 grams in Uruguay. The association with LBW was strongest for Chile (OR = 0.87 per visit) and lowest for Argentina and Venezuela (OR = 0.95). The association decreased in the recent decade compared to earlier years. Our findings suggest that estimates of association between prenatal care and fetal growth are population-specific and may not be generalizable to other populations. Furthermore, as one of the indicators for a country's healthcare system for maternal and child health, prenatal care is a highly variable indicator between countries in South America. PMID:24625630

  3. Compensatory Feto-Placental Upregulation of the Nitric Oxide System during Fetal Growth Restriction

    PubMed Central

    Pisaneschi, Silvia; Strigini, Francesca A. L.; Sanchez, Angel M.; Begliuomini, Silvia; Casarosa, Elena; Ripoli, Andrea; Ghirri, Paolo; Boldrini, Antonio; Fink, Bruno; Genazzani, Andrea R.; Coceani, Flavio; Simoncini, Tommaso

    2012-01-01

    Background Fetal Growth Restriction is often associated with a feto-placental vascular dysfunction conceivably involving endothelial cells. Our study aimed to verify this pathogenic role for feto-placental endothelial cells and, coincidentally, demonstrate any abnormality in the nitric oxide system. Methods Prenatal assessment of feto-placental vascular function was combined with measurement of nitric oxide (in the form of S-nitrosohemoglobin) and its nitrite byproduct, and of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine. Umbilical vein endothelial cells were also harvested to determine their gene profile. The study comprised term pregnancies with normal (n = 40) or small-for-gestational-age (n = 20) newborns, small-for-gestational-age preterm pregnancies (n = 15), and bi-chorial, bi-amniotic twin pregnancies with discordant fetal growth (n = 12). Results Umbilical blood nitrite (p<0.001) and S-nitrosohemoglobin (p = 0.02) rose with fetal growth restriction while asymmetric dimethylarginine decreased (p = 0.003). Nitrite rise coincided with an abnormal Doppler profile from umbilical arteries. Fetal growth restriction umbilical vein endothelial cells produced more nitrite and also exhibited reciprocal changes in vasodilator (upwards) and vasoconstrictor (downwards) transcripts. Elevation in blood nitrite and S-nitrosohemoglobin persisted postnatally in the fetal growth restriction offspring. Conclusion Fetal growth restriction is typified by increased nitric oxide production during pregnancy and after birth. This response is viewed as an adaptative event to sustain placental blood flow. However, its occurrence may modify the endothelial phenotype and may ultimately represent an element of risk for cardiovascular disease in adult life. PMID:23028913

  4. DOSE EFFECT OF GESTATIONAL ETHANOL EXPOSURE ON PLACENTATION AND FETAL GROWTH

    PubMed Central

    Gundogan, Fusun; Gilligan, Jeffrey; Qi, Wei; Chen, Eva; Naram, Rita; de la Monte, Suzanne M

    2015-01-01

    Introduction Prenatal ethanol exposure compromises fetal growth by impairing placentation. Invasive trophoblastic cells, which mediate placentation, express the insulin-IGF regulated gene, aspartyl-asparaginyl β-hydroxylase (ASPH), which has a critical role in cell motility and invasion. The aims of this study were to characterize effects of ethanol on trophoblastic cell motility, and assess ethanol dose -dependent impairments in placentation and fetal development. Methods Pregnant Long Evans dams were fed with isocaloric liquid diets containing 0%, 8%, 18% or 37% ethanol (caloric content) from gestation day (GD) 6 to GD18. Fetal development, placental morphology, density of invasive trophoblasts at the mesometrial triangle, as well as placental and mesometrial ASPH and Notch-1 protein expression were evaluated. Directional motility of control and ethanol-exposed HTR-8/SVneo cells was assessed by ATP Luminescence-Based assay. Results Severity of fetal growth impairment correlated with increasing doses of ethanol. Ethanol exposure produced dose-dependent alterations in branching morphogenesis at the labyrinthine zone, and inhibited physiological transformation of maternal arteries. ASPH and Notch-1 protein expression levels were reduced, corresponding with impairments in placentation. Discussion Prenatal ethanol exposure compromises fetal growth and placentation in a dose-responsive manner. Ethanol’s adverse effects on placental development are mediated by: 1) altered branching morphogenesis in labyrinthine zone; 2) suppression of invasive trophoblastic precursor cells; and 3) inhibition of trophoblastic cell adhesion and motility, corresponding with reduced ASPH and Notch-1 protein expression. PMID:25745824

  5. Organochlorine Compounds and Ultrasound Measurements of Fetal Growth in the INMA Cohort (Spain)

    PubMed Central

    Lopez-Espinosa, Maria-Jose; Murcia, Mario; Iñiguez, Carmen; Vizcaino, Esther; Costa, Olga; Fernández-Somoano, Ana; Basterrechea, Mikel; Lertxundi, Aitana; Guxens, Mònica; Gascon, Mireia; Goñi-Irigoyen, Fernando; Grimalt, Joan O.; Tardón, Adonina; Ballester, Ferran

    2015-01-01

    Background Several studies have reported decreases in birth size associated with exposure to organochlorine compounds (OCs), but uncertainties remain regarding the critical windows of prenatal exposure and the effects on fetal body segments. Objective We examined the relationship between prenatal OC concentrations and fetal anthropometry. Methods We measured 4,4´-dichlorodiphenyldichloroethylene (4,4´-DDE), hexachlorobenzene (HCB), and polychlorinated biphenyl (PCB) congeners (138, 153, and 180) in 2,369 maternal and 1,140 cord serum samples in four Spanish cohorts (2003–2008). We used linear mixed models to obtain longitudinal growth curves for estimated fetal weight (EFW), abdominal circumference (AC), biparietal diameter (BPD), and femur length (FL) adjusted by parental and fetal characteristics. We calculated standard deviation (SD) scores of growth at 0–12, 12–20, and 20–34 weeks of gestation as well as size at gestational week 34 for the four parameters. We studied the association between OCs and the fetal outcomes by cohort-specific linear models and subsequent meta-analyses. Results PCBs were associated with a reduction in AC up to mid-pregnancy, and BPD and FL from gestational week 20 onward. An inverse association was also found between HCB and AC growth in early pregnancy. The reduction of these parameters ranged from –4% to –2% for a doubling in the OC concentrations. No association between 4,4´-DDE and fetal growth was observed. Conclusions To our knowledge, this is the first study to report an association between prenatal exposure to some PCBs and HCB and fetal growth: AC during the first two trimesters of pregnancy, and BPD and FL later in pregnancy. Citation Lopez-Espinosa MJ, Murcia M, Iñiguez C, Vizcaino E, Costa O, Fernández-Somoano A, Basterrechea M, Lertxundi A, Guxens M, Gascon M, Goñi-Irigoyen F, Grimalt JO, Tardón A, Ballester F. 2016. Organochlorine compounds and ultrasound measurements of fetal growth in the INMA cohort

  6. The effect of copper deficiency on fetal growth and liver anti-oxidant capacity in the Cohen diabetic rat model

    SciTech Connect

    Ergaz, Zivanit; Shoshani-Dror, Dana; Guillemin, Claire; Neeman-azulay, Meytal; Fudim, Liza; Weksler-Zangen, Sarah; Stodgell, Christopher J.; Miller, Richard K.; Ornoy, Asher

    2012-12-01

    High sucrose low copper diet induces fetal growth restriction in the three strains of the Cohen diabetic rats: an inbred copper deficient resistant (CDr), an inbred copper deficient sensitive (CDs that become diabetic on high sucrose low copper diet -HSD) and an outbred Wistar derived Sabra rats. Although those growth restricted fetuses also exhibit increased oxidative stress, antioxidants do not restore normal growth. In the present study, we evaluated the role of copper deficiency in the HSD induced fetal growth restriction by adding to the drinking water of the rats 1 ppm or 2 ppm of copper throughout their pregnancy. Fetal and placental growth in correlation with fetal liver copper content and anti-oxidant capacity was evaluated on day 21 of pregnancy. HSD compared to regular chow induced fetal growth restriction, which was most significant in the Cohen diabetic sensitive animals. The addition of 1 ppm and 2 ppm copper to the drinking water normalized fetal growth in a dose dependent manner and reduced the degree of hyperglycemia in the diabetes sensitive rats. The CDs fetuses responded to the HSD with lower catalase like activity, and less reduced superoxide dismutase levels compared to the Sabra strain, and had high malondialdehyde levels even when fed regular chow. Immunostaining was higher for nitrotyrosine among the CDr and higher for hypoxia factor 1 α among the CDs. We conclude that in our model of dietary-induced fetal growth restriction, copper deficiency plays a major etiologic role in the decrease of fetal growth and anti-oxidant capacity. -- Highlights: ► High sucrose low copper diet restricted fetal growth in the Cohen diabetic rat model ► Maternal copper blood levels directly correlated with fetal liver copper content ► Copper supplementation decreased embryonic resorption in the inbred strains ► Copper supplementation reduced hyperglycemia in the sucrose sensitive inbred strain ► Copper supplementation alleviated growth restriction and

  7. ANG II modulation of cardiac growth and remodeling in immature fetal sheep.

    PubMed

    Sandgren, Jeremy; Scholz, Thomas D; Segar, Jeffrey L

    2015-06-01

    ANG II increases fetal blood pressure and stimulates fetal heart growth; however, little is known regarding its direct effects on cardiomyocytes in vivo. We sought to determine whether ANG II stimulates heart growth and cardiomyocyte hypertrophy and/or hyperplasia in utero in the immature fetal heart independent of the effects on cardiac afterload. In twin gestation, fetal sheep at ∼100 days gestation (term 145 days), one fetus received a chronic (6 days) infusion of ANG II alone (50 μg·kg(-1)·min(-1)) or ANG II plus nitroprusside (NTP) to attenuate the increase in blood pressure; noninstrumented twins served as controls. ANG II alone, but not ANG II + NTP resulted in a significant increase in heart mass (left and right ventricle + septum, corrected for body weight) compared with controls. ANG II, but not ANG II+NTP, also significantly increased cardiomyocyte area compared with control and increased the percentage of binucleated myocytes. ANG II with or without concomitant infusion of NTP increased cardiac PCNA expression, a marker of proliferation. Steady-state protein expression of terminal mitogen-activated protein kinases, cyclin B1, cyclin E1, and p21 were similar among groups. We conclude that in vivo, ANG II increases fetal cardiac mass via cardiomyocyte hypertrophy, differentiation, and to a lesser extent hyperplasia. The effects of ANG II on hypertrophy appear dependent upon the increase in blood pressure (mechanical load), whereas effects on proliferation are load-independent. PMID:25810382

  8. Screening for fetal growth restriction with universal third trimester ultrasonography in nulliparous women in the Pregnancy Outcome Prediction (POP) study: a prospective cohort study

    PubMed Central

    Sovio, Ulla; White, Ian R; Dacey, Alison; Pasupathy, Dharmintra; Smith, Gordon C S

    2015-01-01

    Summary Background Fetal growth restriction is a major determinant of adverse perinatal outcome. Screening procedures for fetal growth restriction need to identify small babies and then differentiate between those that are healthy and those that are pathologically small. We sought to determine the diagnostic effectiveness of universal ultrasonic fetal biometry in the third trimester as a screening test for small-for-gestational-age (SGA) infants, and whether the risk of morbidity associated with being small differed in the presence or absence of ultrasonic markers of fetal growth restriction. Methods The Pregnancy Outcome Prediction (POP) study was a prospective cohort study of nulliparous women with a viable singleton pregnancy at the time of the dating ultrasound scan. Women participating had clinically indicated ultrasonography in the third trimester as per routine clinical care and these results were reported as usual (selective ultrasonography). Additionally, all participants had research ultrasonography, including fetal biometry at 28 and 36 weeks' gestational age. These results were not made available to participants or treating clinicians (universal ultrasonography). We regarded SGA as a birthweight of less than the 10th percentile for gestational age and screen positive for SGA an ultrasonographic estimated fetal weight of less than the 10th percentile for gestational age. Markers of fetal growth restriction included biometric ratios, utero-placental Doppler, and fetal growth velocity. We assessed outcomes for consenting participants who attended research scans and had a livebirth at the Rosie Hospital (Cambridge, UK) after the 28 weeks' research scan. Findings Between Jan 14, 2008, and July 31, 2012, 4512 women provided written informed consent of whom 3977 (88%) were eligible for analysis. Sensitivity for detection of SGA infants was 20% (95% CI 15–24; 69 of 352 fetuses) for selective ultrasonography and 57% (51–62; 199 of 352 fetuses) for universal

  9. MARKERS OF INDIVIDUAL SUSCEPTIBILITY AND OUTCOME RELATED TO FETAL AND INFANT GROWTH AND DEVELOPMENT

    EPA Science Inventory

    To evaluate whether exposures to environmental toxins and psychological stress were related to impaired fetal growth or other adverse pregnancy outcomes, we established a prospective epidemiologic study of 187 women who were pregnant and at or near the World Trade Center (...

  10. Timing and trajectories of fetal growth related to cognitive development in childhood.

    PubMed

    von Ehrenstein, Ondine S; Mikolajczyk, Rafael T; Zhang, Jun

    2009-12-01

    The authors investigated timing and trajectories of fetal growth in relation to childhood development in the National Institute of Child Health and Human Development-Scandinavian Study of Successive Small-for-Gestational Age Births (1986-1988) (n = 1,059). Fetal size was assessed by ultrasound at 17, 25, and 33 gestational weeks and at birth. Bayley Scales of Infant Development and the Wechsler Preschool and Primary Scale of Intelligence-Revised tests were conducted at ages 1 and 5 years, respectively, producing mental and psychomotor development indexes and verbal and performance intelligence quotients. Relative fetal size was calculated as a standard deviation score at each data point; growth trajectories were explored with longitudinal mixture models. Fetal size at 17, 25, and 33 weeks was positively associated with mental development index; larger size at 33 weeks and at birth was associated with higher verbal intelligence quotient scores (2.61, 95% confidence interval: 1.06, 4.15 and 1.90, 95% confidence interval: 0.67, 3.13 increase per 1 standard deviation score, respectively); findings were similar for performance intelligence quotient. Seven trajectories were identified; scores were lower for "small" and "medium-to-small" trajectories than for "medium" and "big" (representing normal size) trajectories: mental development index (P < 0.01), performance intelligence quotient (P < 0.001), and verbal intelligence quotient (P < 0.001). Overall, larger fetal size in the second and third trimesters was positively associated with childhood development. Fetal growth trajectories may matter beyond birth. PMID:19889710

  11. Maternal Serum Analytes as Predictors of Fetal Growth Restriction with Different Degrees of Placental Vascular Dysfunction.

    PubMed

    Blitz, Matthew J; Rochelson, Burton; Vohra, Nidhi

    2016-06-01

    Abnormal levels of maternal serum analytes have been associated with fetal growth restriction (FGR) and preeclampsia secondary to placental vascular dysfunction. Accurately identifying the FGR fetuses at highest risk for adverse outcomes remains challenging. Placental function can be assessed by Doppler analysis of the maternal and fetal circulation. Although the combination of multiple abnormal maternal serum analytes and abnormal Doppler findings is strongly associated with adverse outcomes, the predictive value remains too low to be used as a screening test in a low-risk population. Stratification of cases based on the severity of Doppler abnormalities may improve predictive models. PMID:27235917

  12. Maternal Administration of Sildenafil Citrate Alters Fetal and Placental Growth and Fetal-Placental Vascular Resistance in the Growth-Restricted Ovine Fetus.

    PubMed

    Oyston, Charlotte; Stanley, Joanna L; Oliver, Mark H; Bloomfield, Frank H; Baker, Philip N

    2016-09-01

    Intrauterine growth restriction (IUGR) causes short- and long-term morbidity. Reduced placental perfusion is an important pathogenic component of IUGR; substances that enhance vasodilation in the uterine circulation, such as sildenafil citrate (sildenafil), may improve placental blood flow and fetal growth. This study aimed to examine the effects of sildenafil in the growth-restricted ovine fetus. Ewes carrying singleton pregnancies underwent insertion of vascular catheters, and then, they were randomized to receive uterine artery embolization (IUGR) or to a control group. Ewes in the IUGR group received a daily infusion of sildenafil (IUGR+SC; n=10) or vehicle (IUGR+V; n=8) for 21 days. The control group received no treatment (n=9). Umbilical artery blood flow was measured using Doppler ultrasound and the resistive index (RI) calculated. Fetal weight, biometry, and placental weight were obtained at postmortem after treatment completion. Umbilical artery RI in IUGR+V fell less than in controls; the RI of IUGR+SC was intermediate to that of the other 2 groups (mean±SEM for control versus IUGR+V versus IUGR+SC: ∆RI, 0.09±0.03 versus -0.01±0.02 versus 0.03±0.02; F(2, 22)=4.21; P=0.03). Compared with controls, lamb and placental weights were reduced in IUGR+V but not in IUGR+SC (control versus IUGR+V versus IUGR+SC: fetal weight, 4381±247 versus 3447±235 versus 3687±129 g; F(2, 24)=5.49; P=0.01 and placental weight: 559.7±35.0 versus 376.2±32.5 versus 475.2±42.5 g; F(2, 24)=4.64; P=0.01). Sildenafil may be a useful adjunct in the management of IUGR. An increase in placental weight and fall in fetal-placental resistance suggests that changes to growth are at least partly mediated by changes to placental growth rather than alterations in placental efficiency. PMID:27432857

  13. Prenatal Exposure to NO2 and Ultrasound Measures of Fetal Growth in the Spanish INMA Cohort

    PubMed Central

    Iñiguez, Carmen; Esplugues, Ana; Sunyer, Jordi; Basterrechea, Mikel; Fernández-Somoano, Ana; Costa, Olga; Estarlich, Marisa; Aguilera, Inmaculada; Lertxundi, Aitana; Tardón, Adonina; Guxens, Mònica; Murcia, Mario; Lopez-Espinosa, Maria-Jose; Ballester, Ferran

    2015-01-01

    Background Air pollution exposure during pregnancy has been associated with impaired fetal growth. However, few studies have measured fetal biometry longitudinally, remaining unclear as to whether there are windows of special vulnerability. Objective The aim was to investigate the impact of nitrogen dioxide (NO2) exposure on fetal and neonatal biometry in the Spanish INMA study. Methods Biparietal diameter (BPD), femur length (FL), abdominal circumference (AC), and estimated fetal weight (EFW) were evaluated for up to 2,478 fetuses in each trimester of pregnancy. Size at 12, 20, and 34 weeks of gestation and growth between these points, as well as anthropometry at birth, were assessed by SD scores derived using cohort-specific growth curves. Temporally adjusted land-use regression was used to estimate exposure to NO2 at home addresses for up to 2,415 fetuses. Associations were investigated by linear regression in each cohort and subsequent meta-analysis. Results A 10-μg/m3 increase in average exposure to NO2 during weeks 0–12 was associated with reduced growth at weeks 0–12 in AC (–2.1%; 95% CI: –3.7, –0.6) and EFW (–1.6%; 95% CI: –3.0, –0.3). The same exposure was inversely associated with reduced growth at weeks 20–34 in BPD (–2.6%; 95% CI: –3.9, –1.2), AC (–1.8%; 95% CI: –3.3, –0.2), and EFW (–2.1%; 95% CI: –3.7, –0.2). A less consistent pattern of association was observed for FL. The negative association of this exposure with BPD and EFW was significantly stronger in smoking versus nonsmoking mothers. Conclusions Maternal exposure to NO2 in early pregnancy was associated with reduced fetal growth based on ultrasound measures of growth during pregnancy and measures of size at birth. Citation Iñiguez C, Esplugues A, Sunyer J, Basterrechea M, Fernández-Somoano A, Costa O, Estarlich M, Aguilera I, Lertxundi A, Tardón A, Guxens M, Murcia M, Lopez-Espinosa MJ, Ballester F, on behalf of the INMA Project. 2016. Prenatal exposure

  14. Chronic Protein Restriction in Mice Impacts Placental Function and Maternal Body Weight before Fetal Growth

    PubMed Central

    Barbeito-Andrés, Jimena; Klenin, Natasha; Cross, James C.; Hallgrímsson, Benedikt

    2016-01-01

    Mechanisms of resource allocation are essential for maternal and fetal survival, particularly when the availability of nutrients is limited. We investigated the responses of feto-placental development to maternal chronic protein malnutrition to test the hypothesis that maternal low protein diet produces differential growth restriction of placental and fetal tissues, and adaptive changes in the placenta that may mitigate impacts on fetal growth. C57BL/6J female mice were fed either a low-protein diet (6% protein) or control isocaloric diet (20% protein). On embryonic days E10.5, 17.5 and 18.5 tissue samples were prepared for morphometric, histological and quantitative RT-PCR analyses, which included markers of trophoblast cell subtypes. Potential endocrine adaptations were assessed by the expression of Prolactin-related hormone genes. In the low protein group, placenta weight was significantly lower at E10.5, followed by reduction of maternal weight at E17.5, while the fetuses became significantly lighter no earlier than at E18.5. Fetal head at E18.5 in the low protein group, though smaller than controls, was larger than expected for body size. The relative size and shape of the cranial vault and the flexion of the cranial base was affected by E17.5 and more severely by E18.5. The junctional zone, a placenta layer rich in endocrine and energy storing glycogen cells, was smaller in low protein placentas as well as the expression of Pcdh12, a marker of glycogen trophoblast cells. Placental hormone gene Prl3a1 was altered in response to low protein diet: expression was elevated at E17.5 when fetuses were still growing normally, but dropped sharply by E18.5 in parallel with the slowing of fetal growth. This model suggests that nutrients are preferentially allocated to sustain fetal and brain growth and suggests the placenta as a nutrient sensor in early gestation with a role in mitigating impacts of poor maternal nutrition on fetal growth. PMID:27018791

  15. Chronic Protein Restriction in Mice Impacts Placental Function and Maternal Body Weight before Fetal Growth.

    PubMed

    Gonzalez, Paula N; Gasperowicz, Malgorzata; Barbeito-Andrés, Jimena; Klenin, Natasha; Cross, James C; Hallgrímsson, Benedikt

    2016-01-01

    Mechanisms of resource allocation are essential for maternal and fetal survival, particularly when the availability of nutrients is limited. We investigated the responses of feto-placental development to maternal chronic protein malnutrition to test the hypothesis that maternal low protein diet produces differential growth restriction of placental and fetal tissues, and adaptive changes in the placenta that may mitigate impacts on fetal growth. C57BL/6J female mice were fed either a low-protein diet (6% protein) or control isocaloric diet (20% protein). On embryonic days E10.5, 17.5 and 18.5 tissue samples were prepared for morphometric, histological and quantitative RT-PCR analyses, which included markers of trophoblast cell subtypes. Potential endocrine adaptations were assessed by the expression of Prolactin-related hormone genes. In the low protein group, placenta weight was significantly lower at E10.5, followed by reduction of maternal weight at E17.5, while the fetuses became significantly lighter no earlier than at E18.5. Fetal head at E18.5 in the low protein group, though smaller than controls, was larger than expected for body size. The relative size and shape of the cranial vault and the flexion of the cranial base was affected by E17.5 and more severely by E18.5. The junctional zone, a placenta layer rich in endocrine and energy storing glycogen cells, was smaller in low protein placentas as well as the expression of Pcdh12, a marker of glycogen trophoblast cells. Placental hormone gene Prl3a1 was altered in response to low protein diet: expression was elevated at E17.5 when fetuses were still growing normally, but dropped sharply by E18.5 in parallel with the slowing of fetal growth. This model suggests that nutrients are preferentially allocated to sustain fetal and brain growth and suggests the placenta as a nutrient sensor in early gestation with a role in mitigating impacts of poor maternal nutrition on fetal growth. PMID:27018791

  16. Fetal, neonatal, infant, and child international growth standards: an unprecedented opportunity for an integrated approach to assess growth and development.

    PubMed

    Garza, Cutberto

    2015-07-01

    The recent publication of fetal growth and gestational age-specific growth standards by the International Fetal and Newborn Growth Consortium for the 21st Century Project and the previous publication by the WHO of infant and young child growth standards based on the WHO Multicentre Growth Reference Study enable evaluations of growth from ∼9 wk gestation to 5 y. The most important features of these projects are the prescriptive approach used for subject selection and the rigorous testing of the assertion that growth is very similar among geographically and ethnically diverse nonisolated populations when health, nutrition, and other care needs are met and the environment imposes minimal constraints on growth. Both studies documented that with adequate controls, the principal source of variability in growth during gestation and early childhood resides among individuals. Study sites contributed much less to observed variability. The agreement between anthropometric measurements common to both studies also is noteworthy. Jointly, these studies provide for the first time, to my knowledge, a conceptually consistent basis for worldwide and localized assessments and comparisons of growth performance in early life. This is an important contribution to improving the health care of children across key periods of growth and development, especially given the appropriate interest in pursuing "optimal" health in the "first 1000 d," i.e., the period covering fertilization/implantation, gestation, and postnatal life to 2 y of age. PMID:26178022

  17. Indicated Prevention of Fetal Alcohol Spectrum Disorders in South Africa: Effectiveness of Case Management.

    PubMed

    de Vries, Marlene M; Joubert, Belinda; Cloete, Marise; Roux, Sumien; Baca, Beth A; Hasken, Julie M; Barnard, Ronel; Buckley, David; Kalberg, Wendy O; Snell, Cudore L; Marais, Anna-Susan; Seedat, Soraya; Parry, Charles D H; May, Philip A

    2016-01-01

    In the Western Cape Province of South Africa (ZA) a subculture of binge drinking produces the highest global documented prevalence of fetal alcohol spectrum disorders (FASD). FASD prevention research activities in ZA use the Comprehensive Prevention approach from the United States Institute of Medicine. Case management (CM) was delivered as a method of indicated prevention to empower heavy drinking pregnant women to achieve cessation or a reduction in drinking. CM activities incorporated life management, Motivational Interviewing (MI) techniques and the Community Reinforcement Approach (CRA). Data were collected at baseline, 6, 12 and 18 months. Mean drinking decreases 6 months into CM; but overall alcohol consumption rose significantly over time to levels higher than baseline at 12 and 18 months. Alcohol consumption drops significantly from before pregnancy to the second and third trimesters. AUDIT scores indicate that problematic drinking decreases significantly even after the vulnerable fetus/baby was born. CM significantly increases client happiness, which correlates with reduced weekend drinking. CM was successful for women with high-risk drinking behaviour, and was effective in helping women stop drinking, or drink less, while pregnant, reducing the risk of FASD. PMID:26703708

  18. Indicated Prevention of Fetal Alcohol Spectrum Disorders in South Africa: Effectiveness of Case Management

    PubMed Central

    de Vries, Marlene M.; Joubert, Belinda; Cloete, Marise; Roux, Sumien; Baca, Beth A.; Hasken, Julie M.; Barnard, Ronel; Buckley, David; Kalberg, Wendy O.; Snell, Cudore L.; Marais, Anna-Susan; Seedat, Soraya; Parry, Charles D. H.; May, Philip A.

    2015-01-01

    In the Western Cape Province of South Africa (ZA) a subculture of binge drinking produces the highest global documented prevalence of fetal alcohol spectrum disorders (FASD). FASD prevention research activities in ZA use the Comprehensive Prevention approach from the United States Institute of Medicine. Case management (CM) was delivered as a method of indicated prevention to empower heavy drinking pregnant women to achieve cessation or a reduction in drinking. CM activities incorporated life management, Motivational Interviewing (MI) techniques and the Community Reinforcement Approach (CRA). Data were collected at baseline, 6, 12 and 18 months. Mean drinking decreases 6 months into CM; but overall alcohol consumption rose significantly over time to levels higher than baseline at 12 and 18 months. Alcohol consumption drops significantly from before pregnancy to the second and third trimesters. AUDIT scores indicate that problematic drinking decreases significantly even after the vulnerable fetus/baby was born. CM significantly increases client happiness, which correlates with reduced weekend drinking. CM was successful for women with high-risk drinking behaviour, and was effective in helping women stop drinking, or drink less, while pregnant, reducing the risk of FASD. PMID:26703708

  19. Vitamin B12: one carbon metabolism, fetal growth and programming for chronic disease.

    PubMed

    Rush, E C; Katre, P; Yajnik, C S

    2014-01-01

    This review brings together human and animal studies and reviews that examine the possible role of maternal vitamin B12 (B12) on fetal growth and its programming for susceptibility to chronic disease. A selective literature review was undertaken to identify studies and reviews that investigate these issues, particularly in the context of a vegetarian diet that may be low in B12 and protein and high in carbohydrate. Evidence is accumulating that maternal B12 status influences fetal growth and development. Low maternal vitamin B12 status and protein intake are associated with increased risk of neural tube defect, low lean mass and excess adiposity, increased insulin resistance, impaired neurodevelopment and altered risk of cancer in the offspring. Vitamin B12 is a key nutrient associated with one carbon metabolic pathways related to substrate metabolism, synthesis and stability of nucleic acids and methylation of DNA which regulates gene expression. Understanding of factors regulating maternal-fetal one carbon metabolism and its role in fetal programming of non communicable diseases could help design effective interventions, starting with maternal nutrition before conception. PMID:24219896

  20. Ultrasonographic assessment of fetal growth in miniature "Shiba" goats (Capra hircus).

    PubMed

    Kandiel, Mohamed M M; Watanabe, Gen; Taya, Kazuyoshi

    2015-11-01

    The aim of the present study was to monitor fetal growth in relation to gestational stage to generate formulae which could be used to estimate fetal age in goats. Eight miniature Shiba goats (Capra hircus) were examined weekly by transrectal and transabdominal ultrasound scanning during the gestation period between Day 21 and 126 days of gestation. For accurate judgment, all fetometric parameters were measured at least three times per one examination for each animal. Quantification of the growth of the fetus allowed the development of a number of predictors of fetal age. Low correlations were associated with measurement of the chest diameter (R(2)=0.869), trunk diameter (R(2)=0.8969), tibia length (R(2)=0.8662) and placentome diameter (R(2)=0.8999). Moderate correlation was assessed by calculation of the length of six successive lumbar vertebrae (R(2)=0.9296), femur length (R(2)=0.9278), heart axis length (R(2)=0.9382 and 0.9589; for the longitudinal and transverse axis, respectively), occipitonasal length (R(2)=0.9527), umbilical cord diameter (R(2)=0.9119) and orbit diameter (R(2)=0.9239). A high correlation was estimated in investigating the length of six successive thoracic vertebrae (R(2)=0.9674), braincase diameter (R(2)=0.9831) and crown rump length (R(2)=0.9848). In conclusion, the intrauterine fetal biometry estimation through ultrasound might be useful to predict the accurate gestational age in miniature goats. PMID:26427952

  1. Fetal calf serum-mediated inhibition of neurite growth from ciliary ganglion neurons in vitro.

    PubMed

    Davis, G E; Skaper, S D; Manthorpe, M; Moonen, G; Varon, S

    1984-01-01

    Embryonic chick ciliary ganglion (CG) neurons cultured in fetal calf serum-containing medium have been previously reported to extend neurites on polyornithine (PORN) substrata precoated with a neurite-promoting factor (PNPF) from rat schwannoma-conditioned medium. On PORN substrata alone, however, no neuritic growth occurred. This was interpreted as evidence that PORN was an incompetent substratum for ciliary neuritic growth. In this study, we now find that an untreated PORN substratum allows neuritic growth in serum-free defined medium. When PNPF was added to PORN, a more rapid and extensive neuritic response occurred. After 5 hr of culture, a 60% neuritic response occurred on PNPF/PORN, whereas no neurons initiated neurites until 10-12 hr on PORN. The inhibitory effect of fetal calf serum noted above on PORN could be obtained in part by pretreating the substratum with serum for 1 hr. Maximal inhibitory effects in the PORN pretreatment were achieved after 30 min and were not further improved by treatments up to 4 hr. Bovine serum albumin was also found to inhibit neurite growth on PORN to about 60% of the inhibition obtained by an equivalent amount of serum protein. Fetal calf serum was shown to cause a 15% reduction in the percentage of neurons bearing neurites after its addition to 18-hr serum-free PORN cultures and to cause statistically significant reductions in neurite lengths measured 2 hr later. PMID:6481819

  2. Site-specific IGFBP-1 hyper-phosphorylation in fetal growth restriction: clinical and functional relevance.

    PubMed

    Abu Shehab, Majida; Khosravi, Javad; Han, Victor K M; Shilton, Brian H; Gupta, Madhulika B

    2010-04-01

    Phosphorylation enhances IGFBP-1 binding to IGF-I, thereby limiting the bioavailability of IGF-I that may be important in fetal growth. Our goal in this study was to determine whether changes in site-specific IGFBP-1 phosphorylation were unique to fetal growth restriction. To establish a link, we compared IGFBP-1 phosphorylation (sites and degree) in amniotic fluid from FGR (N = 10) and controls (N = 12). The concentration of serine phosphorylated IGFBP-1 showed a negative correlation with birth weight in FGR (P = 0.049). LC-MS/MS analysis revealed all four previously identified phosphorylation sites (Ser98, Ser101, Ser119, and Ser169) to be common to FGR and control groups. Relative phosphopeptide intensities (LC-MS) between FGR and controls demonstrated 4-fold higher intensity for Ser101 (P = 0.026), 7-fold for Ser98/Ser101 (P = 0.02), and 23-fold for Ser169 (P = 0.002) in the FGR group. Preliminary BIAcore data revealed 4-fold higher association and 1.7-fold lower dissociation constants for IGFBP-1/IGF-I in FGR. A structural model of IGFBP-1 bound to IGF-I indicates that all the phosphorylation sites are on relatively mobile regions of the IGFBP-1 sequence. Residues Ser98, Ser101, and Ser169 are close to structured regions that are involved in IGF-I binding and, therefore, could potentially make direct contact with IGF-I. On the other hand, residue Ser119 is in the middle of the unstructured linker that connects the N- and C-terminal domains of IGFBP-1. The model is consistent with the assumption that residues Ser98, Ser101, and Ser169 could directly interact with IGF-I, and therefore phosphorylation at these sites could change IGF-I interactions. We suggest that site-specific increase in IGFBP-1 phosphorylation limits IGF-I bioavailability, which directly contributes to the development of FGR. This study delineates the potential role of higher phosphorylation of IGFBP-1 in FGR and provides the basis to substantiate these findings with larger sample size. PMID

  3. Infant Symbolic Play as an Early Indicator of Fetal Alcohol-Related Deficit

    PubMed Central

    Molteno, Christopher D.; Jacobson, Joseph L.; Carter, R. Colin; Jacobson, Sandra W.

    2010-01-01

    Infant symbolic play was examined in relation to prenatal alcohol exposure and socioenvironmental background and to predict which infants met criteria for fetal alcohol syndrome (FAS) at 5 years. 107 Cape Coloured, South African infants born to heavy drinking mothers and abstainers/light drinkers were recruited prenatally. Complexity of play, socio-demographic and psychological correlates of maternal alcohol use, and quality of parenting were assessed at 13 months, and IQ and FAS diagnosis at 5 years. The effect of drinking on spontaneous play was not significant after control for social environment. By contrast, prenatal alcohol and quality of parenting related independently to elicited play. Elicited play predicted 5-year Digit Span and was poorer in infants subsequently diagnosed with FAS/partial FAS and in nonsyndromal heavily exposed infants, compared with abstainers/light drinkers. Thus, symbolic play may provide an early indicator of risk for alcohol-related deficits. The independent effects of prenatal alcohol and quality of parenting suggest that infants whose symbolic play is adversely affected by alcohol exposure may benefit from stimulation from a responsive caregiver. PMID:20953338

  4. Exposure to ergot alkaloids during gestation reduces fetal growth in sheep

    PubMed Central

    Duckett, Susan K.; Andrae, John G.; Pratt, Scott L.

    2014-01-01

    Tall fescue [Lolium arundinaceum (Schreb.) Darbysh; Schedonorus phoenix (Scop.) Holub] is the primary cool season perennial grass in the eastern U.S. Most tall fescue contains an endophyte (Neotyphodium coenophialum), which produces ergot alkaloids that cause vasoconstriction and could restrict blood flow to the fetus in pregnant animals. The objective of this study was to examine fetal growth during maternal exposure to ergot alkaloids during gestation. Pregnant ewes (n = 16) were randomly assigned to one of two dietary treatments: (1) endophyte-infected (N. coenophialum) tall fescue seed (E+; 0.8 ug of ergovaline /g diet DM) and (2) endophyte-free tall fescue seed (E−; 0.0 ug of ergovaline/g diet DM). Birth weight of lambs was reduced by 37% for E+ compared to E−. Organ and muscle weights were also lighter for E+ than E−. Exposure to ergot alkaloids in utero reduces fetal growth and muscle development. PMID:25191653

  5. Exposure to Ergot Alkaloids During Gestation Reduces Fetal Growth in Sheep

    NASA Astrophysics Data System (ADS)

    Duckett, Susan; Pratt, Scott; Andrae, John

    2014-08-01

    Tall fescue [Lolium arundinaceum (Schreb.) Darbysh; Schedonorus phoenix (Scop.) Holub] is the primary cool season perennial grass in the eastern U.S. Most tall fescue contains an endophyte (Neotyphodium coenophialum), which produces ergot alkaloids that cause vasoconstriction and could restrict blood flow to the fetus in pregnant animals. The objective of this study was to examine fetal growth during maternal exposure to ergot alkaloids during gestation. Pregnant ewes (n = 16) were randomly assigned to one of two dietary treatments: 1) endophyte-infected (Neotyphodium coenophialum) tall fescue seed (E+; 0.8 ug of ergovaline /g diet DM) and 2) endophyte-free tall fescue seed (E-; 0.0 ug of ergovaline/g diet DM). Birth weight of lambs was reduced by 37% for E+ compared to E-. Organ and muscle weights were also lighter for E+ than E-. Exposure to ergot alkaloids in utero reduces fetal growth and muscle development.

  6. Correlations between Prenatal Exposure to Perfluorinated Chemicals and Reduced Fetal Growth

    PubMed Central

    Washino, Noriaki; Saijo, Yasuaki; Sasaki, Seiko; Kato, Shizue; Ban, Susumu; Konishi, Kanae; Ito, Rie; Nakata, Ayako; Iwasaki, Yusuke; Saito, Koichi; Nakazawa, Hiroyuki; Kishi, Reiko

    2009-01-01

    Background Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are man-made, ubiquitous, and persistent contaminants in the environment, wildlife, and humans. Although recent studies have shown that these chemicals interfere with fetal growth in humans, the results are inconsistent. Objectives Our goal was to investigate the correlation between relatively low levels of PFOS and PFOA in maternal serum and birth weight and birth size. Methods We conducted a hospital-based prospective cohort study between July 2002 and October 2005 in Sapporo, Japan. A total of 428 women and their infants were involved in the study. We obtained characteristics of the mothers and infants from self-administered questionnaire surveys and from medical records. We analyzed maternal serum samples for PFOS and PFOA by liquid chromatography–tandem mass spectrometry (LC/MS/MS). Results After adjusting for confounding factors, PFOS levels negatively correlated with birth weight [per log10 unit: β = −148.8 g; 95% confidence interval (CI), −297.0 to −0.5 g]. In addition, analyses stratified by sex revealed that PFOS levels negatively correlated with birth weight only in female infants (per log10 unit: β = −269.4 g; 95% CI, −465.7 to −73.0 g). However, we observed no correlation between PFOA levels and birth weight. Conclusion Our results indicate that in utero exposure to relatively low levels of PFOS was negatively correlated with birth weight. PMID:19440508

  7. Fetal growth in early pregnancy and risk of delivering low birth weight infant: prospective cohort study

    PubMed Central

    Smith, Gordon C S; Malone, Fergal D; Ball, Robert H; Nyberg, David A; Comstock, Christine H; Hankins, Gary D V; Berkowitz, Richard L; Gross, Susan J; Dugoff, Lorraine; Craigo, Sabrina D; Timor-Tritsch, Ilan E; Carr, Stephen R; Wolfe, Honor M; D'Alton, Mary E

    2007-01-01

    Objective To determine if first trimester fetal growth is associated with birth weight, duration of pregnancy, and the risk of delivering a small for gestational age infant. Design Prospective cohort study of 38 033 pregnancies between 1999 and 2003. Setting 15 centres representing major regions of the United States. Participants 976 women from the original cohort who conceived as the result of assisted reproductive technology, had a first trimester ultrasound measurement of fetal crown-rump length, and delivered live singleton infants without evidence of chromosomal or congenital abnormalities. First trimester growth was expressed as the difference between the observed and expected size of the fetus, expressed as equivalence to days of gestational age. Main outcome measures Birth weight, duration of pregnancy, and risk of delivering a small for gestational age infant. Results For each one day increase in the observed size of the fetus, birth weight increased by 28.2 (95% confidence interval 14.6 to 41.2) g. The association was substantially attenuated by adjustment for duration of pregnancy (adjusted coefficient 17.1 (6.6 to 27.5) g). Further adjustments for maternal characteristics and complications of pregnancy did not have a significant effect. The risk of delivering a small for gestational age infant decreased with increasing size in the first trimester (odds ratio for a one day increase 0.87, 0.81 to 0.94). The association was not materially affected by adjustment for maternal characteristics or complications of pregnancy. Conclusion Variation in birth weight may be determined, at least in part, by fetal growth in the first 12 weeks after conception through effects on timing of delivery and fetal growth velocity. PMID:17355993

  8. Prenatal Exposure to Polybrominated Flame Retardants and Fetal Growth in the INMA Cohort (Spain)

    PubMed Central

    2015-01-01

    Our aim was to investigate the relation between PBDEs and fetal growth or newborn anthropometry in a Spanish cohort (2003–2008). PBDE congeners (BDE-47, -99, -153, -154, and -209) were determined in serum of 670 mothers at gestational week 12 and in 534 umbilical cord samples. Abdominal circumference (AC), estimated fetal weight (EFW), femur length (FL), and biparietal diameter (BPD) during gestation were measured by ultrasounds. At birth, weight (BW), head circumference (HC), and length (BL) were also measured. We assessed growth in the intervals between 12–20 and 20–34 weeks of gestation and size at birth by standard deviation (SD)-scores adjusted for constitutional characteristics. We conducted multivariate linear regression analyses between PBDE congeners and their sum (ΣPBDEs) and outcomes. We found statistically significant inverse associations between ΣPBDEs and AC, EFW, and BPD at weeks 20–34 and HC at birth. Regarding congeners, the association was clearer with BDE-99, with inverse associations being found with AC, EFW, and BPD at weeks 20–34, and with BW and HC at delivery. These outcomes decreased between 1.3% and 3.5% for each 2-fold PBDE increase. Concerning matrices, we found statistically significant inverse associations with BPD, HC, and BW when using maternal serum, and for AC and EFW with cord serum. In conclusion, PBDEs may impair fetal growth in late pregnancy and reduce birth size. PMID:26181825

  9. Peri-Implantation Hormonal Milieu: Elucidating Mechanisms of Abnormal Placentation and Fetal Growth1

    PubMed Central

    Mainigi, Monica A.; Olalere, Devvora; Burd, Irina; Sapienza, Carmen; Bartolomei, Marisa; Coutifaris, Christos

    2013-01-01

    ABSTRACT Assisted reproductive technologies (ART) have been associated with several adverse perinatal outcomes involving placentation and fetal growth. It is critical to examine each intervention individually in order to assess its relationship to the described adverse perinatal outcomes. One intervention ubiquitously used in ART is superovulation with gonadotropins. Superovulation results in significant changes in the hormonal milieu, which persist during the peri-implantation and early placentation periods. Epidemiologic evidence suggests that the treatment-induced peri-implantation maternal environment plays a critical role in perinatal outcomes. In this study, using the mouse model, we have isolated the exposure to the peri-implantation period, and we examine the effect of superovulation on placentation and fetal growth. We report that the nonphysiologic peri-implantation maternal hormonal environment resulting from gonadotropin stimulation appears to have a direct effect on fetal growth, trophoblast differentiation, and gene expression. This appears to be mediated, at least in part, through trophoblast expansion and invasion. Although the specific molecular and cellular mechanism(s) leading to these observations remain to be elucidated, identifying this modifiable risk factor will not only allow us to improve perinatal outcomes with ART, but help us understand the pathophysiology contributing to these outcomes. PMID:24352558

  10. Fetal production of growth factors and inflammatory mediators predicts pulmonary hypertension in congenital diaphragmatic hernia

    PubMed Central

    Fleck, Shannon; Bautista, Geoanna; Keating, Sheila M.; Lee, Tzong-Hae; Keller, Roberta L.; Moon-Grady, Anita J.; Gonzales, Kelly; Norris, Philip J.; Busch, Michael P.; Kim, CJ; Romero, Roberto; Lee, Hanmin; Miniati, Doug; MacKenzie, Tippi C.

    2014-01-01

    Background Congenital diaphragmatic hernia (CDH) represents a spectrum of lung hypoplasia and consequent pulmonary hypertension is an important cause of postnatal morbidity and mortality. We studied biomarkers at the maternal-fetal interface to understand factors associated with the persistence of pulmonary hypertension. Methods Maternal and cord blood samples from fetuses with CDH and unaffected controls were analyzed using a human 39plex immunoassay kit. Cellular trafficking between the mother and the fetu was quantified using quantitative real-time PCR for non-shared alleles. Biomarker profiles were then correlated with CDH severity based on the degree of pulmonary hypertension. Results Cord blood levels of epidermal growth factor, platelet-derived growth factor, and several inflammatory mediators increased significantly as the severity of CDH increased, while maternal levels growth factors and mediators decreased significantly with CDH severity. Maternal cells were increased in fetuses with severe CDH compared to controls, with elevated levels of the chemokine CXCL-10 in patients with the highest trafficking. Conclusion Patients with CDH demonstrate pro-inflammatory and chemotactic signals in fetal blood at the time of birth. Since some of these molecules have been implicated in the development of pulmonary hypertension, prenatal strategies targeting specific molecular pathways may be useful adjuncts to current fetal therapies. PMID:23770923

  11. Shining light in dark corners: diagnosis and management of late-onset fetal growth restriction.

    PubMed

    MacDonald, Teresa M; McCarthy, Elizabeth A; Walker, Susan P

    2015-02-01

    Fetal growth restriction (FGR) is the single biggest risk factor for stillbirth. In the absence of any effective treatment for fetal growth restriction, the mainstay of management is close surveillance and timely delivery. While such statements are almost self-evident, the daily clinical challenge of late-onset fetal growth restriction remains; the competing priorities of minimising stillbirth risk, while avoiding excessive obstetric intervention and the neonatal sequelae of iatrogenic preterm birth. This dilemma is made harder because the tools for late-onset FGR diagnosis and surveillance compare poorly to those used in early-onset FGR; screening tests in early pregnancy have limited predictive value; most cases escape clinical detection, a phenomenon set to worsen given the obesity epidemic; there is a failure of consensus on the definition of small for gestational age, and ancillary tools, such as umbilical artery Doppler--of value in identification of preterm FGR--are less useful in the late-preterm period and at term. Most importantly, the problem is common; 96% of all births occur after 32 weeks. This means a poor noise/signal ratio of any test or management algorithm will inevitably have large clinical consequences. Into such a dark corner, we cast some light; a summary on diagnostic criteria, new developments to improve the diagnosis of late-onset FGR and a suggested approach to management. PMID:25557743

  12. Indications for Cardiopulmonary Bypass During Pregnancy and Impact on Fetal Outcomes.

    PubMed

    Yuan, S-M

    2014-01-01

    Background: Cardiac operations in pregnant patients are a challenge for physicians in multidisciplinary teams due to the complexity of the condition which affects both mother and baby. Management strategies vary on a case-by-case basis. Feto-neonatal and maternal outcomes after cardiopulmonary bypass (CPB) in pregnancy, especially long-term follow-up results, have not been sufficiently described. Methods: This review was based on a complete literature retrieval of articles published between 1991 and April 30, 2013. Results: Indications for CPB during pregnancy were cardiac surgery in 150 (96.8 %) patients, most of which consisted of valve replacements for mitral and/or aortic valve disorders, resuscitation due to amniotic fluid embolism, autotransfusion, and circulatory support during cesarean section to improve patient survival in 5 (3.2 %) patients. During CPB, fetuses showed either a brief heart rate drop with natural recovery after surgery or, in most cases, fetal heart rate remained normal throughout the whole course of CPB. Overall feto-neonatal mortality was 18.6 %. In comparison with pregnant patients whose baby survived, feto-neonatal death occurred after a significantly shorter gestational period at the time of onset of cardiac symptoms, cardiac surgery/resuscitation under CPB in the whole patient setting, or cardiac surgery/resuscitation with CPB prior to delivery. Conclusions: The most common surgical indications for CPB during pregnancy were cardiac surgery, followed by resuscitation for cardiopulmonary collapse. CPB was used most frequently in maternal cardiac surgery/resuscitation in the second trimester. Improved CPB conditions including high flow, high pressure and normothermia or mild hypothermia during pregnancy have benefited maternal and feto-neonatal outcomes. A shorter gestational period and the use of CPB during pregnancy were closely associated with feto-neonatal mortality. It is therefore important to attempt delivery ahead of

  13. Role of Insulinlike Growth Factor 1 in Fetal Development and in the Early Postnatal Life of Premature Infants.

    PubMed

    Hellström, Ann; Ley, David; Hansen-Pupp, Ingrid; Hallberg, Boubou; Ramenghi, Luca A; Löfqvist, Chatarina; Smith, Lois E H; Hård, Anna-Lena

    2016-09-01

    The neonatal period of very preterm infants is often characterized by a difficult adjustment to extrauterine life, with an inadequate nutrient supply and insufficient levels of growth factors, resulting in poor growth and a high morbidity rate. Long-term multisystem complications include cognitive, behavioral, and motor dysfunction as a result of brain damage as well as visual and hearing deficits and metabolic disorders that persist into adulthood. Insulinlike growth factor 1 (IGF-1) is a major regulator of fetal growth and development of most organs especially the central nervous system including the retina. Glucose metabolism in the developing brain is controlled by IGF-1 which also stimulates differentiation and prevents apoptosis. Serum concentrations of IGF-1 decrease to very low levels after very preterm birth and remain low for most of the perinatal development. Strong correlations have been found between low neonatal serum concentrations of IGF-1 and poor brain and retinal growth as well as poor general growth with multiorgan morbidities, such as intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, and necrotizing enterocolitis. Experimental and clinical studies indicate that early supplementation with IGF-1 can improve growth in catabolic states and reduce brain injury after hypoxic/ischemic events. A multicenter phase II study is currently underway to determine whether intravenous replacement of human recombinant IGF-1 up to normal intrauterine serum concentrations can improve growth and development and reduce prematurity-associated morbidities. PMID:27603537

  14. Elevated circulating insulin-like growth factor binding protein-1 is sufficient to cause fetal growth restriction.

    PubMed

    Watson, Carole S; Bialek, Peter; Anzo, Makoto; Khosravi, Javad; Yee, Siu-Pok; Han, Victor K M

    2006-03-01

    IGF binding protein-1 (IGFBP-1) inhibits the mitogenic actions of the IGFs. Circulating IGFBP-1 is elevated in newborns and experimental animals with fetal growth restriction (FGR). To establish a causal relationship between high circulating IGFBP-1 and FGR, we have generated transgenic mice using the mouse alpha-fetoprotein gene promoter to target overexpression of human IGFBP-1 (hIGFBP-1) in the fetal liver. These transgenic mice (AFP-BP1) expressed hIGFBP-1 mainly in the fetal hepatocytes, starting at embryonic d 14.5 (E14.5), with lower levels in the gut. The expression peaked at 1 wk postnatally (plasma concentration, 474 +/- 34 ng/ml). At birth, AFP-BP1 pups were 18% smaller [weighed 1.34 +/- 0.02 g compared with 1.62 +/- 0.04 g for wild type (WT); P < 0.05], and they did not demonstrate any postnatal catch-up growth. The placentas of the AFP-BP1 mice were larger than WT from E16.5 onwards (150 +/- 12 for AFP-BP1 vs. 100 +/- 5 mg for WT at E16.5; P < 0.05). Thus, this model of FGR is associated with a larger placenta, but without postnatal catch-up growth. Overall, these data clearly demonstrate that high concentrations of circulating IGFBP-1 are sufficient to cause FGR. PMID:16293667

  15. Limited capacity for glucose oxidation in fetal sheep with intrauterine growth restriction.

    PubMed

    Brown, Laura D; Rozance, Paul J; Bruce, Jennifer L; Friedman, Jacob E; Hay, William W; Wesolowski, Stephanie R

    2015-10-15

    Intrauterine growth-restricted (IUGR) fetal sheep, produced by placental insufficiency, have lower oxygen concentrations, higher lactate concentrations, and increased hepatic glucose production that is resistant to suppression by insulin. We hypothesized that increased lactate production in the IUGR fetus results from reduced glucose oxidation, during basal and maximal insulin-stimulated conditions, and is used to support glucose production. To test this, studies were performed in late-gestation control (CON) and IUGR fetal sheep under basal and hyperinsulinemic-clamp conditions. The basal glucose oxidation rate was similar and increased by 30-40% during insulin clamp in CON and IUGR fetuses (P < 0.005). However, the fraction of glucose oxidized was 15% lower in IUGR fetuses during basal and insulin-clamp periods (P = 0.05). IUGR fetuses also had four-fold higher lactate concentrations (P < 0.001) and lower lactate uptake rates (P < 0.05). In IUGR fetal muscle and liver, mRNA expression of pyruvate dehydrogenase kinase (PDK4), an inhibitor of glucose oxidation, was increased over fourfold. In IUGR fetal liver, but not skeletal muscle, mRNA expression of lactate dehydrogenase A (LDHA) was increased nearly fivefold. Hepatic expression of the gluconeogenic genes, phosphoenolpyruvate carboxykinase (PCK)1, and PCK2, was correlated with expression of PDK4 and LDHA. Collectively, these in vivo and tissue data support limited capacity for glucose oxidation in the IUGR fetus via increased PDK4 in skeletal muscle and liver. We speculate that lactate production also is increased, which may supply carbon for glucose production in the IUGR fetal liver. PMID:26224688

  16. Fetal growth restriction and risk of chronic lung disease among infants born before the 28th week of gestation

    PubMed Central

    Bose, Carl; Van Marter, Linda J.; Laughon, Matthew; O'Shea, T. Michael; Allred, Elizabeth N.; Karna, Padmani; Ehrenkranz, Richard A.; Boggess, Kim; Leviton, Alan

    2009-01-01

    Objective Improvement in survival of extremely premature infants over the past several decades has resulted in an increase in the number infants with chronic lung disease (CLD). Historical neonatal exposures associated with CLD now less frequently precede the disease. There is now increasing interest in exposures and events before delivery that predict CLD. The objective of this study was to identify current antenatal predictors of CLD. Patients and Methods We collected data about antenatal, placental and neonatal characteristics of 1241 newborns delivered before completion of the 28th week of gestation who were enrolled in a 14-center, observational study conducted during the years 2002-2004. Associations between antenatal factors, microbiologic and histologic characteristics of the placenta, and selected neonatal characteristics and CLD risk were first evaluated in univariate analyses. Subsequent multivariate analyses investigated the contribution of antenatal factors, particularly fetal growth restriction (FGR), to CLD risk. Results Among the antenatal factors, birth weight Z-score, used as a marker of FGR, provided the most information about CLD risk. Indicators of placental inflammation and infection were not associated with increased risk of CLD. Within nearly all strata of antenatal, placental and neonatal variables, growth restricted infants were at increased CLD risk compared with infants who were not growth restricted. FGR was the only maternal or antenatal characteristic that was highly predictive of CLD after adjustment for other risk factors. Conclusions FGR is independently associated with the risk of CLD. Thus factors that control fetal somatic growth may have a significant impact on vulnerability to lung injury, and in this way increase CLD risk. Future investigations should focus on the impact of FGR on growth factors that modulate lung growth. PMID:19706590

  17. Prenatal Origins of Temperament: Fetal Growth, Brain Structure, and Inhibitory Control in Adolescence

    PubMed Central

    Schlotz, Wolff; Godfrey, Keith M.; Phillips, David I.

    2014-01-01

    Objective Individual differences in the temperamental dimension of effortful control are constitutionally based and have been associated with an adverse prenatal developmental environment, with structural brain alterations presenting a potential mechanism. We investigated this hypothesis for anatomically defined brain regions implicated in cognitive and inhibitory motor control. Methods Twenty-seven 15–16 year old participants with low, medium, or high fetal growth were selected from a longitudinal birth cohort to maximize variation and represent the full normal spectrum of fetal growth. Outcome measures were parent ratings of attention and inhibitory control, thickness and surface area of the orbitofrontal cortex (lateral (LOFC) and medial (MOFC)) and right inferior frontal gyrus (rIFG), and volumetric measures of the striatum and amygdala. Results Lower birth weight was associated with lower inhibitory control, smaller surface area of LOFC, MOFC and rIFG, lower caudate volume, and thicker MOFC. A mediation model found a significant indirect effect of birth weight on inhibitory control via caudate volume. Conclusions Our findings support a neuroanatomical mechanism underlying potential long-term consequences of an adverse fetal developmental environment for behavioral inhibitory control in adolescence and have implications for understanding putative prenatal developmental origins of externalizing behavioral problems and self-control. PMID:24802625

  18. Effect of Prenatal Hypoxia in Transgenic Mouse Models of Preeclampsia and Fetal Growth Restriction

    PubMed Central

    Rueda-Clausen, C. F.; Thambiraj, D. F.; Poudel, R.; Davidge, S. T.; Baker, P. N.

    2014-01-01

    Mice lacking endothelial nitric oxide synthase (eNOS− /−) or catechol-O-methyl transferase (COMT−/−) exhibit a preeclampsia-like phenotype and fetal growth restriction. We hypothesized that a hypoxic insult would result in a more severe phenotype. Pregnant eNOS−/−, COMT−/− and control (C57BL/6J) mice were randomized to hypoxic (10.5% O2) or normal conditions (20.9% O2) from gestational day 10.5 to 18.5. Hypoxia increased the blood pressure in all genotypes and proteinuria in C57BL/6J and eNOS−/− mice. Fetal survival was significantly reduced following hypoxia, particularly in eNOS−/− mice. Birth weight was decreased in both C57BL/6J and COMT−/− mice. Placentas from COMT−/− mice demonstrated increased peroxynitrite. Despite similar hypoxia-induced effects on maternal blood pressure and proteinuria, eNOS−/− embryos have a decreased tolerance to hypoxia. Compared to C57BL/6J, COMT−/− mice exhibited less severe changes in proteinuria and fetal growth when exposed to prenatal hypoxia. This relative resistance to prenatal hypoxia was associated with a significant increase in placental levels of peroxynitrite. PMID:24084523

  19. Carbon isotopes as indicators of peatland growth?

    NASA Astrophysics Data System (ADS)

    Alewell, Christine; Krüger, Jan Paul; von Sengbusch, Pascal; Szidat, Sönke; Leifeld, Jens

    2016-04-01

    As undisturbed and/or growing peatlands store considerable amounts of carbon and are unique in their biodiversity and species assemblage, the knowledge of the current status of peatlands (growing with carbon sequestration, stagnating or degrading with carbon emissions) is crucial for landscape management and nature conservation. However, monitoring of peatland status requires long term measurements and is only feasible with expert knowledge. The latter determination is increasingly impeded in a scientific world, where taxonomic expert knowledge and funding of long term monitoring is rare. Stable carbon and nitrogen isotopes depth profiles in peatland soils have been shown to be a useful tool to monitor the degradation of peatlands due to permafrost thawing in Northern Sweden (Alewell et al., 2011; Krüger et al., 2014), drainage in Southern Finland (Krüger et al., 2016) as well as land use intensification in Northern Germany (Krüger et al., 2015). Here, we tackle the questions if we are able to differentiate between growing and degrading peats with the use of a combination of carbon stable (δ13C) and radiogenic isotope data (14C) with peat stratification information (degree of humification and macroscopic plant remains). Results indicate that isotope data are a useful tool to approximate peatland status, but that expert taxonomic knowledge will be needed for the final conclusion on peatland growth. Thus, isotope tools might be used for landscape screening to pin point sites for detailed taxonomic monitoring. As the method remains qualitative future research at these sites will need to integrate quantitative approaches to determine carbon loss or gain (soil C balances by ash content or C accumulation methods by radiocarbon data; Krüger et al., 2016). Alewell, C., R. Giesler, J. Klaminder, J. Leifeld, and M. Rollog. 2011. Stable carbon isotopes as indicators for micro-geomorphic changes in palsa peats. Biogeosciences, 8, 1769-1778. Krüger, J. P., Leifeld, J

  20. Generalized disruption of inherited genomic imprints leads to wide-ranging placental defects and dysregulated fetal growth

    PubMed Central

    Himes, K. P.; Koppes, E.; Chaillet, J. Richard

    2012-01-01

    Monoallelic expression of imprinted genes, including ones solely expressed in the placenta, is essential for normal placental development and fetal growth. To better understand the role of placental imprinting in placental development and fetal growth, we examined conceptuses developing in the absence of maternally derived DNA (cytosine-5-)- methyltransferase 1o (DNMT1o). Absence of DNMT1o results in the partial loss of methylation at imprinted differentially methylated domain (DMD) sequences in the embryo and the placenta. Mid-gestation E9.5 DNMT1o-deficient placentas exhibited structural abnormalities of all tissue layers. At E17.5, all examined placentas had aberrant placental morphology, most notably in the spongiotrophoblast and labyrinth layers. Abnormalities included an expanded volume fraction of spongiotrophoblast tissue with extension of the spongiotrophoblast layer into the labyrinth. Many mutant placentas also demonstrated migration abnormalities of glycogen cells. Additionally, the volume fraction of the labyrinth was reduced, as was the surface area for maternal fetal gas exchange. Despite these placental morphologic abnormalities, approximately one-half of DNMT1o-deficient fetuses survived to late gestation (E17.5). Furthermore, DNMT1o- deficient placentas supported a broad range of fetal growth. The ability of some DNMT1o-deficient and morphologically abnormal placentas to support fetal growth in excess of wild type demonstrates the importance of differential methylation of DMDs and proper imprinting of discrete gene clusters to placental morphogenesis and fetal growth. PMID:23085235

  1. Fetal development

    MedlinePlus

    Cunningham FG, Leveno KJ, Bloom SL, et al. Fetal growth and development. In: Cunningham FG, Leveno KL, Bloom SL, et al, eds. Williams Obstetrics . 23rd ed. New York, NY: McGraw-Hill; ... and fetal physiology. In: Gabbe SG, Niebyl JR, Simpson JL, ...

  2. Influence of endurance exercise and diet on human placental development and fetal growth.

    PubMed

    Clapp, J F

    2006-01-01

    The delivery of oxygen and substrate to the maternal-fetal interphase is the major maternal environmental stimulus which either up- or down-regulates feto-placental growth. During pregnancy, sustained exercise sessions cause an intermittent reduction in oxygen and substrate delivery to the interphase that may exceed 50% during the exercise but, it is probable that regular bouts of sustained exercise or exercise training may improve oxygen and substrate delivery at rest. The type of maternal carbohydrate intake (low- versus high-glycemic sources) and food intake frequency also influence substrate availability through their effects on maternal blood glucose levels and insulin sensitivity. As a result, different exercise regimens and/or different types of carbohydrate intake modify feto-placental growth. The magnitude and direction of the effect is determined by their average 24-h effect on oxygen and substrate availability at different time-points in pregnancy. In general, exercise in early and mid pregnancy stimulates placental growth while the relative amount of exercise in late pregnancy determines its effect on late fetal growth. Low-glycemic food sources in the diet decrease growth rate and size at birth while high-glycemic food sources increase it. Thus, it may be possible to improve pregnancy outcomes in both healthy, low-risk women and a variety of high-risk populaces by simply modifying maternal physical activity and dietary carbohydrate intake during pregnancy. PMID:16165206

  3. Growth in Inuit children exposed to polychlorinated biphenyls and lead during fetal development and childhood

    PubMed Central

    Dallaire, Renée; Dewailly, Éric; Ayotte, Pierre; Forget-Dubois, Nadine; Jacobson, Sandra W.; Jacobson, Joseph L.; Muckle, Gina

    2014-01-01

    Background Because of their geographical location and traditional lifestyle, Canadian Inuit children are highly exposed to polychlorinated biphenyls (PCBs) and lead (Pb), environmental contaminants that are thought to affect fetal and child growth. We examined the associations of these exposures with the fetal and postnatal growth of Inuit children. Methods We conducted a prospective cohort study among Inuit from Nunavik (Arctic Québec). Mothers were recruited at their first prenatal visit; children (n = 290) were evaluated at birth and at 8–14 years of age. Concentrations of PCB 153 and Pb were determined in umbilical cord and child blood. Weight, height and head circumference were measured at birth and during childhood. Results Cord blood PCB 153 concentrations were not associated with anthropometric measurements at birth or school age, but child blood PCB 153 concentrations were associated with reduced weight, height and head circumference during childhood. There was no association between cord Pb levels and anthropometric outcomes at birth, but cord blood Pb was related to smaller height and a tendency to a smaller head circumference during childhood. Interpretation Our results suggest that chronic exposure to PCBs during childhood is negatively associated with skeletal growth and weight, while prenatal Pb exposure is related to reduce growth during childhood. This study is the first to link prenatal Pb exposure to poorer growth in school-age children. PMID:25042032

  4. Prenatal Air Pollution Exposure and Ultrasound Measures of Fetal Growth in Los Angeles, California

    PubMed Central

    Ritz, Beate; Qiu, Jiaheng; Lee, Pei-Chen; Lurmann, Fred; Penfold, Bryan; Weiss, Robert Erin; McConnell, Rob; Arora, Chander; Hobel, Calvin; Wilhelm, Michelle

    2014-01-01

    Background Few previous studies examined the impact of prenatal air pollution exposures on fetal development based on ultrasound measures during pregnancy. Methods In a prospective birth cohort of more than 500 women followed during 1993-1996 in Los Angeles, California, we examined how air pollution impacts fetal growth during pregnancy. Exposure to traffic related air pollution was estimated using CALINE4 air dispersion modeling for nitrogen oxides (NOx) and a land use regression (LUR) model for nitrogen monoxide (NO), nitrogen dioxide (NO2) and NOx. Exposures to carbon monoxide (CO), NO2, ozone (O3) and particles <10 μm in aerodynamic diameter (PM10) were estimated using government monitoring data. We employed a linear mixed effects model to estimate changes in fetal size at approximately 19, 29 and 37 weeks gestation based on ultrasound. Results Exposure to traffic-derived air pollution during 29 to 37 weeks was negatively associated with biparietal diameter at 37 weeks gestation. For each interquartile range (IQR) increase in LUR-based estimates of NO, NO2 and NOx, or freeway CALINE4 NOx we estimated a reduction in biparietal diameter of 0.2-0.3 mm. For women residing within 5 km of a monitoring station, we estimated biparietal diameter reductions of 0.9-1.0 mm per IQR increase in CO and NO2. Effect estimates were robust to adjustment for a number of potential confounders. We did not observe consistent patterns for other growth endpoints we examined. Conclusions Prenatal exposure to traffic-derived pollution was negatively associated with fetal head size measured as biparietal diameter in late pregnancy. PMID:24517884

  5. Spontaneous intrauterine umbilical artery thrombosis leading to severe fetal growth restriction.

    PubMed

    Klaritsch, P; Haeusler, M; Karpf, E; Schlembach, D; Lang, U

    2008-04-01

    Intrauterine thrombosis of umbilical cord vessels is a rare event (2.5-4.5/10,000) and usually followed by poor fetal outcome. We present the rare case of spontaneous intrauterine thrombosis of an umbilical artery leading to severe intrauterine growth restriction (IUGR) and provide clinical and pathological findings. A 28-year-old nulliparous third gravida was referred to our institution because of IUGR at 32+4 weeks of gestation. Fetal growth had been appropriate until the 31st week of gestation and had stopped thereafter. There were no signs of abruption of the placenta and no structural abnormalities except an absent paravesical colour Doppler flow in the region of the right umbilical artery. Other Doppler measurements, karyotype and TORCH serology were normal. Intermittent non-reassuring fetal heart rate led to cesarean section at 34+3 weeks of gestation. A healthy girl with measurements on the 3rd centile was born (weight of 1,590 g, length of 41 cm and head circumference of 29 cm). Gross examination displayed an elongated, highly twisted umbilical cord with a length of 70 cm, central insertion and three umbilical vessels. Microscopic examination confirmed the diagnosis of umbilical artery thrombosis along the entire length of the umbilical cord. Calcification within the thrombus and microcalcification in occluded chorionic vessels were observed as well as hemorrhagic endovasculitis and endangiopathia obliterans in the stem villi arteries. This fetal thrombotic vasculopathy (FTV) comprised about 40% of the parenchyma. The coagulation parameters and blood counts of the mother and the infant were normal apart from transient neonatal thrombocytopenia. The reason for thrombosis remained unclear but could be attributed to the elongated and highly twisted umbilical cord. Intrauterine arterial thrombosis may cause severe IUGR. This condition might be detectable by ultrasound in the course of an IUGR workup, especially when no other reasons can be found. PMID:18289672

  6. Infant Symbolic Play as an Early Indicator of Fetal Alcohol-Related Deficit

    ERIC Educational Resources Information Center

    Molteno, Christopher D.; Jacobson, Sandra W.; Carter, R. Colin; Jacobson, Joseph L.

    2010-01-01

    Infant symbolic play was examined in relation to prenatal alcohol exposure and socioenvironmental background and to predict which infants met criteria for fetal alcohol syndrome (FAS) at 5 years. A total of 107 Cape-Colored, South African infants born to heavy drinking mothers and abstainers/light drinkers were recruited prenatally. Complexity of…

  7. Wheat growth monitoring with radar vegetation indices

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Microwave remote sensing can help in the monitoring of crop growth. Many experiments have been carried out to investigate the sensitivity of microwave sensors to crop growth parameters. These have clearly shown that canopy structure and water content can greatly affect the measurements. For agricult...

  8. Chinese herbal medicine for miscarriage affects decidual micro-environment and fetal growth

    PubMed Central

    Piao, L.; Chen, C.-P.; Yeh, C.-C.; Basar, M.; Masch, R.; Cheng, Y.-C.; Lockwood, C. J.; Schatz, F.; Huang, S. J.

    2015-01-01

    Introduction Intrauterine growth restriction complicates 5 - 10% of pregnancies. This study aims to test the hypothesis that Chinese herbal formula, JLFC01, affects pregnancy and fetal development by modulating the pro-inflammatory decidual micro-environment. Methods Human decidua from gestational age-matched elective terminations or incomplete/missed abortion was immunostained using anti-CD68 + anti-CD86 or anti-CD163 antibodies. qRT-PCR and Luminex assay measured the effects of JLFC01 on IL-1β- or TNF-α-induced cytokine expression in first trimester decidual cells and on an established spontaneous abortion/intrauterine growth restriction (SA/IUGR)-prone mouse placentae. The effect of JLFC01 on human endometrial endothelial cell angiogenesis was evaluated by average area, length and numbers of branching points of tube formation. Food intake, litter size, fetal weight, placental weight and resorption rate were recorded in SA/IUGR-prone mouse treated with JLFC01. qRT-PCR, Western blot and immunohistochemistry assessed the expression of mouse placental IGF-I and IGF-IR. Results In spontaneous abortion, numbers of decidual macrophages expressing CD86 and CD163 are increased and decreased, respectively. JLFC01 reduces IL-1β- or TNF-α-induced GM-CSF, M-CSF, C-C motif ligand 2 (CCL2), interferon-γ-inducible protein-10 (IP-10), CCL5 and IL-8 production in first trimester decidual cells. JLFC01 suppresses the activity of IL-1β- or TNF-α-treated first trimester decidual cells in enhancing macrophage-inhibited angiogenesis. In SA/IUGR-prone mice, JLFC01 increases maternal food intake, litter size, fetal and placental weight, and reduces fetal resorption rate. JLFC01 induces IGF-I and IGF-IR expression and inhibits M-CSF, CCL2, CCL5, CCL11, CCL3 and G-CSF expression in the placentae. Discussion JLFC01 improves gestation by inhibiting decidual inflammation, enhancing angiogenesis and promoting fetal growth. PMID:25771406

  9. Fetal Growth and the Risk of Spontaneous Preterm Birth in a Prospective Cohort Study of Nulliparous Women.

    PubMed

    Partap, Uttara; Sovio, Ulla; Smith, Gordon C S

    2016-07-15

    Previous studies have suggested an association between fetal growth restriction and the risk of spontaneous preterm birth (sPTB). However, addressing this association is methodologically challenging. We conducted a prospective cohort study of nulliparous women with a singleton pregnancy in Cambridge, United Kingdom (2008-2012). Ultrasonic fetal biometry was performed at 20 weeks of gestation as per routine clinical care. Participants also had blinded research ultrasonography performed at approximately 28 weeks. Biometric measurements were expressed as gestational-age-adjusted z scores. Fetal growth velocity was quantified by change in z score between 20 weeks and 28 weeks. Risk of sPTB, defined as delivery at ≥28 weeks and <37 weeks associated with labor in the absence of induction, was analyzed using cause-specific Cox regression. Of 3,892 women, 98 (2.5%) had sPTB. When compared with the other decile groups, the lowest decile of growth velocity of the fetal femur between 20 and 28 weeks was associated with increased risk of sPTB (hazard ratio = 2.37, 95% confidence interval: 1.43, 3.93; P < 0.001). Adjustment for maternal characteristics had no material effect (hazard ratio = 2.50, 95% confidence interval: 1.50, 4.14; P < 0.001). There were no significant associations between other fetal measurements and risk of sPTB. To conclude, slow growth velocity of the fetal femur is associated with an increased risk of sPTB. PMID:27370790

  10. Effect of a milk-based food supplement on maternal nutritional status and fetal growth in underweight Chilean women.

    PubMed

    Mardones-Santander, F; Rosso, P; Stekel, A; Ahumada, E; Llaguno, S; Pizarro, F; Salinas, J; Vial, I; Walter, T

    1988-03-01

    The effects on pregnancy outcome and maternal iron status of powdered milk (PUR) and a milk-based fortified product (V-N) were compared in a group of underweight gravidas. These take-home products were distributed during regular prenatal visits. Women in the V-N group had greater weight gain (12.29 vs 11.31 kg, p less than 0.05) and mean birth weights (3178 vs 3105 g, p less than 0.05) than those in the PUR group. Values for various indicators of maternal Fe status were also higher in the V-N group. Compared with self-selected noncompliers, similar in all control variables to compliers, children of women who consumed powdered milk or the milk-based fortified product had mean birth weights that were higher by 258 and 335 g, respectively. Data indicate a beneficial effect of the fortified product on both maternal nutritional status and fetal growth. PMID:3279745

  11. FETAL HEART RATE MONITORING PATTERNS IN WOMEN WITH AMNIOTIC FLUID PROTEOMIC PROFILES INDICATIVE OF INFLAMMATION

    PubMed Central

    Buhimschi, Catalin S.; Abdel-Razeq, Sonya; Cackovic, Michael; Pettker, Christian M.; Dulay, Antonette T.; Bahtiyar, Mert Ozan; Zambrano, Eduardo; Martin, Ryan; Norwitz, Errol R.; Bhandari, Vineet; Buhimschi, Irina A.

    2009-01-01

    We hypothesized that abnormal fetal heart rate monitoring patterns (FHR-MP) occur more often in pregnancies complicated by intra-amniotic inflammation. Therefore, our objective was to examine the relationships between FHR-MP abnormalities, intra-amniotic inflammation and/or infection, acute histological chorioamnionitis and early-onset neonatal sepsis (EONS) in pregnancies complicated by preterm birth. Additionally, the ability of various FHR-MPs to predict EONS was investigated. FHR-MP from 87 singleton premature neonates delivered within 48 hours from amniocentesis [gestational age: 28.9 ± 3.3 weeks] were analyzed blindly using strict NICHD criteria. Strips were evaluated at three time points: at admission, at amniocentesis and prior to delivery. Intra-amniotic inflammation was established based on a previously validated proteomic fingerprint (MR score). Diagnoses of histological chorioamnionitis and EONS were based on well-recognized pathological, clinical and laboratory criteria. We determined that fetuses of women with severe intra-amniotic inflammation had a higher FHR baseline throughout the entire monitoring period and an increased frequency of a non-reactive FHR-MP at admission. Of all FHR-MP, a non-reassuring test at admission had 32% sensitivity, 95% specificity, 73% positive predictive value, 77% negative predictive value, and 76% accuracy in predicting EONS. Although a non-reassuring FHR-MP at admission was significantly associated with EONS after correcting for gestational age (OR: 5.6 [95%CI: 1.2–26.2], p=0.030), the majority of the neonates that developed EONS had an overall reassuring FHR-MP. Non-reassuring FHR-MPs at either amniocentesis or delivery had no association with EONS. We conclude that in cases complicated by preterm birth, a non-reassuring FHR-MP at the initial evaluation is a specific but not a sensitive predictor of EONS. An abnormal FHR-MP can thus raise the level of awareness that a fetus with EONS may be born, but is not a

  12. Role of the Placental Vitamin D Receptor in Modulating Feto-Placental Growth in Fetal Growth Restriction and Preeclampsia-Affected Pregnancies

    PubMed Central

    Murthi, Padma; Yong, Hannah E. J.; Ngyuen, Thy P. H.; Ellery, Stacey; Singh, Harmeet; Rahman, Rahana; Dickinson, Hayley; Walker, David W.; Davies-Tuck, Miranda; Wallace, Euan M.; Ebeling, Peter R.

    2016-01-01

    Fetal growth restriction (FGR) is a common pregnancy complication that affects up to 5% of pregnancies worldwide. Recent studies demonstrate that Vitamin D deficiency is implicated in reduced fetal growth, which may be rescued by supplementation of Vitamin D. Despite this, the pathway(s) by which Vitamin D modulate fetal growth remains to be investigated. Our own studies demonstrate that the Vitamin D receptor (VDR) is significantly decreased in placentae from human pregnancies complicated by FGR and contributes to abnormal placental trophoblast apoptosis and differentiation and regulation of cell-cycle genes in vitro. Thus, Vitamin D signaling is important for normal placental function and fetal growth. This review discusses the association of Vitamin D with fetal growth, the function of Vitamin D and its receptor in pregnancy, as well as the functional significance of a placental source of Vitamin D in FGR. Additionally, we propose that for Vitamin D to be clinically effective to prevent and manage FGR, the molecular mechanisms of Vitamin D and its receptor in modulating fetal growth requires further investigation. PMID:26924988

  13. Role of the Placental Vitamin D Receptor in Modulating Feto-Placental Growth in Fetal Growth Restriction and Preeclampsia-Affected Pregnancies.

    PubMed

    Murthi, Padma; Yong, Hannah E J; Ngyuen, Thy P H; Ellery, Stacey; Singh, Harmeet; Rahman, Rahana; Dickinson, Hayley; Walker, David W; Davies-Tuck, Miranda; Wallace, Euan M; Ebeling, Peter R

    2016-01-01

    Fetal growth restriction (FGR) is a common pregnancy complication that affects up to 5% of pregnancies worldwide. Recent studies demonstrate that Vitamin D deficiency is implicated in reduced fetal growth, which may be rescued by supplementation of Vitamin D. Despite this, the pathway(s) by which Vitamin D modulate fetal growth remains to be investigated. Our own studies demonstrate that the Vitamin D receptor (VDR) is significantly decreased in placentae from human pregnancies complicated by FGR and contributes to abnormal placental trophoblast apoptosis and differentiation and regulation of cell-cycle genes in vitro. Thus, Vitamin D signaling is important for normal placental function and fetal growth. This review discusses the association of Vitamin D with fetal growth, the function of Vitamin D and its receptor in pregnancy, as well as the functional significance of a placental source of Vitamin D in FGR. Additionally, we propose that for Vitamin D to be clinically effective to prevent and manage FGR, the molecular mechanisms of Vitamin D and its receptor in modulating fetal growth requires further investigation. PMID:26924988

  14. Sildenafil citrate for the management of fetal growth restriction and oligohydramnios

    PubMed Central

    Choudhary, Rana; Desai, Kavita; Parekh, Hetal; Ganla, Kedar

    2016-01-01

    Fetal growth restriction (FGR) and preeclampsia are the major causes of neonatal morbidity and mortality, which affect up to 8% of all pregnancies. The pathogenesis in FGR is an abnormal trophoblastic invasion leading to compromised uteroplacental circulation. However, in spite of this understanding and identification of high-risk patients, the management options are limited. There are some new studies which have demonstrated the role of sildenafil citrate in improving vasodilatation of small myometrial vessels and therefore improvement in amniotic fluid index, fetal weight, and even uterine and umbilical artery Doppler patterns. We report here the case of a 31-year-old female with infertility and preconceptional thin endometrium responding well to sildenafil citrate, followed by conception. However, she presented with an early-onset FGR at 26 weeks of gestation, and again after treatment with sildenafil citrate, showed improvement in amniotic fluid index and fetal weight, finally resulting in delivery of a full-term healthy baby with uneventful neonatal course. PMID:27563258

  15. Fetal growth and birth size is associated with maternal anthropometry and body composition.

    PubMed

    Thame, Minerva; Osmond, Clive; Trotman, Helen

    2015-10-01

    The objective was to investigate the association of maternal weight, height and body composition with fetal growth. We recruited 425 women at the University Hospital of the West Indies, Jamaica, who had singleton pregnancies, were less than 15 weeks gestation and had no systemic illness. Maternal weight, height and skinfold thicknesses were measured at the first antenatal visit and lean mass was calculated. Sonographic measurements of the fetus were made at 15, 25 and 35 weeks gestation. Weight, crown-heel length and head circumference were measured at birth. Analyses were confined to 360 (85%) women; 65 women did not complete the study. Maternal height was positively associated with femoral length at 25 and 35 weeks gestation and with head circumference at 35 weeks (all P < 0.02). Maternal weight was positively associated with abdominal circumference and femoral length at 25 weeks, and with larger head and abdominal circumference and longer femur at 35 weeks (all P < 0.02). Maternal lean mass had similar associations to maternal weight and they were both positively associated with estimated fetal weight (all P < 0.02). All three maternal measurements were positively associated with birthweight, length and head circumference. Maternal size was associated with fetal size as early as 25 weeks gestation, with height strongly associated with femoral length, and with weight and lean mass strongly associated with abdominal circumference. PMID:23241104

  16. Sildenafil citrate for the management of fetal growth restriction and oligohydramnios.

    PubMed

    Choudhary, Rana; Desai, Kavita; Parekh, Hetal; Ganla, Kedar

    2016-01-01

    Fetal growth restriction (FGR) and preeclampsia are the major causes of neonatal morbidity and mortality, which affect up to 8% of all pregnancies. The pathogenesis in FGR is an abnormal trophoblastic invasion leading to compromised uteroplacental circulation. However, in spite of this understanding and identification of high-risk patients, the management options are limited. There are some new studies which have demonstrated the role of sildenafil citrate in improving vasodilatation of small myometrial vessels and therefore improvement in amniotic fluid index, fetal weight, and even uterine and umbilical artery Doppler patterns. We report here the case of a 31-year-old female with infertility and preconceptional thin endometrium responding well to sildenafil citrate, followed by conception. However, she presented with an early-onset FGR at 26 weeks of gestation, and again after treatment with sildenafil citrate, showed improvement in amniotic fluid index and fetal weight, finally resulting in delivery of a full-term healthy baby with uneventful neonatal course. PMID:27563258

  17. Effect of fetal growth on maternal protein metabolism in postabsorptive rat

    SciTech Connect

    Ling, P.R.; Bistrian, B.R.; Blackburn, G.L.; Istfan, N.

    1987-03-01

    Rates of protein synthesis were measured in whole fetuses and maternal tissues at 17 and 20 days of gestation in postabsorptive rats using continuous infusion of L-(1-/sup 14/C)leucine. Fetal protein degradation rates were derived from the fractional rates of synthesis and growth. Whole-body (plasma) leucine kinetics in the mother showed a significant reduction of the fraction of plasma leucine oxidized in the mothers bearing older fetuses, a slight increase in the plasma flux, with total leucine oxidation and incorporation into protein remaining similar at the two gestational ages. Estimates of fractional protein synthesis in maternal tissues revealed an increase in placental and hepatic rates at 20 days of gestation, whereas the fractional synthetic rate in muscle remained unchanged. A model for estimation of the redistribution of leucine between plasma and tissues is described in detail. This model revealed a more efficient utilization of leucine in fetal protein synthesis in comparison with other maternal tissues, a greater dependency of the fetus on plasma supply of leucine, and a significant increase (2-fold) in the release of leucine from maternal muscle as the fetal requirements increased proportionately with its size. The latter conclusion, supported by nitrogen analysis and the ratio of bound-to-free leucine in maternal tissues, confirms the importance of maternal stores in maintaining the homeostasis of essential amino acids during late pregnancy.

  18. Baby on board: olfactory cues indicate pregnancy and fetal sex in a non-human primate

    PubMed Central

    Crawford, Jeremy Chase; Drea, Christine M.

    2015-01-01

    Olfactory cues play an integral, albeit underappreciated, role in mediating vertebrate social and reproductive behaviour. These cues fluctuate with the signaller's hormonal condition, coincident with and informative about relevant aspects of its reproductive state, such as pubertal onset, change in season and, in females, timing of ovulation. Although pregnancy dramatically alters a female's endocrine profiles, which can be further influenced by fetal sex, the relationship between gestation and olfactory cues is poorly understood. We therefore examined the effects of pregnancy and fetal sex on volatile genital secretions in the ring-tailed lemur (Lemur catta), a strepsirrhine primate possessing complex olfactory mechanisms of reproductive signalling. While pregnant, dams altered and dampened their expression of volatile chemicals, with compound richness being particularly reduced in dams bearing sons. These changes were comparable in magnitude with other, published chemical differences among lemurs that are salient to conspecifics. Such olfactory ‘signatures’ of pregnancy may help guide social interactions, potentially promoting mother–infant recognition, reducing intragroup conflict or counteracting behavioural mechanisms of paternity confusion; cues that also advertise fetal sex may additionally facilitate differential sex allocation. PMID:25716086

  19. Baby on board: olfactory cues indicate pregnancy and fetal sex in a non-human primate.

    PubMed

    Crawford, Jeremy Chase; Drea, Christine M

    2015-02-01

    Olfactory cues play an integral, albeit underappreciated, role in mediating vertebrate social and reproductive behaviour. These cues fluctuate with the signaller's hormonal condition, coincident with and informative about relevant aspects of its reproductive state, such as pubertal onset, change in season and, in females, timing of ovulation. Although pregnancy dramatically alters a female's endocrine profiles, which can be further influenced by fetal sex, the relationship between gestation and olfactory cues is poorly understood. We therefore examined the effects of pregnancy and fetal sex on volatile genital secretions in the ring-tailed lemur (Lemur catta), a strepsirrhine primate possessing complex olfactory mechanisms of reproductive signalling. While pregnant, dams altered and dampened their expression of volatile chemicals, with compound richness being particularly reduced in dams bearing sons. These changes were comparable in magnitude with other, published chemical differences among lemurs that are salient to conspecifics. Such olfactory 'signatures' of pregnancy may help guide social interactions, potentially promoting mother-infant recognition, reducing intragroup conflict or counteracting behavioural mechanisms of paternity confusion; cues that also advertise fetal sex may additionally facilitate differential sex allocation. PMID:25716086

  20. The effect of fetal growth and nutrient stresses on steroid pathways.

    PubMed

    Stirrat, Laura I; Reynolds, Rebecca M

    2016-06-01

    The early life environment is a crucial time for establishing the trajectory of future health. Low birthweight is considered a marker of an adverse in utero environment and predisposes to cardio-metabolic disease later in life. It has been proposed that this is mediated by glucocorticoids, with life-long activation of the HPA axis. Here we review the evidence to support this hypothesis, with particular emphasis on the effects of fetal growth and nutrient stresses in utero on steroid pathways of the HPA axis. A better understanding of the mechanisms underlying these processes could help to optimize in utero health, and identify individuals at greatest risk of future disease. PMID:26196121

  1. Progesterone and HMOX-1 promote fetal growth by CD8+ T cell modulation

    PubMed Central

    Solano, María Emilia; Kowal, Mirka Katharina; O’Rourke, Greta Eugenia; Horst, Andrea Kristina; Modest, Kathrin; Plösch, Torsten; Barikbin, Roja; Remus, Chressen Catharina; Berger, Robert G.; Jago, Caitlin; Ho, Hoang; Sass, Gabriele; Parker, Victoria J.; Lydon, John P.; DeMayo, Francesco J.; Hecher, Kurt; Karimi, Khalil; Arck, Petra Clara

    2015-01-01

    Intrauterine growth restriction (IUGR) affects up to 10% of pregnancies in Western societies. IUGR is a strong predictor of reduced short-term neonatal survival and impairs long-term health in children. Placental insufficiency is often associated with IUGR; however, the molecular mechanisms involved in the pathogenesis of placental insufficiency and IUGR are largely unknown. Here, we developed a mouse model of fetal-growth restriction and placental insufficiency that is induced by a midgestational stress challenge. Compared with control animals, pregnant dams subjected to gestational stress exhibited reduced progesterone levels and placental heme oxygenase 1 (Hmox1) expression and increased methylation at distinct regions of the placental Hmox1 promoter. These stress-triggered changes were accompanied by an altered CD8+ T cell response, as evidenced by a reduction of tolerogenic CD8+CD122+ T cells and an increase of cytotoxic CD8+ T cells. Using progesterone receptor– or Hmox1-deficient mice, we identified progesterone as an upstream modulator of placental Hmox1 expression. Supplementation of progesterone or depletion of CD8+ T cells revealed that progesterone suppresses CD8+ T cell cytotoxicity, whereas the generation of CD8+CD122+ T cells is supported by Hmox1 and ameliorates fetal-growth restriction in Hmox1 deficiency. These observations in mice could promote the identification of pregnancies at risk for IUGR and the generation of clinical interventional strategies. PMID:25774501

  2. Estimating wheat growth with radar vegetation indices

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study, we computed the Radar Vegetation Index (RVI) using observations made with a ground based multi-frequency polarimetric scatterometer system over an entire wheat growth period. The temporal variations of the backscattering coefficients for L-, C-, and X-band, RVI, vegetation water conte...

  3. Fetal growth restriction and intra-uterine growth restriction: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians.

    PubMed

    Vayssière, C; Sentilhes, L; Ego, A; Bernard, C; Cambourieu, D; Flamant, C; Gascoin, G; Gaudineau, A; Grangé, G; Houfflin-Debarge, V; Langer, B; Malan, V; Marcorelles, P; Nizard, J; Perrotin, F; Salomon, L; Senat, M-V; Serry, A; Tessier, V; Truffert, P; Tsatsaris, V; Arnaud, C; Carbonne, B

    2015-10-01

    Small for gestational age (SGA) is defined by weight (in utero estimated fetal weight or birth weight) below the 10th percentile (professional consensus). Severe SGA is SGA below the third percentile (professional consensus). Fetal growth restriction (FGR) or intra-uterine growth restriction (IUGR) usually correspond with SGA associated with evidence indicating abnormal growth (with or without abnormal uterine and/or umbilical Doppler): arrest of growth or a shift in its rate measured longitudinally (at least two measurements, 3 weeks apart) (professional consensus). More rarely, they may correspond with inadequate growth, with weight near the 10th percentile without being SGA (LE2). Birthweight curves are not appropriate for the identification of SGA at early gestational ages because of the disorders associated with preterm delivery. In utero curves represent physiological growth more reliably (LE2). In diagnostic (or reference) ultrasound, the use of growth curves adjusted for maternal height and weight, parity and fetal sex is recommended (professional consensus). In screening, the use of adjusted curves must be assessed in pilot regions to determine the schedule for their subsequent introduction at national level. This choice is based on evidence of feasibility and the absence of any proven benefits for individualized curves for perinatal health in the general population (professional consensus). Children born with FGR or SGA have a higher risk of minor cognitive deficits, school problems and metabolic syndrome in adulthood. The role of preterm delivery in these complications is linked. The measurement of fundal height remains relevant to screening after 22 weeks of gestation (Grade C). The biometric ultrasound indicators recommended are: head circumference (HC), abdominal circumference (AC) and femur length (FL) (professional consensus). They allow calculation of estimated fetal weight (EFW), which, with AC, is the most relevant indicator for screening

  4. Placental development during early pregnancy in sheep: Effects of embryo origin on fetal and placental growth and global methylation

    PubMed Central

    Grazul-Bilska, Anna T.; Johnson, Mary Lynn; Borowicz, Pawel P.; Baranko, Loren; Redmer, Dale A.; Reynolds, Lawrence P.

    2012-01-01

    The origin of embryos including those created through assisted reproductive technologies (ART) may have profound effects on placental and fetal development, possibly leading to compromised pregnancies associated with poor placental development. To determine the effects of embryo origin on fetal size, and maternal and fetal placental cellular proliferation and global methylation, pregnancies were achieved through natural mating (NAT), or transfer of embryos generated through in vivo (NAT-ET), IVF, or in vitro activation (IVA). On Day 22 of pregnancy, fetuses were measured and placental tissues were collected to immunodetect Ki67 (a marker of proliferating cells) and 5-methyl cytosine (5mC) followed by image analysis, and determination of mRNA expression for three DNA methyltransferases (DNMT). Fetal length and labeling index (proportion of proliferating cells) in maternal caruncles (CAR; maternal placenta) and fetal membranes (FM; fetal placenta) were less (P < 0.001) in NAT-ET, IVF and IVA than in NAT. Expression of 5mC was greater (P < 0.02) in IVF and IVA than in NAT. In CAR, mRNA expression for DNMT1 was greater (P < 0.01) in IVA compared to the other groups, but DNMT3A expression was less (P < 0.04) in NAT-ET and IVA than NAT. In FM, expression of mRNA for DNMT3A was greater (P < 0.01) in IVA compared to the other groups, and was similar in NAT, NAT-ET and IVF groups. Thus, embryo origin may have specific effects on growth and function of ovine utero-placental and fetal tissues through regulation of tissue growth, DNA methylation and likely other mechanisms. These data provide a foundation for determining expression of specific factors regulating placental and fetal tissue growth and function in normal and compromised pregnancies, including those achieved with ART. PMID:23117132

  5. Expression of Nerve Growth Factor (NGF), TrkA, and p75NTR in Developing Human Fetal Teeth

    PubMed Central

    Mitsiadis, Thimios A.; Pagella, Pierfrancesco

    2016-01-01

    Nerve growth factor (NGF) is important for the development and the differentiation of neuronal and non-neuronal cells. NGF binds to specific low- and high-affinity cell surface receptors, respectively, p75NTR and TrkA. In the present study, we examined by immunohistochemistry the expression patterns of the NGF, p75NTR, and TrkA proteins during human fetal tooth development, in order to better understand the mode of NGF signaling action in dental tissues. The results obtained show that these molecules are expressed in a wide range of dental cells of both epithelial and mesenchymal origin during early stages of odontogenesis, as well as in nerve fibers that surround the developing tooth germs. At more advanced developmental stages, NGF and TrkA are localized in differentiated cells with secretory capacities such as preameloblasts/ameloblasts secreting enamel matrix and odontoblasts secreting dentine matrix. In contrast, p75NTR expression is absent from these secretory cells and restricted in proliferating cells of the dental epithelium. The temporospatial distribution of NGF and p75NTR in fetal human teeth is similar, but not identical, with that observed previously in the developing rodent teeth, thus indicating that the genetic information is well-conserved during evolution. The expression patterns of NGF, p75NTR, and TrkA during odontogenesis suggest regulatory roles for NGF signaling in proliferation and differentiation of epithelial and mesenchymal cells, as well as in attraction and sprouting of nerve fibers within dental tissues. PMID:27536251

  6. Fetal ultrasonography.

    PubMed Central

    Garmel, S H; D'Alton, M E

    1993-01-01

    Since its introduction in the 1950s, ultrasonography in pregnancy has been helpful in determining gestational age, detecting multiple pregnancies, locating placentas, diagnosing fetal anomalies, evaluating fetal well-being, and guiding obstetricians with in utero treatment. We review current standards and controversies regarding the indications, safety, accuracy, and limitations of ultrasonography in pregnancy. Images PMID:8236969

  7. Elevated maternal serum folate in the third trimester and reduced fetal growth: a longitudinal study.

    PubMed

    Takimoto, Hidemi; Hayashi, Fumi; Kusama, Kaoru; Kato, Noriko; Yoshiike, Nobuo; Toba, Mikayo; Ishibashi, Tomoko; Miyasaka, Naoyuki; Kubota, Toshiro

    2011-01-01

    This study aimed to examine the association of fetal growth and elevated third trimester maternal serum folate due to folic acid (FA) supplement intake. Dietary intake, use of FA supplements, weight, and blood biomarkers of B-vitamins (serum folate, pyridoxal, vitamin B(12), and plasma total homocysteine) were observed in 33 healthy pregnant women at the third trimester (average gestational age 35 wk). Birth outcomes were assessed through hospital birth records. Infant anthropometry and maternal blood biomarkers were followed up at 1 mo postpartum. Fourteen women were taking FA supplements at the third trimester. Dietary intake was similar among FA users and non-users, but serum folate and pyridoxal were significantly higher in users (11.6±6.7 vs. 6.1±3.2 ng/mL, and 13.8±21.7 vs. 3.2±1.4 ng/mL, respectively). Plasma total homocystein (tHcy) was higher in non-users compared to users, but not significantly. Nine FA users and eight non-users had low serum vitamin B(12) values (<203 pg/mL). Nine FA users and all non-users had low serum pyridoxal values (<7.0 ng/mL). Infant birthweight was significantly lower in users compared to non-users (2,894±318 vs. 3,154±230 g). At 1 mo postpartum, infant weight and length were similar between FA users and non-users, but infant weight gain was larger in users. Higher serum folate values due to FA use in the third trimester was related to reduced fetal size. Excess FA under low vitamin B(6) and B(12) status may affect fetal growth. PMID:21697631

  8. Role of the fetoplacental endothelium in fetal growth restriction with abnormal umbilical artery Doppler velocimetry.

    PubMed

    Su, Emily J

    2015-10-01

    Growth-restricted fetuses with absent or reversed end-diastolic velocities in the umbilical artery are at substantially increased risk for adverse perinatal and long-term outcome, even in comparison to growth-restricted fetuses with preserved end-diastolic velocities. Translational studies show that this Doppler velocimetry correlates with fetoplacental blood flow, with absent or reversed end-diastolic velocities signifying abnormally elevated resistance within the placental vasculature. The fetoplacental vasculature is unique in that it is not subject to autonomic regulation, unlike other vascular beds. Instead, humoral mediators, many of which are synthesized by local endothelial cells, regulate placental vascular resistance. Existing data demonstrate that in growth-restricted pregnancies complicated by absent or reversed umbilical artery end-diastolic velocities, an imbalance in production of these vasoactive substances occurs, favoring vasoconstriction. Morphologically, placentas from these pregnancies also demonstrate impaired angiogenesis, whereby vessels within the terminal villi are sparsely branched, abnormally thin, and elongated. This structural deviation from normal placental angiogenesis restricts blood flow and further contributes to elevated fetoplacental vascular resistance. Although considerable work has been done in the field of fetoplacental vascular development and function, much remains unknown about the mechanisms underlying impaired development and function of the human fetoplacental vasculature, especially in the context of severe fetal growth restriction with absent or reversed umbilical artery end-diastolic velocities. Fetoplacental endothelial cells are key regulators of angiogenesis and vasomotor tone. A thorough understanding of their role in placental vascular biology carries the significant potential of discovering clinically relevant and innovative approaches to prevention and treatment of fetal growth restriction with compromised

  9. The Role of Mucosal Defense in Intestinal Injury of Infants With Fetal Growth Retardation

    PubMed Central

    Panakhova, Nushaba F.

    2016-01-01

    Background: Infants with fetal growth retardation (FGR) are prone to intestinal disorders. Objectives: Aim of the study was to determine the role of mucosal defense ability in formation of gut injury in infants with FGR. Materials and Methods: 44 premature infants who were admitted to the Neonatal Intensive Care Unit were divided into two groups: 20 infants with FGR (FGR group) and 24 appropriate-for-gestational age newborns (AGA group). Control group consisted of 22 premature infants who were delivered after uncomplicated pregnancy. Gut barrier function was evaluated by detecting serum intestinal trefoil factor (ITF) and intestinal fatty acid binding protein (IFABP). The level of serum IFABP and ITF was measured by using ELISA method. Results: FGR group showed significantly higher ITF concentration than AGA group on the first days of life (P ˂ 0.01). High level of ITF in the FGR group significantly declines up to 7th - 10th day of life (P ˂ 0.01). This reduction was accompanied by increase of IFABP which is a marker of ischemic intestinal mucosal injury. Correlation analyses showed that ITF had a negative correlation with IFABP. Conclusions: Infants with fetal growth retardation are characterized by a high level of ITF on the first days of life. This protects intestinal mucosa under hypoxic conditions. Its subsequent decline accompanied by an increase of IFABP reflects the depletion of Goblet cells to secret ITF causing damage to the integrity of intestinal mucosal barrier. PMID:26848381

  10. Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth.

    PubMed

    Aye, Irving L M H; Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

    2015-10-13

    Mothers with obesity or gestational diabetes mellitus have low circulating levels of adiponectin (ADN) and frequently deliver large babies with increased fat mass, who are susceptible to perinatal complications and to development of metabolic syndrome later in life. It is currently unknown if the inverse correlation between maternal ADN and fetal growth reflects a cause-and-effect relationship. We tested the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin/mechanistic target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/6J mice fed an obesogenic diet before mating and throughout gestation had increased fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was activated, peroxisome proliferator-activated receptor-α (PPARα) phosphorylation was reduced, placental transport of glucose and amino acids in vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN infusion in obese dams from E14.5 to E18.5 normalized maternal insulin sensitivity, placental insulin/mTORC1 and PPARα signaling, nutrient transport, and fetal growth without affecting maternal fat mass. Using a mouse model with striking similarities to obese pregnant women, we demonstrate that ADN functions as an endocrine link between maternal adipose tissue and fetal growth by regulating placental function. Importantly, maternal ADN supplementation reversed the adverse effects of maternal obesity on placental function and fetal growth. Improving maternal ADN levels may serve as an effective intervention strategy to prevent fetal overgrowth caused by maternal obesity. PMID:26417088

  11. Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth

    PubMed Central

    Aye, Irving L. M. H.; Rosario, Fredrick J.; Powell, Theresa L.; Jansson, Thomas

    2015-01-01

    Mothers with obesity or gestational diabetes mellitus have low circulating levels of adiponectin (ADN) and frequently deliver large babies with increased fat mass, who are susceptible to perinatal complications and to development of metabolic syndrome later in life. It is currently unknown if the inverse correlation between maternal ADN and fetal growth reflects a cause-and-effect relationship. We tested the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin/mechanistic target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/6J mice fed an obesogenic diet before mating and throughout gestation had increased fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was activated, peroxisome proliferator-activated receptor-α (PPARα) phosphorylation was reduced, placental transport of glucose and amino acids in vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN infusion in obese dams from E14.5 to E18.5 normalized maternal insulin sensitivity, placental insulin/mTORC1 and PPARα signaling, nutrient transport, and fetal growth without affecting maternal fat mass. Using a mouse model with striking similarities to obese pregnant women, we demonstrate that ADN functions as an endocrine link between maternal adipose tissue and fetal growth by regulating placental function. Importantly, maternal ADN supplementation reversed the adverse effects of maternal obesity on placental function and fetal growth. Improving maternal ADN levels may serve as an effective intervention strategy to prevent fetal overgrowth caused by maternal obesity. PMID:26417088

  12. Comparative Analysis of Normal versus Fetal Growth Restriction in Pregnancy: The Significance of Maternal Body Mass Index, Nutritional Status, Anemia, and Ultrasonography Screening

    PubMed Central

    Sawant, Laxmichaya D.; Venkat, Shirin

    2013-01-01

    Fetal growth restriction or intrauterine growth restriction is one of the leading causes of perinatal mortality and morbidity in newborns. Fetal growth restriction is a complex multifactorial condition resulting from several fetal and maternal disorders. The objective of this study was twofold: first to examine the correlation between maternal parameters such as body mass index (BMI), nutritional status, anemia, and placental weight and diameter, and their effects on fetal growth and then to evaluate the effect of early screening by ultrasonography (USG) on the outcome of growth restricted pregnancies. In this study, 53 cases of fetal growth restriction were compared to 53 normal fetuses delivered in consecutive sequence. Growth restricted fetuses were delivered earlier in gestation, when compared with normal growth fetuses. Maternal anemia and malnutrition have significant association with the fetal growth restriction. Maternal anthropometry, such as low BMI, had effects on placental diameter and weight, which, in turn, adversely affected fetal weight. Thus, early USG screening along with robust screening for maternal BMI, nutritional status, and anemia can assist the obstetric team in providing early diagnosis, prompt intervention, and better outcome in pregnancy with fetal growth restriction. PMID:25763389

  13. Dysregulated flow-mediated vasodilatation in the human placenta in fetal growth restriction

    PubMed Central

    Jones, Sarah; Bischof, Helen; Lang, Ingrid; Desoye, Gernot; Greenwood, Sue L; Johnstone, Edward D; Wareing, Mark; Sibley, Colin P; Brownbill, Paul

    2015-01-01

    Increased vascular resistance and reduced fetoplacental blood flow are putative aetiologies in the pathogenesis of fetal growth restriction (FGR); however, the regulating sites and mechanisms remain unclear. We hypothesised that placental vessels dictate fetoplacental resistance and in FGR exhibit endothelial dysfunction and reduced flow-mediated vasodilatation (FMVD). Resistance was measured in normal pregnancies (n = 10) and FGR (n = 10) both in vivo by umbilical artery Doppler velocimetry and ex vivo by dual placental perfusion. Ex vivo FMVD is the reduction in fetal-side inflow hydrostatic pressure (FIHP) following increased flow rate. Results demonstrated a significant correlation between vascular resistance measured in vivo and ex vivo in normal pregnancy, but not in FGR. In perfused FGR placentas, vascular resistance was significantly elevated compared to normal placentas (58 ± 7.7 mmHg and 36.8 ± 4.5 mmHg, respectively; 8 ml min−1; means ± SEM; P < 0.0001) and FMVD was severely reduced (3.9 ± 1.3% and 9.1 ± 1.2%, respectively). In normal pregnancies only, the highest level of ex vivo FMVD was associated with the lowest in vivo resistance. Inhibition of NO synthesis during perfusion (100 μm l-NNA) moderately elevated FIHP in the normal group, but substantially in the FGR group. Human placenta artery endothelial cells from FGR groups exhibited increased shear stress-induced NO generation, iNOS expression and eNOS expression compared with normal groups. In conclusion, fetoplacental resistance is determined by placental vessels, and is increased in FGR. The latter also exhibit reduced FMVD, but with a partial compensatory increased NO generation capacity. The data support our hypothesis, which highlights the importance of FMVD regulation in normal and dysfunctional placentation. Key points A correlation was found between in vivo umbilical artery Doppler velocimetry and resistance to fetal-side flow in the human ex vivo dually

  14. Placental restriction of fetal growth decreases IGF1 and leptin mRNA expression in the perirenal adipose tissue of late gestation fetal sheep.

    PubMed

    Duffield, Jaime A; Vuocolo, Tony; Tellam, Ross; Yuen, Bernard S; Muhlhausler, Beverly S; McMillen, I Caroline

    2008-05-01

    Placental restriction (PR) of fetal growth results in a low birth weight and an increased visceral fat mass in postnatal life. We investigated whether PR alters expression of genes that regulate adipogenesis [IGF1, IGF1 receptor (IGF1R), IGF2, IGF2R, proliferator-activated receptor-gamma, retinoid-X-receptor-alpha], adipocyte metabolism (lipoprotein lipase, G3PDH, GAPDH) and adipokine signaling (leptin, adiponectin) in visceral adipose tissue before birth. PR was induced by removal of the majority of endometrial caruncles in nonpregnant ewes before mating. Fetal blood samples were collected from 116 days gestation, and perirenal visceral adipose tissue (PAT) was collected from PR and control fetuses at 145 days. PAT gene expression was measured by quantitative RT-PCR. PR fetuses had a lower weight (PR 2.90 +/- 0.32 kg; control, 5.12 +/- 0.24 kg; P < 0.0001), mean gestational arterial Po(2) (P < 0.0001), plasma glucose (P < 0.01), and insulin concentrations (P < 0.02), than controls. The expression of IGF1 mRNA in PAT was lower in the PR fetuses (PR, 0.332 +/- 0.063; control, 0.741 +/- 0.083; P < 0.01). Leptin mRNA expression in PAT was also lower in PR fetuses (PR, 0.077 +/- 0.009; control, 0.115 +/- 0.013; P < 0.05), although there was no difference in the expression of other adipokine or adipogenic genes in PAT between PR and control fetuses. Thus, restriction of placental and hence, fetal substrate supply results in decreased IGF1 and leptin expression in fetal visceral adipose tissue, which may alter the functional development of the perirenal fat depot and contribute to altered leptin signaling in the growth-restricted newborn and the subsequent emergence of an increased visceral adiposity. PMID:18272661

  15. Localization of transforming growth factor-beta at the human fetal-maternal interface: role in trophoblast growth and differentiation.

    PubMed

    Graham, C H; Lysiak, J J; McCrae, K R; Lala, P K

    1992-04-01

    -TGF-beta antibody to first-trimester trophoblast cells stimulated proliferation beyond control levels in a 24-h culture and reduced formation of multinucleated cells in a 3-day culture, indicating the presence of endogenous TGF-beta activity. These results indicate that TGF-beta produced at the human fetal-maternal interface plays a major regulatory role in the proliferation and differentiation of the trophoblast. PMID:1374270

  16. Structural equation modeling and nested ANOVA: Effects of lead exposure on maternal and fetal growth in rats

    SciTech Connect

    Hamilton, J.D. ); O'Flaherty, E.J.; Shukla, R.; Gartside, P.S. ); Ross, R. )

    1994-01-01

    This study provided an assessment of the effects of lead on early growth in rats based on structural equation modeling and nested analysis of variance (ANOVA). Structural equation modeling showed that lead in drinking water (250, 500, or 1000 ppm) had a direct negative effect on body weight and tail length (i.e., growth) in female rats during the first week of exposure. During the following 2 weeks of exposure, high correlation between growth measurements taken over time resulted in reduced early postnatal growth. By the fourth week of exposure, reduced growth was not evident. Mating began after 8 weeks of exposure, and exposure continued during gestation. Decreased fetal body weight was detected when the effects of litter size, intrauterine position, and sex were controlled in a nested ANOVA. Lead exposure did not appear to affect fetal skeletal development, possibly because lead did not alter maternal serum calcium and phosphorus levels. The effect of lead on individual fetal body weight suggests that additional studies are needed to examine the effect of maternal lead exposure on fetal development and early postnatal growth. 24 refs., 4 figs., 6 tabs.

  17. First trimester fetal growth restriction and cardiovascular risk factors in school age children: population based cohort study

    PubMed Central

    de Jonge, Layla L; Hofman, Albert; Franco, Oscar H; Steegers, Eric A P; Gaillard, Romy

    2014-01-01

    Objective To examine whether first trimester fetal growth restriction correlates with cardiovascular outcomes in childhood. Design Population based prospective cohort study. Setting City of Rotterdam, the Netherlands. Participants 1184 children with first trimester fetal crown to rump length measurements, whose mothers had a reliable first day of their last menstrual period and a regular menstrual cycle. Main outcomes measures Body mass index, total and abdominal fat distribution, blood pressure, and blood concentrations of cholesterol, triglycerides, insulin, and C peptide at the median age of 6.0 (90% range 5.7-6.8) years. Clustering of cardiovascular risk factors was defined as having three or more of: high android fat mass; high systolic or diastolic blood pressure; low high density lipoprotein cholesterol or high triglycerides concentrations; and high insulin concentrations. Results One standard deviation score greater first trimester fetal crown to rump length was associated with a lower total fat mass (−0.30%, 95% confidence interval −0.57% to −0.03%), android fat mass (−0.07%, −0.12% to −0.02%), android/gynoid fat mass ratio (−0.53, −0.89 to −0.17), diastolic blood pressure (−0.43, −0.84 to −0.01, mm Hg), total cholesterol (−0.05, −0.10 to 0, mmol/L), low density lipoprotein cholesterol (−0.04, −0.09 to 0, mmol/L), and risk of clustering of cardiovascular risk factors (relative risk 0.81, 0.66 to 1.00) in childhood. Additional adjustment for gestational age and weight at birth changed these effect estimates only slightly. Childhood body mass index fully explained the associations of first trimester fetal crown to rump length with childhood total fat mass. First trimester fetal growth was not associated with other cardiovascular outcomes. Longitudinal growth analyses showed that compared with school age children without clustering of cardiovascular risk factors, those with clustering had a smaller first trimester fetal crown

  18. Fetal Alcohol Spectrum Disorder (FASD): neurobehavioral profile, indications for diagnosis and treatment.

    PubMed

    Coriale, Giovanna; Fiorentino, Daniela; Di Lauro, Francesca; Marchitelli, René; Scalese, Bruna; Fiore, Marco; Maviglia, Marcello; Ceccanti, Mauro

    2013-01-01

    It is now known that exposure to alcohol in utero produces a wide spectrum of morphological and behavioural outcomes in the offspring, commonly referred as fetal alcohol spectrum disorders (FASD). A large body of literature documents cognitive deficits and behavioural-emotional difficulties in children with FASD. Researchers have found that individuals with FASD often experience a range of adverse life outcomes, called secondary disabilities, which include disrupted school experience, troubles with the law, confinement, inappropriate sexual behaviours on repeated occasions, and alcohol/drug related problems. Additionally, despite considerable data published on cognitive and behavioural disabilities in children with FASD, relatively little information is available on behavioural or pharmacological interventions for alcohol affected children. This paper will provide a comprehensive review of the neuropsychological and behavioural effects of prenatal alcohol exposure, including a discussion of the emerging neurobehavioral profile. Finally, we will summarize published intervention studies of FASD focusing on their strengths and weaknesses. PMID:24326748

  19. Prenatal Exposure to Traffic-Related Air Pollution and Ultrasound Measures of Fetal Growth in the INMA Sabadell Cohort

    PubMed Central

    Aguilera, Inmaculada; Garcia-Esteban, Raquel; Iñiguez, Carmen; Nieuwenhuijsen, Mark J.; Rodríguez, Àgueda; Paez, Montserrat; Ballester, Ferran; Sunyer, Jordi

    2010-01-01

    Background Few studies have used longitudinal ultrasound measurements to assess the effect of traffic-related air pollution on fetal growth. Objective We examined the relationship between exposure to nitrogen dioxide (NO2) and aromatic hydrocarbons [benzene, toluene, ethylbenzene, m/p-xylene, and o-xylene (BTEX)] on fetal growth assessed by 1,692 ultrasound measurements among 562 pregnant women from the Sabadell cohort of the Spanish INMA (Environment and Childhood) study. Methods We used temporally adjusted land-use regression models to estimate exposures to NO2 and BTEX. We fitted mixed-effects models to estimate longitudinal growth curves for femur length (FL), head circumference (HC), abdominal circumference (AC), biparietal diameter (BPD), and estimated fetal weight (EFW). Unconditional and conditional SD scores were calculated at 12, 20, and 32 weeks of gestation. Sensitivity analyses were performed considering time–activity patterns during pregnancy. Results Exposure to BTEX from early pregnancy was negatively associated with growth in BPD during weeks 20–32. None of the other fetal growth parameters were associated with exposure to air pollution during pregnancy. When considering only women who spent < 2 hr/day in nonresidential outdoor locations, effect estimates were stronger and statistically significant for the association between NO2 and growth in HC during weeks 12–20 and growth in AC, BPD, and EFW during weeks 20–32. Conclusions Our results lend some support to an effect of exposure to traffic-related air pollutants from early pregnancy on fetal growth during mid-pregnancy. PMID:20103496

  20. Spinal fusion with demineralized calf fetal growth plate as novel biomaterial in rat model: a preliminary study

    PubMed Central

    Karimi, Iraj; Oryan, Ahmad; Mahmoudi, Elena; Shafiei-Sarvestani, Zahra

    2014-01-01

    Background Spinal fusions are being performed for various pathologies of the spine such as degenerative diseases, deformities, tumors and fractures. Recently, other bone substitutes such as demineralized bone matrix (DBM) have been developed for spinal fusion. Therefore, this study was conducted to evaluate the intertransverse posterolateral fusion with the Bovine fetal growth plate (DCFGP) and compare it with commercial DBM in rat model. Methods A total of 16 mature male rats (aged 4 months and weighing 200-300 g) were randomly divided in two groups. After a skin incision on posterolateral site, two separate fascial incisions were made 3 mm from the midline. A muscle-splitting approach was used to expose the transverse processes of L4 and L5. Group I (n = 8) underwent with implanted Bovine fetal growth plate among decorticated transverse processes. In group II (n = 8) commercial DBM was placed in the same manner. Fusion was evaluated by manual palpation, radiographical, gross and histopathological analysis. Results The manual palpation, radiological, gross and histopathological findings indicate high potential of the DCFGP in spinal fusion. At the 42nd postoperative day, new bone formation as evidenced by a bridge between L4 and L5 was visualized in all rats implanted with DCFGP and commercial DBM. The newly formed bone tissue was observed in all implanted areas on the 42nd day after operation in the two groups. Conclusions The spinal fusion of the animals of both groups demonstrated more advanced osteogenic potential and resulted in proper fusion of the transverse process of lumbar vertebra. PMID:25694913

  1. Ultrasonographic Fetal Growth Charts: An Informatic Approach by Quantitative Analysis of the Impact of Ethnicity on Diagnoses Based on a Preliminary Report on Salentinian Population

    PubMed Central

    Bochicchio, Mario Alessandro

    2014-01-01

    Clear guidance on fetal growth assessment is important because of the strong links between growth restriction or macrosomia and adverse perinatal outcome in order to reduce associated morbidity and mortality. Fetal growth curves are extensively adopted to track fetal sizes from the early phases of pregnancy up to delivery. In the literature, a large variety of reference charts are reported but they are mostly up to five decades old. Furthermore, they do not address several variables and factors (e.g., ethnicity, foods, lifestyle, smoke, and physiological and pathological variables), which are very important for a correct evaluation of the fetal well-being. Therefore, currently adopted fetal growth charts are inadequate to support the melting pot of ethnic groups and lifestyles of our society. Customized fetal growth charts are needed to provide an accurate fetal assessment and to avoid unnecessary obstetric interventions at the time of delivery. Starting from the development of a growth chart purposely built for a specific population, in the paper, authors quantify and analyse the impact of the adoption of wrong growth charts on fetal diagnoses. These results come from a preliminary evaluation of a new open service developed to produce personalized growth charts for specific ethnicity, lifestyle, and other parameters. PMID:25028648

  2. Ultrasonographic fetal growth charts: an informatic approach by quantitative analysis of the impact of ethnicity on diagnoses based on a preliminary report on Salentinian population.

    PubMed

    Tinelli, Andrea; Bochicchio, Mario Alessandro; Vaira, Lucia; Malvasi, Antonio

    2014-01-01

    Clear guidance on fetal growth assessment is important because of the strong links between growth restriction or macrosomia and adverse perinatal outcome in order to reduce associated morbidity and mortality. Fetal growth curves are extensively adopted to track fetal sizes from the early phases of pregnancy up to delivery. In the literature, a large variety of reference charts are reported but they are mostly up to five decades old. Furthermore, they do not address several variables and factors (e.g., ethnicity, foods, lifestyle, smoke, and physiological and pathological variables), which are very important for a correct evaluation of the fetal well-being. Therefore, currently adopted fetal growth charts are inadequate to support the melting pot of ethnic groups and lifestyles of our society. Customized fetal growth charts are needed to provide an accurate fetal assessment and to avoid unnecessary obstetric interventions at the time of delivery. Starting from the development of a growth chart purposely built for a specific population, in the paper, authors quantify and analyse the impact of the adoption of wrong growth charts on fetal diagnoses. These results come from a preliminary evaluation of a new open service developed to produce personalized growth charts for specific ethnicity, lifestyle, and other parameters. PMID:25028648

  3. Extracellular vesicle–depleted fetal bovine and human sera have reduced capacity to support cell growth

    PubMed Central

    Eitan, Erez; Zhang, Shi; Witwer, Kenneth W.; Mattson, Mark P.

    2015-01-01

    Background Fetal bovine serum (FBS) is the most widely used serum supplement for mammalian cell culture. It supports cell growth by providing nutrients, growth signals, and protection from stress. Attempts to develop serum-free media that support cell expansion to the same extent as serum-supplemented media have not yet succeeded, suggesting that FBS contains one or more as-yet-undefined growth factors. One potential vehicle for the delivery of growth factors from serum to cultured cells is extracellular vesicles (EVs). Methods EV-depleted FBS and human serum were generated by 120,000g centrifugation, and its cell growth–supporting activity was measured. Isolated EVs from FBS were quantified and characterized by nanoparticle tracking analysis, electron microscopy, and protein assay. EV internalization into cells was quantified using fluorescent plate reader analysis and microscopy. Results Most cell types cultured with EV-depleted FBS showed a reduced growth rate but not an increased sensitivity to the DNA-damaging agent etoposide and the endoplasmic reticulum stress–inducing chemical tunicamycin. Supplying cells with isolated FBS-derived EVs enhanced their growth. FBS-derived EVs were internalized by mouse and human cells wherein 65±26% of them interacted with the lysosomes. EV-depleted human serum also exhibited reduced cell growth–promoting activity. Conclusions EVs play a role in the cell growth and survival-promoting effects of FBS and human serum. Thus, it is important to take the effect of EV depletion under consideration when planning EV extraction experiments and while attempting to develop serum-free media that support rapid cell expansion. In addition, these findings suggest roles for circulating EVs in supporting cell growth and survival in vivo. PMID:25819213

  4. The insulin-like growth factor II/mannose-6-phosphate receptor is present in fetal and maternal sheep serum.

    PubMed

    Gelato, M C; Rutherford, C; Stark, R I; Daniel, S S

    1989-06-01

    A large mol wt binding protein for insulin-like growth factor II (IGF-II) has been described in fetal sheep serum. We now provide evidence to demonstrate that this binding protein is the IGF-II/mannose-6-phosphate (Man-6-P) receptor. Serum and plasma were gel filtered on Sephadex G-200, and the column fractions were assayed for binding of radiolabeled IGF-II. There was significant binding of [125I]IGF-II to the void volume fractions in addition to binding to the 150K and 40K carrier proteins. Binding to the void volume fractions was increased in fetal serum as well as maternal serum and dramatically decreased in the nonpregnant adult. Competitive binding studies with [125I]IGF-II and the void volume pools from fetal and maternal sheep serum demonstrated that IGF-I competed less potently than IGF-II, and insulin did not compete. There was no specific binding of [125I]IGF-I to the void volume pools of either fetal or maternal samples. Chemical cross-linking of [125I]IGF-II to aliquots of the void volume pools from fetal and maternal sheep serum samples and analysis with sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence of dithiothreitol demonstrated a specific band at about 240K. Western blotting using a specific antiserum (no. 3637) against rat IGF-II/Man-6-P receptor was performed on aliquots of the Sephadex G-200 void volume pools of fetal, maternal, uterine vein, and adult sheep serum; a band of approximately 210K (without dithiothreitol) was seen. The IGF-II/Man-6-P receptor band was more intense in fetal serum than in either maternal or adult nonpregnant sheep serum. There was also increased binding of [125I]IGF-II in the 40K region of the Sephadex G-200 column fractions in the maternal serum compared to that in serum from nonpregnant adult ewes. When fetal, maternal, and adult nonpregnant sheep serum Sephadex G-200 pools were gel filtered on Sephadex G-50 in 1 mol/liter acetic acid to separate bound from free IGF, and IGF-II was

  5. Acoustic output measured by thermal and mechanical indices during fetal echocardiography at the time of the first trimester scan.

    PubMed

    Nemescu, Dragos; Berescu, Anca

    2015-01-01

    We measured acoustic output, expressed as the thermal index (TI) and mechanical index (MI), during fetal echocardiography at the time of the first trimester scan. TI and MI were retrieved from the saved displays during gray-mode, high-definition color flow Doppler and pulsed-wave Doppler (tricuspid flow) ultrasound examinations of the fetal heart and from the ductus venosus assessment. A total of 399 fetal cardiac examinations were evaluated. There was a significant increase in TI values from B-mode studies (0.07 ± 0.04 [mean ± SD]) to color flow mapping (0.2 ± 0.0) and pulsed-wave Doppler studies (0.36 ± 0.05). The TI from ductus venosus assessment (0.1 ± 0.01) was significantly lower than those from Doppler examinations of the heart. MI values from B-mode scans (0.65 ± 0.12) and color flow mapping (0.71 ± 0.11) were comparable, although different, and both values were higher than those from pulsed-wave Doppler tricuspid evaluation (0.39 ± 0.03). There were no differences in MI values from power Doppler assessment between the tricuspid flow and ductus venosus. Safety indices were remarkably stable and were largely constant, especially for color Doppler (TI), tricuspid flow (MI) and ductus venosus assessment (TI, MI). We acquired satisfactory Doppler images and/or signals at acoustic levels that were lower than the actual recommendations and never reached a TI of 0.5. PMID:25438839

  6. Fetal and Neonatal Levels of Omega-3: Effects on Neurodevelopment, Nutrition, and Growth

    PubMed Central

    Bernardi, Juliana Rombaldi; Escobar, Renata de Souza; Ferreira, Charles Francisco; Silveira, Patrícia Pelufo

    2012-01-01

    Nutrition in pregnancy, during lactation, childhood, and later stages has a fundamental influence on overall development. There is a growing research interest on the role of key dietary nutrients in fetal health. Omega-3 polyunsaturated fatty acids (n-3 LCPUFAs) play an important role in brain development and function. Evidence from animal models of dietary n-3 LCPUFAs deficiency suggests that these fatty acids promote early brain development and regulate behavioral and neurochemical aspects related to mood disorders (stress responses, depression, and aggression and growth, memory, and cognitive functions). Preclinical and clinical studies suggest the role of n-3 LCPUFAs on neurodevelopment and growth. n-3 LCPUFAs may be an effective adjunctive factor for neural development, growth, and cognitive development, but further large-scale, well-controlled trials and preclinical studies are needed to examine its clinical mechanisms and possible benefits. The present paper discusses the use of n-3 LCPUFAs during different developmental stages and the investigation of different sources of consumption. The paper summarizes the role of n-3 LCPUFAs levels during critical periods and their effects on the children's neurodevelopment, nutrition, and growth. PMID:23125553

  7. Exposure to Bisphenol A and Phthalates during Pregnancy and Ultrasound Measures of Fetal Growth in the INMA-Sabadell Cohort

    PubMed Central

    Casas, Maribel; Valvi, Damaskini; Ballesteros-Gomez, Ana; Gascon, Mireia; Fernández, Mariana F.; Garcia-Esteban, Raquel; Iñiguez, Carmen; Martínez, David; Murcia, Mario; Monfort, Nuria; Luque, Noelia; Rubio, Soledad; Ventura, Rosa; Sunyer, Jordi; Vrijheid, Martine

    2015-01-01

    Background: Prenatal exposure to bisphenol A (BPA) and phthalates may affect fetal growth; however, previous findings are inconsistent and based on few studies. Objectives: We assessed whether prenatal exposure to BPA and phthalates was associated with fetal growth in a Spanish birth cohort of 488 mother–child pairs. Methods: We measured BPA and eight phthalates [four di(2-ethylhexyl) phthalate metabolites (DEHPm), mono-benzyl phthalate (MBzP), and three low-molecular-weight phthalate metabolites (LMWPm)] in two spot-urine samples collected during the first and third trimester of pregnancy. We estimated growth curves for femur length (FL), head circumference (HC), abdominal circumference (AC), biparietal diameter (BPD), and estimated fetal weight (EFW) during pregnancy (weeks 12–20 and 20–34), and for birth weight, birth length, head circumference at birth, and placental weight. Results: Overall, results did not support associations of exposure to BPA or DEHPm during pregnancy with fetal growth parameters. Prenatal MBzP exposure was positively associated with FL at 20–34 weeks, resulting in an increase of 3.70% of the average FL (95% CI: 0.75, 6.63%) per doubling of MBzP concentration. MBzP was positively associated with birth weight among boys (48 g; 95% CI: 6, 90) but not in girls (–27 g; 95% CI: –79, 25) (interaction p-value = 0.04). The LMWPm mono-n-butyl phthalate (MnBP) was negatively associated with HC at 12–20 pregnancy weeks [–4.88% of HC average (95% CI: –8.36, –1.36%)]. Conclusions: This study, one of the first to combine repeat exposure biomarker measurements and multiple growth measures during pregnancy, finds little evidence of associations of BPA or phthalate exposures with fetal growth. Phthalate metabolites MBzP and MnBP were associated with some fetal growth parameters, but these findings require replication. Citation: Casas M, Valvi D, Ballesteros-Gomez A, Gascon M, Fernández MF, Garcia-Esteban R, Iñiguez C, Martínez D

  8. Effortful Control Mediates Associations of Fetal Growth with Hyperactivity and Behavioural Problems in 7- to 9-Year-Old Children

    ERIC Educational Resources Information Center

    Schlotz, Wolff; Jones, Alexander; Godfrey, Keith M.; Phillips, David I. W.

    2008-01-01

    Background: Inverse associations of fetal growth with behavioural problems in childhood have been repeatedly reported, suggesting long-term effects of the prenatal developmental environment on behaviour later in life. However, no study so far has examined effects on temperament and potential developmental pathways. Temperamental traits may be…

  9. Ultrasonographic measurement of fetal growth parameters over three successive pregnancies in a captive Malayan tapir (Tapirus indicus).

    PubMed

    Hoyer, M J; van Engeldorp Gastelaars, H M D

    2014-01-01

    This study was conducted to establish representative curves that allow evaluation of fetal growth and estimation of gestational age from measurement of fetal structures by ultrasound in Malayan tapirs (Tapirus indicus). Three pregnancies (i.e. 3 fetuses) were examined in one female Malayan tapir. Transabdominal ultrasonographic examination was performed without anesthesia from 79 ± 8 days to 281 ± 48 days (mean ± S.D.) post mating. To assess fetal growth attempts were made to measure biparietal diameter (BPD), head length (HL), thorax diameter A (TDA), thorax height A (THA), thorax diameter B (TDB), thorax height B (THB), abdomen diameter (AD), abdomen height (AH), humerus length (HUL) and Crown rump length (CRL). The value of each parameter as an estimator of gestational age was assessed by ease of observation and the length of time the parameter was measurable throughout gestation. The most precise predictors for gestational age in this study were BPD and CRL (weeks 10-20 of gestation), as well as AD and AH (weeks 14-43 of gestation). The parameters TDB, THB and HUL (weeks 15-41 of gestation) gave almost as good predictions. Fetal viability was assessed by identifying a fetal heartbeat and movement. All pregnancies resulted in normal deliveries and healthy offspring. The ultrasound examination was well tolerated by the female. The gestation lengths (399 ± 3 days) were within reported ranges. The serial transabdominal ultrasound, without the need for anesthesia, was an effective method to evaluate fetal growth, development and well being in a Malayan tapir. PMID:25042428

  10. Trends in fetal indications for termination of pregnancy between 2002 and 2010 at a tertiary referral centre

    PubMed Central

    Çorbacıoğlu, Aytül; Aslan, Halil; Aydın, Serdar; Akbayır, Özgür; Ersan, Fırat; Alpay, Verda; Dağdeviren, Hediye; Kısacık, Songül

    2012-01-01

    Objective We reviewed the data of the termination of pregnancy (TOP) cases between 2002 and 2010 to evaluate the changes in fetal indications for both early and late TOPs in this period. Material and Methods The data of 962 TOP cases were analysed in two groups according to the periods as in 2002–2006 and 2007–2010. The women were also subdivided into two categories according to their gestational age; <23 weeks’ gestation (early termination) and ≥23 weeks’ gestation (late termination). Results Four hundred and fifty-eight (47.6%) of TOPs were performed between 2002 and 2006 (Group 1) and 504 (52.3%) were performed between 2007 and 2010 (Group 2). The number of early (<23 weeks) and late (≥23 weeks) terminations were 583 (60.6%) and 379 (39.3%), respectively. The vast majority of anomalies were central nervous sytem malformations (51.8%). They were followed by multiple anomalies (10.2%) and chromosomal anomalies (9.4%). Chromosomal and cardiovascular system anomalies were significantly higher in 2007–2010 in comparison to 2002–2006 (p<0.0001 and p=0.002, respectively). There was no statistically significant difference between the fetal indications that led to early termination compared to those that led to late termination. Conclusion The distribution of indications for TOP was influenced by the development in prenatal screening policy, resulting in a significant increase in terminations due to chromosomal and cardiovascular system anomalies. Cultural, educational, religious and legal factors cause differences in the indications for TOP as well as the gestational age that TOPS are performed. PMID:24592014

  11. Fetal Programming and Cardiovascular Pathology

    PubMed Central

    Alexander, Barbara T.; Dasinger, John Henry; Intapad, Suttira

    2016-01-01

    Low birth weight serves as a crude proxy for impaired growth during fetal life and indicates a failure for the fetus to achieve its full growth potential. Low birth weight can occur in response to numerous etiologies that include complications during pregnancy, poor prenatal care, parental smoking, maternal alcohol consumption or stress. Numerous epidemiological and experimental studies demonstrate that birth weight is inversely associated with blood pressure and coronary heart disease. Sex and age impact the developmental programming of hypertension. In addition, impaired growth during fetal life also programs enhanced vulnerability to a secondary insult. Macrosomia, which occurs in response to maternal obesity, diabetes and excessive weight gain during gestation, is also associated with increased cardiovascular risk. Yet, the exact mechanisms that permanently change the structure, physiology and endocrine health of an individual across their lifespan following altered growth during fetal life are not entirely clear. Transmission of increased risk from one generation to the next in the absence of an additional prenatal insult indicates an important role for epigenetic processes. Experimental studies also indicate that the sympathetic nervous system, the renin angiotensin system, increased production of oxidative stress and increased endothelin play an important role in the developmental programming of blood pressure in later life. Thus, this review will highlight how adverse influences during fetal life and early development program an increased risk for cardiovascular disease including high blood pressure and provide an overview of the underlying mechanisms that contribute to the fetal origins of cardiovascular pathology. PMID:25880521

  12. Is the fetoplacental ratio a differential marker of fetal growth restriction in small for gestational age infants?

    PubMed

    Luque-Fernandez, Miguel Angel; Ananth, Cande V; Jaddoe, Vincent W V; Gaillard, Romy; Albert, Paul S; Schomaker, Michael; McElduff, Patrick; Enquobahrie, Daniel A; Gelaye, Bizu; Williams, Michelle A

    2015-04-01

    Higher placental weight relative to birthweight has been described as an adaptive mechanism to fetal hypoxia in small for gestational age (SGA) infants. However, placental weight alone may not be a good marker reflecting intrauterine growth restriction. We hypothesized that fetoplacental ratio (FPR)-the ratio between birthweight and placental weight-may serve as a good marker of SGA after adjustment for surrogates of fetal hypoxemia (maternal iron deficiency anemia, smoking and choriodecidual necrosis). We conducted a within-sibling analysis using data from the US National Collaborative Perinatal Project (1959-1966) of 1,803 women who delivered their first two (or more) consecutive infants at term (n = 3,494). We used variance-component fixed-effect linear regression models to explore the effect of observed time-varying factors on placental weight and conditional logistic regression to estimate the effects of the tertiles of FPRs (1st small, 2nd normal and 3rd large) on the odds of SGA infants. We found placental weights to be 15 g [95 % confidence interval (CI) 8, 23] higher and -7 g (95 % CI -13, -2) lower among women that had anemia and choriodecidual necrosis, respectively. After multivariable adjustment, newborns with a small FPR (1st-tertile ≤7) had twofold higher odds of being SGA (OR 2.0, 95 % CI 1.2, 3.5) than their siblings with a large FPR (3nd-tertile ≥9). A small FPR was associated with higher odds of SGA, suggesting that small FPR may serve as an indicator suggestive of adverse intrauterine environment. This observation may help to distinguish pathological from constitutional SGA. PMID:25630563

  13. Effect of fetal undernutrition and postnatal overfeeding on rat adipose tissue and organ growth at early stages of postnatal development.

    PubMed

    Munoz-Valverde, D; Rodríguez-Rodríguez, P; Gutierrez-Arzapalo, P Y; López de Pablo, A L; Carmen González, M; López-Giménez, R; Somoza, B; Arribas, S M

    2015-01-01

    Intrauterine and perinatal life are critical periods for programming of cardiometabolic diseases. However, their relative role remains controversial. We aimed to assess, at weaning, sex-dependent alterations induced by fetal or postnatal nutritional interventions on key organs for metabolic and cardiovascular control. Fetal undernutrition was induced by dam food restriction (50 % from mid-gestation to delivery) returning to ad libitum throughout lactation (Maternal Undernutrition, MUN, 12 pups/litter). Postnatal overfeeding (POF) was induced by litter size reduction from normally fed dams (4 pups/litter). Compared to control, female and male MUN offspring exhibited: 1) low birth weight and accelerated growth, reaching similar weight and tibial length by weaning, 2) increased glycemia, liver and white fat weights; 3) increased ventricular weight and tendency to reduced kidney weight (males only). Female and male POF offspring showed: 1) accelerated growth; 2) increased glycemia, liver and white fat weights; 3) unchanged heart and kidney weights. In conclusion, postnatal accelerated growth, with or without fetal undernutrition, induces early alterations relevant for metabolic disease programming, while fetal undernutrition is required for heart abnormalities. The progression of cardiac alterations and their role on hypertension development needs to be evaluated. The similarities between sexes in pre-pubertal rats suggest a role of sex-hormones in female protection against programming. PMID:25470520

  14. Increased Fetal Plasma Erythropoietin in Monochorionic Twin Pregnancies With Selective Intrauterine Growth Restriction and Abnormal Umbilical Artery Doppler.

    PubMed

    Chang, Yao-Lung; Chao, An-Shine; Peng, Hsiu-Huei; Chang, Shuenn-Dyh; Su, Sheng-Yuan; Chen, Kuan-Ju; Cheng, Po-Jen; Wang, Tzu-Hao

    2016-08-01

    Hypoxia is the primary stimulus for the production of erythropoietin (EPO) in both fetal and adult life. Here, we investigated fetal plasma EPO concentrations in monochorionic (MC) twin pregnancies with selective intrauterine growth restriction (sIUGR) and abnormal umbilical artery (UA) Doppler. We diagnosed sIUGR in presence of (1) birth-weight discordance >20% and (2) either twin with a birth weight <10th percentile. An abnormal UA Doppler was defined as a persistent absent-reverse end diastolic flow (AREDF). The intertwin EPO ratio was calculated as the plasma EPO level of the smaller (or small-for-gestational-age) twin divided by the EPO concentration of the larger (or appropriate-for-gestational-age (AGA)) twin. Thirty-two MC twin pairs were included. Of these, 17 pairs were normal twins (Group 1), seven pairs were twins with sIUGR without UA Doppler abnormalities (Group 2), and eight pairs were twins with sIUGR and UA Doppler abnormalities (Group 3). The highest EPO ratio was identified in Group 3 (p < .001) but no significant differences were observed between Groups 1 and 2. Fetal hemoglobin levels did not differ significantly in the three groups, and fetal EPO concentration did not correlate with gestational age at birth. We conclude that fetal plasma EPO concentrations are selectively increased in MC twin pregnancies with sIUGR and abnormal UA Doppler, possibly as a result of uncompensated hypoxia. PMID:27161360

  15. Insulin-like growth factor binding protein production and regulation in fetal rat lung cells.

    PubMed

    Price, W A; Moats-Staats, B M; D'Ercole, A J; Stiles, A D

    1993-04-01

    Insulin-like growth factor binding proteins (IGFBPs) are expressed in lung from early in gestation and may modulate IGF-stimulated fetal lung cell proliferation and/or differentiation. To begin to define IGFBP production and regulation in lung cells during development, we prepared primary cultures of 19 day gestation fetal rat lung fibroblasts and epithelial cells and identified IGFBPs secreted into medium. Ligand blot analysis of conditioned media (CM) from both cell types demonstrated IGFBP bands of approximately 39,000-45,000, 32,000, 24,000, and 22,000 M(r). These migration characteristics allowed the identification of the 39,000-45,000 M(r) bands as IGFBP-3 and the 24,000 M(r) band as IGFBP-4, while Western immunoblot analyses localized IGFBP-2 to the 32,000 M(r) band and IGFBP-5 to the 22,000 M(r) band. Polymerase chain reaction amplification of cDNAs generated by reverse transcription of fibroblast and epithelial cell RNA using specific oligodeoxynucleotide primers for IGFBPs 1 through 6, demonstrated the presence of amplified products for IGFBP-2, -3, -4, -5, and -6. In both cell types, IGFBP-2 and -3 production was sustained during 48 h of incubation in serum-free medium, whereas IGFBP-4 abundance increased only during the first 6 to 12 h of incubation. CM from fibroblasts and epithelial cells plated at low densities contained a high abundance of IGFBP-2 per microgram cellular DNA compared with cells at higher densities. In contrast, IGFBP-3 and -4 abundance normalized to cell DNA did not change with differing cell densities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7682822

  16. Does milk and dairy consumption during pregnancy influence fetal growth and infant birthweight? A systematic literature review

    PubMed Central

    Brantsæter, Anne Lise; Olafsdottir, Anna S.; Forsum, Elisabet; Olsen, Sjurdur F.; Thorsdottir, Inga

    2012-01-01

    It is increasingly acknowledged that the maternal diet influences fetal development and health of the child. Milk and milk products contribute essential nutrients and bioactive substances; they are of ample supply and have a long tradition in Nordic countries. To revise and update dietary guidelines for pregnant women valid in Nordic countries, the Pregnancy and Lactation expert group within the NNR5 project identified a need to systematically review recent scientific data on infant growth measures and maternal milk consumption. The objective of this study was to assess the influence of milk and dairy consumption during pregnancy on fetal growth through a systematic review of studies published between January 2000 and December 2011. A literature search was run in June 2011. Two authors independently selected studies for inclusion from the 495 abstracts according to predefined eligibility criteria. A complementary search in January 2012 revealed 64 additional abstracts published during the period June to December 2011, among them one study of interest previously identified. Of the 33 studies extracted, eight were relevant research papers. Five were prospective cohort studies (including a retrospective chart review), one was a case–control study, and two were retrospective cohort studies. For fetal length or infant birth length, three studies reported no association and two reported positive associations with milk or dairy consumption. For birthweight related outcomes, two studies reported no associations, and four studies reported positive associations with milk and/or dairy consumption. There was large heterogeneity in exposure range and effect size between studies. A beneficial fetal growth-increase was most pronounced for increasing maternal milk intake in the lower end of the consumption range. Evidence from prospective cohort studies is limited but suggestive that moderate milk consumption relative to none or very low intake, is positively associated with

  17. Maternal constraint on fetal growth patterns in the rhesus monkey (Macaca mulatta): the intergenerational link between mothers and daughters.

    PubMed

    Price, K C; Coe, C L

    2000-02-01

    The gestational experience of a mother can influence the intrauterine environment she provides her own offspring, allowing prenatal events to affect pregnancy outcomes across several generations. Using a multigenerational database, we determined the reproductive consequences for rhesus monkeys descended from small-for-date and large-for-date birth weight matrilines. Both the maternal half-brothers and -sisters of large-for-date infants exhibited enhanced fetal growth, but for small-for-date probands, only the maternal half-sisters experienced significant intrauterine growth constraint. In addition, the growth-restricted females were at higher risk of poor reproductive outcomes in adulthood, and they perpetuated the matrilineal birth weight pattern by selectively constraining the fetal development of their daughters. Collectively, these findings suggest a mechanism for the intergenerational persistence of suboptimal pregnancy outcomes. PMID:10655322

  18. Exogenous transforming growth factor-beta amplifies its own expression and induces scar formation in a model of human fetal skin repair.

    PubMed Central

    Lin, R Y; Sullivan, K M; Argenta, P A; Meuli, M; Lorenz, H P; Adzick, N S

    1995-01-01

    OBJECTIVE: Fetal skin wounds heal without scarring. To determine the role of TGF-beta 1 in fetal wound healing, mRNA expression of TGF-beta 1 was analyzed in human fetal and adult skin wounds. METHODS: Human fetal skin transplanted to a subcutaneous location on an adult athymic mouse that was subsequently wounded heals without scar, whereas human adult skin heals with scar formation in that location. In situ hybridization for TGF-beta 1 mRNA expression and species-specific immunohistochemistry for fibroblasts, macrophages, and neutrophils were performed in human adult wounds, fetal wounds, and fetal wounds treated with a TGF-beta 1 slow release disk. RESULTS: Transforming growth factor-beta 1 mRNA expression was induced by wounding adult skin. No TGF-beta 1 mRNA upregulation was detected in human fetal skin after wounding. However, when exogenous TGF-beta 1 was added to human fetal skin, induction of TGF-beta 1 mRNA expression in human fetal fibroblasts occurred, an adult-like inflammatory response was detected, and the skin healed with scar formation. CONCLUSIONS: Transforming growth factor-beta 1 is an important modulator in scar formation. Anti-TGF-beta 1 strategies may promote scarless healing in adult wounds. Images Figure 1. Figure 2. Figure 3. Figure 5. Figure 6. PMID:7639582

  19. Nicotine-induced retardation of chondrogenesis through down-regulation of IGF-1 signaling pathway to inhibit matrix synthesis of growth plate chondrocytes in fetal rats

    SciTech Connect

    Deng, Yu; Cao, Hong; Cu, Fenglong; Xu, Dan; Lei, Youying; Tan, Yang; Magdalou, Jacques; Wang, Hui; Chen, Liaobin

    2013-05-15

    Previous studies have confirmed that maternal tobacco smoking causes intrauterine growth retardation (IUGR) and skeletal growth retardation. Among a multitude of chemicals associated with cigarette smoking, nicotine is one of the leading candidates for causing low birth weights. However, the possible mechanism of delayed chondrogenesis by prenatal nicotine exposure remains unclear. We investigated the effects of nicotine on fetal growth plate chondrocytes in vivo and in vitro. Rats were given 2.0 mg/kg·d of nicotine subcutaneously from gestational days 11 to 20. Prenatal nicotine exposure increased the levels of fetal blood corticosterone and resulted in fetal skeletal growth retardation. Moreover, nicotine exposure induced the inhibition of matrix synthesis and down-regulation of insulin-like growth factor 1 (IGF-1) signaling in fetal growth plates. The effects of nicotine on growth plates were studied in vitro by exposing fetal growth plate chondrocytes to 0, 1, 10, or 100 μM of nicotine for 10 days. Nicotine inhibited matrix synthesis and down-regulated IGF-1 signaling in chondrocytes in a concentration-dependent manner. These results suggest that prenatal nicotine exposure induces delayed chondrogenesis and that the mechanism may involve the down-regulation of IGF-1 signaling and the inhibition of matrix synthesis by growth plate chondrocytes. The present study aids in the characterization of delayed chondrogenesis caused by prenatal nicotine exposure, which might suggest a candidate mechanism for intrauterine origins of osteoporosis and osteoarthritis. - Highlights: ► Prenatal nicotine-exposure could induce delayed chondrogenesis in fetal rats. ► Nicotine inhibits matrix synthesis of fetal growth plate chondrocytes. ► Nicotine inhibits IGF-1 signaling pathway in fetal growth plate chondrocytes.

  20. Prenatal Exposure to Organophosphorous Pesticides and Fetal Growth: Pooled Results from Four Longitudinal Birth Cohort Studies

    PubMed Central

    Harley, Kim G.; Engel, Stephanie M.; Vedar, Michelle G.; Eskenazi, Brenda; Whyatt, Robin M.; Lanphear, Bruce P.; Bradman, Asa; Rauh, Virginia A.; Yolton, Kimberly; Hornung, Richard W.; Wetmur, James G.; Chen, Jia; Holland, Nina T.; Barr, Dana Boyd; Perera, Frederica P.; Wolff, Mary S.

    2015-01-01

    Background: Organophosphorous (OP) pesticides are associated with reduced fetal growth in animals, but human studies are inconsistent. Objectives: We pooled data from four cohorts to examine associations of prenatal OP exposure with birth weight (n = 1,169), length (n = 1,152), and head circumference (n = 1,143). Methods: Data were from the CHAMACOS, HOME, Columbia, and Mount Sinai birth cohorts. Concentrations of three diethyl phosphate (ΣDEP) and three dimethyl phosphate (ΣDMP) metabolites of OP pesticides [summed to six dialkyl phosphates (ΣDAPs)] were measured in maternal urine. Linear regression and mixed-effects models were used to examine associations with birth outcomes. Results: We found no significant associations of ΣDEP, ΣDMP, or ΣDAPs with birth weight, length, or head circumference overall. However, among non-Hispanic black women, increasing urinary ΣDAP and ΣDMP concentrations were associated with decreased birth length (β = –0.4 cm; 95% CI: –0.9, 0.0 and β = –0.4 cm; 95% CI: –0.8, 0.0, respectively, for each 10-fold increase in metabolite concentration). Among infants with the PON1192RR genotype, ΣDAP and ΣDMP were negatively associated with length (β = –0.4 cm; 95% CI: –0.9, 0.0 and β = –0.5 cm; 95% CI: –0.9, –0.1). Conclusions: This study confirms previously reported associations of prenatal OP exposure among black women with decreased infant size at birth, but finds no evidence of smaller birth weight, length, or head circumference among whites or Hispanics. Contrary to our hypothesis, we found stronger inverse associations of DAPs and birth outcome in infants with the less susceptible PON1192RR genotype. The large pooled data set facilitated exploration of interactions by race/ethnicity and PON1 genotype, but was limited by differences in study populations. Citation: Harley KG, Engel SM, Vedar MG, Eskenazi B, Whyatt RM, Lanphear BP, Bradman A, Rauh VA, Yolton K, Hornung RW, Wetmur JG, Chen J, Holland NT, Barr DB

  1. Placental restriction of fetal growth reduces cutaneous responses to antigen after sensitization in sheep.

    PubMed

    Wooldridge, Amy L; Bischof, Robert J; Meeusen, Els N; Liu, Hong; Heinemann, Gary K; Hunter, Damien S; Giles, Lynne C; Kind, Karen L; Owens, Julie A; Clifton, Vicki L; Gatford, Kathryn L

    2014-04-01

    Prenatal and early childhood exposures are implicated as causes of allergy, but the effects of intrauterine growth restriction on immune function and allergy are poorly defined. We therefore evaluated effects of experimental restriction of fetal growth on immune function and allergic sensitization in adolescent sheep. Immune function (circulating total red and white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, and the antibody response to Clostridial vaccination) and responses to house dust mite (HDM) allergen and ovalbumin (OVA) antigen sensitization (specific total Ig, IgG1, and IgE antibodies, and cutaneous hypersensitivity) were investigated in adolescent sheep from placentally restricted (PR, n = 23) and control (n = 40) pregnancies. Increases in circulating HDM-specific IgE (P = 0.007) and OVA-specific IgE (P = 0.038) were greater in PR than control progeny. PR did not alter total Ig, IgG1, or IgM responses to either antigen. PR increased OVA-specific but not HDM-specific IgA responses in females only (P = 0.023). Multiple birth increased Ig responses to OVA in a sex-specific manner. PR decreased the proportion of positive cutaneous hypersensitivity responders to OVA at 24 h (P = 0.030) but had no effect on cutaneous responses to HDM. Acute wheal responses to intradermal histamine correlated positively with birth weight in singletons (P = 0.023). Intrauterine growth restriction may suppress inflammatory responses in skin downstream of IgE induction, without impairment in antibody responses to a nonpolysaccharide vaccine. Discord between cutaneous and IgE responses following sensitization suggests new mechanisms for prenatal allergy programming. PMID:24500430

  2. Placental restriction of fetal growth reduces cutaneous responses to antigen after sensitization in sheep

    PubMed Central

    Wooldridge, Amy L.; Bischof, Robert J.; Meeusen, Els N.; Liu, Hong; Heinemann, Gary K.; Hunter, Damien S.; Giles, Lynne C.; Kind, Karen L.; Owens, Julie A.; Clifton, Vicki L.

    2014-01-01

    Prenatal and early childhood exposures are implicated as causes of allergy, but the effects of intrauterine growth restriction on immune function and allergy are poorly defined. We therefore evaluated effects of experimental restriction of fetal growth on immune function and allergic sensitization in adolescent sheep. Immune function (circulating total red and white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, and the antibody response to Clostridial vaccination) and responses to house dust mite (HDM) allergen and ovalbumin (OVA) antigen sensitization (specific total Ig, IgG1, and IgE antibodies, and cutaneous hypersensitivity) were investigated in adolescent sheep from placentally restricted (PR, n = 23) and control (n = 40) pregnancies. Increases in circulating HDM-specific IgE (P = 0.007) and OVA-specific IgE (P = 0.038) were greater in PR than control progeny. PR did not alter total Ig, IgG1, or IgM responses to either antigen. PR increased OVA-specific but not HDM-specific IgA responses in females only (P = 0.023). Multiple birth increased Ig responses to OVA in a sex-specific manner. PR decreased the proportion of positive cutaneous hypersensitivity responders to OVA at 24 h (P = 0.030) but had no effect on cutaneous responses to HDM. Acute wheal responses to intradermal histamine correlated positively with birth weight in singletons (P = 0.023). Intrauterine growth restriction may suppress inflammatory responses in skin downstream of IgE induction, without impairment in antibody responses to a nonpolysaccharide vaccine. Discord between cutaneous and IgE responses following sensitization suggests new mechanisms for prenatal allergy programming. PMID:24500430

  3. Birth Weight, Intrauterine Growth Retardation and Fetal Susceptibility to Porcine Reproductive and Respiratory Syndrome Virus

    PubMed Central

    Ladinig, Andrea; Foxcroft, George; Ashley, Carolyn; Lunney, Joan K.; Plastow, Graham; Harding, John C. S.

    2014-01-01

    The severity of porcine reproductive and respiratory syndrome was compared in pregnant gilts originating from high and low birth weight litters. One-hundred and eleven pregnant gilts experimentally infected with porcine reproductive and respiratory syndrome virus on gestation day 85 (±1) were necropsied along with their fetuses 21 days later. Ovulation rates and litter size did not differ between groups, but fetuses from low birth weight gilts were shorter, lighter and demonstrated evidence of asymmetric growth with large brain:organ weight ratios (i.e. brain sparing). The number of intrauterine growth retarded fetuses, defined by brain:organ weight ratios greater than 1 standard deviation from the mean, was significantly greater in low, compared to high, birth weight gilts. Although γδ T cells significantly decreased over time in high compared to low birth weight gilts, viral load in serum and tissues, gilt serum cytokine levels, and litter outcome, including the percent dead fetuses per litter, did not differ by birth weight group. Thus, this study provided no substantive evidence that the severity of porcine reproductive and respiratory syndrome is affected by dam birth weight. However, intrauterine growth retarded fetuses had lower viral loads in both fetal thymus and in endometrium adjacent to the umbilical stump. Crown rump length did not significantly differ between fetuses that survived and those that died at least one week prior to termination. Taken together, this study clearly demonstrates that birth weight is a transgenerational trait in pigs, and provides evidence that larger fetuses are more susceptible to transplacental PRRSv infection. PMID:25275491

  4. Survey of the Definition of Fetal Viability and the Availability, Indications, and Decision Making Processes for Post-Viability Termination of Pregnancy for Fetal Abnormalities and Health Conditions in Canada.

    PubMed

    Hull, Danna; Davies, Gregory; Armour, Christine M

    2016-06-01

    The purpose of this study was to explore the definition of fetal viability and the availability, indications, and decision making processes for post-viability termination of pregnancy for fetal abnormalities and health conditions in Canada. An online survey of members of the Canadian Association of Genetic Counsellors, the Canadian College of Medical Geneticists, and the Canadian Society for Maternal-Fetal Medicine who provide direct counselling to, or management of, prenatal patients in Canada (total sample size 815). Results of this study showed that the majority of respondents indicated that their centre will offer post-viability termination of pregnancy (98/123; 80 %). Sixty-seven percent (68/101) of respondents reported the definition of fetal viability to be 24 weeks' gestation. Most respondents reported that a collaborative decision making process was used to determine if post-viability termination of pregnancy would be offered (136/170; 80 %). For conditions presumed to be lethal/likely lethal, the majority of respondents would "sometimes" or "always" offer post-viability termination of pregnancy, whereas for conditions presumed to have a mild effect, the majority of respondents would "rarely" or "never" offer post-viability termination of pregnancy. Ninety percent (77/86) of respondents reported that perinatal hospice is offered as an alternative to termination of pregnancy. In conclusion, this study suggests that although post-viability termination is available in many provinces in Canada, variation in the definition of fetal viability and indications appear to exist. While these variations may lead to unequal access to post-viability termination of pregnancy across Canada, they might also represent the complexity of the decision making process and the importance of examining individual factors to ensure that the most appropriate decision is made in each case. PMID:26536885

  5. Somatomedin-C/insulin-like growth factor-I and Insulin-like growth factor-II mRNAs in rate fetal and adult tissues

    SciTech Connect

    Lund, P.K.; Moats-Staats, B.M.; Hynes, M.A.; Simmons, J.G.; Jansen, M.; D'ercole, A.J.; Van Wyk, J.J.

    1986-11-05

    Somatomedin-C or insulin-like growth factor I (Sm-C/IGF-I) and insulin-like growth factor II (IGF-II) have been implicated in the regulation of fetal growth and development. In the present study /sup 32/P-labeled complementary DNA probes encoding human and mouse Sm-C/IGF-I and human IGF-II were used in Northern blot hybridizations to analyze rat Sm-C/IGF-I and IGF-II mRNAs in poly(A/sup +/) RNAs from intestine, liver, lung, and brain of adult rats and fetal rats between day 14 and 17 of gestation. In fetal rats, all four tissues contained a major mRNA of 1.7 kilobase (kb) that hybridized with the human Sm-C/IGF-I cDNA and mRNAs of 7.5, 4.7, 1.7, and 1.2 kb that hybridized with the mouse Sm-C/IGF-I cDNA. Adult rat intestine, liver, and lung also contained these mRNAs but Sm-C/IGF-I mRNAs were not detected in adult rat brain. These findings provide direct support for prior observations that multiple tissues in the fetus synthesize immunoreactive Sm-C/IGF-I and imply a role for Sm-C/IGF-I in fetal development as well as postnatally. Multiple IGF-II mRNAs of estimated sizes 4.7, 3.9, 2.2, 1.75, and 1.2 kb were observed in fetal rat intestine, liver, lung, and brain. The 4.7- and 3.9-kb mRNAs were the major hybridizing IGF-II mRNAs in all fetal tissues. Higher abundance of IGF-II mRNAs in rat fetal tissues compared with adult tissues supports prior hypotheses, based on serum IGF-II concentrations, that IGF-II is predominantly a fetal somatomedin. IGF-II mRNAs are present, however, in some poly(A/sup +/) RNAs from adult rat tissues. The brain was the only tissue in the adult rat where the 4.7- and 3.9-kb IGF-II mRNAs were consistently detected. These findings suggest that a role for IGF-II in the adult rat, particularly in the central nervous system, cannot be excluded.

  6. Sensitivity of Fit Indices to Misspecification in Growth Curve Models

    ERIC Educational Resources Information Center

    Wu, Wei; West, Stephen G.

    2010-01-01

    This study investigated the sensitivity of fit indices to model misspecification in within-individual covariance structure, between-individual covariance structure, and marginal mean structure in growth curve models. Five commonly used fit indices were examined, including the likelihood ratio test statistic, root mean square error of…

  7. Cord Blood 25-hydroxyvitamin D and Fetal Growth in the China-Anhui Birth Cohort Study.

    PubMed

    Zhu, Peng; Tong, Shi-lu; Hu, Wen-biao; Hao, Jia-hu; Tao, Rui-xue; Huang, Kun; Mou, Zhe; Zhou, Qi-fan; Jiang, Xiao-min; Tao, Fang-biao

    2015-01-01

    We determined the association of cord blood 25-hydroxyvitamin D [25(OH)D] with birth weight and the risk of small for gestational age (SGA). As part of the China-Anhui Birth Cohort (C-ABC) study, we measured cord blood levels of 25(OH)D in 1491 neonates in Hefei, China. The data on maternal sociodemographic characteristics, health status, lifestyle, birth outcomes were prospectively collected. Multiple regression models were used to estimate the association of 25(OH)D levels with birth weight and the risk of SGA. Compared with neonates in the lowest decile of cord blood 25(OH)D levels, neonates in four deciles (the fourth, fifth, sixth and seventh deciles) had significantly increased birth weight and decreased risk of SGA. Multiple linear regression models showed that per 10 nmol/L increase in cord blood 25(OH)D, birth weight increased by 61.0 g (95% CI: 31.9, 89.9) at concentrations less than 40 nmol/L, and then decreased by 68.5 g (95% CI: -110.5, -26.6) at concentrations from 40 to 70 nmol/L. This study provides the first epidemiological evidence that there was an inverted U shaped relationship between neonatal vitamin D status and fetal growth, and the risk of SGA reduced at moderate concentration. PMID:26450157

  8. Growth characteristics of the fetal ligament of the head of femur: significance in congenital hip disease.

    PubMed Central

    Walker, J. M.

    1980-01-01

    Measurement of the length and width of the ligament of the head of femur (ligamentum teres) in 140 normal human fetuses between 12 weeks and term provides limits for growth changes in this structure. These observations provide no morphological evidence of a significant difference between males and females, or between the right and left sides, to explain the female and left hip preponderance reported in congenital hip disease. The ligament is shown to be variable in length, width, and shape, and it is not a distinctly linear structure through linearity may increase with age. Tests of femoral head mobility support the opinion that this ligament must play a role in fetal and neonatal hip joint stability. Weak correlation only was demonstrated between the ligament variables and acetabular depth, which suggests that ligament shape and socket shape are not closely related. Comparison of measurements from normal and 12 dysplastic or subluxated joints provides no evidence to support previous observations that this structure is unusually long in abnormal hip joints which are not frankly dislocated. Images FIG. 1 PMID:7445537

  9. Differential expression of vascular endothelial growth factor in human fetal skeletal site-specific tissues: Mandible versus femur.

    PubMed

    Marini, Mirca; Bertolai, Roberto; Ambrosini, Stefano; Sarchielli, Erica; Vannelli, Gabriella Barbara; Sgambati, Eleonora

    2015-04-01

    Vascular endothelial growth factor (VEGF) is a well-known mediator that signals through pathways in angiogenesis and osteogenesis. Angiogenesis and bone formation are coupled during either skeletal development or bone remodeling and repair occurring in postnatal life. In this study, we examined for the first time the expression of VEGF in human fetal mandibular and femoral bone in comparison with the respective adult tissues. Similarly to other craniofacial bones, but at variance with the axial and appendicular skeleton, during development mandible does not arise from mesoderm but neural crest cells of the neuroectoderm germ layer, and undergoes intramembranous instead of endochondral ossification. By quantitative real-time PCR technique, we could show that VEGF gene expression levels were significantly higher in fetal than in adult samples, especially in femoral tissue. Western blotting analysis confirmed higher protein expression of VEGF in the fetal femur respect to the mandible. Moreover, immunohistochemistry revealed that in both fetal tissues VEGF expression was mainly localized in pre- and osteoblasts. Differential expression of VEGF in femoral and mandibular bone tissues could be related to their different structure, function and development during organogenesis. PMID:25769656

  10. Is Placental Mitochondrial Function a Regulator that Matches Fetal and Placental Growth to Maternal Nutrient Intake in the Mouse?

    PubMed Central

    Chiaratti, Marcos R.; Malik, Sajida; Diot, Alan; Rapa, Elizabeth; Macleod, Lorna; Morten, Karl; Vatish, Manu; Boyd, Richard; Poulton, Joanna

    2015-01-01

    Background Effective fetal growth requires adequate maternal nutrition coupled to active transport of nutrients across the placenta, which, in turn requires ATP. Epidemiological and experimental evidence has shown that impaired maternal nutrition in utero results in an adverse postnatal phenotype for the offspring. Placental mitochondrial function might link maternal food intake to fetal growth since impaired placental ATP production, in response to poor maternal nutrition, could be a pathway linking maternal food intake to reduced fetal growth. Method We assessed the effects of maternal diet on placental water content, ATP levels and mitochondrial DNA (mtDNA) content in mice at embryonic (E) day 18 (E18). Females maintained on either low- (LPD) or normal- (NPD) protein diets were mated with NPD males. Results To investigate the possibility of an underlying mitochondrial stress response, we studied cultured human trophoblast cells (BeWos). High throughput imaging showed that amino acid starvation induces changes in mitochondrial morphology that suggest stress-induced mitochondrial hyperfusion. This is a defensive response, believed to increase mitochondrial efficiency, that could underlie the increase in ATP observed in placenta. Conclusions These findings reinforce the pathophysiological links between maternal diet and conceptus mitochondria, potentially contributing to metabolic programming. The quiet embryo hypothesis proposes that pre-implantation embryo survival is best served by a relatively low level of metabolism. This may extend to post-implantation trophoblast responses to nutrition. PMID:26132581

  11. Maternal testosterone and placental function: Effect of electroacupuncture on placental expression of angiogenic markers and fetal growth.

    PubMed

    Fornes, Romina; Hu, Min; Maliqueo, Manuel; Kokosar, Milana; Benrick, Anna; Carr, David; Billig, Håkan; Jansson, Thomas; Manni, Luigi; Stener-Victorin, Elisabet

    2016-09-15

    Women with polycystic ovary syndrome (PCOS) have elevated circulating androgens during pregnancy and are at an increased risk of adverse pregnancy outcomes. Here we tested the hypotheses that maternal androgen excess decrease placental and fetal growth, and placental expression of markers of steroidogenesis, angiogenesis and sympathetic activity, and that acupuncture with low-frequency electrical stimulation prevents these changes. Pregnant rats were exposed to vehicle or testosterone on gestational day (GD)15-19. Low-frequency electroacupuncture (EA) or handling, as a control for the EA procedure, was given to control or testosterone exposed dams on GD16-20. On GD21, blood pressure was measured and maternal blood, fetuses and placentas collected. Placental steroid receptor expression and proteins involved in angiogenic, neurotrophic and adrenergic signaling were analyzed. EA did not affect any variables in control rats except maternal serum corticosterone, which was reduced. EA in testosterone exposed dams compared with controls increased systolic pressure by 30%, decreased circulating norepinephrine and corticosterone, fetal and placental weight and placental VEGFR1 and proNGF protein expression, and increased the VEGFA/VEGFR1 ratio, mature NGF (mNGF) and the mNGF/proNGF ratio. In conclusion, low-frequency EA in control animals did not have any negative influence on any of the studied variables. In contrast, EA in pregnant dams exposed to testosterone increased blood pressure and impaired placental growth and function, leading to decreased fetal growth. PMID:27208621

  12. An Outcome-based Approach for the Creation of Fetal Growth Standards: Do Singletons and Twins Need Separate Standards?

    PubMed Central

    Fahey, John; Platt, Robert W.; Liston, Robert M.; Lee, Shoo K.; Sauve, Reg; Liu, Shiliang; Allen, Alexander C.; Kramer, Michael S.

    2009-01-01

    Contemporary fetal growth standards are created by using theoretical properties (percentiles) of birth weight (for gestational age) distributions. The authors used a clinically relevant, outcome-based methodology to determine if separate fetal growth standards are required for singletons and twins. All singleton and twin livebirths between 36 and 42 weeks’ gestation in the United States (1995–2002) were included, after exclusions for missing information and other factors (n = 17,811,922). A birth weight range was identified, at each gestational age, over which serious neonatal morbidity and neonatal mortality rates were lowest. Among singleton males at 40 weeks, serious neonatal morbidity/mortality rates were lowest between 3,012 g (95% confidence interval (CI): 3,008, 3,018) and 3,978 g (95% CI: 3,976, 3,980). The low end of this optimal birth weight range for females was 37 g (95% CI: 21, 53) less. The low optimal birth weight was 152 g (95% CI: 121, 183) less for twins compared with singletons. No differences were observed in low optimal birth weight by period (1999–2002 vs. 1995–1998), but small differences were observed for maternal education, race, parity, age, and smoking status. Patterns of birth weight-specific serious neonatal morbidity/neonatal mortality support the need for plurality-specific fetal growth standards. PMID:19126584

  13. Effects of Vivax Malaria Acquired Before 20 Weeks of Pregnancy on Subsequent Changes in Fetal Growth

    PubMed Central

    Machado Filho, Amantino C.; da Costa, Elenice P.; da Costa, Emely P.; Reis, Iracema S.; Fernandes, Emanoela A. C.; Paim, Bernardo V.; Martinez-Espinosa, Flor E.

    2014-01-01

    The resistance index (RI), pulsatility index (PI), fetal biometry, fetal heart rate (FHR), placental thickness, and hemoglobin levels were compared in 30 Plasmodium vivax-infected women between 14 and 20 weeks of pregnancy and a control group. Evaluations were performed at the moment of the malaria diagnosis and 26 weeks of pregnancy. The malaria group had lower levels of hemoglobin and greater placental thickness in both assessments, higher FHR in the first evaluation, and lower values on fetal biometry in the second assessment. There were no differences when comparing RI and PI on umbilical arteries between the two groups. Birth weight and height were lower in newborns in the malaria group than the control group. The results suggest that P. vivax infections at an earlier gestational age do not affect umbilical arteries blood flow but do affect fetal biometry in the second trimester of pregnancy and at birth. PMID:24420773

  14. Blood Biomarkers of Late Pregnancy Exposure to Trihalomethanes in Drinking Water and Fetal Growth Measures and Gestational Age in a Chinese Cohort

    PubMed Central

    Cao, Wen-Cheng; Zeng, Qiang; Luo, Yan; Chen, Hai-Xia; Miao, Dong-Yue; Li, Li; Cheng, Ying-Hui; Li, Min; Wang, Fan; You, Ling; Wang, Yi-Xin; Yang, Pan; Lu, Wen-Qing

    2015-01-01

    Background: Previous studies have suggested that elevated exposure to disinfection by-products (DBPs) in drinking water during gestation may result in adverse birth outcomes. However, the findings of these studies remain inconclusive. Objective: The purpose of our study was to examine the association between blood biomarkers of late pregnancy exposure to trihalomethanes (THMs) in drinking water and fetal growth and gestational age. Methods: We recruited 1,184 pregnant women between 2011 and 2013 in Wuhan and Xiaogan City, Hubei, China. Maternal blood THM concentrations, including chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM), were measured as exposure biomarkers during late pregnancy. We estimated associations with gestational age and fetal growth indicators [birth weight, birth length, and small for gestational age (SGA)]. Results: Total THMs (TTHMs; sum of TCM, BDCM, DBCM, and TBM) were associated with lower mean birth weight (–60.9 g; 95% CI: –116.2, –5.6 for the highest vs. lowest tertile; p for trend = 0.03), and BDCM and DBCM exposures were associated with smaller birth length (e.g., –0.20 cm; 95% CI: –0.37, –0.04 for the highest vs. lowest tertile of DBCM; p for trend = 0.02). SGA was increased in association with the second and third tertiles of TTHMs (OR = 2.91; 95% CI: 1.32, 6.42 and OR = 2.25; 95% CI: 1.01, 5.03; p for trend = 0.08). Conclusions: Our results suggested that elevated maternal THM exposure may adversely affect fetal growth. Citation: Cao WC, Zeng Q, Luo Y, Chen HX, Miao DY, Li L, Cheng YH, Li M, Wang F, You L, Wang YX, Yang P, Lu WQ. 2016. Blood biomarkers of late pregnancy exposure to trihalomethanes in drinking water and fetal growth measures and gestational age in a Chinese cohort. Environ Health Perspect 124:536–541; http://dx.doi.org/10.1289/ehp.1409234 PMID:26340795

  15. Spontaneous Preterm Delivery, Particularly with Reduced Fetal Growth, is Associated with DNA Hypomethylation of Tumor Related Genes

    PubMed Central

    Chen, Xinhua; Bai, Guang; Scholl, Theresa O

    2016-01-01

    Background Preterm delivery and sub-optimal fetal growth are associated with each other and affect both mother and infant. Our aim was to determine (i) whether there are detectable differences in DNA methylation between early and late gestation and (ii) whether changes in DNA methylation from entry are associated with spontaneous preterm delivery with and without reduced fetal growth. Methods We conducted a case-control study nested within a large prospective cohort. Gene specific methylation was measured by Methyl-Profiler PCR Array in a Human Breast Cancer Signature Panel of 24 genes from maternal peripheral leukocytes genomic DNA at entry and 3rd trimester (sampled at 16 and 30 weeks of gestation, respectively). Clonal bisulfite DNA sequencing was performed to confirm the changes in selected genes (CYP1B1, GADD45A and CXCL12). Multivariable analysis was used for data analysis. Results There was significantly decrease in DNA methylation in 15 of 24 genes during the 3rd trimester in cases of spontaneous preterm delivery (n=23) as compared to the controls (n=19) (p<0.05–p<0.01 for each gene). Similar results were observed by bisulfite sequencing for 3 genes. The change in DNA methylation between late and early gestation was significantly different in cases (overall decrease in methylation was −4.0 ± 1.5%) compared to the controls (overall increase in methylation was 12.6 ± 2.19%, p<0.0001). A graded pattern of DNA methylation was observed in 15 genes. Cases who delivered preterm with reduced fetal growth had the lowest level of methylation, cases delivering preterm without reduced fetal growth were next and term controls were highest in methylation (p for trend <0.05 to p<0.01 for each gene). Cases of preterm delivery also had significantly lower dietary choline intake. Conclusions These data suggest that epigenetic modification is associated with an increased risk of spontaneous preterm delivery, spontaneous preterm delivery with reduced fetal growth in

  16. Bridging nigrostriatal pathway with fibroblast growth factor-primed peripheral nerves and fetal ventral mesencephalon transplant recuperates from deficits in parkinsonian rats.

    PubMed

    Chiang, Yung-Hsiao; Lin, Shinn-Zong; Zhou, Feng C

    2006-01-01

    Previous studies have indicated that the nigrostriatal dopaminergic (DA) pathway can be reconstructed in hemiparkinsonian rats with a bridge transplantation technique involving fetal ventral mesencephalic transplants and glial cell line-derived neurotrophic factor. In this study, we examined if the nigrostriatal pathway can be restored by combining peripheral nervous tissue with the fetal ventral mesencephalon transplants. Adult rats were injected with 6-hydroxydopamine into left median forebrain bundle. Those with marked rotational behavior, which has been previously shown to indicate complete DA dennervtion, were used for transplant treatments. One month after the lesion, fetal ventral mesencephalic cells were transplanted into the nigral region followed by nigral-striatal grafting of peripheral nerves as a bridge. The bridging nerves (sciatic or intercostals) were pretreated with basic fibrous growth factor (nerve+bFGF+) or Hank's saline (nerve+bFGF-). We found that (a) animals receiving transplants of VM and bFGF+ nerve had a reduction in rotational behavior; (b) animals receiving bFGF-- nerve bridge only had a partial improvement in rotation. Reinnervation of tyrosine hydroxylase (TH)-immunoreactive (ir) fibers into the striatum was found in both of the above groups with more innervation in the former than in the latter. No TH-ir fibers in lesioned striatum or reduction in rotational behavior were found in animals receiving VM only, or VM plus bFGF. Taken together, our data indicate that peripheral nerve, with the aid of bFGF, greatly facilitates the reconstitution of the TH pathway from nigra to striatum and improves motor function in hemiparkinsonian rats. PMID:17121158

  17. Inadequate weight gain in overweight and obese pregnant women: what is the effect on fetal growth?

    PubMed Central

    Catalano, Patrick M.; Mele, Lisa; Landon, Mark B.; Ramin, Susan M.; Reddy, Uma M.; Casey, Brian; Wapner, Ronald J.; Varner, Michael W.; Rouse, Dwight J.; Thorp, John M.; Saade, George; Sorokin, Yoram; Peaceman, Alan M.; Tolosa, Jorge E.

    2014-01-01

    Objective To evaluate inadequate gestational weight gain and fetal growth among overweight and obese women (O/O). Study Design Analysis of prospective singleton term pregnancies in which 1053 O/O gained greater (14.4± 6.2 kg) or 188 who either lost or gained ≤5 kg (1.1± 4.4 kg). Birth weight, fat (FM) and lean mass (LM) were assessed using anthropometry. Small for gestational age (SGA) was defined as ≤ 10th percentile of a standard US population. Univariable and multivariable analysis evaluated the association between weight change and neonatal morphometry. Results There was no significant difference in age, race, smoking, parity, or gestational age between groups. Weight loss or gain ≤ 5 kg was associated with SGA, 18/188 (9.6%) vs. 51/1053 (4.9%); (adjusted OR 2.6, 95% CI 1.4, 4.7; p=0.003). Neonates of women who lost or gained ≤ 5 kg had lower birth weight (3258 ± 443 g vs. 3467 ± 492g, p<0.0001), FM (403±175 vs. 471 ± 193g, p<0.0001), LM (2855±321 vs. 2995 ± 347g, p<0.0001) and smaller length, %FM and head circumference (HC). Adjusting for diabetic status, pre-pregnancy BMI, smoking, parity, study site, gestational age and gender; neonates of women who gained ≤ 5 kg had significantly lower birth weight, LBM, FM, %FM, HC and length. There were no significant differences in neonatal outcomes between those who lost weight and those who gained ≤ 5 kg. Conclusion In O/O weight loss or gain ≤ 5 kg is associated with increased risk of SGA and decreased neonatal FM, LM and HC. PMID:24530820

  18. Lack of Thromboxane Synthase Prevents Hypertension and Fetal Growth Restriction after High Salt Treatment during Pregnancy.

    PubMed

    Pai, Chen-Hsueh; Yen, Ching-Tzu; Chen, Chie-Pein; Yu, I-Shing; Lin, Shu-Wha; Lin, Shu-Rung

    2016-01-01

    Preeclampsia (PE) is a potentially fatal pregnancy-related hypertensive disorder characterized by poor placenta development that can cause fetal growth restriction. PE-associated pathologies, including thrombosis, hypertension, and impaired placental development, may result from imbalances between thromboxane A2 (TXA2) and prostacyclin. Low-dose aspirin, which selectively inhibits TXA2 production, is used to prevent high-risk PE. However, the role of TXA2 in aspirin-mediated protective effects in women with PE is not understood fully. In this study, we examined the role of prostanoids in PE using human samples and an induced PE mouse model. We demonstrated that the administration of salted drinking water (2.7% NaCl) to wild-type mice resulted in elevated placental TXA2 synthase (TXAS) and plasma TXA2, but not prostacyclin, levels, which was also found in our clinical PE placenta samples. The high salt-treated wild-type pregnant mice had shown unchanged maternal body weight, hypertension (MAP increase 15 mmHg), and decreased pup weight (~50%) and size (~24%), but these adverse effects were ameliorated in TXAS knockout (KO) mice. Moreover, increased expression of interleukin-1β and downstream phosphorylated-p38-mitogen-activated protein kinase were concordant with apoptosis induction in the placentas of salt water-treated wild-type mice. These alterations were not observed in TXAS KO mice. Together, our data suggest that TXA2 depletion has anti-PE effects due to the prevention of hypertension and placental damage through downregulation of the interleukin-1β pathway. PMID:26974824

  19. Spiral artery remodeling and trophoblast invasion in preeclampsia and fetal growth restriction: relationship to clinical outcome.

    PubMed

    Lyall, Fiona; Robson, Stephen C; Bulmer, Judith N

    2013-12-01

    Failure to transform uteroplacental spiral arteries is thought to underpin disorders of pregnancy, including preeclampsia and fetal growth restriction (FGR). In this study, spiral artery remodeling and extravillous-cytotrophoblast were examined in placental bed biopsies from normal pregnancy (n = 25), preeclampsia (n = 22), and severe FGR (n = 10) and then compared with clinical parameters. Biopsies were immunostained to determine vessel wall integrity, extravillous-cytotrophoblast location/density, periarterial fibrinoid, and endothelium. Muscle disruption was reduced in myometrial spiral arteries in preeclampsia (P = 0.0001) and FGR (P = 0.0001) compared with controls. Myometrial vessels from cases with birth weight <5th percentile (P<0.001), abnormal uterine Doppler (P<0.01), abnormal umbilical artery Doppler (P<0.001), and preterm delivery (P<0.001) had less muscle destruction compared with >5th percentile. Fewer extravillous-cytotrophoblast surrounded both decidual and myometrial vessels in the normal group and preeclampsia group compared with the FGR group (P = 0.001). For myometrial vessels, the normal group contained more intramural extravillous-cytotrophoblast than in preeclampsia (P = 0.015). Decidual vessels in the FGR group had less fibrinoid deposition compared with controls (P = 0.013). For myometrial vessels, less fibrinoid was deposited in both the preeclampsia group (P = 0.0001) and the FGR group (P = 0.01) when compared with controls, and less fibrinoid was deposited in the preeclampsia group when compared with FGR group (P<0.001). Myometrial vessels obtained from birth weights <5th percentile had less periarterial fibrinoid than those with >5th percentile (P<0.02). A major defect in myometrial spiral artery remodeling occurs in preeclampsia and FGR that is linked to clinical parameters. Interstitial extravillous-cytotrophoblast is not reduced in preeclampsia but is increased in FGR. PMID:24060885

  20. Lack of Thromboxane Synthase Prevents Hypertension and Fetal Growth Restriction after High Salt Treatment during Pregnancy

    PubMed Central

    Pai, Chen-Hsueh; Yen, Ching-Tzu; Chen, Chie-Pein; Yu, I-Shing

    2016-01-01

    Preeclampsia (PE) is a potentially fatal pregnancy-related hypertensive disorder characterized by poor placenta development that can cause fetal growth restriction. PE-associated pathologies, including thrombosis, hypertension, and impaired placental development, may result from imbalances between thromboxane A2 (TXA2) and prostacyclin. Low-dose aspirin, which selectively inhibits TXA2 production, is used to prevent high-risk PE. However, the role of TXA2 in aspirin-mediated protective effects in women with PE is not understood fully. In this study, we examined the role of prostanoids in PE using human samples and an induced PE mouse model. We demonstrated that the administration of salted drinking water (2.7% NaCl) to wild-type mice resulted in elevated placental TXA2 synthase (TXAS) and plasma TXA2, but not prostacyclin, levels, which was also found in our clinical PE placenta samples. The high salt-treated wild-type pregnant mice had shown unchanged maternal body weight, hypertension (MAP increase 15 mmHg), and decreased pup weight (~50%) and size (~24%), but these adverse effects were ameliorated in TXAS knockout (KO) mice. Moreover, increased expression of interleukin-1β and downstream phosphorylated-p38-mitogen-activated protein kinase were concordant with apoptosis induction in the placentas of salt water-treated wild-type mice. These alterations were not observed in TXAS KO mice. Together, our data suggest that TXA2 depletion has anti-PE effects due to the prevention of hypertension and placental damage through downregulation of the interleukin-1β pathway. PMID:26974824

  1. Maternal Dietary Patterns and Fetal Growth: A Large Prospective Cohort Study in China

    PubMed Central

    Lu, Min-Shan; Chen, Qiao-Zhu; He, Jian-Rong; Wei, Xue-Ling; Lu, Jin-Hua; Li, Sheng-Hui; Wen, Xing-Xuan; Chan, Fan-Fan; Chen, Nian-Nian; Qiu, Lan; Mai, Wei-Bi; Zhang, Rui-Fang; Hu, Cui-Yue; Xia, Hui-Min; Qiu, Xiu

    2016-01-01

    There was limited evidence revealing the association of Chinese maternal dietary patterns with fetal growth. We aimed to examine the relationship of maternal dietary patterns during pregnancy to neonatal birth weight and birth weight for gestational age in a Chinese population. A total of 6954 mother-child pairs were included from the Born in Guangzhou Cohort Study. Maternal diet during pregnancy was assessed using a self-administered food frequency questionnaire. Cluster analysis was used to identify dietary patterns. The following six dietary patterns were identified: “Cereals, eggs, and Cantonese soups” (n 1026, 14.8%), “Dairy” (n 1020, 14.7%), “Fruits, nuts, and Cantonese desserts” (n 799, 11.5%), “Meats” (n 1066, 15.3%), “Vegetables” (n 1383, 19.9%), and “Varied” (n 1224, 17.6%). The mean neonatal birth weight Z scores of women in the above patterns were 0.02, 0.07, 0.20, 0.01, 0.06, and 0.14, respectively. Women in the “Fruits, nuts, and Cantonese desserts” and “Varied” groups had significantly heavier infants compared with those in the “Cereals, eggs, and Cantonese soups” group. Compared with women in the “Cereals, eggs, and Cantonese soups” group, those in the “Varied” group had marginally significantly lower odds of having a small-for-gestational age (SGA) infant after adjustment for other confounders (OR 0.77, 95% CI 0.57, 1.04, p = 0.08). These findings suggest that compared to a traditional Cantonese diet high in cereals, eggs, and Cantonese soups, a diet high in fruits, nuts, and Cantonese desserts might be associated with a higher birth weight, while a varied diet might be associated with a greater birth weight and also a decreased risk of having a SGA baby. PMID:27136584

  2. Maternal Dietary Patterns and Fetal Growth: A Large Prospective Cohort Study in China.

    PubMed

    Lu, Min-Shan; Chen, Qiao-Zhu; He, Jian-Rong; Wei, Xue-Ling; Lu, Jin-Hua; Li, Sheng-Hui; Wen, Xing-Xuan; Chan, Fan-Fan; Chen, Nian-Nian; Qiu, Lan; Mai, Wei-Bi; Zhang, Rui-Fang; Hu, Cui-Yue; Xia, Hui-Min; Qiu, Xiu

    2016-01-01

    There was limited evidence revealing the association of Chinese maternal dietary patterns with fetal growth. We aimed to examine the relationship of maternal dietary patterns during pregnancy to neonatal birth weight and birth weight for gestational age in a Chinese population. A total of 6954 mother-child pairs were included from the Born in Guangzhou Cohort Study. Maternal diet during pregnancy was assessed using a self-administered food frequency questionnaire. Cluster analysis was used to identify dietary patterns. The following six dietary patterns were identified: "Cereals, eggs, and Cantonese soups" (n 1026, 14.8%), "Dairy" (n 1020, 14.7%), "Fruits, nuts, and Cantonese desserts" (n 799, 11.5%), "Meats" (n 1066, 15.3%), "Vegetables" (n 1383, 19.9%), and "Varied" (n 1224, 17.6%). The mean neonatal birth weight Z scores of women in the above patterns were 0.02, 0.07, 0.20, 0.01, 0.06, and 0.14, respectively. Women in the "Fruits, nuts, and Cantonese desserts" and "Varied" groups had significantly heavier infants compared with those in the "Cereals, eggs, and Cantonese soups" group. Compared with women in the "Cereals, eggs, and Cantonese soups" group, those in the "Varied" group had marginally significantly lower odds of having a small-for-gestational age (SGA) infant after adjustment for other confounders (OR 0.77, 95% CI 0.57, 1.04, p = 0.08). These findings suggest that compared to a traditional Cantonese diet high in cereals, eggs, and Cantonese soups, a diet high in fruits, nuts, and Cantonese desserts might be associated with a higher birth weight, while a varied diet might be associated with a greater birth weight and also a decreased risk of having a SGA baby. PMID:27136584

  3. Embryo development, fetal growth and postnatal phenotype of eGFP lambs generated by lentiviral transgenesis.

    PubMed

    Crispo, M; Vilariño, M; dos Santos-Neto, P C; Núñez-Olivera, R; Cuadro, F; Barrera, N; Mulet, A P; Nguyen, T H; Anegón, I; Menchaca, A

    2015-02-01

    Lentiviral technology has been recently proposed to generate transgenic farm animals more efficiently and easier than traditional techniques. The objective was to evaluate several parameters of lambs obtained by lentiviral transgenesis in comparison with non-transgenic counterparts. In vitro produced embryos were microinjected (TG group) at two-cell stage with a lentiviral construct containing enhanced green fluorescent protein (eGFP) gene, while embryos produced by in vitro fertilization (IVF group) or intrauterine insemination (IUI group) were not microinjected. Microinjection technique efficiently generated eight-cell transgenic embryos (97.4%; 114/117). Development rate on day 5 after fertilization was similar for TG (39.3%, 46/117) and IVF embryos (39.6%, 44/111). Pregnancy rate was detected in 50.0% (6/12) of recipient ewes with TG embryos, in 46.7% (7/15) with IVF embryos, and in 65.0% (13/20) of IUI ewes (P = NS). Nine lambs were born in TG group, six lambs in IVF group, and 16 lambs in IUI group. All TG lambs (9/9) were GFP positive to real-time PCR and eight (88.9%) showed a strong and evident GFP expression in mucosae, eyes and keratin tissues. Fetal growth monitored every 15 day by ultrasonography did not show significant differences. Transgenic lambs neither differ in morphometric variables in comparison with non transgenic IVF lambs within 3 months after birth. Transmission of the transgene to the progeny was observed in green fluorescent embryos produced by IVF using semen from the TG founder lambs. In conclusion, this study demonstrates the high efficiency of lentiviral technology to produce transgenic sheep, with no clinic differences in comparison with non transgenic lambs. PMID:25048992

  4. Fetal size in a rural melanesian population with minimal risk factors for growth restriction: an observational ultrasound study from Papua New Guinea.

    PubMed

    Unger, Holger W; Karl, Stephan; Wangnapi, Regina A; Siba, Peter; Mola, Glen; Walker, Jane; Mueller, Ivo; Ome, Maria; Rogerson, Stephen J

    2015-01-01

    We conducted a prospective longitudinal study of fetal size in rural Papua New Guinea (PNG) involving 439 ultrasound-dated singleton pregnancies with no obvious risk factors for growth restriction. Sonographically estimated fetal weights (EFWs; N = 788) and birth weights (N = 376) were included in a second-order polynomial regression model (optimal fit) to generate fetal weight centiles. Means for specific fetal biometric measurements were also estimated. Fetal weight centiles from a healthy PNG cohort were consistently lower than those derived from Caucasian and Congolese populations, which overestimated the proportion of fetuses measuring small for gestational age (SGA; < 10th centile). Tanzanian and global reference centiles (Caucasian weight reference adapted to our PNG cohort) were more similar to those observed in our cohort, but the global reference underestimated SGA. Individual biometric measurements did not differ significantly from other cohorts. In rural PNG, a locally derived nomogram may be most appropriate for detection of SGA fetuses. PMID:25385863

  5. Fetal Size in a Rural Melanesian Population with Minimal Risk Factors for Growth Restriction: An Observational Ultrasound Study from Papua New Guinea

    PubMed Central

    Unger, Holger W.; Karl, Stephan; Wangnapi, Regina A.; Siba, Peter; Mola, Glen; Walker, Jane; Mueller, Ivo; Ome, Maria; Rogerson, Stephen J.

    2015-01-01

    We conducted a prospective longitudinal study of fetal size in rural Papua New Guinea (PNG) involving 439 ultrasound-dated singleton pregnancies with no obvious risk factors for growth restriction. Sonographically estimated fetal weights (EFWs; N = 788) and birth weights (N = 376) were included in a second-order polynomial regression model (optimal fit) to generate fetal weight centiles. Means for specific fetal biometric measurements were also estimated. Fetal weight centiles from a healthy PNG cohort were consistently lower than those derived from Caucasian and Congolese populations, which overestimated the proportion of fetuses measuring small for gestational age (SGA; < 10th centile). Tanzanian and global reference centiles (Caucasian weight reference adapted to our PNG cohort) were more similar to those observed in our cohort, but the global reference underestimated SGA. Individual biometric measurements did not differ significantly from other cohorts. In rural PNG, a locally derived nomogram may be most appropriate for detection of SGA fetuses. PMID:25385863

  6. The Effect of Fetal and Childhood Growth over Depression in Early Adulthood in a Southern Brazilian Birth Cohort

    PubMed Central

    Loret de Mola, Christian; Quevedo, Luciana de Avila; Pinheiro, Ricardo Tavares; Gonçalves, Helen; Gigante, Denise Petrucci; Motta, Janaína Vieira dos Santos; Barros, Fernando C.; Horta, Bernardo Lessa

    2015-01-01

    Background Poor nutrition and growth during fetal life and childhood might be associated with depression in adulthood; however, studies evaluating these associations present controversial results, especially when comparing studies using different proxies for fetal growth. We evaluated the association of fetal and childhood growth/nutrition with depression, in adulthood, using different approaches and measurement methods. Method In 1982, hospital births (n = 5914) in Pelotas, southern Brazil, were examined and have been prospectively followed. At 30 years, the presence of major depression and depressive symptoms severity was evaluated using the Mini International Neuropsychiatric Interview (MINI) and Beck Depression Inventory (BDI-II). The present study assessed their association with birth weight, premature birth, small for gestational age (SGA), stunting and conditional growth during childhood. Results At 30 years, 3576 individuals were evaluated and 7.9% had major depression. Low birth weight (PR = 1.01 95%CI [0.64–1.60]), having been born SGA (PR = 0.87 95%CI [0.64–1.19]) and premature birth (PR = 1.22 95%CI [0.72–2.07]) were not associated with major depression in multivariable models. However, those born SGA who were also stunted in childhood had a higher prevalence of major depression (PR = 1.87 95%CI [1.06–3.29]) and greater odds of scoring a higher level of depression in the BDI-II (OR = 2.18 95%CI [1.34–3.53]). Conclusion In this Brazilian cohort of young adults, those born SGA who were also stunted during childhood had a higher risk of depression in adulthood. Our results show that the effect of growth impairment on depression is cumulative. PMID:26469192

  7. Redefining Individual Growth and Development Indicators: Oral Language

    ERIC Educational Resources Information Center

    Bradfield, Tracy A.; Besner, Amanda C.; Wackerle-Hollman, Alisha K.; Albano, Anthony D.; Rodriguez, Michael C.; McConnell, Scott R.

    2014-01-01

    Language skills developed during preschool contribute strongly to later reading and academic achievement. Effective preschool assessment and intervention should focus on core components of language development, specifically oral language skills. The Early Language and Literacy Individual Growth and Development Indicators (IGDIs) are a set of…

  8. Tree height growth indicating drought and nitrogen deposition

    NASA Astrophysics Data System (ADS)

    Gulyás, Krisztina; Berki, Imre

    2016-04-01

    Several studies have been reported the increasing trends of forest growth in Europe in the last decades. Sites, where the water is not limiting factor, the increasing carbon dioxide (CO2) concentration and high nitrogen deposition influenced accelerated tree height growth. However few researches show that the drying climate conditions and water deficit cause slow/not definite trend of tree height growth in forests. The aim of our study presents the effects of drying climate and surplus nitrogen on height growth of sessile oak (Quercus petraea). Almost 50 sessile oak stands (with zonal site condition) have been measured along a humid-arid climatic transect in Hungary. Top heights of the trees are the best dendrometric parameter for indicating the changing site conditions. Observed top heights dates were compared with 50-years climate condition along the humid-arid climatic transect. Tree height growth in the dry and mesic section of climatic gradient slowed at the last 4 decades, because of the increasing frequency of dry periods. Accelerated height growth were measured in the mesic and humid section of transect, where the nitrogen deposition due to local air pollution were higher than the background deposition. These results draw attention to the importance of the drying climate and surplus nitrogen in the global changes. Keywords: climate change impacts, drought periods, surplus deposition, tree height growth Acknowledgements: Research is supported by the "Agroclimate.2" (VKSZ_12-1-2013-0034) EU-national joint funded research project.

  9. Fetal alcohol syndrome

    MedlinePlus

    Fetal alcohol syndrome is growth, mental, and physical problems that may occur in a baby when a mother drinks ... A baby with fetal alcohol syndrome may have the following symptoms: Poor growth while the baby is in the womb and after birth Decreased muscle ...

  10. Utilizing Longitudinal Measures of Fetal Growth to Create a Standard Method to Assess the Impacts of Maternal Disease and Environmental Exposure

    PubMed Central

    Cantonwine, David E.; Ferguson, Kelly K.; Mukherjee, Bhramar; Chen, Yin-Hsiu; Smith, Nicole A.; Robinson, Julian N.; Doubilet, Peter M.; Meeker, John D.; McElrath, Thomas F.

    2016-01-01

    Impaired or suboptimal fetal growth is associated with an increased risk of perinatal morbidity and mortality. By utilizing readily available clinical data on the relative size of the fetus at multiple points in pregnancy, including delivery, future epidemiological research can improve our understanding of the impacts of maternal, fetal, and environmental factors on fetal growth at different windows during pregnancy. This study presents mean and standard deviation ultrasound measurements from a clinically representative US population that can be utilized for creating Z-scores to this end. Between 2006 and 2012, 18, 904 non-anomalous pregnancies that received prenatal care, first and second trimester ultrasound evaluations, and ultimately delivered singleton newborns at Brigham and Women’s hospital in Boston were used to create the standard population. To illustrate the utility of this standard, we created Z-scores for ultrasound and delivery measurements for a cohort study population and examined associations with factors known to be associated with fetal growth. In addition to cross-sectional regression models, we created linear mixed models and generalized additive mixed models to illustrate how these scores can be utilized longitudinally and for the identification of windows of susceptibility. After adjustment for a priori confounders, maternal BMI was positively associated with increased fetal size beginning in the second trimester in cross-sectional models. Female infants and maternal smoking were associated with consistently reduced fetal size in the longitudinal models. Maternal age had a non-significant association with increased size in the first trimester that was attenuated as gestation progressed. As the growth measurements examined here are widely available in contemporary obstetrical practice, these data may be abstracted from medical records by investigators and standardized with the population means presented here. This will enable easy extension

  11. Effects of overfeeding naturally-mated adolescent ewes on maternal, fetal, and postnatal lamb growth.

    PubMed

    Peel, R K; Eckerle, G J; Anthony, R V

    2012-11-01

    The objective of this study was to evaluate the effects of overfeeding naturally-mated adolescent ewes (Ovis aries) on maternal, fetal, and postnatal lamb growth, hormone concentrations, and lamb carcass characteristics. Two experiments were conducted in which singleton-bearing adolescent ewes were fed a diet containing 2.72 Mcal/kg ME at a rate which met NRC gestational age requirements (MN; n = 10 in Exp. 1, n = 7 in Exp. 2) or were fed the same diet ad libitum (15% refusal rate) throughout gestation (HN; n = 7 in Exp. 1, n = 6 in Exp. 2). Ewe BW was greater (P < 0.05) for HN than MN ewes beginning on 75 d and 52 d of gestation for Exp. 1 and 2, respectively. Final BCS was greater (P ≤ 0.05) for HN than MN ewes in both experiments; 3.5 vs. 3.0, respectively, for Exp. 1, and 4.8 vs. 2.9, respectively, for Exp. 2. Fasting maternal blood insulin concentrations were greater (P ≤ 0.05) in HN ewes near term (135 d of gestation), whereas fasting maternal glucose concentrations were greater (P ≤ 0.05) during most of the second half of gestation in HN ewes, for both experiments. Gestation length did not differ (P = 0.69) between treatments in Exp. 1, but in Exp. 2, HN ewes had shorter (P = 0.01) gestation lengths (144 vs. 149 d) and had increased (P = 0.002) dystocia scores. Fetal abdominal circumference was greater (P < 0.05) in lambs from MN than HN ewes at 97 d of gestation in Exp. 1 (20.8 vs. 17.4 cm) but did not differ (P = 0.94) between treatments at 95 d of gestation in Exp. 2 (averaging 20.5 cm). There were no differences (P ≥ 0.15) in lamb BW, abdominal circumference, crown-rump length, and biparietal distance at birth; or in postnatal BW and plasma concentrations of glucose, insulin, and lactate in either experiment. There were no differences (P ≥ 0.18) in HCW, dressing percentage, LM area, fat thickness, or KPH between treatments in Exp. 2. Although there was no difference (P ≥ 0.31) between treatments in concentrations of IGF1 or IGF2 mRNA in liver

  12. Association between maternal seafood consumption before pregnancy and fetal growth: evidence for an association in overweight women. The EDEN mother-child cohort

    PubMed Central

    Drouillet, Peggy; Kaminski, Monique; De Lauzon-Guillain, Blandine; Forhan, Anne; Ducimetière, Pierre; Schweitzer, Michel; Magnin, Guillaume; Goua, Valérie; Thiébaugeorges, Olivier; Charles, Marie-Aline

    2009-01-01

    SUMMARY Studies, in countries with high seafood consumption, suggested its benefit on fetal growth and child development. The objective of our study was to determine the association between seafood consumption in French pregnant women and fetal growth. Pregnant women included in the EDEN mother-child cohort study completed two food frequency questionnaires on their usual diet in the year before and during the last three months of pregnancy (n=1805). Fetal circumferences were measured by ultrasound, and anthropometry at birth. Variables were compared across tertiles of the mother’s seafood consumption by multiple linear regressions adjusted for confounding variables. Analyses were stratified according to maternal overweight because of interaction (p<0.01). As results, there was no association between seafood intake and fetal growth in the whole sample of women. For overweight women (n=464), a higher consumption before pregnancy was associated with higher fetal biparietal and abdominal circumferences and anthropometric measures. From the lowest to the highest tertiles, mean birthweight was 167g higher (p=0.002). No significant association was found with consumption at the end of pregnancy. In conclusion, high seafood consumption before pregnancy is positively associated with fetal growth in overweight women. Follow-up of the infants may help determine potential beneficial consequences for the child’s health and development. PMID:19228317

  13. Cadmium-induced neural tube defects and fetal growth restriction: Association with disturbance of placental folate transport.

    PubMed

    Zhang, Gui-Bin; Wang, Hua; Hu, Jun; Guo, Min-Yin; Wang, Ying; Zhou, Yan; Yu, Zhen; Fu, Lin; Chen, Yuan-Hua; Xu, De-Xiang

    2016-09-01

    Previous studies found that maternal Cd exposure on gestational day (GD)9 caused forelimb ectrodactyly and tail deformity, the characteristic malformations. The aim of the present study was to investigate whether maternal Cd exposure on GD8 induces fetal neural tube defects (NTDs). Pregnant mice were intraperitoneally injected with CdCl2 (2.5 or 5.0mg/kg) on GD8. Neither forelimb ectrodactyly nor tail deformity was observed in mice injected with CdCl2 on GD8. Instead, maternal Cd exposure on GD8 resulted in the incidence of NTDs. Moreover, maternal Cd exposure on GD8 resulted in fetal growth restriction. In addition, maternal Cd exposure on GD8 reduced placental weight and diameter. The internal space of maternal and fetal blood vessels in the labyrinth layer was decreased in the placentas of mice treated with CdCl2. Additional experiment showed that placental PCFT protein and mRNA, a critical folate transporter, was persistently decreased when dams were injected with CdCl2 on GD8. Correspondingly, embryonic folate content was markedly decreased in mice injected with CdCl2 on GD8, whereas Cd had little effect on folate content in maternal serum. Taken together, these results suggest that maternal Cd exposure during organogenesis disturbs transport of folate from maternal circulation to the fetuses through down-regulating placental folate transporters. PMID:27417525

  14. Enhanced or Reduced Fetal Growth Induced by Embryo Transfer into Smaller or Larger Breeds Alters Post-Natal Growth and Metabolism in Pre-Weaning Horses

    PubMed Central

    Peugnet, Pauline; Wimel, Laurence; Duchamp, Guy; Sandersen, Charlotte; Camous, Sylvaine; Guillaume, Daniel; Dahirel, Michèle; Dubois, Cédric; Jouneau, Luc; Reigner, Fabrice; Berthelot, Valérie; Chaffaux, Stéphane; Tarrade, Anne; Serteyn, Didier; Chavatte-Palmer, Pascale

    2014-01-01

    In equids, placentation is diffuse and nutrient supply to the fetus is determined by uterine size. This correlates with maternal size and affects intra-uterine development and subsequent post-natal growth, as well as insulin sensitivity in the newborn. Long-term effects remain to be described. In this study, fetal growth was enhanced or restricted through ET using pony (P), saddlebred (S) and draft (D) horses. Control P-P (n = 21) and S-S (n = 28) pregnancies were obtained by AI. Enhanced and restricted pregnancies were obtained by transferring P or S embryos into D mares (P-D, n = 6 and S-D, n = 8) or S embryos into P mares (S-P, n = 6), respectively. Control and experimental foals were raised by their dams and recipient mothers, respectively. Weight gain, growth hormones and glucose homeostasis were investigated in the foals from birth to weaning. Fetal growth was enhanced in P-D and these foals remained consistently heavier, with reduced T3 concentrations until weaning compared to P-P. P-D had lower fasting glucose from days 30 to 200 and higher insulin secretion than P-P after IVGTT on day 3. Euglycemic clamps in the immediate post-weaning period revealed no difference in insulin sensitivity between P-D and P-P. Fetal growth was restricted in S-P and these foals remained consistently lighter until weaning compared to S-D, with elevated T3 concentrations in the newborn compared to S-S. S-P exhibited higher fasting glycemia than S-S and S-D from days 30 to 200. They had higher maximum increment in plasma glucose than S-D after IVGTT on day 3 and clamps on day 200 demonstrated higher insulin sensitivity compared to S-D. Neither the restricted nor the enhanced fetal environment affected IGF-1 concentrations. Thus, enhanced and restricted fetal and post-natal environments had combined effects that persisted until weaning. They induced different adaptive responses in post-natal glucose metabolism: an early insulin-resistance was induced in

  15. Levels of Adipokines in Amniotic Fluid and Cord Blood Collected from Dichorionic-Diamniotic Twins Discordant for Fetal Growth

    PubMed Central

    Park, Joong Shin; Norwitz, Errol R.; Panyavatthanasinh, Sitthysack; Kim, Sun Min; Lee, JoonHo; Park, Chan-Wook; Kim, Byoung Jae; Jun, Jong Kwan

    2016-01-01

    Objective To compare the concentrations of adipokines in amniotic fluid (AF) and cord blood collected from discordant dichorionic-diamniotic (DCDA) twin fetuses. Study Design The study population included DCDA twins discordant for fetal growth (birth weight difference >10%) who either underwent mid-trimester amniocentesis for routine clinical indication (Cohort 1) or whose amniotic fluid was collected at the time of delivery (Cohort 2). In both cohorts, cord blood was collected at delivery. Results A total of 92 twin pairs were enrolled (n = 49 in Cohort 1; n = 43 in Cohort 2). In Cohort 1, the concentrations of adiponectin (median, 68.5 ng/mL vs 61.4 ng/mL; p<0.05) and leptin (median, 13.9 ng/mL vs 11.2 ng/mL; p<0.1) in mid-trimester AF were significantly higher in smaller compared with larger twins. In Cohort 2, the concentration of serpin E1 (median, 246.0 ng/mL vs 182.8 ng/mL; p<0.01) in AF at delivery was significantly higher in smaller twins, but no difference was noted in adiponectin and leptin concentrations. Levels of adiponectin (median, 10425.5 ng/mL vs 11552.0 ng/mL; p<0.005) and leptin (median, 2.1 ng/mL vs 2.6 ng/mL; p<0.005) were significantly lower in the cord blood of smaller twins whereas cord blood concentrations of serpin E1 (median, 15.5 ng/mL vs 13.3 ng/mL; p<0.05) was higher in the smaller twins. Conclusion In discordant DCDA twin pairs, concentrations of adiponectin, leptin, and serpin E1 in mid-trimester AF, AF at delivery, and cord blood at birth vary significantly but predictably between the smaller and larger twins. PMID:27135745

  16. Redefining Individual Growth and Development Indicators: Phonological Awareness.

    PubMed

    Wackerle-Hollman, Alisha K; Schmitt, Braden A; Bradfield, Tracy A; Rodriguez, Michael C; McConnell, Scott R

    2015-01-01

    Learning to read is one of the most important indicators of academic achievement. The development of early literacy skills during the preschool years is associated with improved reading outcomes in later grades. One of these skill areas, phonological awareness, shows particular importance because of its strong link to later reading success. Presented here are two studies that describe the development and revision of four measures of phonological awareness skills: Individual Growth and Development Indicators Sound Blending, Syllable Sameness, Rhyming, and Alliteration 2.0. The authors discuss the measure development process, revision, and utility within an early childhood Response to Intervention framework. PMID:24232734

  17. Neonatal and fetal exposure to trans-fatty acid retards early growth and adiposity while adversely affecting glucose in mice

    PubMed Central

    Kavanagh, Kylie; Sajadian, Soraya; Jenkins, Kurt A.; Wilson, Martha D.; Carr, J. Jeffery; Wagner, Janice D.; Rudel, Lawrence L.

    2010-01-01

    Industrially produced trans fatty acids (TFAs) consumed in western diets are incorporated into maternal and fetal tissues, and are passed linearly to offspring via breast milk. We hypothesized that TFA exposure in utero and during lactation in infants would promote obesity and poor glycemic control as compared to unmodified fatty acids. We further hypothesized that in utero exposure alone may program for these outcomes in adulthood. To test this hypothesis we fed female C57/BL6 mice identical western diets that differed only in cis- or trans-isomers of C18:1 and then aimed to determine whether maternal transfer of TFAs through pregnancy and lactation alters growth, body composition and glucose metabolism. Mice were unexposed, exposed during pregnancy, during lactation, or throughout pregnancy and lactation to TFA. Body weight and composition (by computed tomography), and glucose metabolism we assessed at weaning and adulthood. TFA exposure through breast milk caused significant early growth retardation (p<0.001) and higher fasting glucose (p=0.01) but insulin sensitivity was not different. Elevated plasma insulin-like growth factor-1 in mice consuming TFA-enriched milk (p=0.02) may contribute to later catch-up growth, leanness and preserved peripheral insulin sensitivity observed in these mice. Mice exposed to TFA in utero underwent rapid early neonatal growth with TFA-free breast milk and had significantly impaired insulin sensitivity (p<0.05) and greater abdominal fat (p=0.01). We conclude that very early catch-up growth resulted in impaired peripheral insulin sensitivity in this model of diet-related fetal and neonatal programming. TFA surprisingly retarded growth and adiposity while still adversely affecting glucose metabolism. PMID:20650350

  18. Antidepressant Use During Pregnancy and the Risk of Preterm Delivery and Fetal Growth Restriction

    PubMed Central

    Toh, Sengwee; Mitchell, Allen A.; Louik, Carol; Werler, Martha M.; Chambers, Christina D.; Hernández-Díaz, Sonia

    2011-01-01

    Objective The associations between prenatal exposure to antidepressants and preterm delivery and fetal growth restriction are controversial and poorly understood. We studied the relation between antidepressant use and these outcomes. Methods Analysis included women with nonmalformed infants interviewed in the Slone Epidemiology Center Birth Defects Study between 1998 and 2008. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for premature and small-for–gestational age (SGA) offsprings, adjusting for sociodemographic, lifestyle, medical, and reproductive factors. Results The frequencies of preterm delivery were 7.3% among the 5710 nonusers (reference), 8.9% among the 192 selective serotonin reuptake inhibitor (SSRI) users (OR, 1.1; 95% CI, 0.6–2.0), and 15.3% among the 59 non-SSRI antidepressant users (OR, 2.2; 95% CI, 1.0–4.9); the respective frequencies of delivering an SGA offspring were 7.2%, 10.9% (OR, 1.7; 95% CI, 1.0–2.7), and 13.6% (OR, 2.2; 95% CI, 1.0–4.9). Compared with nonusers, the frequencies of preterm delivery (7.6%) and SGA offspring (5.7%) were not increased among the 106 women who discontinued SSRIs before the end of the first trimester. Among women who continued SSRIs beyond the first trimester, 10.5% delivered a preterm infant (OR, 1.3; 95% CI, 0.6–2.8) and 17.4% had an SGA offspring (OR, 3.0; 95% CI, 1.7–5.5). Conclusions Women treated with SSRIs late in pregnancy had a higher frequency of delivering SGA infants, and women receiving non-SSRI antidepressants were more likely to deliver premature and SGA offsprings. The findings suggest an effect of underlying mood disorder or an effect common to both drug classes. In any case, prenatal antidepressant use may help identify women at elevated risks of delivering preterm and SGA infants. PMID:19910720

  19. Elsevier Trophoblast Research Award Lecture: Searching for an early pregnancy 3-D morphometric ultrasound marker to predict fetal growth restriction.

    PubMed

    Collins, S L; Stevenson, G N; Noble, J A; Impey, L

    2013-03-01

    Fetal growth restriction (FGR) is a major cause of perinatal morbidity and mortality, even in term babies. An effective screening test to identify pregnancies at risk of FGR, leading to increased antenatal surveillance with timely delivery, could decrease perinatal mortality and morbidity. Placental volume, measured with commercially available packages and a novel, semi-automated technique, has been shown to predict small for gestational age babies. Placental morphology measured in 2-D in the second trimester and ex-vivo post delivery, correlates with FGR. This has also been investigated using 2-D estimates of diameter and site of cord insertion obtained using the Virtual Organ Computer-aided AnaLysis (VOCAL) software. Data is presented describing a pilot study of a novel 3-D method for defining compactness of placental shape. We prospectively recruited women with a singleton pregnancy and BMI of <35. A 3-D ultrasound scan was performed between 11 and 13 + 6 weeks' gestation. The placental volume, total placental surface area and the area of the utero-placental interface were calculated using our validated technique. From these we generated dimensionless indices including sphericity (ψ), standardised placental volume (sPlaV) and standardised functional area (sFA) using Buckingham π theorem. The marker for FGR used was small for gestational age, defined as <10th customised birth weight centile (cSGA). Regression analysis examined which of the morphometric indices were independent predictors of cSGA. Data were collected for 143 women, 20 had cSGA babies. Only sPlaV and sFA were significantly correlated to birth weight (p < 0.001). Regression demonstrated all dimensionless indices were inter-dependent co-factors. ROC curves showed no advantage for using sFA over the simpler sPlaV. The generated placental indices are not independent of placental volume this early in gestation. It is hoped that another placental ultrasound marker based on vascularity can improve the

  20. Effects of macroporous hydroxyapatite carriers on the growth and function of human hepatoblasts derived from fetal hepatocytes.

    PubMed

    Ishii, Takaaki; Saito, Hiroshi; Komizu, Yuji; Tomoshige, Ryuichi; Matsushita, Taku

    2016-08-01

    Improvement of three-dimensional (3D) culture conditions, including substrates for cell growth, is needed for various cell-based applications. In this study, we developed hydroxyapatite (HAp) macroporous carriers having several pore size distributions and tried to obtain the findings about the effective pore sizes for the growth and function of hepatoblasts derived from human fetal hepatocytes. Cellular CYP3A4 activity was significantly enhanced when 20% HAp macroporous carrier was used, reaching 1.49±0.28 pmol/10(6) cells/min of benzyloxyresorufin-O-dealkylation activity, which is comparable to that of primary human hepatocytes from livers of adult donors. Analysis of the pore size (the radius of curvature) distribution of each HAp carrier using a 3D-electron beam surface roughness analyzer revealed two peaks of pore size distribution at 30-40 μm and 70-80 μm, respectively. Thirty-five percent of the pores in the 20% carrier had a size distribution within 50-80 μm. Especially, pores of 70-80 μm were more abundant in the 20% HAp carrier than in the 10% and 30% HAp carriers. These results suggested that a HAp carrier with the pore size distribution of 50-80 μm might be effective for cell growth and function in human hepatoblasts derived from fetal hepatocytes. PMID:26968126

  1. Effect of nebivolol treatment during pregnancy on the genital circulation, fetal growth and postnatal development in the Wistar rat.

    PubMed

    Altoama, Kassem; Yassine Mallem, Mohamed; Thorin, Chantal; Betti, Eric; Desfontis, Jean-Claude

    2015-07-01

    The aim of study was to evaluate the effects of nebivolol, a cardioselective beta-1 adrenergic receptor blocker of the third generation with vasodilatory properties, vs. bisoprolol on the genital circulation, uterine vasculature, fetal growth and postnatal development in pregnant Wistar rats. Non invasive measurements of systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR), and invasive measurement of genital blood flow (GBF) were taken in pregnant rats, by tail cuff and transonic probe methods respectively, after an oral treatment by gastric gavage with nebivolol (8mg/kg/day) or bisoprolol (10mg/kg/day) from day 11 to day 18 of pregnancy. Other morphometrical and histological measurements were performed on the ovarian and uterine arteries to evaluate the effect of nebivolol on the uterine vasculature. Furthermore, postnatal mortality and pup growth were recorded. The data demonstrated that nebivolol (compared with bisoprolol) induced a significant decrease in SBP, HR and GBF while DBP remained unchanged. Moreover, nebivolol increased the diameter and the length of ovarian and uterine arteries and the number of uterine artery segmental branches. The results also showed that the body weight gain of newborns in the nebivolol group was significantly lower vs. bisoprolol and vs. control with a higher mortality rate. The nebivolol action is not only limited to its favorable hemodynamic effects represented by a decrease in blood pressure, but it also produces adverse effects on fetal growth and postnatal development that may limit its therapeutic use in females during pregnancy. PMID:25863257

  2. Review: Cell-free fetal DNA in the maternal circulation as an indication of placental health and disease

    PubMed Central

    Taglauer, E.S.; Wilkins-Haug, L.; Bianchi, D.W.

    2016-01-01

    In human pregnancy, the constant turnover of villous trophoblast results in extrusion of apoptotic material into the maternal circulation. This material includes cell-free (cf) DNA, which is commonly referred to as “fetal”, but is actually derived from the placenta. As the release of cf DNA is closely tied to placental morphogenesis, conditions associated with abnormal placentation, such as preeclampsia, are associated with high DNA levels in the blood of pregnant women. Over the past five years, the development and commercial availability of techniques of massively parallel DNA sequencing have facilitated noninvasive prenatal testing (NIPT) for fetal trisomies 13, 18, and 21. Clinical experience accrued over the past two years has highlighted the importance of the fetal fraction (ff) in cf DNA analysis. The ff is the amount of cell-free fetal DNA in a given sample divided by the total amount of cell-free DNA. At any gestational age, ff has a bell-shaped distribution that peaks between 10 and 20% at 10–21 weeks. ff is affected by maternal body mass index, gestational age, fetal aneuploidy, and whether the gestation is a singleton or multiple. In approximately 0.1% of clinical cases, the NIPT result and a subsequent diagnostic karyotype are discordant; confined placental mosaicism has been increasingly reported as an underlying biologic explanation. Cell-free fetal DNA is a new biomarker that can provide information about the placenta and potentially be used to predict clinical problems. Knowledge gaps still exist with regard to what affects production, metabolism, and clearance of feto-placental DNA. PMID:24388429

  3. Climate indices strongly influence old-growth forest carbon exchange

    DOE PAGESBeta

    Wharton, Sonia; Falk, Matthias

    2016-04-13

    We present a decade and a half (1998–2013) of carbon dioxide fluxes from an old-growth stand in the American Pacific Northwest to identify ecosystem-level responses to Pacific teleconnection patterns, including the El Niño/Southern Oscillation (ENSO). This study provides the longest, continuous record of old-growth eddy flux data to date from one of the longest running Fluxnet stations in the world. From 1998 to 2013, average annual net ecosystem exchange (FNEE) at Wind River AmeriFlux was –32 ± 84 g C m–2 yr–1 indicating that the late seral forest is on average a small net sink of atmospheric carbon. However, interannualmore » variability is high (>300 g C m–2 yr–1) and shows that the stand switches from net carbon sink to source in response to climate drivers associated with ENSO. The old-growth forest is a much stronger sink during La Niña years (mean FNEE = –90 g C m–2 yr–1) than during El Niño when the stand turns carbon neutral or into a small net carbon source (mean FNEE = +17 g C m–2 yr–1). Forest inventory data dating back to the 1930s show a similar correlation with the lower frequency Pacific North American (PNA) and Pacific Decadal Oscillation (PDO) whereby higher aboveground net primary productivity (FANPP) is associated with cool phases of both the PNA and PDO. Furthermore, these measurements add evidence that carbon exchange in old-growth stands may be more sensitive to climate variability across shorter time scales than once thought.« less

  4. Climate indices strongly influence old-growth forest carbon exchange

    NASA Astrophysics Data System (ADS)

    Wharton, Sonia; Falk, Matthias

    2016-04-01

    We present a decade and a half (1998–2013) of carbon dioxide fluxes from an old-growth stand in the American Pacific Northwest to identify ecosystem-level responses to Pacific teleconnection patterns, including the El Niño/Southern Oscillation (ENSO). This study provides the longest, continuous record of old-growth eddy flux data to date from one of the longest running Fluxnet stations in the world. From 1998 to 2013, average annual net ecosystem exchange (F NEE) at Wind River AmeriFlux was ‑32 ± 84 g C m‑2 yr‑1 indicating that the late seral forest is on average a small net sink of atmospheric carbon. However, interannual variability is high (>300 g C m‑2 yr‑1) and shows that the stand switches from net carbon sink to source in response to climate drivers associated with ENSO. The old-growth forest is a much stronger sink during La Niña years (mean F NEE = ‑90 g C m‑2 yr‑1) than during El Niño when the stand turns carbon neutral or into a small net carbon source (mean F NEE = +17 g C m‑2 yr‑1). Forest inventory data dating back to the 1930s show a similar correlation with the lower frequency Pacific North American (PNA) and Pacific Decadal Oscillation (PDO) whereby higher aboveground net primary productivity (F ANPP) is associated with cool phases of both the PNA and PDO. These measurements add evidence that carbon exchange in old-growth stands may be more sensitive to climate variability across shorter time scales than once thought.

  5. Effects of Prenatal Multiple Micronutrient Supplementation on Fetal Growth Factors: A Cluster-Randomized, Controlled Trial in Rural Bangladesh

    PubMed Central

    Gernand, Alison D.; Schulze, Kerry J.; Nanayakkara-Bind, Ashika; Arguello, Margia; Shamim, Abu Ahmed; Ali, Hasmot; Wu, Lee; West, Keith P.; Christian, Parul

    2015-01-01

    Prenatal multiple micronutrient (MM) supplementation improves birth weight through increased fetal growth and gestational age, but whether maternal or fetal growth factors are involved is unclear. Our objective was to examine the effect of prenatal MM supplementation on intrauterine growth factors and the associations between growth factors and birth outcomes in a rural setting in Bangladesh. In a double-blind, cluster-randomized, controlled trial of MM vs. iron and folic acid (IFA) supplementation, we measured placental growth hormone (PGH) at 10 weeks and PGH and human placental lactogen (hPL) at 32 weeks gestation in maternal plasma (n = 396) and insulin, insulin-like growth factor-1 (IGF-1), and IGF binding protein-1 (IGFBP-1) in cord plasma (n = 325). Birth size and gestational age were also assessed. Early pregnancy mean (SD) BMI was 19.5 (2.4) kg/m2 and birth weight was 2.68 (0.41) kg. There was no effect of MM on concentrations of maternal hPL or PGH, or cord insulin, IGF-1, or IGFBP-1. However, among pregnancies of female offspring, hPL concentration was higher by 1.1 mg/L in the third trimester (95% CI: 0.2, 2.0 mg/L; p = 0.09 for interaction); and among women with height <145 cm, insulin was higher by 59% (95% CI: 3, 115%; p = 0.05 for interaction) in the MM vs. IFA group. Maternal hPL and cord blood insulin and IGF-1 were positively, and IGFBP-1 was negatively, associated with birth weight z score and other measures of birth size (all p<0.05). IGF-1 was inversely associated with gestational age (p<0.05), but other growth factors were not associated with gestational age or preterm birth. Prenatal MM supplementation had no overall impact on intrauterine growth factors. MM supplementation altered some growth factors differentially by maternal early pregnancy nutritional status and sex of the offspring, but this should be examined in other studies. Trial Registration ClinicalTrials.gov NCT00860470 PMID:26431336

  6. Adrenal Demedullation and Oxygen Supplementation Independently Increase Glucose-Stimulated Insulin Concentrations in Fetal Sheep With Intrauterine Growth Restriction.

    PubMed

    Macko, Antoni R; Yates, Dustin T; Chen, Xiaochuan; Shelton, Leslie A; Kelly, Amy C; Davis, Melissa A; Camacho, Leticia E; Anderson, Miranda J; Limesand, Sean W

    2016-05-01

    In pregnancies complicated by placental insufficiency and intrauterine growth restriction (IUGR), fetal glucose and oxygen concentrations are reduced, whereas plasma norepinephrine and epinephrine concentrations are elevated throughout the final third of gestation. Here we study the effects of chronic hypoxemia and hypercatecholaminemia on β-cell function in fetal sheep with placental insufficiency-induced IUGR that is produced by maternal hyperthermia. IUGR and control fetuses underwent a sham (intact) or bilateral adrenal demedullation (AD) surgical procedure at 0.65 gestation. As expected, AD-IUGR fetuses had lower norepinephrine concentrations than intact-IUGR fetuses despite being hypoxemic and hypoglycemic. Placental insufficiency reduced fetal weights, but the severity of IUGR was less with AD. Although basal plasma insulin concentrations were lower in intact-IUGR and AD-IUGR fetuses compared with intact-controls, glucose-stimulated insulin concentrations were greater in AD-IUGR fetuses compared with intact-IUGR fetuses. Interestingly, AD-controls had lower glucose- and arginine-stimulated insulin concentrations than intact-controls, but AD-IUGR and AD-control insulin responses were not different. To investigate chronic hypoxemia in the IUGR fetus, arterial oxygen tension was increased to normal levels by increasing the maternal inspired oxygen fraction. Oxygenation of IUGR fetuses enhanced glucose-stimulated insulin concentrations 3.3-fold in intact-IUGR and 1.7-fold in AD-IUGR fetuses but did not lower norepinephrine and epinephrine concentrations. Together these findings show that chronic hypoxemia and hypercatecholaminemia have distinct but complementary roles in the suppression of β-cell responsiveness in IUGR fetuses. PMID:26937714

  7. [Nutrition of pregnant women: consequences for fetal growth and adult diseases].

    PubMed

    Weber, M; Ayoubi, J-M; Picone, O

    2015-01-01

    The developmental origins of human adult disease are thought to be secondary to a perturbation of the embryonic or fetal development, which leads to metabolic disorders such as diabetes or hypertension at adulthood. Maternal undernutrition or overnutrition, repeated glucocorticosteroids administered to the mother, or placental dysfunction are the most frequently considered causal factors. Therefore, it is necessary that the pediatrician is aware of these phenomena, as this knowledge may contribute to the prevention of adult diseases. Little is known yet, however, on the pathophysiological or epigenetic mechanisms that lead to theses observations, and more studies are needed both in humans and animal models. PMID:25440770

  8. Intrauterine growth restriction decreases pulmonary alveolar and vessel growth and causes pulmonary artery endothelial cell dysfunction in vitro in fetal sheep.

    PubMed

    Rozance, Paul J; Seedorf, Gregory J; Brown, Alicia; Roe, Gates; O'Meara, Meghan C; Gien, Jason; Tang, Jen-Ruey; Abman, Steven H

    2011-12-01

    Intrauterine growth restriction (IUGR) increases the risk for bronchopulmonary dysplasia (BPD). Abnormal lung structure has been noted in animal models of IUGR, but whether IUGR adversely impacts fetal pulmonary vascular development and pulmonary artery endothelial cell (PAEC) function is unknown. We hypothesized that IUGR would decrease fetal pulmonary alveolarization, vascular growth, and in vitro PAEC function. Studies were performed in an established model of severe placental insufficiency and IUGR induced by exposing pregnant sheep to elevated temperatures. Alveolarization, quantified by radial alveolar counts, was decreased 20% (P < 0.005) in IUGR fetuses. Pulmonary vessel density was decreased 44% (P < 0.01) in IUGR fetuses. In vitro, insulin increased control PAEC migration, tube formation, and nitric oxide (NO) production. This response was absent in IUGR PAECs. VEGFA stimulated tube formation, and NO production also was absent. In control PAECs, insulin increased cell growth by 68% (P < 0.0001). Cell growth was reduced in IUGR PAECs by 29% at baseline (P < 0.01), and the response to insulin was attenuated (P < 0.005). Despite increased basal and insulin-stimulated Akt phosphorylation in IUGR PAECs, endothelial NO synthase (eNOS) protein expression as well as basal and insulin-stimulated eNOS phosphorylation were decreased in IUGR PAECs. Both VEGFA and VEGFR2 also were decreased in IUGR PAECs. We conclude that fetuses with IUGR are characterized by decreased alveolar and vascular growth and PAEC dysfunction in vitro. This may contribute to the increased risk for adverse respiratory outcomes and BPD in infants with IUGR. PMID:21873446

  9. Ethanol-induced impairment of polyamine homeostasis – A potential cause of neural tube defect and intrauterine growth restriction in fetal alcohol syndrome

    SciTech Connect

    Haghighi Poodeh, Saeid; Alhonen, Leena; Salonurmi, Tuire; Savolainen, Markku J.

    2014-03-28

    Highlights: • Polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. • Alcohol administration perturbs polyamine levels in the tissues with various patterns. • Total absence of polyamines in the embryo head at 9.5 dpc is critical for development. • The deficiency is associated with reduction in endothelial cell sprouting in the head. • Retarded migration of neural crest cells may cause development of neural tube defect. - Abstract: Introduction: Polyamines play a fundamental role during embryogenesis by regulating cell growth and proliferation and by interacting with RNA, DNA and protein. The polyamine pools are regulated by metabolism and uptake from exogenous sources. The use of certain inhibitors of polyamine synthesis causes similar defects to those seen in alcohol exposure e.g. retarded embryo growth and endothelial cell sprouting. Methods: CD-1 mice received two intraperitoneal injections of 3 g/kg ethanol at 4 h intervals 8.75 days post coitum (dpc). The fetal head, trunk, yolk sac and placenta were collected at 9.5 and 12.5 dpc and polyamine concentrations were determined. Results: No measurable quantity of polyamines could be detected in the embryo head at 9.5 dpc, 12 h after ethanol exposure. Putrescine was not detectable in the trunk of the embryo at that time, whereas polyamines in yolk sac and placenta were at control level. Polyamine deficiency was associated with slow cell growth, reduction in endothelial cell sprouting, an altered pattern of blood vessel network formation and consequently retarded migration of neural crest cells and growth restriction. Discussion: Our results indicate that the polyamine pools in embryonic and extraembryonic tissues are developmentally regulated. Alcohol administration, at the critical stage, perturbs polyamine levels with various patterns, depending on the tissue and its developmental stage. The total absence of polyamines in the embryo head at 9.5 dpc may explain why this

  10. Potential Effects of Chlorpyrifos on Fetal Growth Outcomes: Implications for Risk Assessment

    PubMed Central

    Mink, Pamela J.; Kimmel, Carole A.; Li, Abby A.

    2012-01-01

    Chlorpyrifos (CPF) is one of the most widely used organophosphate insecticides in the United States. By December 2000, nearly all residential uses were voluntarily canceled, so that today, CPF is only used to control insect pests on a variety of crops. Periodic review of the potential effects of CPF on all developmental outcomes is necessary in the United States because the Food Quality Protection Act mandates special consideration of risk assessments for infants and children. This article reviews epidemiologic studies examining the association of potential CPF exposure with growth indices, including birth weight, birth length, and head circumference, and animal studies focusing on related somatic developmental endpoints. It differs from earlier reviews by including an additional cohort study and providing in-depth systematic evaluation of the patterns of association across different studies with respect to specificity of biomarkers for CPF, consistency, dose response, strength of association, temporality, and biological plausibility (Hill 1965), as well as consideration of the potential role of effect modification and bias. The review did not identify any strong associations exhibiting consistent exposure-response patterns that were observed in more than one of the four cohort studies evaluated. In addition, the animal data indicate that developmental effects occur at doses that produce substantial maternal toxicity and red blood cell (RBC) acetylcholinesterase (AChE) inhibition. Based on consideration of both the epidemiologic and animal data, maternal RBC AChE inhibition is a more sensitive endpoint for risk assessment than somatic developmental effects reviewed in this article. PMID:22571222

  11. Biochemical properties of Na+/K(+)-ATPase in axonal growth cone particles isolated from fetal rat brain.

    PubMed

    Mercado, R; Hernández, J

    1994-08-01

    Axonal growth cones (AGC) isolated from fetal rat brain have an important specific activity of N+/K(+)-ATPase. Kinetic assays of the enzyme in AGC showed that Km values for ATP or K+ are similar to those reported for the adult brain enzyme. For Na+ the affinity (Km) was lower. Vmax for the three substrates was several times lower in AGC as compared to the adult value. We also observed two apparent inhibition constants of Na+/K(+)-ATPase by ouabain, one of low affinity, possibly corresponding to the alpha 1 isoform and another of high affinity which is different to that described for the alpha 2 isoform of the enzyme. These results support an important role for the sodium pump in the maintainance of volume and cationic balance in neuronal differentiating structures. The functional differences observed also suggest that the enzymatic complex of Na+/K(+)-ATPase in AGC is in a transitional state towards the adult configuration. PMID:7817790

  12. [The imbalance of metal-containing proteins and free metal ions in the amniotic fluid during fetal growth].

    PubMed

    Pogorelova, T N; Linde, V A; Gunko, V O; Selyutina, S N

    2016-01-01

    The levels of zinc, copper, iron, and magnesium ions, and some of their binding proteins have been investigated in an amniotic fluid under the fetal growth retardation (FGR). FGR, developed under conditions of placental insufficiency, is characterized by a decrease in the content of zinc, iron, and magnesium ions and by an increase in the copper content in the amniotic fluid in the II and III trimesters of pregnancy. During these trimesters the levels of ceruloplasmin, ferritin, and Ca2+,Mg2+-ATPase were lower in FGR, while the level of zinc-a-2-glycoprotein was higher than during the same periods of normal pregnancy. Changes in the parameters studied in the amniotic fluid were associated with developmental disorders of the newborns. These changes obviously have a pathogenetic importance in the development of FGR, and the levels of metal ions and their ratio in the amniotic fluid can be used as markers of the pre- and postnatal pathology. PMID:26973190

  13. Fetal Research

    NASA Astrophysics Data System (ADS)

    Hansen, John T.; Sladek, John R.

    1989-11-01

    This article reviews some of the significant contributions of fetal research and fetal tissue research over the past 20 years. The benefits of fetal research include the development of vaccines, advances in prenatal diagnosis, detection of malformations, assessment of safe and effective medications, and the development of in utero surgical therapies. Fetal tissue research benefits vaccine development, assessment of risk factors and toxicity levels in drug production, development of cell lines, and provides a source of fetal cells for ongoing transplantation trials. Together, fetal research and fetal tissue research offer tremendous potential for the treatment of the fetus, neonate, and adult.

  14. NOAA/AVHRR vegetation indices as agrometeorological growth parameter

    NASA Astrophysics Data System (ADS)

    Gupta, R. K.

    1993-05-01

    This paper deals with the utility of NOAA/AVHRR vegetation indices as agrometeorological growth parameters. The area chosen to the study was the Punjab and the Haryana states of India, both comprising districts primarily under wheat cultivation with 68-76% geographical area under agriculture and 89-96% agricultural area under wheat. Application of geometric correction to visible and near IR band images followed by computation of NDVI and RVI images yielded less error than the conventional method of correction to NDVI/RVI images. Images having far-side boundary pixel upto 38 degree scan angle did not cause significant error at district level statistics. RVI was more sensitive than NDVI from emergence to near jointing and maturity to senescence stages. Prior to jointing stage and after dough stage RVI can be transformed to NDVI, to enable its joint use with NDVI. The maximum and mean air temperatures based growing degree days (GDD) related well with the NDVI/RVI temporal profile over the entire crop growth cycle at 98-99% significance level. However, shapewise the maximum temperature based GDD was superior to mean temperature based GDD, whereas minimum temperature based GDD had statistically significant relationship only upto dough stage at 95% significance level. The integrated NDVI (INDVI) values computed for mid of late-tillering to jointing stage were significantly related to the yield (r-square = 0.867, at 99.34% significance level). When INDVI at this stage was coupled with that of mid of milking and dough - nearing maturity stages, the predictability of wheat yields increased (r-square = 0.891, at 99.32% significance level).

  15. CD10/neutral endopeptidase 24.11 regulates fetal lung growth and maturation in utero by potentiating endogenous bombesin-like peptides.

    PubMed Central

    King, K A; Hua, J; Torday, J S; Drazen, J M; Graham, S A; Shipp, M A; Sunday, M E

    1993-01-01

    Bombesin-like peptides (BLPs) are mitogens for bronchial epithelial cells and small cell lung carcinomas, and increase fetal lung growth and maturation in utero and in organ cultures. BLPs are hydrolyzed by the enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) which is expressed in bronchial epithelium and functions to inhibit BLP-mediated growth of small cell lung carcinomas. To determine whether CD10/NEP regulates peptide-mediated lung development, we administered a specific CD10/NEP inhibitor, SCH32615, to fetal mice in utero from gestational days e15-17. Fetal lung tissues were evaluated on e18 for: (a) growth using [3H]thymidine incorporation into nuclear DNA; and (b) maturation using: [3H]-choline incorporation into surfactant phospholipids, electron microscopy for type II pneumocytes, and Northern blot analyses for surfactant apoproteins A, B, and C. Inhibition of CD10/NEP stimulated [3H]thymidine incorporation into DNA (70% above baseline, P < 0.005), [3H]choline incorporation into surfactant phospholipids (38% above baseline, P < 0.005), increased numbers of type II pneumocytes (36% above baseline, P = 0.07), and fivefold higher surfactant protein A transcripts (P < 0.05). CD10/NEP-mediated effects were completely blocked by the specific bombesin receptor antagonist, [D-Phe12, Leu14]bombesin. These observations suggest that CD10/NEP regulates fetal lung growth and maturation mediated by endogenous BLPs. Images PMID:8486767

  16. Measurement of internal diameter changes and pulse wave velocity in fetal descending aorta using the ultrasonic phased-tracking method in normal and growth-restricted fetuses.

    PubMed

    Miyashita, Susumu; Murotsuki, Jun; Muromoto, Jin; Ozawa, Katsusuke; Yaegashi, Nobuo; Hasegawa, Hideyuki; Kanai, Hiroshi

    2015-05-01

    Phased tracking (PT) is an ultrasound-based technique that enables precise measurement of a target velocity. The aims of this study were to use PT to evaluate arterial pulse waveform, pulse wave velocity and fetal pulse pressure in normal and growth-restricted fetuses. One hundred fetuses with normal development and 15 fetuses with growth restriction were analyzed. Ultrasonic raw radiofrequency signals were captured from a direction perpendicular to the vascular axis at the fetal diaphragmatic level for the difference in internal dimensions (DID), or simultaneously from different directions for the pulse wave velocity. Pulsatile movement of the proximal and distal intima of the vessels was analyzed using PT. The fetal DID exhibited no significant changes in growth-restricted fetuses. Pulse wave velocity (3.8 ± 0.32 m/s vs. 2.2 ± 0.069 m/s, p < 0.001) and estimated pulse pressure (6.9 ± 0.90 kPa vs. 2.5 ± 0.18 kPa, p < 0.001) were significantly elevated in growth-restricted fetuses. Assessment of DID and pulse wave velocity of the descending aorta using PT is a feasible, non-invasive approach to evaluation of fetal hemodynamics. PMID:25727918

  17. Sildenafil Therapy Normalizes the Aberrant Metabolomic Profile in the Comt−/− Mouse Model of Preeclampsia/Fetal Growth Restriction

    PubMed Central

    Stanley, Joanna L.; Sulek, Karolina; Andersson, Irene J.; Davidge, Sandra T.; Kenny, Louise C.; Sibley, Colin P.; Mandal, Rupasri; Wishart, David S.; Broadhurst, David I.; Baker, Philip N.

    2015-01-01

    Preeclampsia (PE) and fetal growth restriction (FGR) are serious complications of pregnancy, associated with greatly increased risk of maternal and perinatal morbidity and mortality. These complications are difficult to diagnose and no curative treatments are available. We hypothesized that the metabolomic signature of two models of disease, catechol-O-methyl transferase (COMT−/−) and endothelial nitric oxide synthase (Nos3−/−) knockout mice, would be significantly different from control C57BL/6J mice. Further, we hypothesised that any differences in COMT−/− mice would be resolved following treatment with Sildenafil, a treatment which rescues fetal growth. Targeted, quantitative comparisons of serum metabolic profiles of pregnant Nos3−/−, COMT−/− and C57BL/6J mice were made using a kit from BIOCRATES. Significant differences in 4 metabolites were observed between Nos3−/− and C57BL/6J mice (p < 0.05) and in 18 metabolites between C57BL/6J and COMT−/− mice (p < 0.05). Following treatment with Sildenafil, only 5 of the 18 previously identified differences in metabolites (p < 0.05) remained in COMT−/− mice. Metabolomic profiling of mouse models is possible, producing signatures that are clearly different from control animals. A potential new treatment, Sildenafil, is able to normalize the aberrant metabolomic profile in COMT−/− mice; as this treatment moves into clinical trials, this information may assist in assessing possible mechanisms of action. PMID:26667607

  18. Adiponectin Inhibits Nutrient Transporters and Promotes Apoptosis in Human Villous Cytotrophoblasts: Involvement in the Control of Fetal Growth.

    PubMed

    Duval, Fabien; Santos, Esther Dos; Poidatz, Dorothée; Sérazin, Valérie; Gronier, Héloïse; Vialard, François; Dieudonné, Marie-Noëlle

    2016-05-01

    The placenta exchanges nutrients between the mother and the fetus and requires a constant abundant energy supply. Adiponectin (a cytokine produced primarily by adipose tissue) controls glucose and lipid homeostasis. It is well-known that maternal serum adiponectin levels are inversely related to birth weight, suggesting that adiponectin has a negative effect on fetal growth. This effect appears to be related to the control of nutrient transporters in human placenta. However, the underlying molecular mechanisms have not yet been characterized. In the present work, we studied adiponectin's direct effect on human primary cytotrophoblasts from first-trimester placenta. Our result showed that in placental cells, adiponectin 1) inhibits the expression of the major glucose transporters (GLUT1 and GLUT12) and sodium-coupled neutral amino acid transporters (SNAT1, SNAT2, and SNAT4), 2) enhances total ATP production but decreases lactate production, 3) inhibits mitochondrial biogenesis and function, and 4) stimulates cell death by enhancing the expression of the pro-apoptotic B-cell lymphoma-2 (BCL-2)-associated X protein (BAX) and tumor protein P53 (TP53) gene expression and inducing the caspase activity. Small-interfering RNA mediating the down-regulation of adiponectin receptors (ADIPOR1 and ADIPOR2) was used to demonstrate that adiponectin effects on placental nutrient transport and apoptosis seemed to be essentially mediated by these specific receptors. Taken as a whole, these results strongly suggest that adiponectin regulates human placental function by limiting nutrient transporter expression and inducing apoptosis. These findings may help us to better understand adiponectin's role in placental pathologies such as intrauterine growth restriction, which is characterized by fetal weight loss and drastic apoptosis of placental cells. PMID:27030046

  19. Maternal dietary patterns in pregnancy and fetal growth in Japan: the Osaka Maternal and Child Health Study.

    PubMed

    Okubo, Hitomi; Miyake, Yoshihiro; Sasaki, Satoshi; Tanaka, Keiko; Murakami, Kentaro; Hirota, Yoshio; Kanzaki, Hideharu; Kitada, Mitsuyoshi; Horikoshi, Yorihiko; Ishiko, Osamu; Nakai, Yuichiro; Nishio, Junko; Yamamasu, Seiichi; Yasuda, Jinsuke; Kawai, Seigo; Yanagihara, Kazumi; Wakuda, Koji; Kawashima, Tokio; Narimoto, Katsuhiko; Iwasa, Yoshihiko; Orino, Katsuhiko; Tsunetoh, Itsuo; Yoshida, Junichi; Iito, Junichi; Kaneko, Takuzi; Kamiya, Takao; Kuribayashi, Hiroyuki; Taniguchi, Takeshi; Takemura, Hideo; Morimoto, Yasuhiko; Matsunaga, Ichiro; Oda, Hajime; Ohya, Yukihiro

    2012-05-01

    Maternal nutritional status during pregnancy is an important determinant of fetal growth. Although the effects of several nutrients and foods have been well examined, little is known about the relationship of overall maternal diet in pregnancy to fetal growth, particularly in non-Western populations. We prospectively examined the relationship of maternal dietary patterns in pregnancy to neonatal anthropometric measurements at birth and risk of small-for-gestational-age (SGA) birth among 803 Japanese women with live-born, singleton, term deliveries. Maternal diet in pregnancy was assessed using a validated, self-administered diet history questionnaire. Dietary patterns from thirty-three predefined food groups (g/4184 kJ) were extracted by cluster analysis. The following three dietary patterns were identified: the 'meat and eggs' (n 326), 'wheat products', with a relatively high intake of bread, confectioneries and soft drinks (n 303), and 'rice, fish and vegetables' (n 174) patterns. After adjustment for potential confounders, women in the 'wheat products' pattern had infants with the significantly lowest birth weight (P = 0·045) and head circumference (P = 0·036) among those in the three dietary patterns. Compared with women in the 'rice, fish and vegetables' pattern, women in the 'wheat products' pattern had higher odds of having a SGA infant for weight (multivariate OR 5·2, 95 % CI 1·1, 24·4), but this was not the case for birth length or head circumference. These results suggest that a diet high in bread, confectioneries, and soft drinks and low in fish and vegetables during pregnancy might be associated with a small birth weight and an increased risk of having a SGA infant. PMID:21929833

  20. Association of in Utero Organophosphate Pesticide Exposure and Fetal Growth and Length of Gestation in an Agricultural Population

    PubMed Central

    Eskenazi, Brenda; Harley, Kim; Bradman, Asa; Weltzien, Erin; Jewell, Nicholas P.; Barr, Dana B.; Furlong, Clement E.; Holland, Nina T.

    2004-01-01

    Although pesticide use is widespread, little is known about potential adverse health effects of in utero exposure. We investigated the effects of organophosphate pesticide exposure during pregnancy on fetal growth and gestational duration in a cohort of low-income, Latina women living in an agricultural community in the Salinas Valley, California. We measured nonspecific metabolites of organophosphate pesticides (dimethyl and diethyl phosphates) and metabolites specific to malathion (malathion dicarboxylic acid), chlorpyrifos [O,O-diethyl O-(3,5,6-trichloro-2-pyridinyl) phosphoro-thioate], and parathion (4-nitrophenol) in maternal urine collected twice during pregnancy. We also measured levels of cholinesterase in whole blood and butyryl cholinesterase in plasma in maternal and umbilical cord blood. We failed to demonstrate an adverse relationship between fetal growth and any measure of in utero organophosphate pesticide exposure. In fact, we found increases in body length and head circumference associated with some exposure measures. However, we did find decreases in gestational duration associated with two measures of in utero pesticide exposure: urinary dimethyl phosphate metabolites [βadjusted = −0.41 weeks per log10 unit increase; 95% confidence interval (CI), −0.75–−0.02; p = 0.02], which reflect exposure to dimethyl organophosphate compounds such as malathion, and umbilical cord cholinesterase (βadjusted = 0.34 weeks per unit increase; 95% CI, 0.13–0.55; p = 0.001). Shortened gestational duration was most clearly related to increasing exposure levels in the latter part of pregnancy. These associations with gestational age may be biologically plausible given that organophosphate pesticides depress cholinesterase and acetylcholine stimulates contraction of the uterus. However, despite these observed associations, the rate of preterm delivery in this population (6.4%) was lower than in a U.S. reference population. PMID:15238287

  1. Ovine Surgical Model of Uterine Space Restriction: Interactive Effects of Uterine Anomalies and Multifetal Gestations on Fetal and Placental Growth1

    PubMed Central

    Meyer, Katie M.; Koch, Jill M.; Ramadoss, Jayanth; Kling, Pamela J.; Magness, Ronald R.

    2010-01-01

    Intrauterine growth restriction (IUGR) is observed in conditions with limitations in uterine space (e.g., uterine anomalies and multifetal gestations). IUGR is associated with reduced fetal weight, organ growth, and a spectrum of adult-onset diseases. To examine the interaction of uterine anomalies and multifetal gestations, we developed a surgical uterine space restriction model with a unilateral uterine horn ligation before breeding (unilateral surgery). Placentas and fetuses were studied on Gestational Day (GD) 120 and GD 130 (term = 147 days). Unilateral surgery decreased placentome numbers in singleton and twin pregnancies (25% and 50%, respectively) but not unilateral triplets. Unilateral surgery decreased total placentome weight in twin pregnancies (decreased 24%). Fetuses categorized as uterine space restricted (unilateral twin and both groups of triplets) had 51% fewer placentomes per fetus and a 31% reduction in placentomal weight per fetus compared to the nonrestricted group (control singleton, unilateral singleton, and control twin). By GD 130, uterine space-restricted fetuses exhibited decreased weight, smaller crown-rump, abdominal girth, and thoracic girth as well as decreased fetal heart, kidney, liver, spleen, and thymus weights. Lung and brain weights were unaffected, demonstrating asymmetric IUGR. At GD 130, placental efficiency (fetal weight per total placentomal weight) was elevated in uterine space-restricted fetuses. However, fetal arterial creatinine, blood urea nitrogen, and cholesterol were elevated, suggesting insufficient placental clearance. Maternal-to-fetal glucose and triglycerides ratios were elevated in the uterine space-restricted pregnancies, suggesting placental nutrient transport insufficiency. This model allows for examination of interactive effects of uterine space restriction-induced IUGR on placental adaptation and fetal organ growth. PMID:20574052

  2. Maternal blood and hair manganese concentrations, fetal growth, and length of gestation in the ISA cohort in Costa Rica

    PubMed Central

    Mora, Ana M.; van Wendel de Joode, Berna; Mergler, Donna; Córdoba, Leonel; Cano, Camilo; Quesada, Rosario; Smith, Donald R.; Menezes-Filho, José A.; Eskenazi, Brenda

    2014-01-01

    Background Animal studies have shown that both deficiency and excess manganese (Mn) may result in decreased fetal size and weight, but human studies have reported inconsistent results. Methods We examined the association of blood and hair Mn concentrations measured at different times during pregnancy with fetal growth among term births and length of gestation in a cohort of 380 mother-infant pairs living near banana plantations aerially sprayed with Mn-containing fungicides in Costa Rica. We used linear regression and generalized additive models to test for linear and nonlinear associations. Results Mean (± SD) blood Mn concentration was 24.4 ± 6.6 μg/L and geometric mean (geometric SD) hair Mn concentration was 1.8 (3.2) μg/g. Hair Mn concentrations during the second and third trimesters of gestation were positively related to infant chest circumference (β for 10-fold increase = 0.62 cm; 95% CI: 0.16, 1.08; and β = 0.55 cm; 95% CI: −0.16, 1.26, respectively). Similarly, average maternal hair Mn concentrations during pregnancy were associated with increased chest circumference (β for 10-fold increase = 1.19 cm; 95% CI: 0.43, 1.95) in infants whose mothers did not have gestational anemia, but not in infants of mothers who had gestational anemia (β = 0.39 cm; 95% CI: −0.32, 1.10; pINT = 0.14). All these associations were linear. Blood Mn concentrations did not show consistent linear nor nonlinear relationships with any of the birth outcomes. Conclusions Mn plays an important role in fetal development, but the extent to which environmental exposures may cause adverse health effects to the developing fetus is not well understood. Among women living near banana plantations in Costa Rica, we did not observe linear or nonlinear associations of Mn concentrations with lowered birth weight or head circumference, as reported in previous studies. However, we did find positive linear associations between maternal hair Mn concentrations during pregnancy and infant

  3. Region-Specific Growth Effects in the Developing Rat Prostate Following Fetal Exposure to Estrogenic Ultraviolet Filters

    PubMed Central

    Hofkamp, Luke; Bradley, Sarahann; Tresguerres, Jesus; Lichtensteiger, Walter; Schlumpf, Margret; Timms, Barry

    2008-01-01

    Background and objectives Exposure to environmental endocrine disruptors is a potential risk factor for humans. Many of these chemicals have been shown to exhibit disruption of normal cellular and developmental processes in animal models. Ultraviolet (UV) filters used as sunscreens in cosmetics have previously been shown to exhibit estrogenic activity in in vitro and in vivo assays. We examined the effects of two UV filters, 4-methylbenzylidene camphor (4-MBC) and 3-benzylidene camphor (3-BC), in the developing prostate of the fetal rat. Methods Pregnant Long Evans rats were fed diets containing doses of 4-MBC and 3-BC that resulted in average daily intakes of these chemicals corresponding to the lowest observed adverse effects level (LOAEL) and the no observed adverse effects level (NOAEL) doses in prior developmental toxicity studies. Using digital photographs of serial sections from postnatal day 1 animals, we identified, contoured, and aligned the epithelial ducts from specific regions of the developing prostate, plus the accessory sex glands and calculated the total volume for each region from three-dimensional, surface-rendered models. Results Fetal exposure to 4-MBC (7.0 mg/kg body weight/day) resulted in a significant increase (p < 0.05) in tissue volume in the prostate and accessory sex glands. Treated males exhibited a 62% increase in the number of ducts in the caudal dorsal prostate. Increased distal branching morphogenesis appears to be a consequence of exposure in the ventral region, resulting in a 106% increase in ductal volume. Conclusions 4-MBC exposure during development of the male reproductive accessory sex glands exhibited classical growth effects associated with estrogenic endocrine disruptors. The different regional responses suggest that the two developmental processes of ductal outgrowth and branching morphogenesis are affected independently by exposure to the environmental chemicals. PMID:18629307

  4. Indoor exposure and adverse birth outcomes related to fetal growth, miscarriage and prematurity-a systematic review.

    PubMed

    Patelarou, Evridiki; Kelly, Frank J

    2014-06-01

    The purpose of this review was to summarize existing epidemiological evidence of the association between quantitative estimates of indoor air pollution and all-day personal exposure with adverse birth outcomes including fetal growth, prematurity and miscarriage. We carried out a systematic literature search of MEDLINE and EMBASE databases with the aim of summarizing and evaluating the results of peer-reviewed epidemiological studies undertaken in "westernized" countries that have assessed indoor air pollution and all-day personal exposure with specific quantitative methods. This comprehensive literature search identified 16 independent studies which were deemed relevant for further review and two additional studies were added through searching the reference lists of all included studies. Two reviewers independently and critically appraised all eligible articles using the Critical Appraisal Skills Programme (CASP) tool. Of the 18 selected studies, 14 adopted a prospective cohort design, three were case-controls and one was a retrospective cohort study. In terms of pollutants of interest, seven studies assessed exposure to electro-magnetic fields, four studies assessed exposure to polycyclic aromatic hydrocarbons, four studies assessed PM2.5 exposure and three studies assessed benzene, phthalates and noise exposure respectively. Furthermore, 12 studies examined infant growth as the main birth outcome of interest, six examined spontaneous abortion and three studies assessed gestational age at birth and preterm delivery. This survey demonstrates that there is insufficient research on the possible association of indoor exposure and early life effects and that further research is needed. PMID:24896737

  5. Indoor Exposure and Adverse Birth Outcomes Related to Fetal Growth, Miscarriage and Prematurity—A Systematic Review

    PubMed Central

    Patelarou, Evridiki; Kelly, Frank J.

    2014-01-01

    The purpose of this review was to summarize existing epidemiological evidence of the association between quantitative estimates of indoor air pollution and all-day personal exposure with adverse birth outcomes including fetal growth, prematurity and miscarriage. We carried out a systematic literature search of MEDLINE and EMBASE databases with the aim of summarizing and evaluating the results of peer-reviewed epidemiological studies undertaken in “westernized” countries that have assessed indoor air pollution and all-day personal exposure with specific quantitative methods. This comprehensive literature search identified 16 independent studies which were deemed relevant for further review and two additional studies were added through searching the reference lists of all included studies. Two reviewers independently and critically appraised all eligible articles using the Critical Appraisal Skills Programme (CASP) tool. Of the 18 selected studies, 14 adopted a prospective cohort design, three were case-controls and one was a retrospective cohort study. In terms of pollutants of interest, seven studies assessed exposure to electro-magnetic fields, four studies assessed exposure to polycyclic aromatic hydrocarbons, four studies assessed PM2.5 exposure and three studies assessed benzene, phthalates and noise exposure respectively. Furthermore, 12 studies examined infant growth as the main birth outcome of interest, six examined spontaneous abortion and three studies assessed gestational age at birth and preterm delivery. This survey demonstrates that there is insufficient research on the possible association of indoor exposure and early life effects and that further research is needed. PMID:24896737

  6. Is the somatopause an indication for growth hormone replacement?

    PubMed

    Savine, R; Sönksen, P H

    1999-01-01

    In the normal population, a gradual and progressive fall in spontaneous growth hormone (GH) secretion occurs with increasing age and is reflected in a parallel fall in circulating insulin-like growth factor (IGF)-I, reduction in lean body mass, increase in body fat and rise in low-density lipoprotein (LDL) cholesterol. Aging is also associated with a progressive failure of body functions and particularly with an increasing lack of physical strength and mobility. Many problems of aging are attributable to the progressive loss of lean tissues and to catabolic events. This can be and often is associated with a progressive decline in independence and quality of life, leading eventually to a prolonged dependence on others, followed by a distressing process of death. By analogy with the fall in ovarian function that inevitably eventually occurs in women with increasing age, this fall in GH secretion has been termed the somatopause. In cross-sectional studies on elderly people, the amount of GH secreted spontaneously correlates well with "good risk factors" such as body composition, mobility, lipid profiles and blood pressure. The important question that these scientific facts raises is whether this fall in GH secretion with increasing years is an important physiological safety event of the normal aging process, or whether it marks the development of GH deficiency which would benefit from GH replacement. It is established that a number of the clinical features of the somatopause are shared with the syndrome of adult-onset GH deficiency and Rudman first proposed the importance of GH in maintaining health and vitality with increasing age many years ago. In 1989, GH replacement was shown to be beneficial in adults with GH deficiency, and in 1990 Rudman showed remarkably similar beneficial effects in a group of elderly men with low plasma IGF-I values, but no underlying pituitary pathology, who were administered GH. In these adults, low doses of GH increased lean body mass

  7. Biomedical Instruments for Fetal and Neonatal Surveillance

    NASA Astrophysics Data System (ADS)

    Rolfe, P.; Scopesi, F.; Serra, G.

    2006-10-01

    Specialised instruments have been developed to aid the care of the fetus and the newborn baby. Miniature sensors using optical, electrical, chemical, mechanical and magnetic principles have been produced for capturing key measurands. These include temperature, pressure, flow and dimension, as well as several specific molecules such as glucose, oxygen and carbon dioxide. During pregnancy ultrasound imaging and blood flow techniques provide valuable information concerning fetal abnormalities, fetal growth, fetal breathing and fetal heart rate. Signal processing and pattern recognition can be useful for deriving indicators of fetal distress and clinical status, based on biopotentials as well as ultrasound signals. Fetal pH measurement is a critical requirement during labour and delivery. The intensive care of ill preterm babies involves provision of an optimal thermal environment and respiratory support. Monitoring of blood gas and acid-base status is essential, and this involves both blood sampling for in vitro analysis as well as the use of invasive or non-invasive sensors. For the future it will be vital that the technologies used are subjected to controlled trials to establish benefit or otherwise.

  8. The Navigation Guide—Evidence-Based Medicine Meets Environmental Health: Systematic Review of Nonhuman Evidence for PFOA Effects on Fetal Growth

    PubMed Central

    Lam, Juleen; Sutton, Patrice; Johnson, Paula I.; Atchley, Dylan S.; Sen, Saunak; Robinson, Karen A.; Axelrad, Daniel A.; Woodruff, Tracey J.

    2014-01-01

    Background: In contrast to current methods of expert-based narrative review, the Navigation Guide is a systematic and transparent method for synthesizing environmental health research from multiple evidence streams. The Navigation Guide was developed to effectively and efficiently translate the available scientific evidence into timely prevention-oriented action. Objectives: We applied the Navigation Guide systematic review method to answer the question “Does fetal developmental exposure to perfluorooctanoic acid (PFOA) or its salts affect fetal growth in animals ?” and to rate the strength of the experimental animal evidence. Methods: We conducted a comprehensive search of the literature, applied prespecified criteria to the search results to identify relevant studies, extracted data from studies, obtained additional information from study authors, conducted meta-analyses, and rated the overall quality and strength of the evidence. Results: Twenty-one studies met the inclusion criteria. From the meta-analysis of eight mouse gavage data sets, we estimated that exposure of pregnant mice to increasing concentrations of PFOA was associated with a change in mean pup birth weight of –0.023 g (95% CI: –0.029, –0.016) per 1-unit increase in dose (milligrams per kilogram body weight per day). The evidence, consisting of 15 mammalian and 6 nonmammalian studies, was rated as “moderate” and “low” quality, respectively. Conclusion: Based on this first application of the Navigation Guide methodology, we found sufficient evidence that fetal developmental exposure to PFOA reduces fetal growth in animals. Citation: Koustas E, Lam J, Sutton P, Johnson PI, Atchley DS, Sen S, Robinson KA, Axelrad DA, Woodruff TJ. 2014. The Navigation Guide—evidence-based medicine meets environmental health: systematic review of nonhuman evidence for PFOA effects on fetal growth. Environ Health Perspect 122:1015–1027; http://dx.doi.org/10.1289/ehp.1307177 PMID:24968374

  9. Increasing fetal ovine number per gestation alters fetal plasma clinical chemistry values.

    PubMed

    Zywicki, Micaela; Blohowiak, Sharon E; Magness, Ronald R; Segar, Jeffrey L; Kling, Pamela J

    2016-08-01

    Intrauterine growth restriction (IUGR) is interconnected with developmental programming of lifelong pathophysiology. IUGR is seen in human multifetal pregnancies, with stepwise rises in fetal numbers interfering with placental nutrient delivery. It remains unknown whether fetal blood analyses would reflect fetal nutrition, liver, and excretory function in the last trimester of human or ovine IUGR In an ovine model, we hypothesized that fetal plasma biochemical values would reflect progressive placental, fetal liver, and fetal kidney dysfunction as the number of fetuses per gestation rose. To determine fetal plasma biochemical values in singleton, twin, triplet, and quadruplet/quintuplet ovine gestation, we investigated morphometric measures and comprehensive metabolic panels with nutritional measures, liver enzymes, and placental and fetal kidney excretory measures at gestational day (GD) 130 (90% gestation). As anticipated, placental dysfunction was supported by a stepwise fall in fetal weight, fetal plasma glucose, and triglyceride levels as fetal number per ewe rose. Fetal glucose and triglycerides were directly related to fetal weight. Plasma creatinine, reflecting fetal renal excretory function, and plasma cholesterol, reflecting placental excretory function, were inversely correlated with fetal weight. Progressive biochemical disturbances and growth restriction accompanied the rise in fetal number. Understanding the compensatory and adaptive responses of growth-restricted fetuses at the biochemical level may help explain how metabolic pathways in growth restriction can be predetermined at birth. This physiological understanding is important for clinical care and generating interventional strategies to prevent altered developmental programming in multifetal gestation. PMID:27565903

  10. Duration of maternal undernutrition differentially alters fetal growth and hormone concentrations.

    PubMed

    Field, M E; Anthony, R V; Engle, T E; Archibeque, S L; Keisler, D H; Han, H

    2015-04-01

    To investigate the impact of duration of maternal undernutrition in twin sheep pregnancies, ewes were either fed 100% (C) or 50% of their nutrient requirements from 28 to 78 d gestational age (dGA) and readjusted to 100% beginning at 79 dGA (LC) or continuously restricted from 28 to 135 dGA (LL). Weights of the fetus, empty carcass, brain, and liver were greater in the LC than LL fetuses at 135 dGA (P ≤ 0.05). Although umbilical vein (UmV) glucose concentrations did not differ, the UmV:umbilical artery (UmA) glucose gradient was smaller (0.26 ± 0.03 vs 0.38 ± 0.03 and 0.39 ± 0.04 mmol L(-1); P ≤ 0.05) in LL than C and LC fetuses, respectively. Umbilical vein concentrations of IGF-1 were less (46.7 ± 5.62 vs 74.3 ± 6.71 ng/mL; P ≤ 0.05) in LL than LC fetuses. Additionally, LL fetuses tended (P ≤ 0.10) to have lower UmA concentrations of insulin (0.24 ± 0.13 vs 0.70 ± 0.15 ng/mL) and IGF-1 (66.6 ± 7.51 vs 91.4 ± 8.97 ng/mL) than LC fetuses. Although most of the observed differences occurred between LC and LL pregnancies, LC fetuses tended (P ≤ 0.10) to have greater UmV and UmA pCO2 than C fetuses. Furthermore, the UmV:UmA O2 content gradient tended to be greater (5.02 ± 0.43 vs 3.41 ± 0.47; P ≤ 0.10) in C than LL fetuses. UmA placental lactogen also tended to be greater (46.6 ± 4.40 vs 31.1 ± 4.69 ng/mL; P ≤ 0.10) in LL than C fetuses. These data suggest that in twin pregnancies, maternal undernutrition followed by realimentation induces a different fetal outcome compared with continuous nutrient restriction, and both may differ physiologically from control fed pregnancies. PMID:25460066