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Sample records for fetal growth indicators

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

    PubMed

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

    2016-09-05

    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. 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. 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). Fetal hemodynamic indices in late pregnancy might be helpful for estimating newborn birth weight in women with GDM.

  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 effect of Ramadan fasting on fetal growth and Doppler indices of pregnancy.

    PubMed

    Moradi, Maryam

    2011-02-01

    The aim of this study was to determine the effect of Ramadan fasting on fetal growth and Doppler in-dices of pregnancy. Fifty two healthy pregnant women of second or third trimester, 25 in fasting group and 27 in non fasting group were included. Growth parameters including biparietal diameter (BPD), femoral length (FL), abdominal circumference (AC), estimated fetal weight, amniotic fluid index and also Doppler indices of both uterine and umbilical arteries (including peak systolic and end diastolic velocity, systolic to diastolic ratio, resistive and pulsatility indices) were evaluated by Gray scale and colour Doppler imaging for each women two times, in the beginning and at the end of Ramadan. Increases in BPD, FL, AC and fetal weight within one month were similar in two groups. Amniotic fluid index also were similar in two groups. There was not any statistically significant difference in abnormal Doppler indices of uterine or umbilical artery between two groups. The results of present study show that Ramadan fasting has no adverse effect on fetal growth, amniotic fluid volume or maternofetal circulation.

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

    PubMed

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

    2016-06-01

    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. We investigated the association between specific PFAAs and birth weight, birth length, and head circumference at birth. 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. 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. 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. Bach CC, Bech BH, Nohr EA, Olsen J, Matthiesen NB, Bonefeld-Jørgensen EC, Bossi R, Henriksen TB. 2016. Perfluoroalkyl acids in maternal serum and indices of fetal growth: the

  5. 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

  6. Maternal serum levels of perfluoroalkyl substances and organochlorines and indices of fetal growth: a Scandinavian case–cohort study

    PubMed Central

    Lauritzen, Hilde B.; Larose, Tricia L.; Øien, Torbjørn; Sandanger, Torkjel M.; Odland, Jon Ø.; van de Bor, Margot; Jacobsen, Geir W.

    2017-01-01

    Background: The associations between prenatal exposure to endocrine disruptive chemicals (EDCs) and fetal growth are inconsistent, and few studies have considered small-for-gestational-age (SGA) birth as an outcome. Our current study of Scandinavian parous women aimed to address these inconsistencies and gaps in the literature. Methods: This case–cohort study included 424 mother–child pairs who participated in a prospective, multi-center study of parous women in Norway (Trondheim and Bergen) and Sweden (Uppsala). We used linear and logistic regression with 95% confidence intervals (CIs) to analyze the associations between two perfluoroalkyl substances (PFASs) and five organochlorines (OCs) from early second trimester and indices of fetal growth. Results: Among Swedish women, prenatal exposure to perfluorooctanoate (PFOA), polychlorinated biphenyl (PCB) 153 and hexachlorobenzene (HCB) were associated with higher odds for SGA birth. We found stronger associations among Swedish male offspring. In the Norwegian cohort, we found no significant associations between EDC exposure and indices of fetal growth. Conclusions: Some populations may be more vulnerable to EDCs, possibly due to differences in exposure levels, exposure sources and/or modifiable lifestyle factors. Male offspring may be more vulnerable to endocrine disruption. PMID:27656770

  7. Micronutrients and fetal growth.

    PubMed

    Fall, Caroline H D; Yajnik, Chittaranjan S; Rao, Shobha; Davies, Anna A; Brown, Nick; Farrant, Hannah J W

    2003-05-01

    Fetal undernutrition affects large numbers of infants in developing countries, with adverse consequences for their immediate survival and lifelong health. It manifests as intrauterine growth retardation (IUGR), defined as birth weight <10th percentile, which probably underestimates the number failing to achieve full growth potential. Birth weight is a crude measure of the dynamic process of fetal growth and does not capture effects of fetal undernutrition on body composition and the development of specific tissues. The link between maternal nutrition and fetal nutrition is indirect. The fetus is nourished by a complex supply line that includes the mother's diet and absorption, endocrine status and metabolism, cardiovascular adaptations to pregnancy and placental function. Micronutrients are essential for growth, and maternal micronutrient deficiency, frequently multiple in developing countries, may be an important cause of IUGR. Supplementation of undernourished mothers with micronutrients has several benefits but there is little hard evidence of improved fetal growth. However, this has been inadequately tested. Most trials have only used single micronutrients and many were inconclusive because of methodological problems. Several food-based studies (some uncontrolled) suggest benefits from improving maternal dietary quality with micronutrient-dense foods. One trial of a multivitamin supplement (HIV-positive mothers, Tanzania) showed increased birth weight and fewer fetal deaths. Well-conducted randomized controlled trials of adequate sample size and including measures of effectiveness are needed in populations at high risk of micronutrient deficiency and IUGR and should include food-based interventions and better measurements of fetal growth, maternal metabolism, and long-term outcomes in the offspring.

  8. Stillbirth and fetal growth restriction.

    PubMed

    Bukowski, Radek

    2010-09-01

    The association between stillbirth and fetal growth restriction is strong and supported by a large body of evidence and clinically employed for the stillbirth prediction. However, although assessment of fetal growth is a basis of clinical practice, it is not trivial. Essentially, fetal growth is a result of the genetic growth potential of the fetus and placental function. The growth potential is the driving force of fetal growth, whereas the placenta as the sole source of nutrients and oxygen might become the rate limiting element of fetal growth if its function is impaired. Thus, placental dysfunction may prevent the fetus from reaching its full genetically determined growth potential. In this sense fetal growth and its aberration provides an insight into placental function. Fetal growth is a proxy for the test of the effectiveness of placenta, whose function is otherwise obscured during pregnancy.

  9. Effect of diuretics on fetal growth: A drug effect or confounding by indication? Pooled Danish and Scottish cohort data

    PubMed Central

    Olesen, Charlotte; de Vries, Corinne S; Thrane, Nana; MacDonald, Tom M; Larsen, Helle; Sørensen, Henrik Toft

    2001-01-01

    Aims The diabetogenic effect of diuretics, as well as the indication for prescribing them, may impact on fetal growth. We analysed whether the purchase of prescription drugs for diuretics during pregnancy was associated with measures of fetal growth. Methods During 1991–98 all women who purchased prescription drugs for diuretics during pregnancy were identified in the Northern Jutland Prescription Database (NJDP), Denmark, and in the Medicines Monitoring Unit's Database (MEMO), Scotland. Information on birth weight and gestational age was obtained from the Danish Birth Registry, the Danish Hospital Discharge Registry and the Scottish Tayside Neonatal Database. Information on diabetes, hypertension and prepregnancy weight were obtained by hospital record review in a sample of women in the Danish cohort. Women who did not purchase prescription diuretics during pregnancy were used as a reference group in both cohorts. Results Danish women who purchased prescription loop diuretics during pregnancy gave birth to infants with higher birth weights than women who did not use diuretics; mean difference 104.7 g (95% CI; 2.6, 206.9). However, the high prevalence of diabetes (10.3%) among Danish women who purchased prescription loop diuretics during pregnancy might explain this result. Both the Danish and the Scottish women who purchased prescription diuretics during their pregnancy were at increased risk of preterm delivery (< 37 completed weeks); ORs: 1.8 (CI; 1.2, 2.7)NJDP, 1.9 (CI; 0.9, 4.3)MEMO. The proportion of hypertension among women who purchased prescription thiazides was 15.8%, and the risk of having an infant with a birth weight (BW) < 2500 g was increased; ORs: 2.6 (CI; 1.4, 5.0)NJDP, 2.4 (CI; 0.8, 7.8)MEMO. Conclusions Prescribing diuretics during pregnancy was associated with differences in birth weight and incidence of preterm delivery. Confounding by indication may explain the findings. PMID:11259987

  10. Application of clinical indices of fetal growth and wellbeing to a novel laboratory species, the spiny mouse.

    PubMed

    Dickinson, Hayley; Griffiths, Tania; Walker, David W; Jenkin, Graham

    2008-11-01

    Ultrasound was used to measure growth of the spiny mouse fetus throughout gestation and to record Doppler measurements of heart rate and umbilical blood flow to monitor fetal blood supply and wellbeing. Female spiny mice were anesthetized on 6 occasions throughout pregnancy. Ultrasound was performed with a Philips HDI 5000 machine using a compact linear CL15-7 transducer. Fetal heart rate and growth parameters increased across gestation. Blood flow through the umbilical artery and vein showed increasing velocity over gestation, and reduced resistance index. Blood flow through the ductus venosus also increased in velocity over gestation; however the resistance index remained constant. We have determined changes in umbilical blood flow throughout pregnancy in the spiny mouse, which resemble those seen in human pregnancy. We also confirm that ultrasound can be used as a valuable, non-invasive technique for measuring fetal growth and wellbeing in the spiny mouse.

  11. Hormonal regulation of fetal growth.

    PubMed

    Gicquel, C; Le Bouc, Y

    2006-01-01

    Fetal growth is a complex process depending on the genetics of the fetus, the availability of nutrients and oxygen to the fetus, maternal nutrition and various growth factors and hormones of maternal, fetal and placental origin. Hormones play a central role in regulating fetal growth and development. They act as maturational and nutritional signals in utero and control tissue development and differentiation according to the prevailing environmental conditions in the fetus. The insulin-like growth factor (IGF) system, and IGF-I and IGF-II in particular, plays a critical role in fetal and placental growth throughout gestation. Disruption of the IGF1, IGF2 or IGF1R gene retards fetal growth, whereas disruption of IGF2R or overexpression of IGF2 enhances fetal growth. IGF-I stimulates fetal growth when nutrients are available, thereby ensuring that fetal growth is appropriate for the nutrient supply. The production of IGF-I is particularly sensitive to undernutrition. IGF-II plays a key role in placental growth and nutrient transfer. Several key hormone genes involved in embryonic and fetal growth are imprinted. Disruption of this imprinting causes disorders involving growth defects, such as Beckwith-Wiedemann syndrome, which is associated with fetal overgrowth, or Silver-Russell syndrome, which is associated with intrauterine growth retardation. Optimal fetal growth is essential for perinatal survival and has long-term consequences extending into adulthood. Given the high incidence of intrauterine growth retardation and the high risk of metabolic and cardiovascular complications in later life, further clinical and basic research is needed to develop accurate early diagnosis of aberrant fetal growth and novel therapeutic strategies.

  12. 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…

  13. 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…

  14. Indices and Detectors for Fetal MCG Actography

    PubMed Central

    Lutter, William J.

    2011-01-01

    Several recent studies have demonstrated the usefulness of fetal magnetocardiogram (fMCG) actography, a relatively new method of detecting fetal movement that can be performed in conjunction with fMCG assessment of fetal heart rate and rhythm. In this work, we formulate indices of fetal activity that incorporate information from all channels to achieve improved sensitivity. We also utilize statistical detection to provide an objective means of inferring significant fetal activity. PMID:21427015

  15. Indices and detectors for fetal MCG actography.

    PubMed

    Lutter, William J; Wakai, Ronald T

    2011-06-01

    Several recent studies have demonstrated the usefulness of fetal magnetocardiogram (fMCG) actography, a relatively new method of detecting fetal movement that can be performed in conjunction with fMCG assessment of fetal heart rate and rhythm. In this study, we formulate indices of fetal activity that incorporate information from all channels to achieve improved sensitivity. We also utilize statistical detection to provide an objective means of inferring significant fetal activity.

  16. 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

    2015-03-05

    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. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  17. 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

  18. 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

  19. Fetal growth potential and pregnancy outcome.

    PubMed

    Bukowski, Radek

    2004-02-01

    Although the association of fetal growth restriction and adverse pregnancy outcomes is well known, lack of sensitivity limits its clinical value. To a large extent, this limitation is a result of traditionally used method to define growth restriction by comparing fetal or birth weight to population norms. The use of population norms, by virtue of their inability to fully consider individual variation, results in high false positive and negative rates. An alternative, calculating fetal individually optimal growth potential, based on physiological determinants of individual growth, is superior in predicting adverse outcomes of pregnancy. Impairment of fetal growth potential identifes some adverse pregnancy outcomes that are not associated with growth restrction defined by population norms. When compared with traditional population-based norms, fetal growth potential is a better predictor of several important adverse outcomes of pregnancy which include: stillbirth, neonatal mortality and morbidity, and long-term adverse neonatal outcomes like neonatal encephalopathy, cerebral palsy and cognitive abilities. Impairment of individual growth potential is also strongly associated with spontaneous preterm delivery. Although definitive interventional trials have not been conducted as yet to validate the clinical value of fetal growth potential, many observational studies, conducted in various populations, indicate its significant promise in this respect.

  20. The effect of low-dose aspirin on fetal weight of idiopathic asymmetrically intrauterine growth restricted fetuses with abnormal umbilical artery Doppler indices: a randomized clinical trial.

    PubMed

    Ali, Mohammed K; Abbas, Ahmed M; Yosef, Ali H; Bahloul, Mustafa

    2017-07-11

    To investigate the effect of aspirin on fetal weight in fetuses with idiopathic asymmetrical intrauterine growth restriction (IUGR) complicated by abnormal umbilical artery Doppler indices. The study was a randomized controlled trial conducted at Woman's Health Hospital, Assiut, Egypt, between June 2016 and the January 2017 included 60 pregnant women (28-30 weeks) with idiopathic asymmetrical IUGR associated with abnormal umbilical artery Doppler indices. Women were randomly assigned to group I (aspirin 75 mg) daily for four weeks or group II (no intervention). The primary outcome was the fetal weight after four weeks. Secondary outcomes included Doppler blood flow changes in the umbilical artery plus delivery and neonatal outcomes. The estimated fetal weight and umbilical artery blood flow increased significantly in aspirin group (p = .00) when compared with no intervention group. As regard neonatal outcomes; aspirin group showed better results and encouraging outcomes (p < .05). Aspirin improves fetal weight and umbilical artery blood flow in idiopathic asymmetrical IUGR fetuses complicated by abnormal umbilical artery Doppler blood flow.

  1. Fetal Growth and Timing of Parturition in Humans

    PubMed Central

    Sundaram, Rajeshwari; Sun, Wenyu; Troendle, James

    2008-01-01

    Animal studies indicate that either the fetus or the intrauterine environment, both of which set the pattern for fetal growth, may affect the timing of parturition. The authors examined the association between fetal growth and timing of spontaneous onset of labor in humans among low-risk white US women with singleton pregnancies (1987–1991). They restricted the data to pregnancies which had a reliable date of the last menstrual period, normal fetal growth in the first half of pregnancy, and no history of or current pregnancy complications that might have impaired fetal growth (n = 3,360). Subjects received ultrasound examinations at 15–22 and 31–35 weeks’ gestation. Fetal growth was adjusted for parity, fetal sex, and maternal prepregnancy weight and height. Results showed that slower or faster fetal growth in the second half of pregnancy resulted in substantially lower or higher birth weight, respectively. However, fetal growth in the second half of pregnancy, even at extremes (2 standard deviations below or above the mean), did not have a meaningful impact on the timing of parturition; neither did fetal growth acceleration or deceleration in late pregnancy. Thus, in low-risk pregnancies where fetal growth is normal in early gestation, fetal growth in the second half of pregnancy does not affect the timing of normal parturition. PMID:18775925

  2. Fetal growth and timing of parturition in humans.

    PubMed

    Zhang, Jun; Sundaram, Rajeshwari; Sun, Wenyu; Troendle, James

    2008-10-15

    Animal studies indicate that either the fetus or the intrauterine environment, both of which set the pattern for fetal growth, may affect the timing of parturition. The authors examined the association between fetal growth and timing of spontaneous onset of labor in humans among low-risk white US women with singleton pregnancies (1987-1991). They restricted the data to pregnancies which had a reliable date of the last menstrual period, normal fetal growth in the first half of pregnancy, and no history of or current pregnancy complications that might have impaired fetal growth (n = 3,360). Subjects received ultrasound examinations at 15-22 and 31-35 weeks' gestation. Fetal growth was adjusted for parity, fetal sex, and maternal prepregnancy weight and height. Results showed that slower or faster fetal growth in the second half of pregnancy resulted in substantially lower or higher birth weight, respectively. However, fetal growth in the second half of pregnancy, even at extremes (2 standard deviations below or above the mean), did not have a meaningful impact on the timing of parturition; neither did fetal growth acceleration or deceleration in late pregnancy. Thus, in low-risk pregnancies where fetal growth is normal in early gestation, fetal growth in the second half of pregnancy does not affect the timing of normal parturition.

  3. Are gestational age, birth weight, and birth length indicators of favorable fetal growth conditions? A structural equation analysis of Filipino infants.

    PubMed

    Bollen, Kenneth A; Noble, Mark D; Adair, Linda S

    2013-07-30

    The fetal origins hypothesis emphasizes the life-long health impacts of prenatal conditions. Birth weight, birth length, and gestational age are indicators of the fetal environment. However, these variables often have missing data and are subject to random and systematic errors caused by delays in measurement, differences in measurement instruments, and human error. With data from the Cebu (Philippines) Longitudinal Health and Nutrition Survey, we use structural equation models, to explore random and systematic errors in these birth outcome measures, to analyze how maternal characteristics relate to birth outcomes, and to take account of missing data. We assess whether birth weight, birth length, and gestational age are influenced by a single latent variable that we call favorable fetal growth conditions (FFGC) and if so, which variable is most closely related to FFGC. We find that a model with FFGC as a latent variable fits as well as a less parsimonious model that has birth weight, birth length, and gestational age as distinct individual variables. We also demonstrate that birth weight is more reliably measured than is gestational age. FFGCs were significantly influenced by taller maternal stature, better nutritional stores indexed by maternal arm fat and muscle area during pregnancy, higher birth order, avoidance of smoking, and maternal age 20-35 years. Effects of maternal characteristics on newborn weight, length, and gestational age were largely indirect, operating through FFGC. Copyright © 2013 John Wiley & Sons, Ltd.

  4. Metabolic requirements for fetal growth.

    PubMed

    Milley, J R; Simmons, M A

    1979-09-01

    Table 1 outlines a metabolic balance sheet for the sheep fetus. It is clear that maternal substrate concentrations as well as placental function are important in assuring the provision of adequate substrate to meet fetal metabolic and growth requirements. It is intriguing that the fetus appears to use substrates not usually regarded as important in extrauterine diets (lactate) and to use substrates for catabolic purposes normally thought to be primarily anabolic substrates (amino acids). This information emphasizes the hazards of extrapolating metabolic and nutritional patterns seen in extrauterine life in reaching conclusions concerning the fetus. It likewise emphasizes the importance of ongoing studies in maternal and fetal nutrition and metabolism.

  5. Fetal growth restriction: current knowledge.

    PubMed

    Nardozza, Luciano Marcondes Machado; Caetano, Ana Carolina Rabachini; Zamarian, Ana Cristina Perez; Mazzola, Jaqueline Brandão; Silva, Carolina Pacheco; Marçal, Vivian Macedo Gomes; Lobo, Thalita Frutuoso; Peixoto, Alberto Borges; Araujo Júnior, Edward

    2017-05-01

    Fetal growth restriction (FGR) is a condition that affects 5-10% of pregnancies and is the second most common cause of perinatal mortality. This review presents the most recent knowledge on FGR and focuses on the etiology, classification, prediction, diagnosis, and management of the condition, as well as on its neurological complications. The Pubmed, SCOPUS, and Embase databases were searched using the term "fetal growth restriction". Fetal growth restriction (FGR) may be classified as early or late depending on the time of diagnosis. Early FGR (<32 weeks) is associated with substantial alterations in placental implantation with elevated hypoxia, which requires cardiovascular adaptation. Perinatal morbidity and mortality rates are high. Late FGR (≥32 weeks) presents with slight deficiencies in placentation, which leads to mild hypoxia and requires little cardiovascular adaptation. Perinatal morbidity and mortality rates are lower. The diagnosis of FGR may be clinical; however, an arterial and venous Doppler ultrasound examination is essential for diagnosis and follow-up. There are currently no treatments to control FGR; the time at which pregnancy is interrupted is of vital importance for protecting both the mother and fetus. Early diagnosis of FGR is very important, because it enables the identification of the etiology of the condition and adequate monitoring of the fetal status, thereby minimizing risks of premature birth and intrauterine hypoxia.

  6. Periconceptional seafood intake and fetal growth

    PubMed Central

    Mohanty, April F; Thompson, Mary Lou; Burbacher, Thomas M; Siscovick, David S; Williams, Michelle A; Enquobahrie, Daniel A

    2015-01-01

    Background Previous reports of associations of maternal seafood intake with fetal growth were inconsistent. Further, little is known whether associations differ across seafood subtypes or fetal growth indices. Methods Among 3,141 participants of the Omega study, a pregnancy cohort study, we investigated associations of periconceptional shell-, lean-, and fatty-fish intake with fetal growth indices. We categorized food frequency questionnaire reported seafood intake into frequencies of: <0.2 servings/month, 0.2 servings/month-<0.5 servings/week, 0.5-1 servings/week, and >1 servings/week. We abstracted birthweight, birth length, and head circumference from medical records. Using generalized linear models with a log link, the Poisson family, and robust standard errors, we estimated relative risks and 95% confidence intervals (CIs) for low birthweight (LBW, <2500 g) and linear regression models to estimate mean differences for continuous fetal growth indices across seafood intake categories. Results Medians (interquartile ranges) of shell-, lean-, and fatty-fish intake were 0.3 (0-0.9), 0.5 (0-1.0), and 0.5 (0.1-1.0) servings/week, respectively. Lean fish intake of >1 servings/week (versus <0.2 servings/month) was associated with a 2.2-fold higher risk of LBW [95% CI: 1.2, 4.1]. Shellfish intake of >1 servings/week (versus <0.2 servings/month) was associated with a 0.6 kg/m3 higher mean ponderal index [95% CI: 0.0, 1.2 kg/m3]. There was no evidence for associations of total seafood or seafood subtype intake with other fetal growth indices. Conclusions Higher intakes of lean- and shell-fish were associated with a higher risk of LBW and higher mean ponderal index, respectively. Findings highlight the importance of considerations of seafood subtype in similar investigations. PMID:26147526

  7. Periconceptional Seafood Intake and Fetal Growth.

    PubMed

    Mohanty, April F; Thompson, Mary Lou; Burbacher, Thomas M; Siscovick, David S; Williams, Michelle A; Enquobahrie, Daniel A

    2015-09-01

    Previous reports of associations of maternal seafood intake with fetal growth were inconsistent. Further, little is known whether associations differ across seafood subtypes or fetal growth indices. Among 3141 participants of the Omega study, a pregnancy cohort study, we investigated associations of periconceptional shell, lean, and fatty fish intake with fetal growth indices. We categorised food frequency questionnaire reported seafood intake into frequencies of: <0.2 servings/month, 0.2 servings/month -<0.5 servings/week, 0.5-1 servings/week, and >1 servings/week. We abstracted birthweight, birth length, and head circumference from medical records. Using generalised linear models with a log link, the Poisson family, and robust standard errors, we estimated relative risks and 95% confidence intervals (CI) for low birthweight (LBW, <2500 g) and linear regression models to estimate mean differences for continuous fetal growth indices across seafood intake categories. Medians (interquartile range) of shell, lean, and fatty fish intake were 0.3 (0-0.9), 0.5 (0-1.0), and 0.5 (0.1-1.0) servings/week, respectively. Lean fish intake of >1 servings/week (vs. <0.2 servings/month) was associated with a 2.2-fold higher risk of LBW (95% CI 1.2, 4.1). Shellfish intake of >1 servings/week (vs. <0.2 servings/month) was associated with a 0.6 kg/m(3) higher mean ponderal index (95% CI 0.0, 1.2 kg/m(3) ). There was no evidence for associations of total seafood or seafood subtype intake with other fetal growth indices. Higher intakes of lean fish and shellfish were associated with a higher risk of LBW and higher mean ponderal index, respectively. Findings highlight the importance of considerations of seafood subtype in similar investigations. © 2015 John Wiley & Sons Ltd.

  8. Effect of Placenta Previa on Fetal Growth

    PubMed Central

    HARPER, Lorie M.; ODIBO, Anthony O.; MACONES, George A.; CRANE, James P.; CAHILL, Alison G.

    2011-01-01

    Objective To estimate the association between placenta previa and abnormal fetal growth. Study Design Retrospective cohort study of consecutive women undergoing ultrasound between 15–22 weeks. Groups were defined by the presence or absence of complete or partial placenta previa. The primary outcome was intrauterine growth restriction (IUGR), defined as a birth weight <10th percentile by the Alexander growth standard. Univariable, stratified and multivariable analyses were used to estimate the effect of placenta previa on fetal growth restriction. Results Of 59,149 women, 724 (1.2%) were diagnosed with a complete or partial previa. After adjusting for significant confounding factors (black race, gestational diabetes, preeclampsia, and single umbilical artery,), the risk of IUGR remained similar (adjusted odds ratio 1.1, 95% CI 0.9–1.5). The presence of bleeding did not impact the risk of growth restriction. Conclusion Placenta previa is not associated with fetal growth restriction. Serial growth ultrasounds are not indicated in patients with placenta previa. PMID:20599185

  9. Altered fetal growth, placental abnormalities, and stillbirth.

    PubMed

    Bukowski, Radek; Hansen, Nellie I; Pinar, Halit; Willinger, Marian; Reddy, Uma M; Parker, Corette B; Silver, Robert M; Dudley, Donald J; Stoll, Barbara J; Saade, George R; Koch, Matthew A; Hogue, Carol; Varner, Michael W; Conway, Deborah L; Coustan, Donald; Goldenberg, Robert L

    2017-01-01

    Worldwide, stillbirth is one of the leading causes of death. Altered fetal growth and placental abnormalities are the strongest and most prevalent known risk factors for stillbirth. The aim of this study was to identify patterns of association between placental abnormalities, fetal growth, and stillbirth. Population-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in 5 geographic areas in the U.S. Fetal growth abnormalities were categorized as small (<10th percentile) and large (>90th percentile) for gestational age at death (stillbirth) or delivery (live birth) using a published algorithm. Placental examination by perinatal pathologists was performed using a standardized protocol. Data were weighted to account for the sampling design. Among 319 singleton stillbirths and 1119 singleton live births at ≥24 weeks at death or delivery respectively, 25 placental findings were investigated. Fifteen findings were significantly associated with stillbirth. Ten of the 15 were also associated with fetal growth abnormalities (single umbilical artery; velamentous insertion; terminal villous immaturity; retroplacental hematoma; parenchymal infarction; intraparenchymal thrombus; avascular villi; placental edema; placental weight; ratio birth weight/placental weight) while 5 of the 15 associated with stillbirth were not associated with fetal growth abnormalities (acute chorioamnionitis of placental membranes; acute chorioamionitis of chorionic plate; chorionic plate vascular degenerative changes; perivillous, intervillous fibrin, fibrinoid deposition; fetal vascular thrombi in the chorionic plate). Five patterns were observed: placental findings associated with (1) stillbirth but not fetal growth abnormalities; (2) fetal growth abnormalities in stillbirths only; (3) fetal growth abnormalities in live births only; (4) fetal growth abnormalities in stillbirths and live births in a similar manner; (5) a different pattern of

  10. Fetal growth in rats treated with lapachol.

    PubMed

    Felício, André Carvalho; Chang, Cláudia Veiga; Brandão, Marcos Antônio; Peters, Vera Maria; Guerra, Martha de Oliveira

    2002-10-01

    Lapachol is a naphthoquinone well known for its therapeutic potential. Previous studies have shown that lapachol does not interfere with embryonic development during the pre-implantation period. However, when administered during the organogenic period at the same dose level, it induces a high fetal death incidence. To evaluate the effect of lapachol during fetogenesis, 20 pregnant Wistar rats were randomly divided into two groups: vehicle (10 mL of a 50% aqueous ethanol solution/kg body weight) and treated (100 mg of lapachol/kg body weight). Lapachol was administered from the 17th to 20th day of pregnancy. The following variables were analyzed: maternal body weight from 16th to 21st day of pregnancy, food intake from 17th to 21st day of pregnancy, clinical signs of physical discomfort, ovarian weights, implantations, resorptions and mortality indices, fetal and placenta weights, external malformations, and fetal organ weights. Results indicated that lapachol was not toxic to mothers, although it was fetotoxic leading to fetal growth retardation.

  11. Neurodevelopment after fetal growth restriction.

    PubMed

    Baschat, Ahmet A

    2014-01-01

    Fetal growth restriction (FGR) can emerge as a complication of placental dysfunction and increases the risk for neurodevelopmental delay. Marked elevations of umbilical artery (UA) Doppler resistance that set the stage for cardiovascular and biophysical deterioration with subsequent preterm birth characterize early-onset FGR. Minimal, or absent UA Doppler abnormalities and isolated cerebral Doppler changes with subtle deterioration and a high risk for unanticipated term stillbirth are characteristic for late-onset FGR. Nutritional deficiency manifested in lagging head growth is the most powerful predictor of developmental delay in all forms of FGR. Extremes of blood flow resistance and cardiovascular deterioration, prematurity and intracranial hemorrhage increase the risks for psychomotor delay and cerebral palsy. In late-onset FGR, regional cerebral vascular redistribution correlates with abnormal behavioral domains. Irrespective of the phenotype of FGR, prenatal tests that provide precise and independent stratification of risks for adverse neurodevelopment have yet to be determined.

  12. Monitoring fetal maturation - objectives, techniques and indices of autonomic function.

    PubMed

    Hoyer, Dirk; Zebrowski, Jan; Cysarz, Dirk; Goncalves, Hernani; Pytlik, Adelina; Amorim-Costa, Celia; Bernardes, Joao; Ayres-de-Campos, Diogo; Witte, Otto; Schleussner, Ekkehard; Stroux, Lisa; Redman, Christopher; Georgieva, Antoniya; Payne, Stephen; Clifford, Gari; Signorini, Maria; Magenes, Giovanni; Andreotti, Fernando; Malberg, Hagen; Zaunseder, Sebastian; Lakhno, Igor; Schneider, Uwe

    2017-02-10

    Monitoring the fetal behavior does not only have implications for acute care but also for identifying developmental disturbances that burden the entire later life. The concept, of "fetal programming", also known as "developmental origins of adult disease hypothesis", e.g. applies for cardiovascular, metabolic, hyperkinetic, cognitive disorders. Since the autonomic nervous system is involved in all of those systems, cardiac autonomic control may provide relevant functional diagnostic and prognostic information. The fetal heart rate patterns (HRP) are one of the few functional signals in the prenatal period that relate to autonomic control and, therefore, is predestinated for its evaluation. The development of sensitive markers of fetal maturation and its disturbances requires the consideration of physiological fundamentals, recording technology and HRP parameters of autonomic control. Based on the ESGCO2016 special session on monitoring the fetal maturation we herein report the most recent results on: (i) functional fetal autonomic brain age score (fABAS), Recurrence Quantitative Analysis and Binary Symbolic Dynamics of complex HRP resolve specific maturation periods, (ii) magnetocardiography (MCG) based fABAS was validated for cardiotocography (CTG), (iii) 30 min recordings are sufficient for obtaining episodes of high variability, important for intrauterine growth restriction (IUGR) detection in handheld Doppler, (iv) novel parameters from PRSA to identify Intra IUGR fetuses, (v) Electrocardiographic (ECG) recordings allowed a stable heart beat detection in the maturation periods between 20 to 28 weeks of gestation only, (vi) correlation between maternal and fetal HRV is disturbed in pre-eclampsia. The reported novel developments significantly extend the possibilities for the established CTG methodology. Novel HRP indices improve the accuracy of assessment due to their more appropriate consideration of complex autonomic processes across the recording technologies

  13. Micronutrients in fetal growth and development.

    PubMed

    McArdle, H J; Ashworth, C J

    1999-01-01

    The roles that the different vitamins and minerals play in fetal growth and development are reviewed, primarily with respect to growth and differentiation in humans; but, as appropriate, data provided from animal and cellular studies are also considered.

  14. Altered fetal growth, placental abnormalities, and stillbirth

    PubMed Central

    Bukowski, Radek; Hansen, Nellie I.; Pinar, Halit; Willinger, Marian; Reddy, Uma M.; Parker, Corette B.; Silver, Robert M.; Dudley, Donald J.; Stoll, Barbara J.; Saade, George R.; Koch, Matthew A.; Hogue, Carol; Varner, Michael W.; Conway, Deborah L.; Coustan, Donald; Goldenberg, Robert L.

    2017-01-01

    Background Worldwide, stillbirth is one of the leading causes of death. Altered fetal growth and placental abnormalities are the strongest and most prevalent known risk factors for stillbirth. The aim of this study was to identify patterns of association between placental abnormalities, fetal growth, and stillbirth. Methods and findings Population-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in 5 geographic areas in the U.S. Fetal growth abnormalities were categorized as small (<10th percentile) and large (>90th percentile) for gestational age at death (stillbirth) or delivery (live birth) using a published algorithm. Placental examination by perinatal pathologists was performed using a standardized protocol. Data were weighted to account for the sampling design. Among 319 singleton stillbirths and 1119 singleton live births at ≥24 weeks at death or delivery respectively, 25 placental findings were investigated. Fifteen findings were significantly associated with stillbirth. Ten of the 15 were also associated with fetal growth abnormalities (single umbilical artery; velamentous insertion; terminal villous immaturity; retroplacental hematoma; parenchymal infarction; intraparenchymal thrombus; avascular villi; placental edema; placental weight; ratio birth weight/placental weight) while 5 of the 15 associated with stillbirth were not associated with fetal growth abnormalities (acute chorioamnionitis of placental membranes; acute chorioamionitis of chorionic plate; chorionic plate vascular degenerative changes; perivillous, intervillous fibrin, fibrinoid deposition; fetal vascular thrombi in the chorionic plate). Five patterns were observed: placental findings associated with (1) stillbirth but not fetal growth abnormalities; (2) fetal growth abnormalities in stillbirths only; (3) fetal growth abnormalities in live births only; (4) fetal growth abnormalities in stillbirths and live births in a similar manner

  15. Nutritional regulation of the placental lactogen receptor in fetal liver: Implications for fetal metabolism and growth

    SciTech Connect

    Freemark, M.; Comer, M.; Mularoni, T.; D'Ercole, A.J.; Grandis, A.; Kodack, L. )

    1989-09-01

    We have recently identified and purified from fetal liver a distinct receptor that mediates the effects of placental lactogen (PL) on amino acid transport, glycogen synthesis, and somatomedin production in fetal tissues. At present, the factors that regulate the number and affinity of PL receptors in the fetus are unknown. Since maternal nutrition plays a critical role in fetal metabolism and growth, we have examined the role of nutrition in the regulation of the PL receptor in fetal lambs. Pregnant ewes at 123-126 days gestation were fed ad libitum (FED), fasted for 3 days (FASTED), or fasted for 3 days and then refed for an additional 3 days (REFED). The ewes were then killed, and the binding of (125I)ovine (o) PL to hepatic microsomes from the fetal lambs was examined. Maternal fasting caused a 60-75% reduction in the specific binding of oPL to fetal liver; the effect of fasting was reversed in part by refeeding. The decrease in oPL binding resulted from an 80% reduction in the number of fetal oPL-binding sites (Scatchard analysis); there were no changes in the affinity of the oPL receptor (Kd, 0.6 nM), the subunit structure of the receptor, or the degree of occupancy of the receptor in vivo by endogenous fetal hormones. The specific bindings of GH (0.6%), PRL (0.3%), and insulin (35%) to fetal liver were not affected by maternal fasting, indicating that caloric restriction exerted a specific effect on oPL binding in the fetus. The number of fetal oPL-binding sites was positively correlated with the fetal liver glycogen content (r = 0.69; P less than 0.01) and the fetal plasma concentrations of glucose (r = 0.68; P less than 0.01) and insulin-like growth factor-I (r = 0.74; P less than 0.001), suggesting a role for the PL receptor in the regulation of fetal carbohydrate metabolism and growth.

  16. Influence of fetal blood flow redistribution on fetal and childhood growth and fat distribution: the Generation R Study.

    PubMed

    Kooijman, M N; Gaillard, R; Reiss, Ikm; Hofman, A; Steegers, Eap; Jaddoe, Vwv

    2016-12-01

    A suboptimal intrauterine environment leads to fetal blood flow redistribution and fetal growth restriction. Not much is known about childhood growth consequences. We examined the associations of fetal blood flow redistribution with birth outcomes, and repeatedly measured fetal and childhood growth and fat mass measures. Prospective cohort study. Population-based. One thousand one hundred and ninety-five pregnant women and their children. We measured umbilical and cerebral artery blood flow at a gestational age of 30.3 weeks (95% range, 28.5-32.6 weeks). A higher umbilical/cerebral (U/C) pulsatility index ratio is an indicator of preferential blood flow to the brain cerebral circulation at the expense of the lower body parts. Fetal and childhood growth were repeatedly measured from the third trimester until childhood. We measured the total body fat mass, lean fat mass and android/gynoid fat mass ratio by dual-energy X-ray absorptiometry and preperitoneal fat by ultrasound at 6 years. A higher fetal U/C ratio was associated with increased risks of preterm birth and small size for gestational age at birth [odds ratios, 1.41 (95% confidence interval, 1.08-1.85) and 1.63 (95% confidence interval, 1.21-2.19), respectively, per SDS increase in U/C ratio]. Longitudinal growth analyses showed that a higher fetal U/C ratio was associated with persistently lower head circumference, length and weight from third trimester fetal life until childhood (all P < 0.05). The fetal U/C ratio was not associated with total body and abdominal fat measures at 6 years. Our results suggest that fetal blood flow redistribution affects fetal development and has persistent consequences for childhood growth. Fetal blood flow redistribution affects fetal development and has persistent consequences for childhood growth. © 2016 Royal College of Obstetricians and Gynaecologists.

  17. Defining Normal and Abnormal Fetal Growth: Promises and Challenges

    PubMed Central

    Zhang, Jun; Merialdi, Mario; Platt, Lawrence D.; Kramer, Michael S.

    2010-01-01

    Normal fetal growth is a critical component of a healthy pregnancy and influences the long-term health of the offspring. However, defining normal and abnormal fetal growth has been a long-standing challenge in clinical practice and research. The authors review various references and standards that are widely used to evaluate fetal growth, and discuss common pitfalls of current definitions of abnormal fetal growth. Pros and cons of different approaches to customize fetal growth standards are described. The authors further discuss recent advances towards an integrated definition for fetal growth restriction. Such a definition may incorporate fetal size with the status of placental health measured by maternal and fetal Doppler velocimetry and biomarkers, biophysical findings and genetics. Although the concept of an integrated definition appears promising, further development and testing are required. An improved definition of abnormal fetal growth should benefit both research and clinical practice. PMID:20074690

  18. Childhood cognitive development after fetal growth restriction.

    PubMed

    Llurba, E; Baschat, A A; Turan, O M; Harding, J; McCowan, L M

    2013-04-01

    To examine the relationship between prenatal umbilical artery (UA) and internal carotid artery (ICA) Doppler findings and cognitive development at 3 and 6 years in low-birth-weight children. This was a study of 209 low-birth-weight (< 10(th) centile) children born after 28 gestational weeks with UA resistance index (RI) measured within 2 weeks before delivery. Children with normal UA- and ICA-RI were defined as small-for-gestational age (SGA) and those with abnormal UA or ICA Doppler findings as having fetal growth restriction (FGR). Cognitive ability at 3 and 6 years' corrected age was assessed using the fourth edition of the Stanford-Binet Intelligence Scale (SBIS) and compared between SGA and FGR groups. An SBIS score < 85 was considered to indicate delayed development. The median gestational age at diagnosis of abnormal fetal growth was 36.6 (range, 28-41) weeks. There were 87 (41.6%) children classified as having FGR and 122 (58.4%) as SGA. The mean global SBIS score at 3 years was 109.4 (SD, 22.8) and at 6 years it was 110.5 (SD, 13.9). Overall, 22 (10.5%) children had delayed development at 3 years. Total SBIS scores and individual domain scores did not differ between FGR and SGA groups at 3 or 6 years and similar proportions in each group had delayed development. Abnormal prenatal UA and ICA Doppler findings are not associated with lower developmental scores in low-birth-weight children delivered in the third trimester of pregnancy. Copyright © 2013 ISUOG. Published by John Wiley & Sons, Ltd.

  19. [Medically indicated preterm birth. Maternal and fetal consequences].

    PubMed

    Vargas González, Alejandro; Canales Muñoz, José Luis; Torres Gómez, Luis Guillermo; Barba Bustos, Ana María

    2002-03-01

    One of the principal challenges of obstetrics is to reduce the percentage of perinatal mortality. Preterm birth is considered the main cause of neonatal morbidity and mortality. Preterm birth by medical indication, is a condition rarely documented in medical literature, but it requires analysis to determine the effect in perinatal health. In a third care hospital setting, a prospective study was performed on 154 pregnant women that delivered preterm babies between 25 and 36 weeks of gestation. The Relative Risk (RR) was obtained to compare the association between the medical indication of the preterm birth, the use of fetal pulmonary maturants, type of delivery, the health status of the newborn at birth and hospital discharge. The main causes of preterm birth by medical indication were: premature rupture of membranes, preeclampsia, intrauterine growth retardation and fetal distress. Neonatal mortality was 13%. The rate of cesarean section was higher than expected. Despite the various types of delivery, there were no significant differences between mortality, length of hospital stay or hospital complications. The probability of death to preterm born was explained to gestational age and was not modified for medical decision to interrupt pregnancy.

  20. Analysis of Cry Features in Newborns with Differential Fetal Growth.

    ERIC Educational Resources Information Center

    Zeskind, Philip Sanford; Ramey, Craig T.

    1981-01-01

    Describes the relationship between neonatal crying and anthropometric indices of fetal growth. No differences were found between cry features of underweight and overweight infants; both groups required more stimulation than average weight infants to elicit crying. It is suggested that certain cry features may reflect the risk status of neonates…

  1. Reproductive health indicators and fetal medicine - many things will change.

    PubMed

    Olsen, Jørn; Pedersen, Lars Henning

    2016-06-01

    Reproductive epidemiologists study disease outcomes over three time periods: (i) from conception, or before, to birth, (ii) from birth to death and (iii) from death and into the next generations. They have traditionally been short of data from the time of conception to birth, and we use data at birth to estimate fetal growth or the incidence of congenital malformations. Although we are interested in incidence data for defects that start early in gestation, we have to use prevalence data at birth. Cumulative incidence will only be similar to prevalence at birth given no competing risks - or no fetal death after the onset of the lesion. Routinely use of ultrasound methods in fetal medicine will change our monitoring of structural birth defects. We may now be able to link exposures to events with the right time sequence, for example on fetal growth deviations and get better data on fetal deaths also for twins and triplets. The scientific challenges will mainly come from induced abortions following ultrasound examinations. Ultrasound data from the time of pregnancy will be of crucial importance for studies on fetal programming or "developmental origins of health and disease" (DOHaD). In humans, babies that are small at birth have an increased risk of, eg, cardiovascular disease, as shown by DJ Barker in the 1980s (1), but this association is probably not a direct consequence of the low birth weight but rather caused by external or internal exposures during fetal life. DOHaD studies that use outcomes at birth, including weight, as exposures or intermediates may be biased. One notorious example is the apparent protective effect of smoking on the mortality of children with a low birth weight (2). This bias, partly related to collider stratification bias, is potentially less important in studies using direct ultrasound assessments. The risk of reverse causation may also be reduced in longitudinal studies based on ultrasound data. Fetal ultrasound examinations are also done

  2. Expectant management of severe preterm preeclampsia: a comparison of maternal and fetal indications for delivery.

    PubMed

    Mooney, Samantha S; Lee, Rilka M; Tong, Stephen; Brownfoot, Fiona C

    2016-12-01

    To examine the delivery indication (maternal or fetal) for patients with preterm preeclampsia and assess whether disease characteristics at presentation are predictive of delivery indication. We conducted a retrospective cohort study at a tertiary hospital in Melbourne, Australia (Mercy Hospital for Women). We assessed indication for delivery for participants presenting with preeclampsia from 23(+0) to 32(+6) weeks gestation. We compared baseline disease characteristics, disease features at delivery and postnatal outcomes between those delivered for maternal or fetal indications, or for both maternal and fetal indications. Two hundred sixty six participants presented with preterm preeclampsia and 108 were eligible for inclusion in our study. More participants were delivered for maternal indications at 65.7% compared to those requiring delivery on fetal grounds at 19.4% or for both indications at 14.8% (p < 0.0001). Maternal disease characteristics at presentation were similar between groups; however, there was a higher proportion of growth restriction and abnormal Dopplers among those delivered on fetal grounds. Participants delivered on maternal grounds gained less gestation, had higher blood pressure and higher incidence of abnormal liver function tests than those delivering for fetal indications at delivery. Participants with preterm preeclampsia were predominantly delivered due to maternal disease progression compared to fetal compromise.

  3. Assessment of fetal growth on the basis of signal strength in fetal magnetocardiography.

    PubMed

    Van Leeuwen, P; Beuvink, Y; Lange, S; Klein, A; Geue, D; Grönemeyer, D

    2004-11-30

    Fetal magnetocardiography has shown that fetal P wave and QRS complex durations increase with gestational age, reflecting change in cardiac muscle mass. The latter should, in principle, be associated with an increase in signal strength. We examined two approaches for determining QRS signal strength in a healthy fetus on a weekly basis in the second and third trimester. Twenty-two fetal magnetocardiograms of the same fetus were obtained using a 61 channel Magnes 1300 biomagnetometer (20th-42nd week of gestation). In the signal averaged fetal beat produced at each week, signal strength was assessed on the basis of 1) peak-to-peak QRS signal amplitudes and 2) strength of an equivalent current dipole (ECD) computed at R peak. The results were assessed on the basis of correlation to week of gestation and by comparison to changes in QRS interval duration. All values increased with advancing gestation and regression analysis suggested a nonlinear dependency on age. ECD strength reflected gestational age slightly more reliably (r2=0.93) than signal amplitude values (mean, median, maximum: r2=089, 0.88, 0.85, respectively). ECD strength and mean signal amplitude also correlated well (r=0.97, p<0.0005) Values calculated from QRS complexes determined immediately before and after a clear change in fetal position (acquisition week 24) demonstrated a certain instability in both approaches. Nonetheless, the overall correlation of the amplitude to gestational age compared favorably with that of QRS complex duration. This indicates that not only magnetocardiographically determined fetal cardiac time intervals but also signal strength may be used to assess fetal growth.

  4. Role of insulin in the growth of fetal rat tissues.

    PubMed

    Cooke, P S; Nicoll, C S

    1984-02-01

    The effect of insulin on the growth of fetal rat tissues was investigated using a transplant system. Paws from 15-day-old fetal rats were transplanted under the kidney capsule of 1-month-old syngeneic hosts, where they grew and differentiated normally. After 11 days of incubation, growth of transplants in hosts made diabetic by streptozotocin injection was reduced by 37% compared to growth in nondiabetic controls, but tissue differentiation and bone formation were normal in the absence of insulin. Injections of insulin (2 U, twice daily) into diabetic hosts restored paw growth to normal. Growth of transplants in hypophysectomized (HX) and in HX-diabetic hosts was reduced to the same degree (i.e. by 65%). Thus, the growth decrements produced by host hypophysectomy and diabetes are not additive. In contrast to the results with insulin-deficient hosts, the transplants failed to differentiate normally in the HX hosts. Injections of exogenous insulin (3 U, twice daily) to produce transient hyperinsulinemia failed to increase transplant growth in intact hosts over 11 days of incubation. The transplants were exposed to frequent periods of hyperglycemia and hyperinsulinemia by injecting 0.66 g glucose/100 g BW four times per day into intact hosts during 6 days of incubation. This treatment also failed to stimulate transplant growth. These results indicate that normal growth of transplanted fetal paw tissue is partially dependent on insulin, but whether the insulin acts directly or indirectly to support growth is not known. Supranormal insulin levels or frequent periods of hyperglycemia with hyperinsulinemia are not capable of producing overgrowth of the fetal paws. The HX, diabetic, and HX-diabetic host rats did not grow, as judged by tail length increase, and they lost weight. Accordingly, the juvenile host tissues have an obligatory dependence on insulin and GH for normal growth, but the fetal tissue is only partially dependent, because the paw transplants continued to

  5. Fetal hydantoin syndrome: inhibition of placental folic acid transport as a potential mechanism for fetal growth retardation in the rat

    SciTech Connect

    Will, M.; Barnard, J.A.; Said, H.M.; Ghishan, F.K.

    1985-04-01

    Maternal hydantoin ingestion during pregnancy results in a well defined clinical entity termed ''fetal hydantoin syndrome''. The clinical characteristics of this syndrome includes growth retardation, and congenital anomalies. Because folic acid is essential for protein synthesis and growth, and since hydantoin interferes with intestinal transport of folic acid, the authors postulated that part of the fetal hydantoin syndrome may be due to inhibition of placental folic acid by maternal hydantoin. Therefore, they studied in vivo placental folate transport in a well-established model for fetal hydantoin syndrome in the rat. Our results indicate that maternal hydantoin ingestion, significantly decreased fetal weight and placental and fetal uptake of folate compared to controls. To determine whether maternal hydantoin ingestion has a generalized or specific effect on placental function, they examined placental and fetal zinc transport in the same model. Our results indicate that zinc transport is not altered by hydantoin ingestion. They conclude that maternal hydantoin ingestion results in fetal growth retardation which may be due in part to inhibition of placental folate transport.

  6. Prognostic Value of Fetal Thymus Size in Intrauterine Growth Restriction.

    PubMed

    Ekin, Atalay; Gezer, Cenk; Taner, Cuneyt Eftal; Solmaz, Ulas; Gezer, Naciye Sinem; Ozeren, Mehmet

    2016-03-01

    Our aim was to evaluate the size of the fetal thymus by sonography in pregnancies with intrauterine growth restriction (IUGR) and to search for a possible relationship between a small fetal thymus and adverse perinatal outcomes. The transverse diameter of the fetal thymus was prospectively measured in 150 healthy and 143 IUGR fetuses between 24 and 40 weeks' gestation. The fetuses with IUGR were further divided according to normal or abnormal Doppler assessment of the umbilical and middle cerebral arteries and ductus venosus. Measurements were compared with reference ranges from controls. To determine which perinatal outcomes were independently associated with a small fetal thymus, a multivariate logistic regression analysis was performed. Thymus size was significantly lower in IUGR fetuses compared to controls (P < .05). Among IUGR fetuses, thymus size was significantly smaller in IUGR fetuses with abnormal Doppler flow compared to normal flow (P < .05). A small thymus in IUGR fetuses was independently associated with early delivery (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.05-1.49; P= .023), respiratory distress syndrome (OR, 1.36; 95% CI, 1.09-1.78; P= .005), early neonatal sepsis (OR, 1.65; 95% CI, 1.11-2.42; P= .001), and a longer stay in the neonatal intensive care unit (OR, 1.33; 95% CI, 1.08-1.71; P = .017). Intrauterine growth restriction is associated with fetal thymic involution, and a small fetal thymus is an early indicator of adverse perinatal outcomes in pregnancies complicated by IUGR. © 2016 by the American Institute of Ultrasound in Medicine.

  7. Effects of stage of gestation and nutrient restriction during early to mid-gestation on maternal and fetal visceral organ mass and indices of jejunal growth and vascularity in beef cows.

    PubMed

    Meyer, A M; Reed, J J; Vonnahme, K A; Soto-Navarro, S A; Reynolds, L P; Ford, S P; Hess, B W; Caton, J S

    2010-07-01

    The objectives were to evaluate effects of maternal nutrient restriction and stage of gestation on maternal and fetal visceral organ mass and indices of jejunal growth and vascularity in beef cows. Thirty multiparous beef cows (BW = 571 +/- 63 kg; BCS = 5.4 +/- 0.7) carrying female fetuses (d 30 of gestation) were allocated to receive a diet of native grass hay (CON; 12.1% CP, 70.7% IVDMD, DM basis) to meet NRC recommendations for BW gain during early gestation or a nutrient-restricted diet of millet straw (NR; 9.9% CP, 54.5% IVDMD, DM basis) to provide 68.1% of NE(m) and 86.7% of MP estimated requirements. On d 125 of gestation, 10 CON and 10 NR cows were killed and necropsied. Five remaining CON cows received the CON diet, and 5 NR cows were realimented with a concentrate supplement (13.2% CP, 77.6% IVDMD, DM basis) and the CON hay to achieve a BCS similar to CON cows by d 220 of gestation. Remaining cows were necropsied on d 245 of gestation. Cow BW and eviscerated BW (EBW) were less (P < 0.01) for NR than CON at d 125 but did not differ (P > 0.63) at d 245. Cows fed the CON diet had greater (P < 0.09) total gastrointestinal (GI) tract, omasal, and pancreatic weights. Stomach complex, ruminal, and liver weights were greater for CON than NR cows (P < 0.09) on d 125. Total GI, stomach complex, and pancreatic weights increased (P < 0.001) with day of gestation. Restricted cows had decreased (P = 0.09) duodenal RNA:DNA compared with CON. Duodenal DNA was less (P = 0.01) and jejunal RNA:DNA (P = 0.09) was greater for cows at d 125 vs. 245. Cow jejunal capillary area density increased with day of gestation (P = 0.02). Fetal BW and EBW were unaffected by dietary treatment (P > or = 0.32). Total GI tract and all components increased in mass with day of gestation (P < 0.001). Fetuses from NR dams had greater (P = 0.003) reticular mass at d 245 than CON fetuses. Fetuses from NR cows had greater (P = 0.02) percent jejunal proliferation at d 125 and greater (P = 0.03) total

  8. Human fetal growth and organ development: 50 years of discoveries.

    PubMed

    Pardi, Giorgio; Cetin, Irene

    2006-04-01

    Knowledge about human fetal growth and organ development has greatly developed in the last 50 years. Anatomists and physiologists had already described some crucial aspects, for example, the circulation of blood during intrauterine life through the fetal heart, the liver as well as the placenta. However, only in the last century physiologic studies were performed in animal models. In the human fetus, the introduction of ultrasound and Doppler velocimetry has provided data about the growth and development of the fetus and of the circulation through the different fetal districts. Moreover, in the last 2 decades we have learned about fetal oxygenation and fetal nutrient supply caused by the availability of fetal blood samples obtained under relatively steady state conditions. These studies, together with studies using stable isotope methodologies, have clarified some aspects of the supply of the major nutrients for the fetus such as glucose, amino acids, and fatty acids. At the same time, the relevance of placental function has been recognized as a major determinant of fetal diseases leading to intrauterine growth restriction. More recently, the availability of new tools such as 3-dimensional ultrasound and magnetic resonance imaging, have made possible the evaluation of the growth and development of fetal organs. This knowledge in the healthy fetus will improve the ability of clinicians to recognize abnormal phenotypes of the different fetal organs, thus allowing to stage fetal diseases.

  9. Association between maternal-fetal HLA-DR relationships and fetal growth.

    PubMed

    Hoff, C; Peevy, K J; Spinnato, J A; Giattina, K; Peterson, R D

    1993-12-01

    To determine whether maternal-fetal human leukocyte antigen (HLA) antigenic relationships are associated with differential fetal growth in weight. A cohort of 659 primigravid women were enrolled in this study in the prepartum period and their neonates were subsequently examined. Anthropometric, maternal cigarette smoking behavior, health, pregnancy, and delivery data were collected; serogenetic typing was conducted on maternal and cord bloods to determine maternal and neonatal HLA antigenic phenotypes. Women and their neonates were assigned to one of the four different types of maternal-fetal relationships existing at each of the HLA-A, B, DR, and DQ loci. Birthweights were treated quantitatively and qualitatively (neonates classified as growth-retarded or normal). After controlling for other factors influencing birthweight (e.g., smoking, maternal body size), significantly lower birthweight trends (P < .01) were found when neonates expressed a single HLA-DR antigen and their mothers expressed a second HLA-DR antigen that was foreign (allogeneic) to their neonate. Our findings supports the hypothesis that lack of maternal immune exposure to fetal HLA antigens is associated with a slowing of fetal growth. However, in this situation slowed fetal growth is most likely to occur when the fetus is potentially exposed to maternal HLA-DR alloantigens. We believe this sheds new light on immunologic events at the maternal-fetal interface influencing fetal growth. We present one possible explanation to account for this finding.

  10. Diagnosis and Management of Fetal Growth Restriction

    PubMed Central

    Bamfo, Jacqueline E. A. K.; Odibo, Anthony O.

    2011-01-01

    Fetal growth restriction (FGR) remains a leading contributor to perinatal mortality and morbidity and metabolic syndrome in later life. Recent advances in ultrasound and Doppler have elucidated several mechanisms in the evolution of the disease. However, consistent classification and characterization regarding the severity of FGR is lacking. There is no cure, and management is reliant on a structured antenatal surveillance program with timely intervention. Hitherto, the time to deliver is an enigma. In this paper, the challenges in the diagnosis and management of FGR are discussed. The biophysical profile, Doppler, biochemical and molecular technologies that may refine management are reviewed. Finally, a model pathway for the clinical management of pregnancies complicated by FGR is presented. PMID:21547092

  11. Fetal growth sustained by parenteral nutrition in pregnancy.

    PubMed

    Rivera-Alsina, M E; Saldana, L R; Stringer, C A

    1984-07-01

    Severe maternal nutritional deprivation has been associated with intrauterine growth retardation, premature labor, and increased perinatal mortality and morbidity. The authors present four cases in which total parenteral nutrition was used successfully to support fetal growth in such diverse complications as twin pregnancy with maternal jejunoileal bypass, regional enteritis, and acute pancreatitis. Maintenance of fetal growth as evidenced by serial sonographic examination allows achievement of fetal lung maturation before delivery. In all the cases presented there was no perinatal mortality or morbidity. The main clinical implication of the report is the possible application of total parenteral nutrition to maintain adequate growth in fetuses small for gestational age because of maternal nutritional deprivation.

  12. Development of customized fetal growth charts in twins.

    PubMed

    Ghi, Tullio; Prefumo, Federico; Fichera, Anna; Lanna, Mariano; Periti, Enrico; Persico, Nicola; Viora, Elsa; Rizzo, Giuseppe

    2017-05-01

    Twin gestations are at significantly higher risk of fetal growth restriction in comparison with singletons. Using fetal biometric charts customized for obstetrical and parental characteristics may facilitate an accurate assessment of fetal growth. The objective of the study was to construct reference charts for the gestation of fetal biometric parameters stratified by chorionicity and customized for obstetrical and parental characteristics. Fetal biometric measurements obtained from serial ultrasound examinations in uncomplicated twin pregnancies delivering after 36 weeks of gestation were collected by 19 Italian fetal medicine units under the auspices of the Società Italiana di Ecografia Ostetrica e Ginecologica. The measurements acquired in each fetus at each examination included biparietal diameter, head circumference, abdominal circumference, and femur length. Multilevel linear regression models were used to adjust for the serial ultrasonographic measurements obtained and the clustering of each fetus in twin pregnancy. The impact of maternal and paternal characteristics (height, weight, ethnicity), parity, fetal sex, and mode of conception was also considered. Models for each parameter were stratified by fetal chorionicity and compared with our previously constructed growth curves for singletons. The data set included 1781 twin pregnancies (dichorionic, n = 1289; monochorionic diamniotic, n = 492) with 8923 ultrasonographic examinations with a median of 5 (range, 2-8) observations per pregnancy in dichorionic and 6 in (range, 2-11) monochorionic pregnancies. Growth curves of twin pregnancies differed from those of singletons, and differences were more marked in monochorionic twins and during the third trimester. A significant influence of parental characteristics was found. Curves of fetal biometric measurements in twins are influenced by parental characteristics. There is a reduction in the growth rate during the third trimester. The reference limits for

  13. Thyroid hormones in fetal growth and prepartum maturation.

    PubMed

    Forhead, A J; Fowden, A L

    2014-06-01

    The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are essential for normal growth and development of the fetus. Their bioavailability in utero depends on development of the fetal hypothalamic-pituitary-thyroid gland axis and the abundance of thyroid hormone transporters and deiodinases that influence tissue levels of bioactive hormone. Fetal T4 and T3 concentrations are also affected by gestational age, nutritional and endocrine conditions in utero, and placental permeability to maternal thyroid hormones, which varies among species with placental morphology. Thyroid hormones are required for the general accretion of fetal mass and to trigger discrete developmental events in the fetal brain and somatic tissues from early in gestation. They also promote terminal differentiation of fetal tissues closer to term and are important in mediating the prepartum maturational effects of the glucocorticoids that ensure neonatal viability. Thyroid hormones act directly through anabolic effects on fetal metabolism and the stimulation of fetal oxygen consumption. They also act indirectly by controlling the bioavailability and effectiveness of other hormones and growth factors that influence fetal development such as the catecholamines and insulin-like growth factors (IGFs). By regulating tissue accretion and differentiation near term, fetal thyroid hormones ensure activation of physiological processes essential for survival at birth such as pulmonary gas exchange, thermogenesis, hepatic glucogenesis, and cardiac adaptations. This review examines the developmental control of fetal T4 and T3 bioavailability and discusses the role of these hormones in fetal growth and development with particular emphasis on maturation of somatic tissues critical for survival immediately at birth.

  14. The secular growth acceleration: does it appear during fetal life?

    PubMed

    Frančišković, Vedran; Zaputović, Sanja; Finderle, Aleks; Petrović, Oleg

    2014-12-01

    To test if secular growth acceleration occurs during fetal life. ANOVA Kruskal-Wallis and Mann-Whitney U-test have been used for the biometric characteristics comparison of nowadays fetal population with those three decades ago and to test the hypothesis about the existence of secular growth acceleration during fetal life. For this purpose, we first calculated mean values of particular biometric parameters for the whole pregnancy. During the period 2002-2009 biparietal diameter, fetal length and abdominal circumference measurements in singleton uncomplicated pregnancies between 22 and 41 gestational weeks were obtained. Gestational age was estimated according to Naegele's rule and confirmed with an early ultrasound examination. Pregnancies with fetal cromosomopathies and malformations were excluded as well as those resulting in perinatal death. There were no statistically significant differences of the examined fetal biometric parameters measured by ultrasound between contemporary fetal population and those from 35 years ago. Our investigation did not undoubtedly prove that significant changes of fetal biometric parameters occurred in the last three decades. It is possible that secular growth acceleration does not exist in prenatal period but also the observed time period could have been short for this phenomenon to manifest.

  15. Socioeconomic status accounts for rapidly increasing geographic variation in the incidence of poor fetal growth.

    PubMed

    Ball, Stephen J; Jacoby, Peter; Zubrick, Stephen R

    2013-06-25

    Fetal growth is an important risk factor for infant morbidity and mortality. In turn, socioeconomic status is a key predictor of fetal growth; however, other sociodemographic factors and environmental effects may also be important. This study modelled geographic variation in poor fetal growth after accounting for socioeconomic status, with a fixed effect for socioeconomic status and a combination of spatially-correlated and spatially-uncorrelated random effects. The dataset comprised 88,246 liveborn singletons, aggregated within suburbs in Perth, Western Australia. Low socioeconomic status was strongly associated with an increased risk of poor fetal growth. An increase in geographic variation of poor fetal growth from 1999-2001 (interquartile odds ratio among suburbs = 1.20) to 2004-2006 (interquartile odds ratio = 1.40) indicated a widening risk disparity by socioeconomic status. Low levels of residual spatial patterns strengthen the case for targeting policies and practices in areas of low socioeconomic status for improved outcomes. This study indicates an alarming increase in geographic inequalities in poor fetal growth in Perth which warrants further research into the specific aspects of socioeconomic status that act as risk factors.

  16. Knockout maternal adiponectin increases fetal growth in mice: potential role for trophoblast IGFBP-1.

    PubMed

    Qiao, Liping; Wattez, Jean-Sebastien; Lee, Samuel; Guo, Zhuyu; Schaack, Jerome; Hay, William W; Zita, Matteo Moretto; Parast, Mana; Shao, Jianhua

    2016-11-01

    The main objective of this study was to investigate whether maternal adiponectin regulates fetal growth through the endocrine system in the fetal compartment. Adiponectin knockout (Adipoq (-/-) ) mice and in vivo adenovirus-mediated reconstitution were used to study the regulatory effect of maternal adiponectin on fetal growth. Primary human trophoblast cells were treated with adiponectin and a specific peroxisome proliferator-activated receptor α (PPARα) agonist or antagonist to study the underlying mechanism through which adiponectin regulates fetal growth. The body weight of fetuses from Adipoq (-/-) dams was significantly greater than that of wild-type dams at both embryonic day (E)14.5 and E18.5. Adenoviral vector-mediated maternal adiponectin reconstitution attenuated the increased fetal body weight induced by maternal adiponectin deficiency. Significantly increased blood glucose, triacylglycerol and NEFA levels were observed in Adipoq (-/-) dams, suggesting that nutrient supply contributes to maternal adiponectin-regulated fetal growth. Although fetal blood IGF-1 concentrations were comparable in fetuses from Adipoq (-/-) and wild-type dams, remarkably low levels of IGF-binding protein 1 (IGFBP-1) were observed in the serum of fetuses from Adipoq (-/-) dams. IGFBP-1 was identified in the trophoblast cells of human and mouse placentas. Maternal fasting robustly increased IGFBP-1 levels in mouse placentas, while reducing fetal weight. Significantly low IGFBP-1 levels were found in placentas of Adipoq (-/-) dams. Adiponectin treatment increased IGFBP-1 levels in primary cultured human trophoblast cells, while the PPARα antagonist, MK886, abolished this stimulatory effect. These results indicate that, in addition to nutrient supply, maternal adiponectin inhibits fetal growth by increasing IGFBP-1 expression in trophoblast cells.

  17. Endocrine interactions in the control of fetal growth.

    PubMed

    Fowden, Abigail L; Forhead, Alison J

    2013-01-01

    Hormones are both growth stimulatory and growth inhibitory in utero. They act as environmental and maturational signals in regulating tissue accretion and differentiation during late gestation. They ensure that fetal development is appropriate for the nutrient supply and is optimal for neonatal survival. Growth-stimulatory hormones, such as insulin, the insulin-like growth factors and the thyroid hormones, have anabolic effects on fetal metabolism and increase cellular nutrient uptake and energy production for tissue accretion. Thyroid hormones also have specific effects on tissue differentiation at key developmental milestones. Similarly, leptin appears to affect development of specific fetal tissues and may counterbalance the maturational actions of other hormones near term. Glucocorticoids inhibit growth in utero but are essential for prepartum tissue differentiation in preparation for delivery. They also affect fetal bioavailability of most of the other growth-regulatory hormones. In addition, many of these hormones alter the placental capacity to supply nutrients for fetal growth. In producing a fetoplacental epigenome specific to the prevailing intrauterine environment, hormones interact to produce phenotypical diversity with potential health consequences long after birth.

  18. Fetal growth velocities in Hong Kong Chinese infants.

    PubMed

    Fok, T F; Hon, K L; So, H K; Wong, E; Ng, P C; Chang, A; Lau, J; Chow, C B; Lee, W H

    2005-01-01

    Few studies have investigated the velocities of fetal growth. The aim of the present study was to determine the pattern of 'fetal' growth velocities in a Chinese population. The gestation-specific measurements of the body weight, body length and head circumference in a representative sample of 5,045 male and 4,484 female newborns delivered between 26 and 42 weeks of gestation at 12 hospitals in Hong Kong were obtained. Peak growth velocity occurred before 30 weeks of gestation for head circumference, at week 30 for length and at week 30 for weight. When compared with data obtained from a French population, a significant difference in the growth velocity for body weight was observed below 32 weeks between French and Chinese infants, suggesting an ethnic difference in fetal growth of this parameter.

  19. Ultrasonographic evaluation of equine fetal growth throughout gestation in normal mares using a convex transducer.

    PubMed

    Murase, Harutaka; Endo, Yoshiro; Tsuchiya, Takeru; Kotoyori, Yasumitsu; Shikichi, Mitsumori; Ito, Katsumi; Sato, Fumio; Nambo, Yasuo

    2014-07-01

    It has not been common to perform regular ultrasound examination of the fetus in equine practice, due to the increasing volume of the uterus caused by fetal development. The convex three-dimensional transducer is bulb-shaped and is able to observe wide areas. In addition, its operation is simple, making it easy to create appropriate angles for various indices using a transrectal approach. The aim of this study was to measure Thoroughbred fetal growth indices throughout gestation using a convex transducer and to clarify the detectable period of some indices for clinical use. We demonstrated changes in fetal indices, such as crown rump length (CRL), fetal heart rate (FHR), fetal eye and kidney and the combined thickness of uterus and placenta (CTUP). CTUP increased from 30 weeks of gestation, and FHR peaked at 8 weeks and then decreased to term. CRL could be observed until 13 weeks due to its wide angle, longer than in previous reports. Fetal eye and kidney could be observed from 10 and 28 weeks, respectively, and these increased with pregnancy progress. The present results showed the advantage of transrectal examination using a convex transducer for evaluation of normal fetal development. Although ultrasonographic examination in mid- to late-gestation is not common in equine reproductive practice, our comprehensive results would be a useful basis for equine pregnancy examination.

  20. Restriction of placental and fetal growth in sheep alters fetal blood pressure responses to angiotensin II and captopril

    PubMed Central

    Edwards, L J; Simonetta, G; Owens, J A; Robinson, J S; McMillen, I C

    1999-01-01

    We have measured arterial blood pressure between 115 and 145 days gestation in normally grown fetal sheep (control group; n = 16) and in fetal sheep in which growth was restricted by experimental restriction of placental growth and development (PR group; n = 13). There was no significant difference in the mean gestational arterial blood pressure between the PR (42.7 ± 2.6 mmHg) and control groups (37.7 ± 2.3 mmHg). Mean arterial blood pressure and arterial PO2 were significantly correlated in control animals (r = 0.53, P < 0.05, n = 16), but not in the PR group.There were no changes in mean arterial blood pressure in either the PR or control groups in response to captopril (7.5 μg captopril min−1; PR group n = 7, control group n = 6) between 115 and 125 days gestation. After 135 days gestation, there was a significant decrease (P < 0.05) in the fetal arterial blood pressure in the PR group but not in the control group during the captopril infusion (15 μg captopril min−1; PR group n = 7, control group n = 6).There was a significant effect (F = 14.75; P < 0.001) of increasing doses of angiotensin II on fetal diastolic blood pressure in the PR and control groups. The effects of angiotensin II were different (F = 8.67; P < 0.05) in the PR and control groups at both gestational age ranges.These data indicate that arterial blood pressure may be maintained by different mechanisms in growth restricted fetuses and normally grown counterparts and suggests a role for the fetal renin-angiotensin system in the maintenance of blood pressure in growth restricted fetuses. PMID:10066914

  1. Fetal growth and maternal glomerular filtration rate: a systematic review.

    PubMed

    Vesterinen, Hanna M; Johnson, Paula I; Atchley, Dylan S; Sutton, Patrice; Lam, Juleen; Zlatnik, Marya G; Sen, Saunak; Woodruff, Tracey J

    2015-01-01

    Glomerular filtration rate (GFR) may influence concentrations of biomarkers of exposure and their etiologic significance in observational studies of associations between environmental contaminants and fetal growth. It is unknown whether the size of a developing fetus affects maternal GFR such that a small fetus leads to reduced plasma volume expansion (PVE), reduced GFR and subsequent higher concentrations of biomarkers in maternal serum. Our objective was to answer the question: "Is there an association between fetal growth and maternal GFR in humans?" We adapted and applied the Navigation Guide systematic review methodology to assess the evidence of an association between fetal growth and GFR, either directly or indirectly via reduction in PVE. We identified 35 relevant studies. We rated 31 human and two non-human observational studies as "low" quality and two experimental non-human studies as "very low" quality. We rated all three evidence streams as "inadequate". The association between fetal growth and GFR was "not classifiable" according to pre-specified definitions. There is currently insufficient evidence to support the plausibility of a reverse causality hypothesis for associations between exposure to environmental chemicals during pregnancy and fetal growth. Further research would be needed to confirm or disprove this hypothesis.

  2. Influence of maternal folate status on human fetal growth parameters.

    PubMed

    van Uitert, Evelyne M; Steegers-Theunissen, Régine P M

    2013-04-01

    Worldwide periconceptional folic acid supplement use is recommended to prevent neural tube defects. This also stimulated research on maternal folate status in association with fetal growth, an important predictor of perinatal and future development and health. We provide an overview of literature on associations between maternal folate status during pregnancy determined by folate biomarker concentrations in blood, folic acid supplement use and dietary folate intake, and fetal growth parameters. Literature was searched in PubMed up to November 2011. Some studies suggest inverse associations between serum folate, folic acid supplement use and dietary folate intake and risk of a low birth weight or small for gestational age infant. The strongest evidence, however, revealed positive associations between birth weight and red blood cell folate, folic acid supplement use and dietary folate intake. Red blood cell folate appeared to be most consistently associated with other fetal growth parameters. These findings contribute to the knowledge of the impact of maternal folate status on fetal growth, and subsequently perinatal health and disease risks in later life. Future research is recommended to examine effects of windows, duration and dose of folic acid supplement use and use of folate-rich dietary patterns in different populations on fetal growth parameters. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    PubMed

    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 a 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 paper 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.

  4. Fetal growth in different racial groups.

    PubMed Central

    Alvear, J; Brooke, O G

    1978-01-01

    Three racial groups of mothers and their newborn babies-- North European 75, Negro 75, and "Indian" Asian 37--were matched for parity, gestational age, sex, maternal age, maternal smoking habits, and social class. Multiple anthropometric measurements, including skinfold thickness, limb circumferences, and various linear measurements were made on the mothers and their infants to determine the effects of race and smoking on fetal size. Indian-Asian mothers, though shorter and lighter than Europeans and Negroes, had similar skinfold thickness and weight: height2 ratios and gained as much weight during pregnancy. Their infants, however, were lighter than the others, and had smaller head and limb circumferences, although their linear measurements were the same. Negro and European infants were almost identical in size. We found no effect on any of the fetal measurements which could be attributed to smoking. PMID:626515

  5. Placental adaptations to the maternal-fetal environment: implications for fetal growth and developmental programming.

    PubMed

    Sandovici, Ionel; Hoelle, Katharina; Angiolini, Emily; Constância, Miguel

    2012-07-01

    The placenta is a transient organ found in eutherian mammals that evolved primarily to provide nutrients for the developing fetus. The placenta exchanges a wide array of nutrients, endocrine signals, cytokines and growth factors with the mother and the fetus, thereby regulating intrauterine development. Recent studies show that the placenta is not just a passive organ mediating maternal-fetal exchange. It can adapt its capacity to supply nutrients in response to intrinsic and extrinsic variations in the maternal-fetal environment. These dynamic adaptations are thought to occur to maximize fetal growth and viability at birth in the prevailing conditions in utero. However, some of these adaptations may also affect the development of individual fetal tissues, with patho-physiological consequences long after birth. Here, this review summarizes current knowledge on the causes, possible mechanisms and consequences of placental adaptive responses, with a focus on the regulation of transporter-mediated processes for nutrients. This review also highlights the emerging roles that imprinted genes and epigenetic mechanisms of gene regulation may play in placental adaptations to the maternal-fetal environment. Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  6. Early pregnancy maternal and fetal angiogenic factors and fetal and childhood growth: the Generation R Study.

    PubMed

    Bergen, N E; Bouwland-Both, M I; Steegers-Theunissen, R P M; Hofman, A; Russcher, H; Lindemans, J; Jaddoe, V W V; Steegers, E A P

    2015-06-01

    What are the effects of maternal and fetal soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) concentrations on fetal and childhood growth patterns? An angiogenic profile that is characterized by both low early pregnancy maternal sFlt-1 and PlGF concentrations and higher sFlt-1 concentrations, lower PlGF concentrations or a higher sFlt-1:PlGF ratio in umbilical cord blood is associated with a reduced fetal and childhood growth. An imbalance in maternal and fetal sFlt-1 and PlGF concentrations has been suggested to affect pregnancy outcomes. However, their effects on longitudinal fetal and childhood growth remain largely unknown. This study was performed in 5980 mothers and 4108 of their children, participating in the Generation R Study; a population-based prospective cohort study from fetal life onwards in Rotterdam, the Netherlands (2001-2005). Blood samples were obtained from mothers in early and mid-pregnancy and from the umbilical vein at delivery. Fetal and childhood growth characteristics (weight and length) were measured repeatedly by ultrasound and physical examinations until the age of 6 years. We assessed the associations of maternal and fetal angiogenic factors with fetal and childhood growth using repeated measurement regression models. Logistic regression models were used to determine associations between angiogenic factors and small for gestational age at birth (SGA). Compared with early pregnancy maternal sFlt-1 concentrations in the lowest quintile, early pregnancy maternal sFlt-1 concentrations in the highest quintile were associated with a higher fetal weight growth resulting in a higher birthweight (difference in birthweight 0.33 standard deviation score (SDS); 95% Confidence Interval (CI) 0.25-0.41), a lower risk of SGA (Odds Ratio (OR) 0.36; 95% CI 0.27-0.48) and a subsequent higher weight growth until the age of 6 years. Early pregnancy maternal PlGF concentrations in the lowest quintile were associated with a

  7. 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.

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

    PubMed

    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.

  9. 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

  10. Vitamin E: maternal concentrations are associated with fetal growth2

    PubMed Central

    Scholl, Theresa O; Chen, Xinhua; Sims, Melissa; Stein, T Peter

    2007-01-01

    Background Few data exist on the effects of the 2 most abundant isomers of vitamin E (α- and γ-tocopherols) on fetal growth. Objective We measured maternal plasma concentrations of α- and γ-tocopherols and examined their relation with measures of fetal growth. We also examined the relation, controlled for associated maternal factors, of diet and supplement use to tocopherol concentrations at week 28 of gestation. Design A cohort of 1231 gravid women from Camden, NJ, was studied from entry to care (16.0 ± 0.15 wk gestation); plasma tocopherol concentrations were measured at entry and at week 28. Results Plasma concentrations of α-tocopherol at entry and at week 28 were positively related to increased fetal growth (birth weight for gestation), a decreased risk of small-for-gestational-age births, and an increased risk of large-for-gestational-age births. Concentration of α-tocopherol at week 28 was positively related to use of prenatal multivitamins and dietary intake of vitamin E; concentration of γ-tocopherol was related positively to dietary fat intake and negatively to multivitamin use. Conclusion Early and late circulating concentrations of α-tocopherol are positively associated with fetal growth. PMID:17158428

  11. Maternal and paternal height and BMI and patterns of fetal growth: the Pune Maternal Nutrition Study.

    PubMed

    Wills, Andrew K; Chinchwadkar, Manoj C; Joglekar, Charudatta V; Natekar, Asit S; Yajnik, Chittaranjan S; Fall, Caroline H D; Kinare, Arun S

    2010-09-01

    We examined the differential associations of each parent's height and BMI with fetal growth, and examined the pattern of the associations through gestation. Data are from 557 term pregnancies in the Pune Maternal Nutrition Study. Size and conditional growth outcomes from 17 to 29 weeks to birth were derived from ultrasound and birth measures of head circumference, abdominal circumference, femur length and placental volume (at 17 weeks only). Parental height was positively associated with fetal head circumference and femur length. The associations with paternal height were detectible earlier in gestation (17-29 weeks) compared to the associations with maternal height. Fetuses of mothers with a higher BMI had a smaller mean head circumference at 17 weeks, but caught up to have larger head circumference at birth. Maternal but not paternal BMI, and paternal but not maternal height, were positively associated with placental volume. The opposing associations of placenta and fetal head growth with maternal BMI at 17 weeks could indicate prioritisation of early placental development, possibly as a strategy to facilitate growth in late gestation. This study has highlighted how the pattern of parental-fetal associations varies over gestation. Further follow-up will determine whether and how these variations in fetal/placental development relate to health in later life.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  13. 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…

  14. 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…

  15. Laparoscopy guided Doppler ultrasound measurement of fetal blood flow indices during early to mid-gestation in pigs.

    PubMed

    Brüssow, Klaus-Peter; Kurth, Jürgen; Vernunft, Andreas; Becker, Frank; Tuchscherer, Armin; Kanitz, Wilhelm

    2012-01-01

    The objectives of this study were to obtain relevant blood flow indices of umbilical arteries (UmA) of porcine fetuses using a laparoscopic ultrasound probe and to relate these data with fetal size at early to mid gestation. Fetal parameters and flow indices, i.e., fetal length and area, fetal heart rate (FHR), systolic pulse duration (T1), interpulse duration (T2), T2/T1 ratio, peak systolic velocity (PSV), time averaged velocity (TAV), resistance index (RI) and pulsatility index (PI), were measured in 182 fetuses of 26 pregnant Landrace gilts on pregnancy day (PD) 36 (122 fetuses from 17 gilts), PD42 (19 fetuses from 3 gilts) and PD51 (42 fetuses from 6 gilts). Fetal heart rate was higher on PD36 than on PD42 (P<0.05). No differences (P>0.05) were obtained concerning systolic pulse duration, flow velocities and RI. On PD42, the PI was lower (P<0.05), while the interpulse duration (P=0.06) and T2/T1 ratio tended (P=0.08) to be higher on PD42 compared with PD36 and to PD51. To find differences in UmA blood flow parameters concerning fetal size, i.e., fetal length, fetuses were retrospectively grouped as follows: small (lower 25%), medium (mean 50%) and large (upper 25%), respectively. Although, fetuses differed in size (P<0.001) within and between days of pregnancy, FHR, PSV, TAV, RI and PI did not differ (P>0.05) among the size classes. Only systolic pulse duration tended to be longer (P=0.05) in large compared with small fetuses on PD36, and interpulse duration was lower in large fetuses on PD36 in comparison with PD51 (P<0.05). Though there was no link between fetal blood flow indices and fetal intrauterine growth retardation (IUGR), with further studies based on these flow indices, it might be possible to evaluate nutrient- or stress-related influences on fetal growth and development, particularly in the case of IUGR.

  16. Placental phenotype and the insulin-like growth factors: resource allocation to fetal growth.

    PubMed

    Sferruzzi-Perri, Amanda N; Sandovici, Ionel; Constancia, Miguel; Fowden, Abigail L

    2017-03-24

    The placenta is the main determinant of fetal growth and development in utero. It supplies all the nutrients and oxygen required for fetal growth and secretes hormones that facilitate maternal allocation of nutrients to the fetus. Furthermore, the placenta responds to nutritional and metabolic signals in the mother by altering its structural and functional phenotype which can lead to changes in maternal resource allocation to the fetus. The molecular mechanisms by which the placenta senses and responds to environmental cues are poorly understood. This review discusses the role of the insulin-like growth factors (IGFs) in controlling placental resource allocation to fetal growth, particularly in response to adverse gestational environments. In particular, it assesses the impact of the IGFs and their signalling machinery on placental morphogenesis, substrate transport and hormone secretion, primarily in the laboratory species, although it draws on data from human and other species where relevant. It also considers the role of the IGFs as environmental signals in linking resource availability, to fetal growth through changes in the morphological and functional phenotype of the placenta. As altered fetal growth is associated with increased perinatal morbidity and mortality and a greater risk of developing adult-onset diseases in later life, understanding the role of IGFs during pregnancy in regulating placental resource allocation to fetal growth is important for identifying the mechanisms underlying the developmental programming of offspring phenotype by suboptimal intrauterine growth. This article is protected by copyright. All rights reserved.

  17. Fetal growth, gestation length and phosphoglucomutase-1 phenotype.

    PubMed

    Johnstone, F D; West, J D; Prescott, R J; Steel, J M; Flockhart, J A; Greer, I A; Drago, G A; Whitehouse, D B

    1993-12-01

    This study investigates reports that phosphoglucomutase-1 (PGM1) phenotype is associated with fetal growth and gestation length. A total of 350 women were studied, 234 having uncomplicated pregnancies and 114 with a baby weighing greater than 90th centile, corrected for parity, gestation and fetal sex. All women had gestation confirmed by early ultrasound. Conventional cellulose acetate electrophoresis was used to distinguish the three common PGM1 phenotypes and polyacrylamide gel isoelectric focusing to distinguish the ten PGM1 subtypes. Neither PGM1 phenotype nor subtype were found to be associated with gestation length or standardised birth weight. Logistic regression, where maternal age, parity, fetal sex, maternal weight, gestation and smoking were introduced as explanatory variables in addition to PGM1 phenotype testing against the dependent variables birth weight, standardised birth weight and gestation length, did not show differences related to PGM1 phenotype. Two possible reasons for the discrepancy with previously published data are discussed. We conclude that the study provides no support for the belief that PGM1 phenotype is related to fetal growth or gestation length and that the original observations could have arisen as a result of statistical artefact due to multiple testing.

  18. [Drug dependence, smoking and fetal growth retardation].

    PubMed

    Hanzal, E; Hoffmann, G; Kölbl, H

    1992-07-01

    Illicit drug abuse, as well as smoking, are known risk factors in the development of intrauterine growth retardation. In an attempt to clarify the influence of these two aetiological factors, a retrospective analysis was carried out. 35 drug- and nicotine-addicted pregnant women were compared to 104 smokers and 101 non-smoking controls with regard to foetal outcome. Relative risk estimates for intrauterine growth retardation of the drug and nicotine group were 3.14 (95% confidence limits 1.88-5.25; p = 0.0001) whereas the smoking group had 1.39 (95% confidence limits 0.96-2.02; p = 0.0482) compared to non-smoking controls. The foetal outcome was best in the latter group: children of drug-addicted mothers had a considerably higher morbidity and mortality rate. This study shows an almost threefold risk for intrauterine growth retardation in drug-addicts who smoke, compared to nicotine abuse alone.

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

    PubMed Central

    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.

    2016-01-01

    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

  20. 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.

  1. Fetal Functional Brain Age Assessed from Universal Developmental Indices Obtained from Neuro-Vegetative Activity Patterns

    PubMed Central

    Hoyer, Dirk; Tetschke, Florian; Jaekel, Susan; Nowack, Samuel; Witte, Otto W.; Schleußner, Ekkehard; Schneider, Uwe

    2013-01-01

    Fetal brain development involves the development of the neuro-vegetative (autonomic) control that is mediated by the autonomic nervous system (ANS). Disturbances of the fetal brain development have implications for diseases in later postnatal life. In that context, the fetal functional brain age can be altered. Universal principles of developmental biology applied to patterns of autonomic control may allow a functional age assessment. The work aims at the development of a fetal autonomic brain age score (fABAS) based on heart rate patterns. We analysed n = 113 recordings in quiet sleep, n = 286 in active sleep, and n = 29 in active awakeness from normals. We estimated fABAS from magnetocardiographic recordings (21.4–40.3 weeks of gestation) preclassified in quiet sleep (n = 113, 63 females) and active sleep (n = 286, 145 females) state by cross-validated multivariate linear regression models in a cross-sectional study. According to universal system developmental principles, we included indices that address increasing fluctuation range, increasing complexity, and pattern formation (skewness, power spectral ratio VLF/LF, pNN5). The resulting models constituted fABAS. fABAS explained 66/63% (coefficient of determination R2 of training and validation set) of the variance by age in quiet, while 51/50% in active sleep. By means of a logistic regression model using fluctuation range and fetal age, quiet and active sleep were automatically reclassified (94.3/93.1% correct classifications). We did not find relevant gender differences. We conclude that functional brain age can be assessed based on universal developmental indices obtained from autonomic control patterns. fABAS reflect normal complex functional brain maturation. The presented normative data are supplemented by an explorative study of 19 fetuses compromised by intrauterine growth restriction. We observed a shift in the state distribution towards active awakeness. The lower WGA dependent f

  2. 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

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

    PubMed

    Merialdi, Mario; Widmer, Mariana; Gülmezoglu, Ahmet Metin; Abdel-Aleem, Hany; Bega, George; Benachi, Alexandra; Carroli, Guillermo; Cecatti, Jose Guilherme; Diemert, Anke; Gonzalez, Rogelio; Hecher, Kurt; Jensen, Lisa N; Johnsen, Synnøve L; Kiserud, Torvid; Kriplani, Alka; Lumbiganon, Pisake; Tabor, Ann; Talegawkar, Sameera A; Tshefu, Antoinette; Wojdyla, Daniel; Platt, Lawrence

    2014-05-02

    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. 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. 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 of the Child Growth Standards.

  4. Intrauterine growth restriction: effects of physiological fetal growth determinants on diagnosis.

    PubMed

    Haram, Kjell; Søfteland, Eirik; Bukowski, Radek

    2013-01-01

    The growth of the fetus, which is strongly associated with the outcome of pregnancy, reflects interplay of several physiological and pathological factors. The assessment of fetal growth is based on comparison of birthweight (BW) or estimated fetal weight (EFW) to standards which define reference ranges at a spectrum of gestational ages. Most birthweight standards do not take into account effects of physiological determinants of fetal growth. Additionally, gestational age in many standards is based on the menstrual history and is often inaccurate. Fetal growth norms should be based on an early ultrasound estimate of gestational age. Customized standards, which have included only ultrasound-dated pregnancies, seem to be superior to population-based birthweight norms in predicting perinatal mortality and morbidity. Adjustment for individual variation in customized growth curves reduces false-positive diagnosis of IUGR and may lead to a very significant reduction in intervention for suspected IUGR. Customized growth potential identifies better the risk for adverse outcome than the currently used national standards, but customized charts may fail in detecting growth-restricted stillbirth. An individual's birthweight is the sum of physiological and pathological influences operating during pregnancy. Growth potential norms are a better discriminator of aberrations of fetal growth than population, ultrasound, and customized norms.

  5. Intrauterine Growth Restriction: Effects of Physiological Fetal Growth Determinants on Diagnosis

    PubMed Central

    Haram, Kjell

    2013-01-01

    The growth of the fetus, which is strongly associated with the outcome of pregnancy, reflects interplay of several physiological and pathological factors. The assessment of fetal growth is based on comparison of birthweight (BW) or estimated fetal weight (EFW) to standards which define reference ranges at a spectrum of gestational ages. Most birthweight standards do not take into account effects of physiological determinants of fetal growth. Additionally, gestational age in many standards is based on the menstrual history and is often inaccurate. Fetal growth norms should be based on an early ultrasound estimate of gestational age. Customized standards, which have included only ultrasound-dated pregnancies, seem to be superior to population-based birthweight norms in predicting perinatal mortality and morbidity. Adjustment for individual variation in customized growth curves reduces false-positive diagnosis of IUGR and may lead to a very significant reduction in intervention for suspected IUGR. Customized growth potential identifies better the risk for adverse outcome than the currently used national standards, but customized charts may fail in detecting growth-restricted stillbirth. An individual's birthweight is the sum of physiological and pathological influences operating during pregnancy. Growth potential norms are a better discriminator of aberrations of fetal growth than population, ultrasound, and customized norms. PMID:23864862

  6. Placental vascular dysfunction, fetal and childhood growth, and cardiovascular development: the generation R study.

    PubMed

    Gaillard, Romy; Steegers, Eric A P; Tiemeier, Henning; Hofman, Albert; Jaddoe, Vincent W V

    2013-11-12

    Suboptimal fetal nutrition may influence early growth and cardiovascular development. We examined whether umbilical and uterine artery resistance indices, as measures of feto-placental and utero-placental vascular function, respectively, are associated with fetal and childhood growth and cardiovascular development. This study was embedded in a population-based prospective cohort study among 6716 mothers and their children. Umbilical artery pulsatility index and uterine artery resistance index and fetal growth were measured in third trimester. Childhood growth was repeatedly assessed from birth to the age of 6 years. We measured body fat distribution, left ventricular mass, and blood pressure at the age of 6 years. Higher third trimester umbilical and uterine artery vascular resistance were associated with lower fetal length and weight growth in third trimester resulting in a smaller size at birth among boys and girls (P values < 0.05). These differences in length and weight growth became smaller from the age of 6 months onwards, but were still present at the age of 6 years. Higher third trimester umbilical artery vascular resistance, but not uterine artery vascular resistance, was associated with higher childhood body mass index, total fat mass, android/gynoid fat mass ratio, and systolic blood pressure, and with a lower left ventricular mass (P values<0.05). These associations were not explained by birth weight. Stronger associations tended to be present among girls as compared with boys. Higher third trimester feto-placental vascular resistance, but not utero-placental vascular resistance, was associated with slower fetal growth rates and cardiovascular adaptations in childhood.

  7. Early fetal heart ultrasonography as additional indicator for chromosomopathies.

    PubMed

    Dmitrovic, A; Jeremic, K; Babic, U M; Perovic, M; Mihailovic, T; Opric, D; Zecevic, N; Gojnić-Dugalić, M

    2016-01-01

    First trial of estimating values of scans of fetal heart structures (FHS) in first trimester of pregnancy, as more primary facts of possible chromosomopathies. The study included 2,643 fetuses that were examined in first trimester of pregnancy on Sono CT convex (C5-2MHz), endovaginal (ev 8-4MHz), and linear transducers (L12-5MHz) during a period of eight years. Fetal heart was evaluated using appropriate software with broad-band transducers and color Doppler, Sono CT, and HD ZOOM technologies. The scan was performed by three experienced physicians. FHS were based on: left and right ventricle morphology; AV valves (atrioventricular) position and existence of primal ostium; relationship of left ventricle outflow tract (LVOT) and right ventricle outflow tract (RVOT) and great vessels on three vessel view (3VV) and estimation of ductal and aortic arch. Several developments, one being the ability to identify fetuses at risk for cardiac defects combining nuchal translucency (NT), ductus venosus (DV) Doppler, and evaluation of tricuspid regurgitation, have prompted reconsideration of the role of the first trimester prognostic factor of fetal evaluation. In low-risk pregnancies group, 36 (1.8%) fetuses were found to have congenital heart disease (CHD), and in high-risk pregnancies the number of fetuses with CHD was 75 (12%). Genetic amniocentesis or chorionic villus sampling (CVS) was performed in all fetuses with CHD. Forty-two (37.8%) fetuses with CHD were found to have chromosomal anomalies. Out of 111 fetuses with CHD 39 (35.1%) had an nuchal translucency (NT) above three mm. Out of 42 fetuses with chromosomal anomalies and CHD, 29 (69%) had an increased NT. Using first trimester fetal echosonography constitutes a further step in the earlier recognition of chromosomopathies, even in low risk groups. Still further steps are necessary as all facts of good clinical practice. In order to offer further benefits during pregnancies, improvements in diagnostics are still

  8. Effect of Dietary Iron on Fetal Growth in Pregnant Mice

    PubMed Central

    Hubbard, Andrea C; Bandyopadhyay, Sheila; Wojczyk, Boguslaw S; Spitalnik, Steven L; Hod, Eldad A; Prestia, Kevin A

    2013-01-01

    Iron deficiency is the most common nutritional disorder. Children and pregnant women are at highest risk for developing iron deficiency because of their increased iron requirements. Iron-deficiency anemia during pregnancy is associated with adverse effects on fetal development, including low birth weight, growth retardation, hypertension, intrauterine fetal death, neurologic impairment, and premature birth. We hypothesized that pregnant mice fed an iron-deficient diet would have a similar outcome regarding fetal growth to that of humans. To this end, we randomly assigned female C57BL/6 mice to consume 1 of 4 diets (high-iron–low-bioavailability, high-iron–high-bioavailability, iron-replete, and iron-deficient) for 4 wk before breeding, followed by euthanasia on day 17 to 18 of gestation. Compared with all other groups, dams fed the high-iron–high-bioavailability diet had significantly higher liver iron. Hct and Hgb levels in dams fed the iron-deficient diet were decreased by at least 2.5 g/dL as compared with those of all other groups. In addition, the percentage of viable pups among dams fed the iron-deficient diet was lower than that of all other groups. Finally, compared with all other groups, fetuses from dams fed the iron-deficient diet had lower fetal brain iron levels, shorter crown–rump lengths, and lower weights. In summary, mice fed an iron-deficient diet had similar hematologic values and fetal outcomes as those of iron-deficient humans, making this a useful model for studying iron-deficiency anemia during pregnancy. PMID:23582419

  9. Methionine, homocysteine, one carbon metabolism and fetal growth.

    PubMed

    Kalhan, Satish C; Marczewski, Susan E

    2012-06-01

    Methionine and folate are the key components of one carbon metabolism, providing the methyl groups for numerous methyl transferase reactions via the ubiquitous methyl donor, s-adenosyl methionine. Methionine metabolism is responsive to nutrient intake, is regulated by several hormones and requires a number of vitamins (B12, pyridoxine, riboflavin) as co-factors. The critical relationship between perturbations in the mother's methionine metabolism and its impact on fetal growth and development is now becoming evident. The relation of folate intake to fetal teratogenesis has been known for some time. Studies in human pregnancy show a continuous decrease in plasma homocysteine, and an increase in plasma choline concentrations with advancing gestation. A higher rate of transsulfuration of methionine in early gestation and of transmethylation in the 3rd trimester was seen in healthy pregnant women. How these processes are impacted by nutritional, hormonal and other influences in human pregnancy and their effect on fetal growth has not been examined. Isocaloric protein restriction in pregnant rats, resulted in fetal growth restriction and metabolic reprogramming. Isocaloric protein restriction in the non-pregnant rat, resulted in differential expression of a number of genes in the liver, a 50% increase in whole body serine biosynthesis and high rate of transmethylation, suggesting high methylation demands. These responses were associated with a significant decrease in intracellular taurine levels in the liver suggesting a role of cellular osmolarity in the observed metabolic responses. These unique changes in methionine and one carbon metabolism in response to physiological, nutritional and hormonal influences make these processes critical for cellular and organ function and growth.

  10. Maternal growth factor regulation of human placental development and fetal growth.

    PubMed

    Forbes, Karen; Westwood, Melissa

    2010-10-01

    Normal development and function of the placenta is critical to achieving a successful pregnancy, as normal fetal growth depends directly on the transfer of nutrients from mother to fetus via this organ. Recently, it has become apparent from both animal and human studies that growth factors within the maternal circulation, for example the IGFs, are important regulators of placental development and function. Although these factors act via distinct receptors to exert their effects, the downstream molecules activated upon ligand/receptor interaction are common to many growth factors. The expression of numerous signaling molecules is altered in the placentas from pregnancies affected by the fetal growth complications, fetal growth restriction, and macrosomia. Thus, targeting these molecules may lead to more effective treatments for complications of pregnancy associated with altered placental development. Here, we review the maternal growth factors required for placental development and discuss their mechanism of action.

  11. Atenolol and fetal growth in pregnancies complicated by hypertension.

    PubMed

    Lydakis, C; Lip, G Y; Beevers, M; Beevers, D G

    1999-06-01

    Atenolol use may be associated with growth retardation when given in pregnancy, although the relationship to trimester of initiation, duration of treatment, and its use as monotherapy is still uncertain. To compare the obstetric and fetal outcome between women receiving atenolol (as monotherapy) and other antihypertensive drug monotherapies, and also to investigate the effect of duration of treatment on fetal growth, we performed a retrospective cohort study of 312 pregnancies in 223 women attending an Antenatal Hypertension Clinic. Atenolol (as monotherapy) was given in 78 pregnancies (25.0%), other types of antihypertensive drugs as monotherapy were given in 53 pregnancies (17.0%), and multiple drug combinations were given in 90 pregnancies (28.8%). In 91 pregnancies (29.2%) no antihypertensive drugs were given. Atenolol was found to be associated with lower birth weight and ponderal index values, with a trend toward a higher prevalence of preterm (<37 weeks) delivery and small-for-gestational-age babies when compared to other antihypertensive drugs as monotherapy, or to no treatment. The adverse effect of atenolol was more pronounced in women receiving the drug earlier in their pregnancy, and continuing the drug for a longer duration. In conclusion, atenolol should be avoided in the early stages of pregnancy and given with caution at the later stages, as it is associated with fetal growth retardation, which is related to duration of treatment.

  12. 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

  13. 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

  14. IGF2 DNA methylation is a modulator of newborn's fetal growth and development.

    PubMed

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

    2012-10-01

    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.

  15. Impact of placental insufficiency on fetal skeletal muscle growth.

    PubMed

    Brown, Laura D; Hay, William W

    2016-11-05

    Intrauterine growth restriction (IUGR) caused by placental insufficiency is one of the most common and complex problems in perinatology, with no known cure. In pregnancies affected by placental insufficiency, a poorly functioning placenta restricts nutrient supply to the fetus and prevents normal fetal growth. Among other significant deficits in organ development, the IUGR fetus characteristically has less lean body and skeletal muscle mass than their appropriately-grown counterparts. Reduced skeletal muscle growth is not fully compensated after birth, as individuals who were born small for gestational age (SGA) from IUGR have persistent reductions in muscle mass and strength into adulthood. The consequences of restricted muscle growth and accelerated postnatal "catch-up" growth in the form of adiposity may contribute to the increased later life risk for visceral adiposity, peripheral insulin resistance, diabetes, and cardiovascular disease in individuals who were formerly IUGR. This review will discuss how an insufficient placenta results in impaired fetal skeletal muscle growth and how lifelong reductions in muscle mass might contribute to increased metabolic disease risk in this vulnerable population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. 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

  17. Birth weight, gestational age, fetal growth and childhood asthma hospitalization

    PubMed Central

    2014-01-01

    Background Childhood asthma may have a fetal origin through fetal growth and development of the immunocompetence or respiratory organs. Objective We examined to which extent short gestational age, low birth weight and fetal growth restriction were associated with an increased risk of asthma hospitalization in childhood. Methods We undertook a cohort study based on several national registers in Denmark, Sweden and Finland. We included all live singleton born children in Denmark during 1979-2005 (N = 1,538,093), in Sweden during 1973-2004 (N = 3,067,670), and a 90% random sample of singleton children born in Finland during 1987-2004 (N = 1,050,744). The children were followed from three years of age to first hospitalization for asthma, emigration, death, their 18th birthday, or the end of study (the end of 2008 in Denmark, and the end of 2007 in Sweden or Finland), whichever came first. We computed the pseudo-values for each observation and used them in a generalized estimating equation to estimate relative risks (RR) for asthma hospitalization. Results A total of 131,783 children were hospitalized for asthma during follow-up. The risk for asthma hospitalization consistently increased with lower birth weight and shorter gestational age. A 1000-g decrease in birth weight corresponded to a RR of 1.17 (95% confidence interval (CI) 1.15-1.18). A one-week decrease in gestational age corresponded to a RR of 1.05 (95% CI 1.04-1.06). Small for gestational age was associated with an increased risk of asthma hospitalization in term but not in preterm born children. Conclusions Fetal growth and gestational age may play a direct or indirect causal role in the development of childhood asthma. PMID:24602245

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

    PubMed

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

    2015-04-01

    To determine normative ranges for fetal ocular biometrics between 19 and 38 weeks gestational age (GA) using volumetric MRI reconstruction. The 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). All biometry correlated with GA (Volume, Pearson's correlation coefficient (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. Orbital volume had the greatest correlation with GA, although 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. © 2015 John Wiley & Sons, Ltd. © 2015 John Wiley & Sons, Ltd.

  19. Effect of placenta previa on fetal growth restriction and stillbirth.

    PubMed

    Yeniel, A Ozgur; Ergenoglu, A Mete; Itil, Ismail Mete; Askar, Niyazi; Meseri, Reci

    2012-08-01

    To examine the association between placenta previa and adverse perinatal outcomes such as low birth weight, preterm delivery, stillbirth and fetal growth restriction (FGR). This retrospective cohort study includes 12,034 delivered pregnant women who were recruited for the study between 2004 and 2010 in Ege University Hospital. Data were collected by browsing the clinic's archives. The association between placenta previa and adverse perinatal outcomes was determined via Chi-square tests and Student's t test. Logistic regression analysis was used to adjust for confounding factors in evaluating the association between placenta previa and the adverse perinatal outcomes. There was no significant relationship between placenta previa and FGR or stillbirth. Low birth weight and preterm delivery were significantly higher in the placenta previa group. According to logistic regression analysis, low birth weight was associated with an OR of 3.01 (95 % CI 2.05-4.52) and preterm delivery was associated with an OR of 8.14 (95 % CI 5.60-11.83); while, placenta previa did not affect FGR and stillbirth significantly. Although there is no consensus on the association between placenta previa and FGR in previous studies, we suggest that placenta previa is not a reason for placental insufficiency. Management of placenta previa especially depends on maternal hemodynamic parameters such as heavy hemorrhage and hypotensive shock rather than fetal well-being protocols based on serial growth ultrasound and fetal Doppler investigation.

  20. [Sonography of fetal growth behavior in maternal diabetes mellitus].

    PubMed

    Hielscher, K; Renziehausen, K; Döring, E

    1989-01-01

    In the Gynaecological Hospital affiliated to the District Hospital of Karl-Marx-Stadt, which is a care centre for pregnant diabetic women, 363 diabetic women of classes White A-F 1779 were subjected to ultrasonic examinations between 1982 and 1988. In this connection, nominal-value graphs were prepared to show the biparietal diameter (BIP), the medium thorax diameter and the head-thorax index in dependence upon the gestational age. These nominal-value graphs give a general idea of the specific fetal growth behaviour in case of diabetes mellitus. They permit to reliably diagnose a fetal hypertrophy or hypotrophy. Moreover, they provide a starting point for a more effective coverage of gestational diabetics and open up new prospects for insulinisation.

  1. Insulin-like growth factors in embryonic and fetal growth and skeletal development (Review)

    PubMed Central

    AGROGIANNIS, GEORGIOS D.; SIFAKIS, STAVROS; PATSOURIS, EFSTRATIOS S.; KONSTANTINIDOU, ANASTASIA E.

    2014-01-01

    The insulin-like growth factors (IGF)-I and -II have a predominant role in fetal growth and development. IGFs are involved in the proliferation, differentiation and apoptosis of fetal cells in vitro and the IGF serum concentration has been shown to be closely correlated with fetal growth and length. IGF transcripts and peptides have been detected in almost every fetal tissue from as early in development as pre-implantation to the final maturation stage. Furthermore, IGFs have been demonstrated to be involved in limb morphogenesis. However, although ablation of Igf genes in mice resulted in growth retardation and delay in skeletal maturation, no impact on outgrowth and patterning of embryonic limbs was observed. Additionally, various molecular defects in the Igf1 and Igf1r genes in humans have been associated with severe intrauterine growth retardation and impaired skeletal maturation, but not with truncated limbs or severe skeletal dysplasia. The conflicting data between in vitro and in vivo observations with regard to bone morphogenesis suggests that IGFs may not be the sole trophic factors involved in fetal skeletal growth and that redundant mechanisms may exist in chondro- and osteogenesis. Further investigation is required in order to elucidate the functions of IGFs in skeletal development. PMID:24859417

  2. Insulin-like growth factors in embryonic and fetal growth and skeletal development (Review).

    PubMed

    Agrogiannis, Georgios D; Sifakis, Stavros; Patsouris, Efstratios S; Konstantinidou, Anastasia E

    2014-08-01

    The insulin-like growth factors (IGF)-I and -II have a predominant role in fetal growth and development. IGFs are involved in the proliferation, differentiation and apoptosis of fetal cells in vitro and the IGF serum concentration has been shown to be closely correlated with fetal growth and length. IGF transcripts and peptides have been detected in almost every fetal tissue from as early in development as pre‑implantation to the final maturation stage. Furthermore, IGFs have been demonstrated to be involved in limb morphogenesis. However, although ablation of Igf genes in mice resulted in growth retardation and delay in skeletal maturation, no impact on outgrowth and patterning of embryonic limbs was observed. Additionally, various molecular defects in the Igf1 and Igf1r genes in humans have been associated with severe intrauterine growth retardation and impaired skeletal maturation, but not with truncated limbs or severe skeletal dysplasia. The conflicting data between in vitro and in vivo observations with regard to bone morphogenesis suggests that IGFs may not be the sole trophic factors involved in fetal skeletal growth and that redundant mechanisms may exist in chondro- and osteogenesis. Further investigation is required in order to elucidate the functions of IGFs in skeletal development.

  3. Periconceptional growth hormone treatment alters fetal growth and development in lambs.

    PubMed

    Koch, J M; Wilmoth, T A; Wilson, M E

    2010-05-01

    fetal growth and development. Lambs born to ewes treated with GH were larger at birth and had altered organ development, which may indicate that early maternal GH treatment may lead to permanent changes in the developing fetus. The ewe lambs maintained their growth performance to at least 100 d of postnatal life and appeared to have an altered GH axis, as demonstrated by the altered response to GHRH.

  4. Growth perturbations in a phenotype with rapid fetal growth preceding preterm labor and term birth.

    PubMed

    Lampl, Michelle; Kusanovic, Juan Pedro; Erez, Offer; Gotsch, Francesca; Espinoza, Jimmy; Goncalves, Luis; Lee, Wesley; Gomez, Ricardo; Nien, Jyh Kae; Frongillo, Edward A; Romero, Roberto

    2009-01-01

    The variability in fetal growth rates and gestation duration in humans is not well understood. Of interest are women presenting with an episode of preterm labor and subsequently delivering a term neonate, who is small relative to peers of similar gestational age. To further understand these relationships, fetal growth patterns predating an episode of preterm labor were investigated. Retrospective analysis of fetal biometry assessed by serial ultrasound in a prospectively studied sample of pregnancies in Santiago, Chile, tested the hypothesis that fetal growth patterns among uncomplicated pregnancies (n = 3,706) and those with an episode of preterm labor followed by term delivery (n = 184) were identical across the time intervals 16-22 weeks, 22-28 weeks, and 28-34 weeks in a multilevel mixed-effects regression. The hypothesis was not supported. Fetal weight growth rate was faster from 16 weeks among pregnancies with an episode of preterm labor (P < 0.05), declined across midgestation (22-28 weeks, P < 0.05), and rebounded between 28 and 34 weeks (P = 0.06). This was associated with perturbations in abdominal circumference growth and proportionately larger biparietal diameter from 22 gestational weeks (P = 0.03), greater femur (P = 0.01), biparietal diameter (P = 0.001) and head circumference (P = 0.02) dimensions relative to abdominal circumference across midgestation (22-28 weeks), followed by proportionately smaller femur diaphyseal length (P = 0.02) and biparietal diameter (P = 0.03) subsequently. A distinctive rapid growth phenotype characterized fetal growth preceding an episode of preterm labor among this sample of term-delivered neonates. Perturbations in abdominal circumference growth and patterns of proportionality suggest an altered growth strategy pre-dating the preterm labor episode.

  5. Maternal insulin-like growth factor binding protein-1, body mass index, and fetal growth

    PubMed Central

    Holmes, R.; Holly, J; Soothill, P.

    2000-01-01

    AIM—To examine the hypothesis that the maternal insulin-like growth factor system may constrain fetal growth.
METHODS—A prospective observational study of maternal serum insulin-like growth factor binding protein-1 (IGFBP-1) and fetal growth was undertaken in neonates with birthweights below the 5th centile. They had been classified either as having fetal growth restriction (FGR) due to placental dysfunction (increased umbilical artery Doppler pulsatility index (PI); n = 25) or as being small for gestational age (SGA; normal umbilical artery PI, growth velocity and amniotic fluid; n = 27). Eighty nine controls had normal birthweights (5th-95th centile), umbilical artery PI, growth velocity, and amniotic fluid. IGFBP-1 was measured by radioimmunoassay.
RESULTS—Among the controls, there was no significant correlation between IGFBP-1 and birthweight after allowing for body mass index (BMI). Maternal BMI was high in FGR and after adjusting for this, IGFBP-1 was increased (109 ng/ml) compared with SGA babies (69ng/ml) and controls (57 ng/ml) and correlated with the umbilical artery PI.
CONCLUSIONS—Maternal IGFBP-1 is probably not part of normal placental function. Its increase in FGR could be the cause or consequence of impaired placental perfusion, but high IGFBP-1 concentrations might further reduce the availability of maternal IGF-I to the placenta. This could worsen placental function and so adversely affect fetal growth.
 PMID:10685983

  6. 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.

  7. Imprinted gene expression in fetal growth and development.

    PubMed

    Lambertini, L; Marsit, C J; Sharma, P; Maccani, M; Ma, Y; Hu, J; Chen, J

    2012-06-01

    Experimental studies showed that genomic imprinting is fundamental in fetoplacental development by timely regulating the expression of the imprinted genes to overlook a set of events determining placenta implantation, growth and embryogenesis. We examined the expression profile of 22 imprinted genes which have been linked to pregnancy abnormalities that may ultimately influence childhood development. The study was conducted in a subset of 106 placenta samples, overrepresented with small and large for gestational age cases, from the Rhode Island Child Health Study. We investigated associations between imprinted gene expression and three fetal development parameters: newborn head circumference, birth weight, and size for gestational age. Results from our investigation show that the maternally imprinted/paternally expressed gene ZNF331 inversely associates with each parameter to drive smaller fetal size, while paternally imprinted/maternally expressed gene SLC22A18 directly associates with the newborn head circumference promoting growth. Multidimensional Scaling analysis revealed two clusters within the 22 imprinted genes which are independently associated with fetoplacental development. Our data suggest that cluster 1 genes work by assuring cell growth and tissue development, while cluster 2 genes act by coordinating these processes. Results from this epidemiologic study offer solid support for the key role of imprinting in fetoplacental development.

  8. [Impairments of placental amino acid metabolism in fetal growth restriction].

    PubMed

    Pogorelova, T N; Gunko, V O; Avrutskaya, V V; Kaushanskaya, L V; Durnitsyna, O A

    2017-05-01

    The content of the amino acids in the placenta during physiological pregnancy and fetal growth restriction (FGR) has been investigated my means of the method of ion-exchange chromatography. It has been found that in FGR the placental amino acid pool is characterized by a decreased content of arginine, proline, alanine, serine, cysteine, methionine, tryptophan, leucine, threonine, tyrosine, phenylalanine, glutamine and an increased content of dicarboxylic amino acids, lysine, histidine and glycine. These changes are accompanied by altered activity of some enzymes of amino acid metabolism, and the degree of these changes correlates with the level of corresponding amino acids.

  9. The role of growth hormone in fetal development.

    PubMed

    Waters, M J; Kaye, P L

    2002-06-01

    Studies across several species, particularly the mouse, show that growth hormone (GH, somatotrophin) is an important determinant of litter size, and to a lesser extent, of birth length. GH acts at all stages of development, from ovulation through preimplantation development to the late fetus, with actions on both embryo/fetus and mother contributing to successful fetal development. The fact that these are not more obvious in vivo is likely a result of redundancy of cytokine hormone action, particularly in relation to prolactin, which shares common actions and receptor locations with GH.

  10. The use of ultrasound to assess fetal growth in a guinea pig model of fetal growth restriction.

    PubMed

    Swanson, A M; Mehta, V; Ofir, K; Rowe, M; Rossi, C; Ginsberg, Y; Griffin, H; Barker, H; White, T; Boyd, M; David, A L

    2017-04-01

    Fetal growth restriction (FGR) is a common and potentially severe pregnancy complication. Currently there is no treatment available. The guinea pig is an attractive model of human pregnancy as placentation is morphologically very similar between the species. Nutrient restriction of the dam creates growth-restricted fetuses while leaving an intact uteroplacental circulation, vital for evaluating novel therapies for FGR. Growth-restricted fetuses were generated by feeding Dunkin Hartley guinea pig dams 70% of ad libitum intake from four weeks before and throughout pregnancy. The effect of maternal nutrient restriction (MNR) on dams and fetuses was carefully monitored, and ultrasound measurements of pups collected. There was no difference in maternal weight at conception, however by five weeks post conception MNR dams were significantly lighter ( P < 0.05). MNR resulted in significantly smaller pup size from 0.6-0.66 gestation. Ultrasound is a powerful non-invasive tool for assessing the effect of therapeutic interventions on fetal growth, allowing longitudinal measurement of fetuses. This model and method yield data applicable to the human condition without the need for animal sacrifice and will be useful in the translation of therapies for FGR into the clinic.

  11. Third trimester growth restriction patterns: individualized assessment using a fetal growth pathology score.

    PubMed

    Deter, Russell L; Lee, Wesley; Sangi-Haghpeykar, Haleh; Kingdom, John; Romero, Roberto

    2017-07-06

    To qualitatively and quantitatively characterize third trimester growth patterns in fetuses/neonates with growth restriction using Individualized Growth Assessment. Serial fetal size measurements from 73 fetuses with proven growth restriction were evaluated using a novel composite parameter, the Fetal Growth Pathology Score (FGPS1). Third trimester FGPS1 measurements plotted against fetal age were examined for patterns. Identified patterns were characterized using the four components of the FGP1 [head circumference (HC), abdominal circumference (AC), femur diaphysis length (FDL), estimated weight (EWT)]. A secondary characterization using age of onset, duration and magnitude of the growth abnormality process was also performed. Frequencies and magnitudes of abnormal values in different FGPS1 patterns were compared. Five growth restriction patterns were found in 70/73 (95.9%) of the cases, with progressive worsening [Pattern 1 (37.0%)] and abnormal growth identified only at last scan [Pattern 2 (27.4%)] being the most common. These two patterns were usually statistically different from each other and the other three with respect to size parameter abnormalities and abnormal growth process characteristics (MANOVA). Growth abnormalities in all parameters of the FGPS1 contributed to the five abnormality patterns although AC and EWT were most important. The age of onset, duration and magnitude were similar between patterns except for Pattern 2, which had a late onset and a short duration (GLM + contrasts). Our study represents the first detailed evaluation of third trimester growth restriction using methods that consider the growth potential of each fetus. Five distinctive and repetitive patterns were found, suggesting that fetal growth restriction evolves in different ways. Further research is needed to determine the relationships of these patterns to physiological/biochemical changes and adverse outcomes associated with growth restriction.

  12. Parenteral administration of L-arginine enhances fetal survival and growth in sheep carrying multiple fetuses.

    PubMed

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

    2011-05-01

    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.

  13. NDRG1 deficiency attenuates fetal growth and the intrauterine response to hypoxic injury.

    PubMed

    Larkin, Jacob; Chen, Baosheng; Shi, Xiao-Hua; Mishima, Takuya; Kokame, Koichi; Barak, Yaacov; Sadovsky, Yoel

    2014-03-01

    Intrauterine mammalian development depends on the preservation of placental function. The expression of the protein N-myc downstream-regulated gene 1 (NDRG1) is increased in placentas of human pregnancies affected by fetal growth restriction and in hypoxic primary human trophoblasts, where NDRG1 attenuates cell injury. We sought to assess the function of placental NDRG1 in vivo and tested the hypothesis that NDRG1 deficiency in the mouse embryo impairs placental function and consequently intrauterine growth. We found that Ndrg1 knock-out embryos were growth restricted in comparison to wild-type or heterozygous counterparts. Furthermore, hypoxia reduced the survival of female, but not male, knock-out embryos. Ndrg1 deletion caused significant alterations in placental gene expression, with a marked reduction in transcription of several lipoproteins in the placental labyrinth. These transcriptional changes were associated with reduced fetal:maternal serum cholesterol ratio exclusively in hypoxic female embryos. Collectively, our findings indicate that NDRG1 promotes fetal growth and regulates the metabolic response to intrauterine hypoxic injury in a sexually dichotomous manner.

  14. 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.

  15. Sexual dimorphism in epigenomic responses of stem cells to extreme fetal growth.

    PubMed

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

    2014-10-10

    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(+) haematopoietic stem/progenitor cells 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 is associated with substantially greater epigenetic dysregulation in males, whereas large for gestational age growth predominantly affects females. The findings are consistent with extreme fetal growth interacting with variable fetal susceptibility to influence cellular ageing and metabolic characteristics through epigenetic mechanisms, potentially generating biomarkers that could identify infants at higher risk for chronic disease later in life.

  16. 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

  17. Maternal and fetal risk factors affecting perinatal mortality in early and late fetal growth restriction.

    PubMed

    Demirci, Oya; Selçuk, Selçuk; Kumru, Pınar; Asoğlu, Mehmet Reşit; Mahmutoğlu, Didar; Boza, Barış; Türkyılmaz, Gürcan; Bütün, Zafer; Arısoy, Resul; Tandoğan, Bülent

    2015-12-01

    To determine the factors which affect the perinatal deaths in early and late fetal growth restriction (FGR) fetuses using threshold of estimated fetal weight (EFW) < 5(th) percentile. This retrospective study included singleton 271 FGR fetuses, defined as an EFW < 5(th) percentile. All fetuses considered as growth restrictions were confirmed by birth weight. Fetuses with multiple pregnancy, congenital malformation, chromosomal abnormality, and premature rupture of membrane were excluded. Samples were grouped in early and late FGR. Early FGR fetuses was classified as gestational age at birth ≤ 34 weeks and late FGR was classified as gestational age at birth > 34 weeks. Factors which affect the perinatal deaths were analyzed descriptively in early and late FGR. The perinatal mortality was calculated by adding the number of stillbirths and neonatal deaths. The study included 86 early and 185 late FGR fetuses, 31 resulted in perinatal deaths, 28 perinatal deaths were in early FGR, and three perinatal deaths were in late FGR. Perinatal deaths occurred more commonly in early FGR fetuses with an EFW < 3(rd) percentile. Prior stillbirth, preeclampsia, the degree of increasing vascular impedance of umbilical artery(UA) and uterine artery (UtA) showed significant correlation with perinatal death in early FGR. All three perinatal deaths in late FGR occurred in fetuses with EFW < 3(rd) percentile and severe oligohydramnios. Also, placental abruption and perinatal death was found significantly higher in increased vascular impedance of UtAs whatever the umbilical artery Doppler. Only EFW < 3(rd) percentile and severe olgohydramnios seem to be contributing factors affecting perinatal death in late FGR in comparison with early FGR. Copyright © 2015. Published by Elsevier B.V.

  18. Growth hormone and Pit-1 expression in bovine fetal lymphoid cells.

    PubMed

    Chen, H T; Schuler, L A; Schultz, R D

    1997-11-01

    Bovine fetal lymphoid cells were examined for growth hormone (GH) and the transcription factor Pit-1/GHF-1 mRNA. GH and Pit-1/GHF-1 transcripts were detected in thymocytes and splenocytes from fetuses at 60, 90, 120, and 270 d of gestation using reverse transcription-polymerase chain reaction (RT-PCR). Northern analysis indicated that the lymphoid GH mRNA was approximately 350 nucleotides larger than in the pituitary. RT-PCR analysis demonstrated that the coding regions as well as 3' untranslated region of the lymphocyte GH and pituitary transcripts were the same. Analysis of the 5'-untranslated region of the lymphocyte GH mRNA showed that transcription began upstream from the start site in the pituitary gland, suggesting differences in regulation in these tissues. Fetal thymocytes and splenocytes expressed Pit-1/GHF-1 mRNA; however, they contained only the 2.5-kb transcript. The GH and Pit-1/GHF-1 mRNA in fetal lymphoid cells supports the hypothesis that lymphocyte-derived GH may function as an autocrine and/or paracrine factor during the development and maturation of the bovine fetal immune system.

  19. The effects of smoking and hypertensive disorders on fetal growth

    PubMed Central

    Rasmussen, Svein; Irgens, Lorentz M

    2006-01-01

    Background It is well known that smoking and pregnancy induced hypertension (PIH) are associated with decreased fetal growth. It has been reported that in preeclampsia the fetal growth deficit attributable to smoking is higher, which has been contradicted in other studies. We therefore evaluated the effects on fetal growth of early- and late onset PIH and chronic hypertension and how cigarette smoking modify these effects. We also quantified the proportion of small for gestational age (SGA) cases attributable to PIH, chronic hypertension, and smoking. Methods Population-based study based on record of 215598 singleton pregnancies from the Medical Birth Registry of Norway. Results In severe preeclampsia, mild preeclampsia, transient hypertension, and normotension in term birth, odds ratios (ORs) of SGA in smokers compared with non-smokers were 1.4 (95% confidence interval 0.9, 2.2), 1.6 (1.3, 1.9), 2.3 (1.8, 3.1), and 2.0 (1.9, 2.1), respectively. For preterm births, corresponding ORs were 1.3 (0.9, 2.0), 1.8 (1.1, 3.0), 4.1 (1.9, 9.0), and 1.7 (1.4, 2.0), respectively. The effect of early onset PIH was stronger than that in term births, while the effect of smoking was equal in preterm and term newborns. Only in non-smokers who delivered at term, the rates of SGA significantly increased with the severity of PIH (ORs = 1.3 (1.1, 1.5), 1.8 (1.7, 2.0), and 2.5 (2.2, 3.0) for transient hypertension, mild-, and severe preeclampsia, respectively). The combined effects of smoking and hypertension were generally not synergistic. The effect of smoking was not stronger in women who had chronic hypertension. Nor were the effects of chronic hypertension stronger in smokers. PIH explained 21.9 and 2.5% of preterm and term cases of SGA, respectively, while smoking explained 12% of SGA cases. Conclusion The effects of hypertensive disorder and smoking were generally not synergistic, which suggest that they may exert their main actions on separate sites or work through separate

  20. Sex Differences in Placental Mitochondrial Function Associated with Ozone-Induced Fetal Growth Restriction.

    EPA Science Inventory

    Fetal growth restriction is a major underlying cause of infant mortality worldwide. Unfortunately little is known about the mechanisms that drive compromised growth and the role of placental maladaptation on fetal development. In the current study placentas from male and female r...

  1. 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…

  2. Sildenafil citrate increases fetal weight in a mouse model of fetal growth restriction with a normal vascular phenotype.

    PubMed

    Dilworth, Mark Robert; Andersson, Irene; Renshall, Lewis James; Cowley, Elizabeth; Baker, Philip; Greenwood, Susan; Sibley, Colin Peter; Wareing, Mark

    2013-01-01

    Fetal growth restriction (FGR) is defined as the inability of a fetus to achieve its genetic growth potential and is associated with a significantly increased risk of morbidity and mortality. Clinically, FGR is diagnosed as a fetus falling below the 5(th) centile of customised growth charts. Sildenafil citrate (SC, Viagra™), a potent and selective phosphodiesterase-5 inhibitor, corrects ex vivo placental vascular dysfunction in FGR, demonstrating potential as a therapy for this condition. However, many FGR cases present without an abnormal vascular phenotype, as assessed by Doppler measures of uterine/umbilical artery blood flow velocity. Thus, we hypothesized that SC would not increase fetal growth in a mouse model of FGR, the placental-specific Igf2 knockout mouse, which has altered placental exchange capacity but normal placental blood flow. Fetal weights were increased (by 8%) in P0 mice following maternal SC treatment (0.4 mg/ml) via drinking water. There was also a trend towards increased placental weight in treated P0 mice (P = 0.056). Additionally, 75% of the P0 fetal weights were below the 5(th) centile, the criterion used to define human FGR, of the non-treated WT fetal weights; this was reduced to 51% when dams were treated with SC. Umbilical artery and vein blood flow velocity measures confirmed the lack of an abnormal vascular phenotype in the P0 mouse; and were unaffected by SC treatment. (14)C-methylaminoisobutyric acid transfer (measured to assess effects on placental nutrient transporter activity) per g placenta was unaffected by SC, versus untreated, though total transfer was increased, commensurate with the trend towards larger placentas in this group. These data suggest that SC may improve fetal growth even in the absence of an abnormal placental blood flow, potentially affording use in multiple sub-populations of individuals presenting with FGR.

  3. Sildenafil Citrate Increases Fetal Weight in a Mouse Model of Fetal Growth Restriction with a Normal Vascular Phenotype

    PubMed Central

    Dilworth, Mark Robert; Andersson, Irene; Renshall, Lewis James; Cowley, Elizabeth; Baker, Philip; Greenwood, Susan; Sibley, Colin Peter; Wareing, Mark

    2013-01-01

    Fetal growth restriction (FGR) is defined as the inability of a fetus to achieve its genetic growth potential and is associated with a significantly increased risk of morbidity and mortality. Clinically, FGR is diagnosed as a fetus falling below the 5th centile of customised growth charts. Sildenafil citrate (SC, Viagra™), a potent and selective phosphodiesterase-5 inhibitor, corrects ex vivo placental vascular dysfunction in FGR, demonstrating potential as a therapy for this condition. However, many FGR cases present without an abnormal vascular phenotype, as assessed by Doppler measures of uterine/umbilical artery blood flow velocity. Thus, we hypothesized that SC would not increase fetal growth in a mouse model of FGR, the placental-specific Igf2 knockout mouse, which has altered placental exchange capacity but normal placental blood flow. Fetal weights were increased (by 8%) in P0 mice following maternal SC treatment (0.4 mg/ml) via drinking water. There was also a trend towards increased placental weight in treated P0 mice (P = 0.056). Additionally, 75% of the P0 fetal weights were below the 5th centile, the criterion used to define human FGR, of the non-treated WT fetal weights; this was reduced to 51% when dams were treated with SC. Umbilical artery and vein blood flow velocity measures confirmed the lack of an abnormal vascular phenotype in the P0 mouse; and were unaffected by SC treatment. 14C-methylaminoisobutyric acid transfer (measured to assess effects on placental nutrient transporter activity) per g placenta was unaffected by SC, versus untreated, though total transfer was increased, commensurate with the trend towards larger placentas in this group. These data suggest that SC may improve fetal growth even in the absence of an abnormal placental blood flow, potentially affording use in multiple sub-populations of individuals presenting with FGR. PMID:24204949

  4. Fetal Growth and Childhood Cancer: A Population-Based Study

    PubMed Central

    Sørensen, Henrik Toft; Grotmol, Tom; Engeland, Anders; Stephansson, Olof; Gissler, Mika; Tretli, Steinar; Troisi, Rebecca

    2013-01-01

    OBJECTIVE: The etiology of childhood cancers is largely unknown. Studies have suggested that birth characteristics may be associated with risk. Our goal was to evaluate the risk of childhood cancers in relation to fetal growth. METHODS: We conducted a case-control study nested within Nordic birth registries. The study included cancer cases diagnosed in Denmark, Finland, Norway, and Sweden among children born from 1967 to 2010 and up to 10 matched controls per case, totaling 17 698 cases and 172 422 controls. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were derived from conditional logistic regression. RESULTS: Risks of all childhood cancers increased with increasing birth weight (Ptrend ≤ .001). Risks of acute lymphoid leukemia and Wilms tumor were elevated when birth weight was >4000 g and of central nervous system tumors when birth weight was >4500 g. Newborns large for gestational age were at increased risk of Wilms tumor (OR: 2.1 [95% CI: 1.2–3.6]) and connective/soft tissue tumors (OR: 2.1 [95% CI: 1.1–4.4]). In contrast, the risk of acute myeloid leukemia was increased among children born small for gestational age (OR: 1.8 [95% CI: 1.1–3.1]). Children diagnosed with central nervous system tumors at <1 year of age had elevated risk with increasing head circumference (Ptrend < .001). Those with head circumference >39 cm had the highest risk (OR: 4.7 [95% CI: 2.5–8.7]). CONCLUSIONS: In this large, Nordic population-based study, increased risks for several childhood tumors were associated with measures of fetal growth, supporting the hypothesis that tumorigenesis manifesting in childhood is initiated in utero. PMID:24167169

  5. Consensus definition of fetal growth restriction: a Delphi procedure.

    PubMed

    Gordijn, S J; Beune, I M; Thilaganathan, B; Papageorghiou, A; Baschat, A A; Baker, P N; Silver, R M; Wynia, K; Ganzevoort, W

    2016-09-01

    To determine, by expert consensus, a definition for early and late fetal growth restriction (FGR) through a Delphi procedure. A Delphi survey was conducted among an international panel of experts on FGR. Panel members were provided with 18 literature-based parameters for defining FGR and were asked to rate the importance of these parameters for the diagnosis of both early and late FGR on a 5-point Likert scale. Parameters were described as solitary parameters (parameters that are sufficient to diagnose FGR, even if all other parameters are normal) and contributory parameters (parameters that require other abnormal parameter(s) to be present for the diagnosis of FGR). Consensus was sought to determine the cut-off values for accepted parameters. A total of 106 experts were approached, of whom 56 agreed to participate and entered the first round, and 45 (80%) completed all four rounds. For early FGR (< 32 weeks), three solitary parameters (abdominal circumference (AC) < 3(rd) centile, estimated fetal weight (EFW) < 3(rd) centile and absent end-diastolic flow in the umbilical artery (UA)) and four contributory parameters (AC or EFW < 10(th) centile combined with a pulsatility index (PI) > 95(th) centile in either the UA or uterine artery) were agreed upon. For late FGR (≥ 32 weeks), two solitary parameters (AC or EFW < 3(rd) centile) and four contributory parameters (EFW or AC < 10(th) centile, AC or EFW crossing centiles by > two quartiles on growth charts and cerebroplacental ratio < 5(th) centile or UA-PI > 95(th) centile) were defined. Consensus-based definitions for early and late FGR, as well as cut-off values for parameters involved, were agreed upon by a panel of experts. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

  6. 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.

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

    PubMed Central

    Yamashita, F; Hayashi, M

    1985-01-01

    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. We 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. PMID:3921362

  8. Transforming growth factor-β (TGF-β) signaling in healthy human fetal skin: a descriptive study.

    PubMed

    Walraven, M; Beelen, R H J; Ulrich, M M W

    2015-05-01

    TGF-β plays an important role in growth and development but is also involved in scarring and fibrosis. Differences for this growth factor are known between scarless fetal wound healing and adult wound healing. Nonetheless, most of the data in this area are from animal studies or in vitro studies and, thus, information about the human situation is incomplete and scarce. The aim of this study was to compare the canonical TGF-β signaling in unwounded human fetal and adult skin. Q-PCR, immunohistochemistry, Western Blot and Luminex assays were used to determine gene expression, protein levels and protein localization of components of this pathway in healthy skin. All components of the canonical TGF-β pathway were present in unwounded fetal skin. Compared to adult skin, fetal skin had differential concentrations of the TGF-β isoforms, had high levels of phosphorylated receptor-Smads, especially in the epidermis, and had low expression of several fibrosis-associated target genes. Further, the results indicated that the processes of receptor endocytosis might also differ between fetal and adult skin. This descriptive study showed that there are differences in gene expression, protein concentrations and protein localization for most components of the canonical TGF-β pathway between fetal and adult skin. The findings of this study can be a starting point for further research into the role of TGF-β signaling in scarless healing. Copyright © 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  9. Comparative efficiency of measures of early fetal growth restriction for predicting adverse perinatal outcomes.

    PubMed

    Tuuli, Methodius G; Cahill, Alison; Stamilio, David; Macones, George; Odibo, Anthony O

    2011-06-01

    To estimate the comparative efficiency of first-trimester fetal growth restriction, second-trimester fetal growth restriction, and first-to-second-trimester growth lag for predicting adverse perinatal outcomes. This is a retrospective cohort study of pregnancies with reliable dating based on last menstrual periods and first-trimester ultrasound examinations. Pregnancies with multiple fetuses, aneuploidy, and major structural anomalies were excluded. Fetal crown-rump lengths at 10-14 weeks, estimated fetal weights based on fetal biometry at 18-22 weeks, and interval growth were measured and converted to gestational age-adjusted Z-scores. The primary outcome was small for gestational age (SGA) at delivery. Secondary outcomes were low birth weight, preterm delivery, stillbirth, and preeclampsia. Receiver-operating characteristics curves were used to identify the optimal definitions of early fetal growth restriction associated with SGA and to compare screening efficiencies. Multivariable logistic regression was used to adjust for confounders. Among 8,978 pregnancies meeting inclusion criteria, 551 (6.5%) neonates were SGA. Crown-rump length Z-score less than -1.0, estimated fetal weights Z-score less than -1.0, and growth Z-score less than -1.0 were identified as the optimal definitions of early fetal growth restriction associated with SGA (adjusted odds ratio 1.41 [95% confidence interval (CI) 1.13-1.74], 3.44 [95% CI 2.85-4.15] and 2.61 [95% CI 2.09-3.25], respectively). The sensitivity and specificity of first- and second-trimester fetal growth restriction for predicting SGA were 21.4% and 83.4%, and 37.2% and 85.5%, respectively. The area under the receiver-operating characteristics curve for second-trimester fetal growth restriction was greater than that for first-trimester fetal growth restriction and first-to-second-trimester growth lag (0.70 compared with 0.59 and 0.66, P<.001). Second-trimester fetal growth restriction is superior to first-trimester fetal

  10. Relationship of maternal amino acids and proteins to fetal growth and mental development.

    PubMed

    Moghissi, K S; Churchill, J A; Kurrie, D

    1975-10-15

    The relationship of maternal amino acids, proteins, and certain other factors to fetal development (weight and cranial volume at birth and mental and motor scores at 8 months of age) was investigated in 129 gravidas. Maternal prepregnancy weight was significantly related to birth weight and cranial volume in the newborn. Among amino acids, glycine, lysine, and total amino acids were positively correlated with birth weight, whereas valine and threonine showed a negative correlation. Cranial volume at birth was significantly related to the level of glycine and alpha1 globulin. Other protein and amino acids which contributed to cranial volume included threonine, histidine, glutamic acid, and beta globulin, negatively correlated, whereas glutamine was positively correlated. Alpha1 globulin (negatively) and glycine (positively) made significant contributions to motor development. For mental development, alpha 1 globulin and histidine showed a negative correlation, whereas isoleucine was positively correlated. Findings indicated that the concentrations of certain maternal amino acids and proteins in the third trimester of pregnancy correlated significantly with fetal growth and development. This study suggests: (1) specific proteins or amino acids may be responsible for different developmental measures; (2) injudicious dietary restrictions in pregnancy should be avoided; (3) the determination of alpha1 globulin and a few amino acids such as glycine, lysine, and histidine in late pregancy may be used as predictors of fetal growth and development.

  11. The frontal cortex IGF system is down regulated in the term, intrauterine growth restricted fetal baboon.

    PubMed

    Xie, L; Antonow-Schlorke, I; Schwab, M; McDonald, T J; Nathanielsz, P W; Li, C

    2013-10-01

    The IGF system exerts systemic and local actions during development. We previously demonstrated that fetal cerebral cortical IGF1 is reduced at 0.5 gestation in our IUGR baboon nonhuman primate model. We hypothesized that by term protein expression of several key IGF system stimulatory peptide pathway components and downstream nutrient signaling effectors of IGF, mammalian target of rapamycin (mTOR) and S6, would decrease, indicating reduced cellular nutrient uptake and protein synthesis. We fed 7 control baboons ad libitum while 6 baboons ate a globally reduced diet (70% of feed eaten by controls) from 0.16 gestation through pregnancy that produces IUGR. Fetuses were removed at Cesarean section at 0.9 gestation. Frontal cortex sections were stained for IGFI, IGFII, IGFRI, IGFR2, IGFBP2, 3, 5 and 6, and mTOR and ribosomal protein S6 and double stained with NeuN a neuron-specific nuclear antigen. All proteins stained neuronal cytoplasm except IGFRI which showed only glial cell cytoplasmic and blood vessel staining. IUGR fetuses showed decreased frontal cortical immunoreactive IGFI, IGFII, IGFRI, IGFBP2, 5 and 6, and mTOR and S6 (p < 0.05). IGFBP3 increased (p < 0.05) and IGFR2 was unchanged (p > 0.05). There were no differences between male and female fetal brains. When fetal nutrient availability is decreased, IUGR down regulates the IGF system and its mTOR signaling pathway in the fetal frontal cortex coincident with slowed growth. These findings emphasize the importance of the local tissue IGF system in fetal primate brain development. © 2013.

  12. Ethnic/racial disparities in the fetal growth outcomes of Ecuadorian newborns.

    PubMed

    Margaret Weigel, M; Sanchez, Maria Elena Caiza

    2013-02-01

    Size at birth is an important indicator of future infant morbidity and mortality. Ethnic/racial disparities in birth weight and other fetal growth outcomes are well documented for US and Canadian minority groups but not for those in Latin America. The study compared the growth outcomes of 1,227 full-term Ecuadorian newborns delivered by Afro-descendant and indigenous minority women with those of ethnic majority (mestizo) women. Minority newborns had higher risk for congenital microcephaly but no excess risk for low birth weight or stunted linear growth compared to mestizos. However, minority newborns were significantly heavier at birth, weighing an average of 3-5% more than mestizos. Afro-Ecuadorians newborns also were fatter. The risk profile of Ecuadorian ethnic groups for certain fetal growth outcomes differs from some of those reported for North American minorities. Further studies are needed to investigate the origins of these between-group differences and to develop ethnic specific interventions for adverse growth outcomes.

  13. Alterations in fetal thymic and liver hematopoietic cells as indicators of exposure to developmental immunotoxicants.

    PubMed Central

    Holladay, S D; Luster, M I

    1996-01-01

    Recent studies indicate that immune development in humans and other species may be altered after perinatal exposure to immunotoxic environmental contaminants. However, limited information is available regarding appropriate tests that may adequately detect developmental immunotoxic compounds. Experiments in which pregnant laboratory rodents were exposed to a variety of immunotoxic environmental agents indicate that fetal thymus and liver immune cells may be quantitatively and qualitatively altered by immunotoxicant exposure and, thus, may serve as sensitive markers of developmental immunotoxicant exposure. In particular, depression of fetal thymic cell counts appears to be a common event following gestational exposure to immunotoxicants that produce this response in adult animals. Total hematopoietic cell counts in fetal liver, however, may be a poor indicator of immunotoxicant exposure. Altered marker expression in both fetal thymus and liver appears to be a highly sensitive indicator of gestational immunotoxicant exposure. Together, these reports suggest that immune tests with high predictability for immunosuppression in adults may also be appropriate for the detection of developmental immunotoxic agents. PMID:8880003

  14. Maternal exposure to perfluorinated acids and fetal growth.

    PubMed

    Hamm, Michele P; Cherry, Nicola M; Chan, Emily; Martin, Jonathan W; Burstyn, Igor

    2010-11-01

    The widespread detection of perfluorinated acids (PFAs) in humans and known developmental toxicity in animals has raised concern about their potential effects on human reproductive health. Our objective was to determine whether increasing maternal exposure to PFAs is associated with adverse effects on fetal growth and length of gestation in women giving birth in Alberta, Canada. We examined the concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorohexane sulfonate (PFHxS) in a cohort of 252 pregnant women who gave birth to live singletons. Each of the women had undergone an early second trimester prenatal screen, and her serum was analyzed for PFA concentrations. Data on infant and maternal variables were collected from the delivery record completed at birth. Adjusted changes in birth weight per natural log (ng/ml) of PFOA (median 1.5 ng/ml), PFHxS (median 0.97 ng/ml), and PFOS (median 7.8 ng/ml) were -37.4 g (95% confidence interval (CI): -86.0 to 11.2 g), 21.9 g (-23.4 to 67.2 g), and 31.3 g (-43.3 to 105.9 g), respectively. Mean birth weight z-score, standardized for gestational age and gender, length of gestation, and risk of preterm birth did not appear to be influenced by maternal PFA exposure. When PFA concentrations were divided into tertiles, similar patterns were observed. These results suggest that maternal PFA exposure has no substantial effect on fetal weight and length of gestation at the concentrations observed in this population.

  15. Inhibition of peroxisome proliferator-activated receptor γ: a potential link between chronic maternal hypoxia and impaired fetal growth

    PubMed Central

    Julian, Colleen G.; Yang, Ivana V.; Browne, Vaughn A.; Vargas, Enrique; Rodriguez, Carmelo; Pedersen, Brent S.; Moore, Lorna G.; Schwartz, David A.

    2014-01-01

    Chronic exposure to hypoxia raises the risk of pregnancy disorders characterized by maternal vascular dysfunction and diminished fetal growth. In an effort to identify novel pathways for these hypoxia-related effects, we assessed gene expression profiles of peripheral blood mononuclear cells (PBMCs) obtained from 43 female, high-altitude or sea-level residents in the nonpregnant state or during pregnancy (20 or 36 wk). Hypoxia-related fetal growth restriction becomes apparent between 25 and 29 wk of gestation and continues until delivery. Our sampling strategy was designed to capture changes occurring before (20 wk) and during (36 wk) the time frame of slowed fetal growth. PBMC gene expression profiles were generated using human gene expression microarrays and compared between altitudes. Biological pathways were identified using pathway analysis. Modest transcriptional differences were observed between altitudes in the nonpregnant state. Of the genes that were differentially expressed at high altitude vs. sea level during pregnancy (20 wk: 59 probes mapped to 41 genes; 36 wk: 985 probes mapped to 700 genes), several are of pathological relevance for fetal growth restriction. In particular, transcriptional changes were consistent with the negative regulation of peroxisome proliferator-activated receptor γ (PPARγ) at high altitude; such effects were accompanied by reduced birth weight (P <0.05) and head circumference (P <0.01) at high altitude vs. sea level. Our findings indicate that chronic exposure to hypoxia during pregnancy alters maternal gene expression patterns in general and, in particular, expression of key genes involved in metabolic homeostasis that have been proposed to play a role in the pathophysiology of fetal growth restriction.—Julian, C. G., Yang, I. V., Browne, V. A., Vargas, E., Rodriguez, C., Pedersen, B. S., Moore, L. G., Schwartz, D. A. Inhibition of peroxisome proliferator-activated receptor γ: a potential link between chronic maternal

  16. Fetal Growth and Neurodevelopmental Outcome in Congenital Heart Disease.

    PubMed

    Williams, Ismée A; Fifer, William P; Andrews, Howard

    2015-08-01

    We evaluated differences in growth between fetuses with and without congenital heart disease (CHD) and tested associations between growth and early childhood neurodevelopment (ND). In this prospective cohort study, fetuses with hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and tetralogy of Fallot (TOF) and controls had biparietal diameter (BPD), head (HC) and abdominal circumference (AC), femur length (FL), and estimated fetal weight (EFW) recorded serially during pregnancy at 18-26 weeks GA (F1), at 27-33 weeks GA (F2), and at 34-40 weeks GA (F3). CHD subjects underwent Bayley Scales of Infant Development-III ND testing at 18 months. Differences between CHD fetuses and controls were assessed using t tests and generalized linear modeling. Correlations between biometry and ND informed regression modeling. We enrolled 41 controls and 68 fetuses with CHD (N = 24 HLHS, N = 21 TGA, N = 23 TOF), 46 of whom had ND scores available. At 18-26 weeks, CHD fetuses were smaller than controls in all biometric parameters. Differences in growth rates were observed for HC, BPD, and AC, but not for FL or EFW. Cognitive score correlated with HC/AC at F2 (r = -0.33, P = 0.04) and mean HC/AC across gestation (r = -0.35, P = 0.03). Language correlated with FL/BPD at F2 (r = 0.34, P = 0.04). In stepwise linear regression, mean HC/AC predicted Cognition (B = -102, P = 0.026, R (2) = 0.13) and FL/BPD at F2 predicted Language score (B = 127, P = 0.03, R (2) = 0.12). Differences in growth between CHD fetuses and controls can be measured early in pregnancy. In CHD fetuses, larger abdominal relative to head circumference is associated with better 18-month neurodevelopment.

  17. Fetal Growth and Neurodevelopmental Outcome in Congenital Heart Disease

    PubMed Central

    Fifer, William P.; Andrews, Howard

    2017-01-01

    We evaluated differences in growth between fetuses with and without congenital heart disease (CHD) and tested associations between growth and early childhood neurodevelopment (ND). In this prospective cohort study, fetuses with hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and tetralogy of Fallot (TOF) and controls had biparietal diameter (BPD), head (HC) and abdominal circumference (AC), femur length (FL), and estimated fetal weight (EFW) recorded serially during pregnancy at 18and controls were assessed using–26 weeks GA (F1), at 27–33 weeks GA (F2), and at 34–40 weeks GA (F3). CHD subjects underwent Bayley Scales of Infant Development-III ND testing at 18 months. Differences between CHD fetuses and controls were assessed using t tests and generalized linear modeling. Correlations between biometry and ND informed regression modeling. We enrolled 41 controls and 68 fetuses with CHD (N = 24 HLHS, N = 21 TGA, N = 23 TOF), 46 of whom had ND scores available. At 18–26 weeks, CHD fetuses were smaller than controls in all biometric parameters. Differences in growth rates were observed for HC, BPD, and AC, but not for FL or EFW. Cognitive score correlated with HC/AC at F2 (r = −0.33, P = 0.04) and mean HC/AC across gestation (r = −0.35, P = 0.03). Language correlated with FL/BPD at F2 (r = 0.34, P = 0.04). In stepwise linear regression, mean HC/AC predicted Cognition (B = −102, P = 0.026, R2 = 0.13) and FL/BPD at F2 predicted Language score (B = 127, P = 0.03, R2 = 0.12). Differences in growth between CHD fetuses and controls can be measured early in pregnancy. In CHD fetuses, larger abdominal relative to head circumference is associated with better 18-month neurodevelopment. PMID:25753684

  18. Early- versus Late-Onset Fetal Growth Restriction Differentially Affects the Development of the Fetal Sheep Brain.

    PubMed

    Alves de Alencar Rocha, Anna Karynna; Allison, Beth J; Yawno, Tamara; Polglase, Graeme R; Sutherland, Amy E; Malhotra, Atul; Jenkin, Graham; Castillo-Melendez, Margie; Miller, Suzanne L

    2017-01-01

    Fetal growth restriction (FGR) is a common complication of pregnancy, principally caused by suboptimal placental function, and is associated with high rates of perinatal mortality and morbidity. Clinical studies suggest that the time of onset of placental insufficiency is an important contributor towards the neurodevelopmental impairments that are evident in children who had FGR. It is however currently unknown how early-onset and late-onset FGR differentially affect brain development. The aim of this study was to examine neuropathology in early-onset and late-onset FGR fetal sheep and to determine whether they differentially alter brain development. We induced placental insufficiency and FGR via single umbilical artery ligation at either 88 days (early-onset) or 105 days (late-onset) of fetal sheep gestation (term is approx. 147 days), reflecting a period of rapid white matter brain development. Fetal blood samples were collected for the first 10 days after surgery, and all fetuses were sacrificed at 125 days' gestation for brain collection and subsequent histopathology. Our results show that early-onset FGR fetuses became progressively hypoxic over the first 10 days after onset of placental insufficiency, whereas late-onset FGR fetuses were significantly hypoxic compared to controls from day 1 after onset of placental insufficiency (SaO2 46.7 ± 7.4 vs. 65.7 ± 3.9%, respectively, p = 0.03). Compared to control brains, early-onset FGR brains showed widespread white matter injury, with a reduction in both CNPase-positive and MBP-positive density of staining in the periventricular white matter (PVWM), subcortical white matter, intragyral white matter (IGWM), subventricular zone (SVZ), and external capsule (p < 0.05 for all). Total oligodendrocyte lineage cell counts (Olig-2-positive) did not differ across groups, but mature oligodendrocytes (MBP-positive) were reduced, and neuroinflammation was evident in early-onset FGR brains with reactive astrogliosis (GFAP

  19. Doppler-based fetal heart rate analysis markers for the detection of early intrauterine growth restriction.

    PubMed

    Stroux, Lisa; Redman, Christopher W; Georgieva, Antoniya; Payne, Stephen J; Clifford, Gari D

    2017-09-01

    One indicator for fetal risk of mortality is intra-uterine growth restriction (IUGR). Whether markers reflecting the impact of growth restriction on the cardiovascular system, computed from a Doppler-derived heart rate signal, would be suitable in its detection antenatally were studied MATERIAL AND METHODS: We used a cardiotocography archive of 1163 IUGR cases and 1163 healthy controls, matched for gestation and gender. We assessed the discriminative power of short-term variability (STV) and long-term variability (LTV) of the fetal heart rate, computed over episodes of high and low variation aiming to separate growth-restricted fetuses from controls. Metrics characterizing the sleep state distribution within a trace were also considered for inclusion into an IUGR detection model RESULTS: Significant differences in the risk markers comparing growth-restricted with healthy fetuses were found. When used in a logistic regression classifier, their performance for identifying IUGR was considerably superior before 34 weeks gestation. LTV in active sleep was superior to STV (AUROC of 72% compared to 71%). Most predictive was the number of minutes in high variation per hour (AUROC of 75%). A multivariate IUGR prediction model improved the AUROC to 76%. We suggest that heart rate variability markers together with surrogate information on sleep states can contribute to the detection of early-onset IUGR. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  20. Maternal left ventricular dimension in pregnancies complicated by fetal growth retardation.

    PubMed

    Veille, J C; Morton, M J; Paul, M S

    1991-08-01

    Previous studies using two-dimensional chest radiographs have found a significant correlation between prematurity, fetal growth retardation, and the size of the maternal heart. Accordingly, we evaluated maternal left ventricular size and function by M-mode echocardiography near the end of gestation in 42 women with suspected fetal growth retardation and in 79 women whose pregnancies were normal. No significant differences were found between the two groups, implying that maternal left ventricular size and function is adequate in pregnancies complicated by "idiopathic" fetal growth retardation.

  1. Effect of maternal asthma and gestational asthma therapy on fetal growth.

    PubMed

    Bakhireva, Ludmila N; Schatz, Michael; Chambers, Christina D

    2007-03-01

    Asthma is a common chronic condition that might seriously complicate pregnancy and fetal development. This article provides a comprehensive review of the existing literature regarding the effect on fetal growth of maternal asthma and common asthma medications used during pregnancy, including short-and long-acting beta (2)-agonists, inhaled and oral corticosteroids, chromones, leukotriene receptor agonists, and theophylline. Evaluated outcomes of fetal growth include low birth weight, mean birth weight, small for gestational age, birth length and head circumference, and measures of asymmetrical growth retardation. Methodological and practical considerations related to safety of asthma medications in pregnancy and management of gestational asthma are discussed.

  2. Maternal coffee intake and associated risk factors: effects on fetal growth and activity.

    PubMed

    Conde, Ana; Teves, Cláudia; Figueiredo, Bárbara

    2011-01-01

    Empirical studies have shown that fetal growth and activity can be affected by several risk factors, such as maternal anxiety, depression and tobacco or alcohol consumption. Caffeine intake has received less attention in the literature, as well as the analysis of the mutual interplay of the range of such risk factors. This study aimed to examine effects of mother's coffee intake and associated risk factors during early pregnancy on fetal growth and activity. The sample involved 47 fetuses (51.1% male and 48.9% female) with gestational ages between 20-22 weeks whose mothers were recruited in a Portuguese antenatal obstetric unit. Repeated measures of mother's anxiety (STAI-S) and depression (EPDS) and information about socio-demographics and substances consumption were collected during the first and second trimesters of pregnancy. Fetal activity and biometry were measured during the 2(nd) trimester ultrasound. Results showed that 1) 23.4% of the pregnant women (N = 11) had regular coffee intake; 2) no significant differences were found neither on fetal growth nor on fetal movements considering mother's coffee intake; 3) when mother's socio-demographics and substances consumption were considered, tobacco consumption and anxiety at the 2(nd) trimester appeared as significant predictors of fetal growth and mother's coffee intake and anxiety symptoms at the 2(nd) trimester emerged as significant predictors of fetal movements. An adverse impact of maternal coffee intake during pregnancy was found on fetal activity but not on fetal growth. A deeper understanding of the multiple pathways by which these risk factors affect fetal growth and activity is needed.

  3. THYROID HORMONE IS REQUIRED FOR GROWTH ADAPTATION TO PRESSURE LOAD IN THE OVINE FETAL HEART

    PubMed Central

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

    2012-01-01

    Thyroid hormone exerts broad effects on the adult heart, however little is known regarding the role of thyroid hormone on regulating 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 placement of a restrictive pulmonary artery band (PAB) was performed at 126 ± 1 d gestation (term 145 d). Four groups of animals (n = 5–6 in each group): 1) control; 2) fetal THX; 3) fetal PAB; and 4) fetal PAB + THX; were monitored for 1 week prior to being euthanized. 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 kg fetal weight, was significantly increased in PAB (6.27 ± 0.85 g/kg) compared to control animals (4.72 ± 0.12 g/kg). THX significantly attenuated the increase in cardiac mass associated with PAB (4.94 ± 0.13 g/kg) while THX alone had no detectable effect on heart mass (4.95 ± 0.27 g/kg). The percentage of binucleated cardiomyocytes was significantly decreased in THX and PAB +THX (~16%) compared to the non-THX groups (~27%). No differences in levels of activated Akt, ERK or JNK 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 physiologic and pathophysiologic states. Specifically, thyroid hormone is required for adaptive fetal cardiac growth in response to pressure overload. PMID:23104936

  4. 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.

  5. Sex differences in the fetal heart rate variability indices of twins.

    PubMed

    Tendais, Iva; Figueiredo, Bárbara; Gonçalves, Hernâni; Bernardes, João; Ayres-de-Campos, Diogo; Montenegro, Nuno

    2015-03-01

    To evaluate the differences in linear and complex heart rate dynamics in twin pairs according to fetal sex combination [male-female (MF), male-male (MM), and female-female (FF)]. Fourteen twin pairs (6 MF, 3 MM, and 5 FF) were monitored between 31 and 36.4 weeks of gestation. Twenty-six fetal heart rate (FHR) recordings of both twins were simultaneously acquired and analyzed with a system for computerized analysis of cardiotocograms. Linear and nonlinear FHR indices were calculated. Overall, MM twins presented higher intrapair average in linear indices than the other pairs, whereas FF twins showed higher sympathetic-vagal balance. MF twins exhibited higher intrapair average in entropy indices and MM twins presented lower entropy values than FF twins considering the (automatically selected) threshold rLu. MM twin pairs showed higher intrapair differences in linear heart rate indices than MF and FF twins, whereas FF twins exhibited lower intrapair differences in entropy indices. The results of this exploratory study suggest that twins have sex-specific differences in linear and nonlinear indices of FHR. MM twins expressed signs of a more active autonomic nervous system and MF twins showed the most active complexity control system. These results suggest that fetal sex combination should be taken into consideration when performing detailed evaluation of the FHR in twins.

  6. First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a non-human primate model.

    PubMed

    Lo, Jamie O; Schabel, Matthias C; Roberts, Victoria H J; Wang, Xiaojie; Lewandowski, Katherine S; Grant, Kathleen A; Frias, Antonio E; Kroenke, Christopher D

    2017-03-01

    throughout the placenta and reveal gradients in blood deoxyhemoglobin concentration that range from highly oxygenated blood (long T2*) proximal to spiral arteries to highly deoxygenated blood (short T2*). Distributions of T2*throughout the placenta show significant global reduction in T2* (and hence high blood deoxyhemoglobin concentration) in ethanol-exposed vs control animals at gestational day 110 (P=.02). Fetal brain measurements indicated impaired growth and development at gestational day 110, but less so at gestational day 135 in ethanol-exposed vs control animals. Chronic first-trimester ethanol exposure significantly reduces placental perfusion and oxygen supply to the fetal vasculature later in pregnancy. These perturbations of placental function are associated with fetal growth impairments. However, differences between ethanol-exposed and control animals in placental function and fetal developmental outcomes were smaller at gestational day 135 than at gestational day 110. These findings are consistent with placental adaptation to early perturbations that allow for compensated placental function and maintenance of fetal growth. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Leptin increases growth of primary ossification centers in fetal mice

    PubMed Central

    Bertoni, Laura; Ferretti, Marzia; Cavani, Francesco; Zavatti, Manuela; Resca, Elisa; Benelli, Augusta; Palumbo, Carla

    2009-01-01

    The effect of peripheral leptin on fetal primary ossification centers during the early phases of bone histogenesis was investigated by administration of leptin to pregnant mice. Fourteen pregnant mice were divided into two groups. The treated pregnant group was subcutaneously injected in the intrascapular region with supraphysiologic doses (2 mg kg−1) of leptin (Vinci Biochem, Firenze, Italy) in a volume of 0.1 mL per 10 g body weight, at the 7th, 9th and 11th day of gestation. The control group was treated with physiological solution in the same manner and same times as the treated group. The new-born mice were killed 1 day after birth and the primary ossification centers were stained with Alizarin Red S after diaphanizing the soft tissues in 1% potassium hydroxide. The development of both endochondral and intramembranous ossification centers was morphometrically analysed in long bones. The results showed that the ossification centers of mice born by mothers treated with leptin grow more rapidly in both length and cross-sectional area compared with mice born by the untreated mothers. As the development of long bones depends on endochondral ossification occurring at proximal and distal epiphyseal plates as well as on intramembranous ossification along the periosteal surface, it appears that leptin activates the differentiation and proliferation of both chondrocytes and osteoblasts. The role of leptin as a growth factor of cartilage and bone is discussed in the light of the data reported in the literature. PMID:19682137

  8. [Maternal serum IgA in intrauterine fetal growth retardation].

    PubMed

    Briese, V; Straube, W

    1983-01-01

    The problem was to prove the significance of IgA estimations in maternal serum samples with regard to the diagnosis and the monitoring of intrauterine fetal growth retardation. IgA was estimated in serum samples from two groups of patients. The first was formed from 62 serum samples of 14 primi- and multiparae delivered from new-borns with a birth weight below the 10th centile. The second was the control group. 82 serum samples from 18 gravidae were available. The IgA estimations were carried out by means of single radial immunodiffusion according to Mancini and co-workers. The IgA values of the two groups were different considering that linear regression model was used; negative correlation between IgA and pregnancy weeks in group with retarded new-borns (y = -151,78 X + 7579,8; r = -0,39) and positive correlation of these parameters in control group (y = 73,59 X -429,38; r = 0,26). It could be that IgA is an additional parameter within placental function tests of the 3rd trimester of pregnancy.

  9. Leptin increases growth of primary ossification centers in fetal mice.

    PubMed

    Bertoni, Laura; Ferretti, Marzia; Cavani, Francesco; Zavatti, Manuela; Resca, Elisa; Benelli, Augusta; Palumbo, Carla

    2009-11-01

    The effect of peripheral leptin on fetal primary ossification centers during the early phases of bone histogenesis was investigated by administration of leptin to pregnant mice. Fourteen pregnant mice were divided into two groups. The treated pregnant group was subcutaneously injected in the intrascapular region with supraphysiologic doses (2 mg kg(-1)) of leptin (Vinci Biochem, Firenze, Italy) in a volume of 0.1 mL per 10 g body weight, at the 7th, 9th and 11th day of gestation. The control group was treated with physiological solution in the same manner and same times as the treated group. The new-born mice were killed 1 day after birth and the primary ossification centers were stained with Alizarin Red S after diaphanizing the soft tissues in 1% potassium hydroxide. The development of both endochondral and intramembranous ossification centers was morphometrically analysed in long bones. The results showed that the ossification centers of mice born by mothers treated with leptin grow more rapidly in both length and cross-sectional area compared with mice born by the untreated mothers. As the development of long bones depends on endochondral ossification occurring at proximal and distal epiphyseal plates as well as on intramembranous ossification along the periosteal surface, it appears that leptin activates the differentiation and proliferation of both chondrocytes and osteoblasts. The role of leptin as a growth factor of cartilage and bone is discussed in the light of the data reported in the literature.

  10. [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.

  11. 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

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

    PubMed

    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

    2016-02-01

    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. 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. 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. 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. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Functional brain development in growth-restricted and constitutionally small fetuses: a fetal magnetoencephalography case-control study.

    PubMed

    Morin, E C; Schleger, F; Preissl, H; Braendle, J; Eswaran, H; Abele, H; Brucker, S; Kiefer-Schmidt, I

    2015-08-01

    Fetal magnetoencephalography records fetal brain activity non-invasively. Delayed brain responses were reported for fetuses weighing below the tenth percentile. To investigate whether this delay indicates delayed brain maturation resulting from placental insufficiency, this study distinguished two groups of fetuses below the tenth percentile: growth-restricted fetuses with abnormal umbilical artery Doppler velocity (IUGR) and constitutionally small-for-gestational-age fetuses with normal umbilical artery Doppler findings (SGA) were compared with fetuses of adequate weight for gestational age (AGA), matched for age and behavioural state. A case-control study of matched pairs. Fetal magnetoencephalography-Center at the University Hospital of Tuebingen. Fourteen IUGR fetuses and 23 SGA fetuses were matched for gestational age and fetal behavioural state with 37 healthy, normal-sized fetuses. A 156-channel fetal magentoencephalography system was used to record fetal brain activity. Light flashes as visual stimulation were applied to the fetus. The Student's t-test for paired groups was performed. Latency of fetal visual evoked magnetic responses (VER). The IUGR fetuses showed delayed VERs compared with controls (IUGR, 233.1 ms; controls, 184.6 ms; P = 0.032). SGA fetuses had similar evoked response latencies compared with controls (SGA, 216.1 ms; controls, 219.9 ms; P = 0.828). Behavioural states were similarly distributed. Visual evoked responses are delayed in IUGR fetuses, but not in SGA. Fetal behavioural state as an influencing factor of brain response latency was accounted for in the comparison. This reinforces that delayed brain maturation is the result of placental insufficiency. © 2015 Royal College of Obstetricians and Gynaecologists.

  14. Fetal growth from mid- to late pregnancy is associated with infant development: the Generation R Study.

    PubMed

    Henrichs, Jens; Schenk, Jacqueline J; Barendregt, Charlotte S; Schmidt, Henk G; Steegers, Eric Ap; Hofman, Albert; Jaddoe, Vincent W V; Moll, Henriette A; Verhulst, Frank C; Tiemeier, Henning

    2010-07-01

    The aim of this study was to investigate within a population-based cohort of 4384 infants (2182 males, 2202 females) whether fetal growth from early pregnancy onwards is related to infant development and whether this potential relationship is independent of postnatal growth. Ultrasound measurements were performed in early, mid-, and late pregnancy. Estimated fetal weight was calculated using head and abdominal circumference and femur length. Infant development was measured with the Minnesota Infant Development Inventory at 12 months (SD 1.1mo, range 10-17mo). Information on postnatal head size and body weight at 7 months was obtained from medical records. After adjusting for potential confounders and for postnatal growth, faster fetal weight gain from mid- to late pregnancy predicted a reduced risk of delayed social development (odds ratio [OR] 0.82; 95% confidence interval [CI] 0.71-0.95, p=0.008), self-help abilities (OR 0.84; 95% CI 0.73-0.98, p=0.023), and overall infant development (OR 0.65; 95% CI 0.49-0.87, p=0.003). Similar findings were observed for fetal head growth from mid- to late pregnancy. Faster fetal growth predicts a lower risk of delayed infant development independent of postnatal growth. These results suggest that reduced fetal growth between mid- and late pregnancy may determine subsequent developmental outcomes.

  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.

  16. Metabolomics Reveals Metabolic Alterations by Intrauterine Growth Restriction in the Fetal Rabbit Brain

    PubMed Central

    van Vliet, Erwin; Eixarch, Elisenda; Illa, Miriam; Arbat-Plana, Ariadna; González-Tendero, Anna; Hogberg, Helena T.; Zhao, Liang; Hartung, Thomas; Gratacos, Eduard

    2013-01-01

    Background Intrauterine Growth Restriction (IUGR) due to placental insufficiency occurs in 5–10% of pregnancies and is a major risk factor for abnormal neurodevelopment. The perinatal diagnosis of IUGR related abnormal neurodevelopment represents a major challenge in fetal medicine. The development of clinical biomarkers is considered a promising approach, but requires the identification of biochemical/molecular alterations by IUGR in the fetal brain. This targeted metabolomics study in a rabbit IUGR model aimed to obtain mechanistic insight into the effects of IUGR on the fetal brain and identify metabolite candidates for biomarker development. Methodology/Principal Findings At gestation day 25, IUGR was induced in two New Zealand rabbits by 40–50% uteroplacental vessel ligation in one horn and the contralateral horn was used as control. At day 30, fetuses were delivered by Cesarian section, weighed and brains collected for metabolomics analysis. Results showed that IUGR fetuses had a significantly lower birth and brain weight compared to controls. Metabolomics analysis using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) and database matching identified 78 metabolites. Comparison of metabolite intensities using a t-test demonstrated that 18 metabolites were significantly different between control and IUGR brain tissue, including neurotransmitters/peptides, amino acids, fatty acids, energy metabolism intermediates and oxidative stress metabolites. Principle component and hierarchical cluster analysis showed cluster formations that clearly separated control from IUGR brain tissue samples, revealing the potential to develop predictive biomarkers. Moreover birth weight and metabolite intensity correlations indicated that the extent of alterations was dependent on the severity of IUGR. Conclusions IUGR leads to metabolic alterations in the fetal rabbit brain, involving neuronal viability, energy metabolism, amino acid levels, fatty

  17. Can anomalies of fetal brain circulation be useful in the management of growth restricted fetuses?

    PubMed

    Hernandez-Andrade, Edgar; Serralde, Jesus Andres Benavides; Cruz-Martinez, Rogelio

    2012-02-01

    Assessment of the fetal cerebral circulation provides important information on the hemodynamic changes associated with chronic hypoxia and intrauterine growth restriction. Despite the incorporation of new US parameters, the landmark for the fetal brain hemodynamic evaluation is still the middle cerebral artery. However, new vascular territories, such as the anterior and posterior cerebral arteries, might provide additional information on the onset of the brain sparing effect. The fractional moving blood volume estimation and three-dimensional power Doppler ultrasound indices are new techniques that seem to be promising in identifying cases at earlier stages of vascular deterioration; still, they are not available for clinical application and more information is needed on the reproducibility and advantages of three-dimensional power Doppler ultrasound blood flow indices. In the past, the brain sparing effect was considered as a protective mechanism; however, recent information challenges this concept. There is growing evidence of an association between brain sparing effect and increased risk of abnormal neurodevelopment after birth. Even in mild late-onset intrauterine growth restriction affected fetuses with normal umbilical artery blood flow, increased cerebral blood perfusion can be associated with a substantial risk of abnormal neuroadaptation and neurodevelopment during childhood.

  18. The World Health Organization Fetal Growth Charts: A Multinational Longitudinal Study of Ultrasound Biometric Measurements and Estimated Fetal Weight

    PubMed Central

    Carroli, Guillermo; Widmer, Mariana; Neerup Jensen, Lisa; Giordano, Daniel; Abdel Aleem, Hany; Talegawkar, Sameera A.; Benachi, Alexandra; Diemert, Anke; Tshefu Kitoto, Antoinette; Thinkhamrop, Jadsada; Lumbiganon, Pisake; Tabor, Ann; Kriplani, Alka; Gonzalez Perez, Rogelio; Hecher, Kurt; Hanson, Mark A.; Gülmezoglu, A. Metin; Platt, Lawrence D.

    2017-01-01

    Background Perinatal mortality and morbidity continue to be major global health challenges strongly associated with prematurity and reduced fetal growth, an issue of further interest given the mounting evidence that fetal growth in general is linked to degrees of risk of common noncommunicable diseases in adulthood. Against this background, WHO made it a high priority to provide the present fetal growth charts for estimated fetal weight (EFW) and common ultrasound biometric measurements intended for worldwide use. Methods and Findings We conducted a multinational prospective observational longitudinal study of fetal growth in low-risk singleton pregnancies of women of high or middle socioeconomic status and without known environmental constraints on fetal growth. Centers in ten countries (Argentina, Brazil, Democratic Republic of the Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand) recruited participants who had reliable information on last menstrual period and gestational age confirmed by crown–rump length measured at 8–13 wk of gestation. Participants had anthropometric and nutritional assessments and seven scheduled ultrasound examinations during pregnancy. Fifty-two participants withdrew consent, and 1,387 participated in the study. At study entry, median maternal age was 28 y (interquartile range [IQR] 25–31), median height was 162 cm (IQR 157–168), median weight was 61 kg (IQR 55–68), 58% of the women were nulliparous, and median daily caloric intake was 1,840 cal (IQR 1,487–2,222). The median pregnancy duration was 39 wk (IQR 38–40) although there were significant differences between countries, the largest difference being 12 d (95% CI 8–16). The median birthweight was 3,300 g (IQR 2,980–3,615). There were differences in birthweight between countries, e.g., India had significantly smaller neonates than the other countries, even after adjusting for gestational age. Thirty-one women had a miscarriage, and three fetuses had

  19. The World Health Organization Fetal Growth Charts: A Multinational Longitudinal Study of Ultrasound Biometric Measurements and Estimated Fetal Weight.

    PubMed

    Kiserud, Torvid; Piaggio, Gilda; Carroli, Guillermo; Widmer, Mariana; Carvalho, José; Neerup Jensen, Lisa; Giordano, Daniel; Cecatti, José Guilherme; Abdel Aleem, Hany; Talegawkar, Sameera A; Benachi, Alexandra; Diemert, Anke; Tshefu Kitoto, Antoinette; Thinkhamrop, Jadsada; Lumbiganon, Pisake; Tabor, Ann; Kriplani, Alka; Gonzalez Perez, Rogelio; Hecher, Kurt; Hanson, Mark A; Gülmezoglu, A Metin; Platt, Lawrence D

    2017-01-01

    Perinatal mortality and morbidity continue to be major global health challenges strongly associated with prematurity and reduced fetal growth, an issue of further interest given the mounting evidence that fetal growth in general is linked to degrees of risk of common noncommunicable diseases in adulthood. Against this background, WHO made it a high priority to provide the present fetal growth charts for estimated fetal weight (EFW) and common ultrasound biometric measurements intended for worldwide use. We conducted a multinational prospective observational longitudinal study of fetal growth in low-risk singleton pregnancies of women of high or middle socioeconomic status and without known environmental constraints on fetal growth. Centers in ten countries (Argentina, Brazil, Democratic Republic of the Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand) recruited participants who had reliable information on last menstrual period and gestational age confirmed by crown-rump length measured at 8-13 wk of gestation. Participants had anthropometric and nutritional assessments and seven scheduled ultrasound examinations during pregnancy. Fifty-two participants withdrew consent, and 1,387 participated in the study. At study entry, median maternal age was 28 y (interquartile range [IQR] 25-31), median height was 162 cm (IQR 157-168), median weight was 61 kg (IQR 55-68), 58% of the women were nulliparous, and median daily caloric intake was 1,840 cal (IQR 1,487-2,222). The median pregnancy duration was 39 wk (IQR 38-40) although there were significant differences between countries, the largest difference being 12 d (95% CI 8-16). The median birthweight was 3,300 g (IQR 2,980-3,615). There were differences in birthweight between countries, e.g., India had significantly smaller neonates than the other countries, even after adjusting for gestational age. Thirty-one women had a miscarriage, and three fetuses had intrauterine death. The 8,203 sets of ultrasound

  20. Human chorionic gonadotropin (hCG) concentrations during the late first trimester are associated with fetal growth in a fetal sex-specific manner.

    PubMed

    Barjaktarovic, Mirjana; Korevaar, Tim I M; Jaddoe, Vincent W V; de Rijke, Yolanda B; Visser, Theo J; Peeters, Robin P; Steegers, Eric A P

    2017-02-01

    Human chorionic gonadotropin (hCG) is a pregnancy-specific hormone that regulates placental development. hCG concentrations vary widely throughout gestation and differ based on fetal sex. Abnormal hCG concentrations are associated with adverse pregnancy outcomes including fetal growth restriction. We studied the association of hCG concentrations with fetal growth and birth weight. In addition, we investigated effect modification by gestational age of hCG measurement and fetal sex. Total serum hCG (median 14.4 weeks, 95 % range 10.1-26.2), estimated fetal weight (measured by ultrasound during 18-25th weeks and >25th weeks) and birth weight were measured in 7987 mother-child pairs from the Generation R cohort and used to establish fetal growth. Small for gestational age (SGA) was defined as a standardized birth weight lower than the 10th percentile of the study population. There was a non-linear association of hCG with birth weight (P = 0.009). However, only low hCG concentrations measured during the late first trimester (11th and 12th week) were associated with birth weight and SGA. Low hCG concentrations measured in the late first trimester were also associated with decreased fetal growth (P = 0.0002). This was the case for both male and female fetuses. In contrast, high hCG concentrations during the late first trimester were associated with increased fetal growth amongst female, but not male fetuses. Low hCG in the late first trimester is associated with lower birth weight due to a decrease in fetal growth. Fetal sex differences exist in the association of hCG concentrations with fetal growth.

  1. Fractional fetal thigh volume in the prediction of normal and abnormal fetal growth during the third trimester of pregnancy.

    PubMed

    Simcox, Louise E; Myers, Jenny E; Cole, Tim J; Johnstone, Edward D

    2017-10-01

    Currently, 2-dimensional ultrasound estimation of fetal size rather than fetal growth is used to define fetal growth restriction, but single estimates in late pregnancy lack sensitivity and may identify small for gestational age rather than growth restriction. Single or longitudinal measures of 3-dimensional fractional thigh volume may address this problem. We sought to derive normal values for 3-dimensional fractional thigh volume in the third trimester, determine if fractional thigh volume is superior to 2-dimensional ultrasound biometry alone for detecting fetal growth restriction, and determine whether individualized growth assessment parameters have the potential to identify fetal growth restriction remote from term delivery. This was a longitudinal prospective cohort study of 115 unselected pregnancies in a tertiary referral unit (St Mary's Hospital, Manchester, United Kingdom). Standard 2-dimensional ultrasound biometry measurements were obtained, along with fractional thigh volume measurements (based on 50% of the femoral diaphysis length). Measurements were used to calculate estimated fetal weight (Hadlock). Individualized growth assessment parameters and percentage deviations in longitudinally measured biometrics were determined using a Web-based system (iGAP; http://iGAP. bcm.edu). Small for gestational age was defined <10th and fetal growth restriction <3rd customized birthweight centile. Logistic regression was used to compare estimated fetal weight (Hadlock), estimated fetal weight (biparietal diameter-abdominal circumference-fractional thigh volume), fractional thigh volume, and abdominal circumference for the prediction of small for gestational age or fetal growth restriction at birth. Screening performance was assessed using area under the receiver operating characteristic curve. There was a better correlation between fractional thigh volume and estimated fetal weight ((biparietal diameter-abdominal circumference-fractional thigh volume) obtained

  2. The role of blood flow distribution in the regulation of cerebral oxygen availability in fetal growth restriction.

    PubMed

    Luria, Oded; Bar, Jacob; Kovo, Michal; Malinger, Gustavo; Golan, Abraham; Barnea, Ofer

    2012-04-01

    Fetal growth restriction (FGR) elicits hemodynamic compensatory mechanisms in the fetal circulation. These mechanisms are complex and their effect on the cerebral oxygen availability is not fully understood. To quantify the contribution of each compensatory mechanism to the fetal cerebral oxygen availability, a mathematical model of the fetal circulation was developed. The model was based on cardiac-output distribution in the fetal circulation. The compensatory mechanisms of FGR were simulated and their effects on cerebral oxygen availability were analyzed. The mathematical analysis included the effects of cerebral vasodilation, placental resistance to blood flow, degree of blood shunting by the ductus venosus and the effect of maternal-originated placental insufficiency. The model indicated a unimodal dependency between placental blood flow and cerebral oxygen availability. Optimal cerebral oxygen availability was achieved when the placental blood flow was mildly reduced compared to the normal flow. This optimal ratio was found to increase as the hypoxic state of FGR worsens. The model indicated that cerebral oxygen availability is increasingly dependent on the cardiac output distribution as the fetus gains weight. Copyright © 2011 IPEM. Published by Elsevier Ltd. All rights reserved.

  3. [Immigration: indicators or growth and nutrition].

    PubMed

    de Aranzabal Agudo, M

    2003-03-01

    In the last few years, many immigrant and adopted children from poor countries have come to live in Spain and the number is increasing. In this article we indicate which standard references can help pediatricians to determine the nutritional status and growth of these children whose social, personal and familial histories are different from our own and sometimes unknown. In these cases application of the standard national growth charts of the receiving country is recommended.

  4. Fundal Height: An Accurate Indicator of Fetal Growth?

    MedlinePlus

    ... generally defined as the distance from the pubic bone to the top of the uterus measured in centimeters. After 20 weeks of pregnancy, your fundal height measurement often matches the number of weeks you've ...

  5. Effects of a restricted fetal growth environment on human kidney morphology, cell apoptosis and gene expression.

    PubMed

    Wang, Yan-Ping; Chen, Xu; Zhang, Zhi-Kun; Cui, Hong-Yan; Wang, Peng; Wang, Yue

    2015-12-01

    Kidney development is key to the onset of hypertension and cardiovascular diseases in adults, and in the fetal stage will be impaired by a lack of nutrients in utero in animal models. However, few human studies have been performed. Kidney samples from fetuses in a fetal growth restriction (FGR) environment were collected and the morphological characteristics were observed. Potentially molecular mechanisms were explored by analyzing apoptosis and kidney-development related gene expression. The results indicated that no malformations were observed in the kidney samples of the FGR group, but the mean kidney weight and volume were significantly decreased. Moreover, the ratio of apoptotic cells and Bax-positive cells was increased and the ratio of Bcl-2-positive cells was decreased in the FGR group, indicating potential apoptosis induction under an in utero FGR environment. Finally, aberrant expression of renin and angiotensinogen indicated potential kidney functional abnormalities in the FGR group. Our study suggested increased apoptosis and decreased renin and angiotensinogen expression during human kidney development in an FGR environment. The current results will be helpful to further explore the molecular mechanism of FGR and facilitate future studies of hypertension and cardiovascular diseases and the establishment of preventive methods. © The Author(s) 2014.

  6. IGF2 stimulates fetal growth in a sex and organ dependent manner.

    PubMed

    White, Veronica; Jawerbaum, Alicia; Mazzucco, Maria Belen; Gauster, Martin; Desoye, Gernot; Hiden, Ursula

    2017-09-14

    IGF2 is a key determinant of fetal growth, and altered expression of IGF2 is implicated in fetal growth disorders and maternal metabolic derangements including gestational diabetes. Here we studied how increased levels of IGF2 in late pregnancy affect fetal growth. We employed a rat model of repeated intra-fetal IGF2 administration in late pregnancy, i.e. during GD19-GD21, and measured the consequences on fetal organ weight and expression of insulin/IGF-axis components. IGF2 treatment tended to increase fetal weight, but only weight increase of fetal stomach reached significance (+33±9%; P<0.01). Sex dependent data analysis revealed a sexual dimorphism of IGF2 action: In male fetuses, IGF2 administration significantly increased fetal weight (+13±3%; P<0.05) and weight of fetal stomach (+42±10%; P<0.01), intestine (+26±5%; P<0.05), liver (+13±4%; P<0.05) and pancreas (+25±8%; P<0.05). Weights of heart, lungs and kidneys were unchanged. In female fetuses, IGF2 increased only stomach weight (+26±9%; P<0.05). Furthermore, gene expression of insulin/IGF-axis in heart, lungs, liver and stomach was more sensitive towards IGF2 treatment in male than in female fetuses. Data suggest that elevated circulating IGF2 in late pregnancy predominantly stimulates organ growth of the digestive system, and male fetuses are more susceptible towards the IGF2 effects than female fetuses.Pediatric Research accepted article preview online, 14 September 2017. doi:10.1038/pr.2017.221.

  7. Comparison of Fetal and Neonatal Growth Curves in Detecting Growth Restriction

    PubMed Central

    Marconi, Anna Maria; Ronzoni, Stefania; Bozzetti, Patrizia; Vailati, Simona; Morabito, Alberto; Battaglia, Frederick C

    2009-01-01

    Objective To evaluate the outcome of intrauterine growth restriction (IUGR) infants with abnormal pulsatility index of the umbilical artery according to the neonatal birth weight/gestational age standards and the intrauterine growth charts. Methods We analyzed 53 pregnancies with severe IUGR classified as Group 2 (22 IUGR: abnormal pulsatility index and normal fetal heart rate) and Group 3 (31 IUGR: abnormal pulsatility index and fetal heart rate). Neonatal birth weight/gestational age distribution, body size measurements, maternal characteristics and obstetric outcome, and neonatal major and minor morbidity and mortality were compared with those obtained in 79 singleton pregnancies with normal fetal growth and pulsatility index, matched for gestational age [appropriate for gestational age (AGA) group]. Differences were analyzed with the χ2 test and the Student’s t test. Differences between means corrected for gestational age in the different groups were assessed by analysis of covariance test. A P value <0.05 was considered significant. Results At delivery, utilizing the neonatal standards, 25/53 (47%) IUGR showed a birthweight above the 10th percentile (IUGRAGA) whereas in 28, birthweight was below the 10th percentile (IUGRSGA). All body size measurements were significantly higher in AGA than in IUGRAGA and IUGRSGA. Forty-nine out of 79 (62%) AGA and 49/53 (92%) IUGR were admitted in the neonatal intensive care unit (p<0.001). One out of 79 (1%) AGA and 6/53 (11%) IUGR newborns died within 28 days (p<0.02). Major and minor morbidity was not different. Conclusion This study shows that neonatal outcome is similar in IUGR of the same clinical severity, whether or not they could be defined AGA or SGA according to the neonatal standards. Neonatal curves are misleading in detecting low birthweight infants and should be utilized only when obstetrical data are unavailable. PMID:19037030

  8. Phenotypic and molecular characterization of intrauterine fetal growth restriction in interspecies sheep pregnancy.

    PubMed

    Chávez-García, A; Vázquez-Martínez, E R; Murcia, C; Rodríguez, A; Cerbón, M; Mejía, O

    2015-10-01

    Interspecies pregnancies between closely related species are usually performed in livestock to obtain improved and enriched offspring. Indeed, different hybrids have been obtained for research purposes since many years ago, and the maternal-fetal interactions have been studied as a possible strategy for species preservation. The aim of this study was to characterize by physiological and molecular approaches the interspecies pregnancy between bighorn sheep () and domestic sheep (). Hybrids were obtained by artificial insemination; the blood pressure and protein urine levels were measured during the last two-thirds of gestation. After parturition, offspring and placentas were weighed and measured and cotyledons were counted and weighed and their surface area determined. Plasma samples were obtained between wk 8 and 21 of gestation to assess progesterone (P4), vascular endothelial growth factor (VEGF), and placental growth factor (PlGF) levels and cell-free RNA was isolated during the same period to assess hypoxia-inducible factor-1 α (α) gene expression. Hybrid and normal pregnancies were analyzed using physiological and molecular parameters during the last two-thirds of gestation (wk 8-21). The results show that during the measurement period, ewes with a hybrid pregnancy presented normal blood pressure and no alteration in urinary protein content. However, compared with sheep with a normal pregnancy, those with a hybrid pregnancy had a decrease in fetal and placental growth as well as in the cotyledonary surface area. Furthermore, in the hybrid group, there was placental insufficiency, characterized by a decrease in P4 production, as well as indications of endothelial dysfunction, characterized an increase in plasma levels of VEGF and PlGF as well as in plasma gene expression of α. Overall, the results indicate that hybrids of and presented intrauterine growth restriction, essentially due to altered endothelial function and chronic placental insufficiency

  9. Perfluoroalkyl and polyfluoroalkyl substances and human fetal growth: a systematic review.

    PubMed

    Bach, Cathrine Carlsen; Bech, Bodil Hammer; Brix, Nis; Nohr, Ellen Aagaard; Bonde, Jens Peter Ellekilde; Henriksen, Tine Brink

    2015-01-01

    Exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) is ubiquitous in most regions of the world. The most commonly studied PFASs are perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). Animal studies indicate that maternal PFAS exposure is associated with reduced fetal growth. However, the results of human studies are inconsistent. To summarize the evidence of an association between exposure to PFASs, particularly PFOS and PFOA, and human fetal growth. Systematic literature searches were performed in MEDLINE and EMBASE. We included original studies on pregnant women with measurements of PFOA or PFOS in maternal blood during pregnancy or the umbilical cord and associations with birth weight or related outcomes according to the PFAS level. Citations and references from the included articles were investigated to locate more relevant articles. Study characteristics and results were extracted to structured tables. The completeness of reporting as well as the risk of bias and confounding were assessed. Fourteen studies were eligible. In utero PFOA exposure was associated with decreased measures of continuous birth weight in all studies, even though the magnitude of the association differed and many results were statistically insignificant. PFOS exposure and birth weight were associated in some studies, while others found no association. Higher PFOS and PFOA concentrations were associated with decreased average birth weight in most studies, but only some results were statistically significant. The impact on public health is unclear, but the global exposure to PFASs warrants further investigation.

  10. Association between small for gestational age and intrauterine fetal death: comparing a customized South Korean growth standard versus a population-based fetal growth chart.

    PubMed

    Moon, Myoungjin; Baek, Min Jung; Ahn, Eunhee; Odibo, Anthony O

    2016-03-01

    To determine if a customized growth standard developed for an ethnically homogeneous South Korean population is better at identifying (SGA) fetuses at risk for intra-uterine fetal death (IUFD), compared with a current population based-growth standard. A retrospective cohort study comparing the identification of SGA fetuses at risk for IUFD using a customized versus a population based-chart. The association between a SGA infant defined as a birth weight <10th percentile using the South Korean population chart versus the customized chart and IUFD were compared. Intrauterine fetal death was defined as fetal demise occurring after 20 weeks gestation. Statistical analyses including OR, 95% confidence interval (CI), and screening accuracy using each chart were performed. The customized singleton chart identified 11 (8.2%) of the SGA pregnancies detected by the population chart and classified 15 additional fetuses as SGA. Those identified as SGA using the customized chart had an OR for IUFD that was approximately 15 times as high as those identified using the population chart. The customized chart also showed a higher sensitivity and specificity for identifying SGA pregnancies at risk for IUFD. In this ethnically homogenous population, the customized growth chart showed improved discrimination in identifying SGA pregnancies at risk for fetal death than the population-based growth chart.

  11. Fetal growth restriction and cardiovascular outcome in early human infancy: a prospective longitudinal study.

    PubMed

    Mäkikallio, Kaarin; Shah, Jyotsna; Slorach, Cameron; Qin, Hong; Kingdom, John; Keating, Sarah; Kelly, Ed; Manlhiot, Cedric; Redington, Andrew; Jaeggi, Edgar

    2016-09-01

    The association between low birth weight and premature cardiovascular disease has led to the "prenatal origin of adult disease-hypothesis". We postulated that fetal growth restriction is associated with cardiovascular changes detectable at birth and in early infancy. Fifty-two appropriately grown fetuses (AGA) and 60 growth-restricted fetuses (FGR) with (n = 20) or without (n = 40) absent or reversed end-diastolic umbilical artery blood flow were prospectively examined by echocardiography before birth, at 1 week and 6 months of life. The impact of growth restriction on postnatal blood pressure, heart rate, cardiovascular dimensions, and function, as well as on vascular morphology of umbilical cord vessels was studied. FGR fetuses displayed significant blood flow redistribution and were delivered earlier with lower birth weights than AGA fetuses. After adjustment for gender, gestational age, and weight at birth, there were no intergroup differences in blood pressure, heart rate, left ventricular morphology, mass, and performance, and in cord vessel morphology. During the first 6 months of life brachioradial pulse wave velocity increased more in FGR fetuses, while other parameters describing vascular stiffness remained comparable between the groups. Fetal growth restriction had no detectable adverse impact on cardiovascular dimensions and function at birth. Cardiovascular findings also remained comparable during the first 6 months of life between the groups except a higher increase in brachioradial pulse wave velocity in the FGR group. Our observations suggest that abnormalities that link reduced intrauterine growth with premature cardiovascular diseases may commence later in childhood, indicating a potential window for screening and prevention.

  12. [Systemic production of cytokines and growth factors in various forms of syndrome of delayed fetal growth].

    PubMed

    Makarenko, M V

    2014-11-01

    The syndrome of delayed fetal growth (SDFG) is one of the most wide-spread pathological conditions while course of pregnancy; it is characterized by disorder of the feto-placental system function. Its incidence is from 3 to 8%. The studying of peculiarities of the system and local immune disorders, coinciding with SDFG, would permit to establish the immune mechanisms of its formation. Revealing of immunoregulation disorders on systemic and local levels would promote the creation of a concept, depicting participation of the immune system in formation of asymmetrical and symmetrical forms of SDFG, to elaborate new approaches for prognosis and diagnosis.

  13. Local tissue growth patterns underlying normal fetal human brain gyrification quantified in utero

    PubMed Central

    Rajagopalan, Vidya; Scott, Julia; Habas, Piotr A.; Kim, Kio; Corbett-Detig, James; Rousseau, Francois; Barkovich, A. James; Glenn, Orit A.; Studholme, Colin

    2011-01-01

    Existing knowledge of growth patterns in the living fetal human brain is based upon in utero imaging studies by MRI and ultrasound, which describe overall growth and provided mainly qualitative findings. However, formation of the complex folded cortical structure of the adult brain requires, in part, differential rates of regional tissue growth. To better understand these local tissue growth patterns, we applied recent advances in fetal MRI motion correction and computational image analysis techniques to 40 normal fetal human brains covering a period of primary sulcal formation (20-28 gestational weeks). Growth patterns were mapped by quantifying tissue locations that were expanding more or less quickly than the overall cerebral growth rate, which reveal increasing structural complexity. We detected increased local relative growth rates in the formation of the pre- and post-central gyri, right superior temporal gyrus and opercula, which differentiated between the constant growth rate in underlying cerebral mantle and the accelerating rate in the cortical plate undergoing folding. Analysis focused on the cortical plate revealed greater volume increases in parietal and occipital regions compared to the frontal lobe. Cortical plate growth patterns constrained to narrower age ranges showed that gyrification, reflected by greater growth rates, was more pronounced after 24 gestational weeks. Local hemispheric volume asymmetry was located in the posterior peri-Sylvian area associated with structural lateralization in the mature brain. These maps of fetal brain growth patterns construct a spatially specific baseline of developmental biomarkers with which to correlate abnormal development in the human. PMID:21414909

  14. Proline metabolism in the conceptus: implications for fetal growth and development.

    PubMed

    Wu, G; Bazer, F W; Datta, S; Johnson, G A; Li, P; Satterfield, M C; Spencer, T E

    2008-11-01

    Although there are published studies of proline biochemistry and nutrition in cultured cells and postnatal animals, little is known about proline metabolism and function in the conceptus (embryo/fetus, associated placental membranes, and fetal fluids). Because of the invasive nature of biochemical research on placental and fetal growth, animal models are often used to test hypotheses of biological importance. Recent evidence from studies with pigs and sheep shows that proline is a major substrate for polyamine synthesis via proline oxidase, ornithine aminotransferase, and ornithine decarboxylase in placentae. Both porcine and ovine placentae have a high capacity for proline catabolism and polyamine production. In addition, allantoic and amniotic fluids contain enzymes to convert proline into ornithine, which is delivered through the circulation to placental tissues. There is exquisite metabolic coordination among integrated pathways that support highest rates of polyamine synthesis and concentrations in placentae during early gestation when placental growth is most rapid. Interestingly, reduced placental and fetal growth are associated with reductions in placental proline transport, proline oxidase activity, and concentrations of polyamines in gestating dams with either naturally occurring or malnutrition-induced growth retardation. Conversely, increasing proline availability in maternal plasma through nutritional or pharmacological modulation in pigs and sheep enhances concentrations of proline and polyamines in placentae and fetal fluids, as well as fetal growth. These novel findings suggest an important role for proline in conceptus metabolism, growth and development, as well as a potential treatment for intrauterine growth restriction, which is a significant problem in both human medicine and animal agriculture.

  15. Placental mTOR links maternal nutrient availability to fetal growth.

    PubMed

    Roos, Sara; Powell, Theresa L; Jansson, Thomas

    2009-02-01

    The mTOR (mammalian target of rapamycin) signalling pathway functions as a nutrient sensor, both in individual cells and, more globally, in organs such as the fat body in Drosophila and the hypothalamus in the rat. The activity of placental amino acid transporters is decreased in IUGR (intrauterine growth restriction), and recent experimental evidence suggests that these changes contribute directly to the restricted fetal growth. We have shown that mTOR regulates the activity of the placental L-type amino acid transporter system and that placental mTOR activity is decreased in IUGR. The present review summarizes the emerging evidence implicating placental mTOR signalling as a key mechanism linking maternal nutrient and growth factor concentrations to amino acid transport in the human placenta. Since fetal growth is critically dependent on placental nutrient transport, placental mTOR signalling plays an important role in the regulation of fetal growth.

  16. Development of quantitative Doppler indices for uteroplacental and fetal blood flow during the third trimester.

    PubMed

    Joern, H; Funk, A; Goetz, M; Kuehlwein, H; Klein, A; Fendel, H

    1996-01-01

    The aim of our study was to describe the development of uteroplacental and fetal blood flow during the third trimester. Doppler examination was carried out on 393 uncomplicated pregnancies with uncomplicated term delivery. Using a pulsed color Doppler, we calculated the maximum systolic, mean and maximum end-diastolic velocity after correcting the angle of insonation. Patients under tocolysis or other medication influencing blood flow parameters were excluded from this cross-sectional study. Summarizing the results gained by Doppler ultrasound investigation of the uteroplacental and fetal blood vessels, we created quantiles as quantitative Doppler indices for the maximum systolic, mean (TAMX = time averaged maximum velocity) and maximum end-diastolic velocity. The following conclusions could be drawn: (1) resistance to the blood flow in the maternal portion of the placenta does not change during the third trimester; (2) resistance to the blood flow on the fetal side of the placenta decreases up to week 42 of gestation; (3) cerebral vascular resistance decreases constantly up to gestational week 42; and (4) vascular resistance to the blood flow of the kidney decreases only slightly during the third trimester. This study offers clinically important values for quantitative Doppler flow velocimetry for the first time. We hope that our findings improve the usefulness of Doppler ultrasound as a diagnostic tool in obstetrical management.

  17. Maternal Nutrient Restriction in Guinea Pigs as an Animal Model for Inducing Fetal Growth Restriction.

    PubMed

    Elias, Alexander A; Ghaly, Andrew; Matushewski, Brad; Regnault, Timothy R H; Richardson, Bryan S

    2016-02-01

    We determined the impact of moderate maternal nutrient restriction (MNR) in guinea pigs on pregnancy outcomes, maternal/fetal growth parameters, and blood analytes to further characterize the utility of this model for inducing fetal growth restriction (FGR). Thirty guinea pig sows were fed ad libitum (Control) or 70% of the control diet prepregnant switching to 90% at midpregnancy (MNR). Animals were necropsied near term with weights obtained on all sows, fetuses, and placenta. Fetal blood sampling and organ dissection were undertaken in appropriate for gestational age (AGA) fetuses from Control litters and FGR fetuses from MNR litters using > or < 80 g which approximated the 10th percentile for the population weight distribution of the Control fetuses. MNR fetal demise rates (1/43) were extremely low in contrast to that seen with uterine artery ligation/ablation models, albeit with increased preterm delivery in MNR sows (3 of 15). We confirm that MNR fetuses are smaller and have increased placental/fetal weight ratios as often seen in human FGR infants. We provide justification for using a fetal weight threshold for categorizing AGA Control and FGR-MNR cohorts reducing population variance, and show that FGR-MNR fetuses have asymmetrical organ growth, and are polycythemic and hypoglycemic which are also well associated with moderate FGR in humans. These findings further support the utility of moderate MNR in guinea pigs for inducing FGR with many similarities to that in humans with moderate growth restriction whether resulting from maternal undernourishment or placental insufficiency.

  18. Maternal snoring during pregnancy is not associated with fetal growth restriction.

    PubMed

    Tauman, Riva; Sivan, Yakov; Katsav, Shlomit; Greenfeld, Michal; Many, Ariel

    2012-08-01

    A small number of studies have, thus far, evaluated the association between maternal snoring and fetal growth revealing conflicting results. No study has compared fetal growth between women with habitual snoring who snored before pregnancy and women with habitual snoring that started to snore during pregnancy. To examine the effect of maternal snoring on fetal outcome and to investigate the differences between "chronic snorers" and "new-onset snorers". Women of singleton, uncomplicated, full-term pregnancies completed a questionnaire. Obstetric and labor records were reviewed. Newborn records were reviewed for gestational age, birth weight, Apgar score and gender. 246 low risk women were studied. Mean BMI at the beginning of pregnancy was 22.3 ± 3.5 kg/m(2). 32% reported habitual snoring. Of those, 26% were chronic snorers and 74% were new-onset snorers. Neither significant difference in fetal growth was found between snorers and non-snorers nor between chronic snorers and new-onset snorers. Increased rate of nulliparous women was found in new-onset snorers compared with both chronic snorers and non-snorers (54 vs. 25 and 29% respectively; p = 0.001). In pregnant women with no apparent risk factors, maternal snoring does not affect fetal growth. No differences in maternal characteristics or fetal outcome were found between chronic snorers and new-onset snorers.

  19. Fetal growth and postnatal growth failure in very-low-birthweight infants.

    PubMed

    Marks, Kyla-Anna; Reichman, Brian; Lusky, Ayala; Zmora, Ehud

    2006-02-01

    To determine in a cohort of very-low-birthweight (VLBW) infants the incidence of postnatal growth failure and the influence of intrauterine growth and neonatal morbidities on the risk for severe postnatal growth failure (PNGF). The study was based on analysis of data from the Israel Neonatal Network database on VLBW infants born between 1995 and 2001. Z-score was determined for weight at birth and discharge, and severe PNGF was defined as a decline in z-score of greater than 2. Univariate analysis and multi-linear regression determined the effect of fetal growth and neonatal morbidities on the risk for severe PNGF. Severe PNGF occurred in 10.6% of the cohort. The mean+/-SD birthweight (BW) z-score was -0.59+/-0.74, decreasing to -1.67+/-0.77 at discharge. The incidence of severe PNGF increased significantly with decreasing BW and gestational age. Each 1-unit increase in z-score BW was associated with a 2.37-fold increased risk for severe PNGF. Severe respiratory distress syndrome, patent ductus arteriosus, sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia were associated with severe PNGF. Severe PNGF among VLBW infants was markedly influenced by intrauterine growth as well as major morbidities. In the assessment of postnatal growth among VLBW infants, growth status at birth should be considered.

  20. An evaluation of fetal glucogenesis in intrauterine growth-retarded pregnancies.

    PubMed

    Marconi, A M; Cetin, I; Davoli, E; Baggiani, A M; Fanelli, R; Fennessey, P V; Battaglia, F C; Pardi, G

    1993-07-01

    The presence of fetal glucogenesis was evaluated in nine patients with pregnancies complicated by intrauterine growth retardation (IUGR) at the time of fetal blood sampling (FBS) between 29 and 35 weeks of pregnancy. Eight were singleton pregnancies and one was a twin pregnancy in which blood samples were obtained from both twins. A maternal primed-constant infusion of D(U-13C]glucose was performed, and the presence of fetal glucogenesis was assessed by a comparison of steady-state maternal and fetal glucose enrichments. No significant difference was present between maternal and fetal molar percent excess ([MPE] P = .97), and the mean fetal to maternal (F/M) MPE ratio (0.99 +/- 0.01) was not significantly different from 1 (P = .76). F/M MPE ratio was independent of the time of FBS and umbilical venous glucose and lactate concentrations. Thus fetal glucogenesis is not demonstrable in a group of fairly severe growth-retarded fetuses after an overnight fast with this relatively noninvasive approach.

  1. Placental pulsatility index: a new, more sensitive parameter for predicting adverse outcome in pregnancies suspected of fetal growth restriction.

    PubMed

    Gudmundsson, Saemundur; Flo, Kari; Ghosh, Gisela; Wilsgaard, Tom; Acharya, Ganesh

    2017-02-01

    The pulsatility indices of the umbilical and uterine arteries are used as the surrogate measures of utero-placental perfusion. Combining the two might simplify the evaluation of total placental vascular impedance, possibly improve prediction of adverse outcomes, and help identify pregnancies with suspected fetal growth restriction that need more intense surveillance. Umbilical and uterine blood flow velocities were recorded using pulsed-wave Doppler in a longitudinal study of 53 low-risk pregnancies (248 observations) during 20-40 weeks of gestation. Pulsatility indices was calculated for each of these vessels. A new placental pulsatility index was constructed as: (umbilical artery pulsatility index + mean of the left and right uterine artery pulsatility indices)/2, and mean +2 SD defined as abnormal. Gestational age-specific reference percentiles were calculated for the second half of pregnancy and related to values obtained from 340 pregnancies with suspected intra-uterine growth restriction to test its ability to predict adverse pregnancy outcome. The placental pulsatility index was closely associated with gestational age and decreased with advancing gestation in normal pregnancy. The placental pulsatility index had a higher sensitivity and comparable specificity in predicting adverse outcome in pregnancies suspected of intra-uterine fetal growth restriction when compared with conventional umbilical and uterine artery pulsatility indices. The new placental pulsatility index, reflecting placental vascular impedance on both the fetal and maternal side of placenta, improves prediction of adverse outcome in pregnancies suspected of intra-uterine fetal growth restriction. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

  2. A uniform management approach to optimize outcome in fetal growth restriction.

    PubMed

    Seravalli, Viola; Baschat, Ahmet A

    2015-06-01

    A uniform approach to the diagnosis and management of fetal growth restriction (FGR) consistently produces better outcome, prevention of unanticipated stillbirth, and appropriate timing of delivery. Early-onset and late-onset FGR represent two distinct clinical phenotypes of placental dysfunction. Management challenges in early-onset FGR revolve around prematurity and coexisting maternal hypertensive disease, whereas in late-onset disease failure of diagnosis or surveillance leading to unanticipated stillbirth is the primary issue. Identifying the surveillance tests that have the highest predictive accuracy for fetal acidemia and establishing the appropriate monitoring interval to detect fetal deterioration is a high priority. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Expectant management of severe preterm preeclampsia: is intrauterine growth restriction an indication for immediate delivery?

    PubMed

    Chammas, M F; Nguyen, T M; Li, M A; Nuwayhid, B S; Castro, L C

    2000-10-01

    Expectant management of severe preterm preeclampsia is gaining widespread acceptance in clinical practice. The objective of our study was 2-fold-to determine the frequency of fetal deterioration with expectant management of severe preterm preeclampsia and to evaluate whether the presence of intrauterine growth restriction on admission is associated with a shorter admission-to-delivery interval or more deliveries resulting from nonreassuring fetal status in comparison with pregnancies with preeclampsia but without intrauterine growth restriction. This was an observational study of women with singleton pregnancies at <34 completed weeks' gestation who were admitted to the hospital with the diagnosis of severe preeclampsia and managed expectantly. Fetal status on admission, admission-to-delivery interval, indication for delivery, and neonatal outcome were examined. Forty-seven women were studied during a 3-year period (1996-1999). Gestational age at admission was 29.8 +/- 2.6 weeks. The mean admission-to-delivery interval for the entire group was 6.0 +/- 5.1 days; in 42.5% delivery was for fetal indications. In comparison with the absence of intrauterine growth restriction, the presence of intrauterine growth restriction at admission resulted in a significantly shorter admission-to-delivery interval (3.1 +/- 2.1 vs 6.6 +/- 6.1 days; P <.05). Most fetuses with intrauterine growth restriction (85.7%) were delivered before 1 week. Although 57% of fetuses with intrauterine growth restriction were delivered for fetal indications, versus 39% of fetuses without intrauterine growth restriction, these rates were not found to be significantly different. Neonatal outcomes, as reflected by Apgar scores, number of admissions to and duration of stay in the neonatal intensive care unit, and neonatal mortality rates, were similar. Pregnancies complicated by severe preterm preeclampsia and the presence of intrauterine growth restriction at admission may not benefit from expectant

  4. Parenteral administration of L-arginine prevents fetal growth restriction in undernourished ewes.

    PubMed

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

    2010-07-01

    Intrauterine growth restriction (IUGR) is a major health problem worldwide that currently lacks an effective therapeutic solution. This study was conducted with an ovine IUGR model to test the hypothesis that parenteral administration of l-arginine (Arg) is effective in enhancing fetal growth. Beginning on d 28 of gestation, ewes were fed a diet providing 100% (control-fed) or 50% (underfed) of NRC-recommended nutrient requirements. Between d 60 of gestation and parturition, underfed ewes received i.v. infusions of saline or 155 micromol Arg-HCl/kg body weight 3 times daily, whereas control-fed ewes received only saline. The birth weights of lambs from saline-infused underfed ewes were 23% lower (P < 0.01) than those of lambs from control-fed dams. Administration of Arg to underfed ewes increased (P < 0.01) concentrations of Arg (69%), ornithine (55%), proline (29%), methionine (37%), leucine (36%), isoleucine (35%), cysteine (19%), and FFA (43%) in maternal serum, decreased maternal circulating levels of ammonia (18%) and triglycerides (32%), and enhanced birth weights of lambs by 21% compared with saline-infused underfed ewes. There was no difference in birth weights of lambs between the control-fed and the Arg-infused underfed ewes. These novel results indicate that parenteral administration of Arg to underfed ewes prevented fetal growth restriction and provide support for its clinical use to ameliorate IUGR in humans. The findings also lay a new framework for studying cellular and molecular mechanisms responsible for the beneficial effects of Arg in regulating conceptus growth and development.

  5. Parenteral Administration of l-Arginine Prevents Fetal Growth Restriction in Undernourished Ewes12

    PubMed Central

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

    2010-01-01

    Intrauterine growth restriction (IUGR) is a major health problem worldwide that currently lacks an effective therapeutic solution. This study was conducted with an ovine IUGR model to test the hypothesis that parenteral administration of l-arginine (Arg) is effective in enhancing fetal growth. Beginning on d 28 of gestation, ewes were fed a diet providing 100% (control-fed) or 50% (underfed) of NRC-recommended nutrient requirements. Between d 60 of gestation and parturition, underfed ewes received i.v. infusions of saline or 155 μmol Arg-HCl/kg body weight 3 times daily, whereas control-fed ewes received only saline. The birth weights of lambs from saline-infused underfed ewes were 23% lower (P < 0.01) than those of lambs from control-fed dams. Administration of Arg to underfed ewes increased (P < 0.01) concentrations of Arg (69%), ornithine (55%), proline (29%), methionine (37%), leucine (36%), isoleucine (35%), cysteine (19%), and FFA (43%) in maternal serum, decreased maternal circulating levels of ammonia (18%) and triglycerides (32%), and enhanced birth weights of lambs by 21% compared with saline-infused underfed ewes. There was no difference in birth weights of lambs between the control-fed and the Arg-infused underfed ewes. These novel results indicate that parenteral administration of Arg to underfed ewes prevented fetal growth restriction and provide support for its clinical use to ameliorate IUGR in humans. The findings also lay a new framework for studying cellular and molecular mechanisms responsible for the beneficial effects of Arg in regulating conceptus growth and development. PMID:20505020

  6. Impact of donor and recipient adiposity on placental and fetal growth in adolescent sheep.

    PubMed

    Wallace, Jacqueline M; Milne, John S; Adam, Clare L; Aitken, Raymond P

    2017-04-01

    The influence of maternal obesity during oocyte development and its putative interaction with nutrient reserves at conception on pregnancy outcome were examined in an adolescent sheep model. Donor ewes were nutritionally managed to achieve contrasting adiposity (control (CD)/obese (ObD)) for 6 weeks prior to superovulation and inseminated by a non-obese sire. Morulae from 6 CD and 7 ObD were transferred in singleton into adolescent recipients of identical age but differing adiposity, classified as relatively fat or thin respectively. Thereafter, all were overnourished to promote rapid growth/adiposity (2 × 2 design, 13/14 pregnancies/group). A fifth recipient group of intermediate adiposity received embryos from another 5 CD, was offered a moderate intake to maintain adiposity throughout gestation and acted as controls for normal pregnancy outcome (optimally treated control (OTC), 19 pregnancies). Donor obesity did not influence ovulation, fertilisation or recovery rates or impact embryo morphology. Gestation length and colostrum yield were unaffected by donor or recipient adiposity and were reduced relative to OTC. Total fetal cotyledon and lamb birth weights were independent of initial donor adiposity but reduced in relatively thin vs relatively fat recipients and lower than those in the OTC group. In spite of high placental efficiency, the incidence of fetal growth restriction was greatest in the thin recipients. Thus, maternal adiposity at conception, but not pre-conception maternal obesity, modestly influences the feto-placental growth trajectory, whereas comparison with the OTC indicates that high gestational intakes to promote rapid maternal growth remain the dominant negative influence on pregnancy outcome in young adolescents. These findings inform dietary advice for pregnant adolescent girls.

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

    PubMed

    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

    2015-03-05

    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, it

  8. 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

  9. Fetal growth restriction and 18-year growth and nutritional status: Aboriginal birth cohort 1987-2007.

    PubMed

    Sayers, Susan; Mott, Susan; Singh, Gurmeet

    2011-01-01

    The main objective of the work is to compare the growth and nutritional status of Australian Aboriginal term infants born with (n = 81) and without fetal growth restriction (n = 260). A prospective birth cohort study of 341 Aboriginal babies from the Top End of the Northern Territory of Australia was recruited at birth (1987-1990) and re-examined at a mean age of 18.3 years (2006-2008) for outcome measures of growth and nutrition status. Those with growth restriction at birth were 3 cm shorter (P = 0.0026) and 9 kg lighter (P = 0.0001) with head circumferences 0.95 cm smaller (P = 0.0008) than those without growth restriction. The proportions of growth restricted participants with body mass index <18.5 kg/m(2) were significantly greater (P = 0.028), and those with BMI > 25 kg/m(2) and with fat percentage >85th percentile were significantly smaller (P = 0.012 and 0.004, respectively). In this cohort, those Aboriginal babies born smaller and lighter have remained smaller and lighter at 18 years of age. However, the highest risk of later chronic noncommunicable disease has been reported in subjects who were born small and become relatively larger in later life. The continued study of this Aboriginal birth cohort will give us an opportunity to determine if and when in later life the effects of birth weight are modified by environmental nutritional factors.

  10. Relationship between birth weight or fetal growth rate and postnatal allergy: a systematic review protocol.

    PubMed

    Wooldridge, Amy L; McMillan, Mark; Marshall, Helen S; Gatford, Kathryn L

    2016-11-01

    The objective of this systematic review is to synthesize the best available evidence on the relationship between size at birth or fetal growth and postnatal allergy. Specifically, this review aims to assess evidence regarding relationships between absolute birth weight at term, birth weight corrected for gestational age, expressed as relative to population or customized growth data, or fetal growth measures and physician-diagnosed or parent- and self-reported postnatal clinical allergic disease (eczema/atopic dermatitis, hay fever/rhinitis, allergic asthma or anaphylaxis).The specific review question is: what is the association between the absolute birth weight at full-term or birth weight relative to population or customized data and corrected for gestational age or direct measures of fetal growth, and physician-diagnosed or parent- and self-reported clinical allergic disease (eczema/atopic dermatitis, hay fever/rhinitis, allergic asthma or anaphylaxis)?

  11. Fetal heart circumference as a predictor of menstrual age in fetuses affected by disturbances in growth.

    PubMed

    Hill, L M; Guzick, D; Peterson, C; DiNofrio, D; Maloney, J; Nedzeksy, P

    1993-08-01

    The purpose of this study was twofold: (1) to evaluate the relationship between fetal heart circumference and gestational age and (2) to determine the effect, if any, of disturbances in fetal growth on heart circumference. Heart circumference was measured in 262 women with normal gestations (control group) and in two study groups consisting of 52 large-for-gestational age 32 small-for-gestational age fetuses. Standardized, gestational age-adjusted values in the two study groups were compared with normative data provided by the control group. There was a close correlation (R2 = 0.94) between heart circumference and gestational age in normally growing fetuses. Disturbances of fetal growth (i.e., macrosomia and growth retardation) were found to have an inconsistent effect on heart circumference. Heart circumference cannot be used as an independent parameter for gestational age evaluation in fetuses with disturbances of growth.

  12. Inhibiting matrix metalloproteinases with prinomastat produces abnormalities in fetal growth and development in rats.

    PubMed

    Younis, Husam S; Jessen, Bart A; Wu, Ellen Y; Stevens, Gregory J

    2006-04-01

    Matrix metalloproteinases (MMPs) play key roles in remodeling of the extracellular matrix during embryogenesis and fetal development. The objective of this study was to determine the effects of prinomastat, a potent selective MMP inhibitor, on fetal growth and development. Prinomastat (25, 100, 250 mg/kg/day, p.o.) was administered to pregnant female Sprague-Dawley rats on gestational days (GD) 6-17. A Cesarian section was carried out on GD 20 and the fetuses were evaluated for viability and skeletal and soft tissue abnormalities. Prinomastat treatment at the 250 mg/kg/day dose produced a decrease in body weight and food consumption in the dams. A dose-dependent increase in post-implantation loss was observed in the 100 and 250 mg/kg/day-dose groups, resulting in only 22% of the dams having viable litters for evaluation at the 250 mg/kg/day dose. Fetal skeletal tissue variations and malformations were present in all prinomastat treated groups and their frequency increased with dose. Variations and malformation in fetal soft tissue were also increased at the 100 and 250 mg/kg/day doses. Prinomastat also interfered with fetal growth of rat embryo cultures in vitro. These data confirm that MMP inhibition has a profound effect on fetal growth and development in vivo and in vitro. Birth Defects Research (Part B) 77:95-103, 2006. (c) 2006 Wiley-Liss, Inc.

  13. Maternal and fetal metabonomic alterations in prenatal nicotine exposure-induced rat intrauterine growth retardation.

    PubMed

    Feng, Jiang-hua; Yan, You-e; Liang, Gai; Liu, Yan-song; Li, Xiao-jun; Zhang, Ben-jian; Chen, Liao-bin; Yu, Hong; He, Xiao-hua; Wang, Hui

    2014-08-25

    Prenatal nicotine exposure causes adverse birth outcome. However, the corresponding metabonomic alterations and underlying mechanisms of nicotine-induced developmental toxicity remain unclear. The aims of this study were to characterize the metabolic alterations in biofluids in nicotine-induced intrauterine growth retardation (IUGR) rat model. In the present study, pregnant Wistar rats were intragastrically administered with different doses of nicotine (0.5, 1.0 and 2.0 mg/kg d) from gestational day (GD) 11-20. The metabolic profiles of the biofluids, including maternal plasma, fetal plasma and amniotic fluid, were analyzed using (1)H nuclear magnetic resonance (NMR)-based metabonomic techniques. Prenatal nicotine exposure caused noticeably lower body weights, higher IUGR rates of fetal rats, and elevated maternal and fetal corticosterone (CORT) levels compared to the controls. The correlation analysis among maternal, fetal serum CORT levels and fetal bodyweight suggested that the levels of maternal and fetal serum CORT presented a positive correlation (r=0.356, n=32, P<0.05), while there was a negative correlation between fetal (r=-0.639, n=32, P<0.01) and maternal (r=-0.530, n=32, P<0.01) serum CORT level and fetal bodyweight. The fetal metabonome alterations included the stimulation of lipogenesis and the decreased levels of glucose and amino acids. The maternal metabonome alterations involved the enhanced blood glucose levels, fatty acid oxygenolysis, proteolysis and amino acid accumulation. These results suggested that prenatal nicotine exposure is associated with an altered maternal and fetal metabonome, which may be related to maternal increased glucocorticoid level induced by nicotine. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. 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.

  15. Evolving indications for the EXIT procedure: the usefulness of combining ultrasound and fetal MRI.

    PubMed

    Mota, Raquel; Ramalho, Carla; Monteiro, Joaquim; Correia-Pinto, Jorge; Rodrigues, Manuela; Guimarães, Hercília; Spratley, Jorge; Macedo, Filipe; Matias, Alexandra; Montenegro, Nuno

    2007-01-01

    The EXIT procedure (EX utero Intrapartum Treatment) encompasses a multidisciplinary approach to situations in which airway obstruction is anticipated. Uteroplacental circulation is maintained to avoid neonatal hypoxemia while intubation is attempted. Not only is it useful in congenital diaphragmatic hernia with intrauterine tracheal occlusion, but new indications have been proposed. We present two cases in which EXIT procedure was adopted (huge cervical mass with tracheal compression and a highly vascularized cephalocervical mass) for the same purpose on different grounds. Our two cases stress once more the importance of combining fetal ultrasound and magnetic resonance imaging in the characterization of cervical masses and its usefulness in programming the procedure with a multidisciplinary team.

  16. Effect of prenatal betamethasone on fetal, uteroplacental, and maternal blood flow velocity in pregnancies complicated by fetal growth restriction.

    PubMed

    Niroomanesh, Shirin; Shojaei, Kobra; Moghadam, Sahar F; Mohammadi, Noshin; Rahimi, Zahra; RezaeiKeyhanaei, Khadija

    2015-09-01

    To assess Doppler flow velocity in fetal, uteroplacental, and maternal arteries before and after betamethasone therapy among singleton pregnancies complicated by fetal growth restriction (FGR). A prospective, longitudinal, multicenter study was conducted at three university-affiliated hospitals in Tehran, Iran, between January 1 and November 30, 2013. The inclusion criteria were FGR, a gestational age of 24-34 weeks, no fetal anomalies, and no previous betamethasone therapy. Doppler blood flow was measured in uterine, umbilical, and middle cerebral arteries before treatment, and 24 hours and 5 days after completion of betamethasone therapy (two 12-mg doses at a 24-hour interval). Overall, 40 women were enrolled. Doppler blood flow through the uterine and umbilical arteries showed significant but transient changes across the three timepoints (P<0.001), whereas the middle cerebral artery showed no changes. Prenatal betamethasone led to transient improvements in blood flow in the uterine and umbilical arteries among pregnancies affected by FGR. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  17. Maternal/fetal mortality and fetal growth restriction: Role of nitric oxide and virulence factors in intrauterine infection in rats

    PubMed Central

    Wroblewska-Seniuk, Katarzyna; Nowicki, Stella; Lebouguénec, Chantal; Nowicki, Bogdan; Yallampalli, Chandra

    2011-01-01

    Objective The mechanism of infection-related mortality of pregnant rats and the intrauterine growth restriction (IUGR) are not understood. We assessed if nitric oxide (NO) has differential effects on infection with E. coli Dr/Afa mutants lacking either AfaE or AfaD invasins. Material and Methods Sprague-Dawley rats were intrauterinally infected with the clinical strain of E. coli AfaE+D+ or one of its isogenic mutants in the presence or absence of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Maternal/fetal mortality, feto-placental weight, and the infection rate were evaluated. Results Maternal and/or fetal mortality was associated with the presence of at least one virulence factor (AfaE+D+>AfaE+D−>AfaE-D+) and was increased by L-NAME treatment. The fetal and placental weights were lower than controls and they were further reduced by L-NAME treatment. Conclusions These results demonstrate that NO enhanced AfaE and AfaD mediated virulence and play an important role in Dr/Afa+ E. coli gestational tropism. PMID:21481839

  18. Gestational dietary protein is associated with sex specific decrease in blood flow, fetal heart growth and post-natal blood pressure of progeny.

    PubMed

    Hernandez-Medrano, Juan H; Copping, Katrina J; Hoare, Andrew; Wapanaar, Wendela; Grivell, Rosalie; Kuchel, Tim; Miguel-Pacheco, Giuliana; McMillen, I Caroline; Rodgers, Raymond J; Perry, Viv E A

    2015-01-01

    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 14 mo 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 60 d prior to 98 days post conception (dpc). Fetuses and placentae were excised at 98 dpc (n = 48). Fetal development an median uterine artery blood flow were assessed monthly from 36 dpc 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 (-60 d up to 23 dpc) 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. 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.

  19. 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

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

    USDA-ARS?s Scientific Manuscript database

    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...

  1. 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.…

  2. 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.…

  3. Management of Very Early-onset Fetal Growth Restriction: Results from 92 Consecutive Cases.

    PubMed

    Hoellen, Friederike; Beckmann, Annika; Banz-Jansen, Constanze; Weichert, Jan; Rody, Achim; Bohlmann, Michael K

    2016-01-01

    To evaluate management of early-onset intrauterine growth restriction (IUGR) and to define outcome according to obstetric setting. During an 11-year period (2000-2011), data of patients presenting with IUGR and preterm delivery of less than 30 weeks of gestation at a tertiary perinatal center were retrospectively reviewed. A total of 92 pregnancies were investigated. Delivery was indicated for fetal reasons in 38 out of 92 patients. Sixteen children of our cohort died within one year post partum, out of which eight had suffered from severe early-onset IUGR causing iatrogenic preterm delivery. Concerning the fetal outcome, gestational age at delivery and antenatal exposure to corticosteroids were found to be crucial. In some cases, respiratory distress syndrome prophylaxis and a "wait and see" approach to management in favor of a prolongation of the pregnancy might be favorable. Randomized prospective trials in early-onset IUGR with threatened preterm deliveries are needed in order to define guidelines for an individually tailored management of early-onset preterm infants. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  4. 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

  5. Diabetes-associated changes in the fetal insulin/insulin-like growth factor system are organ specific in rats.

    PubMed

    White, Verónica; Jawerbaum, Alicia; Mazzucco, María B; Gauster, Martin; Desoye, Gernot; Hiden, Ursula

    2015-01-01

    Diabetes in pregnancy affects fetal growth and development. The insulin/insulin-like growth factors (IGF) system comprising insulin, IGF, their receptors, and binding proteins, has been implicated in fetal growth regulation. This study tested the hypothesis that maternal diabetes alters the fetal insulin/IGF system in a tissue-specific manner. Wistar rats were rendered diabetic by neonatal administration of streptozotocin and mated with control rats. At day 21 of gestation, the weights of fetuses, placentas, and fetal organs (heart, lung, liver, stomach, intestine, and pancreas) were determined. Maternal and fetal plasma concentrations of insulin, IGF1, and IGF2 were measured by ELISA, and expression of IGF1, IGF2, IGF1R, IGF2R, IR, IGFBP1, BP2, and BP3 in placenta and fetal organs by qPCR. The well-known increase in fetal growth in this model of mild diabetes is accompanied by elevated insulin and IGF1 levels and alterations of the insulin/IGF system in the fetus and the placenta. These alterations were organ and gene specific. The insulin/IGF system was generally upregulated, especially in the fetal heart, while it was downregulated in fetal lung. In our model of mild diabetes, the effect of maternal diabetes on fetal weight and fetal insulin/IGF system expression is organ specific with highly sensitive organs such as lung and heart, and organs that were less affected, such as stomach.

  6. A Comparative Analysis of Prenatal Care and Fetal Growth in Eight South American Countries

    PubMed Central

    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

  7. 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.

  8. 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

  9. Effects of chronic carbon monoxide exposure on fetal growth and development in mice.

    PubMed

    Venditti, Carolina C; Casselman, Richard; Smith, Graeme N

    2011-12-14

    Carbon monoxide (CO) is produced endogenously, and can also be acquired from many exogenous sources: ie. cigarette smoking, automobile exhaust. Although toxic at high levels, low level production or exposure lends to normal physiologic functions: smooth muscle cell relaxation, control of vascular tone, platelet aggregation, anti- inflammatory and anti-apoptotic events. In pregnancy, it is unclear at what level maternal CO exposure becomes toxic to the fetus. In this study, we hypothesized that CO would be embryotoxic, and we sought to determine at what level of chronic CO exposure in pregnancy embryo/fetotoxic effects are observed. Pregnant CD1 mice were exposed to continuous levels of CO (0 to 400 ppm) from conception to gestation day 17. The effect on fetal/placental growth and development, and fetal/maternal CO concentrations were determined. Maternal and fetal CO blood concentrations ranged from 1.12- 15.6 percent carboxyhemoglobin (%COHb) and 1.0- 28.6%COHb, respectively. No significant difference was observed in placental histological morphology or in placental mass with any CO exposure. At 400 ppm CO vs. control, decreased litter size and fetal mass (p < 0.05), increased fetal early/late gestational deaths (p < 0.05), and increased CO content in the placenta and the maternal spleen, heart, liver, kidney and lung (p < 0.05) were observed. Exposure to levels at or below 300 ppm CO throughout pregnancy has little demonstrable effect on fetal growth and development in the mouse.

  10. Ultrasonography estimates of fetal growth in fetuses affected by trisomy 21.

    PubMed

    Bernstein, Sarah N; Saller, Devereux N; Catov, Janet M; Canavan, Timothy P

    2016-06-01

    To construct growth curves specific for fetuses with trisomy 21 (T21) and to compare them with the reference-based standard. A retrospective cohort study was conducted of ultrasonography examinations from women with singleton pregnancies with a confirmed diagnosis of T21 who sought care at an academic tertiary-care center in the USA between January 1, 2003, and December 31, 2013. Growth curves were constructed using linear regression and compared with the Hadlock standard. The study included 425 ultrasonography examinations from 235 women. The head circumference and femur length were smaller than the reference standards at all gestational ages (head circumference: P=0.017; femur length: P<0.001). The abdominal circumference was larger than the reference standard from 29weeks onward (P<0.001). The biparietal diameter was smaller in the second trimester and in the late third trimester (P<0.001). The overall estimated fetal weight was not different from the reference standard. The T21-specific growth curves indicate anthropometric differences between T21 fetuses and the general population. Once validated, such individual growth curves could allow for more accurate prenatal assessment and management of fetuses affected by T21. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  11. Cumulative Effective Hölder Exponent Based Indicator for Real-Time Fetal Heartbeat Analysis during Labour

    NASA Astrophysics Data System (ADS)

    Struzik, Zbigniew R.; van Wijngaarden, Willem J.

    We introduce a special purpose cumulative indicator, capturing in real time the cumulative deviation from the reference level of the exponent h (local roughness, Hölder exponent) of the fetal heartbeat during labour. We verify that the indicator applied to the variability component of the heartbeat coincides with the fetal outcome as determined by blood samples. The variability component is obtained from running real time decomposition of fetal heartbeat into independent components using an adaptation of an oversampled Haar wavelet transform. The particular filters used and resolutions applied are motivated by obstetricial insight/practice. The methodology described has the potential for real-time monitoring of the fetus during labour and for the prediction of the fetal outcome, allerting the attending staff in the case of (threatening) hypoxia.

  12. Recombinant vascular endothelial growth factor 121 injection for the prevention of fetal growth restriction in a preeclampsia mouse model.

    PubMed

    Sulistyowati, Sri; Bachnas, Muhammad Adrianes; Anggraini, Nuri Dyah; Yuliantara, Eric Edwin; Prabowo, Wisnu; Anggraini, Nutria Widya Purna; Pramono, Mochammad Besari Adi; Adityawarman; Dachlan, Erry Gumilar; Andonotopo, Wiku

    2017-02-01

    To discover the potential role of recombinant VEGF121 (rVEGF121) injection for the prevention of fetal growth restriction in a preeclampsia (PE) mouse model (Mus musculus). This is an experimental study of 30 pregnant mice that were randomly divided into three groups: normal, PE, and PE with rVEGF121 injection. The PE mouse model was created by injecting anti Qa-2 10 ng iv, which is deleterious to Qa-2 expression (homologous to HLA-G), from the first to the fourth day of gestation. PE was validated by measuring serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor(PIGF) and also by kidney histopathology. Recombinant VEGF121 was given on the ninth day until the 11th day of pregnancy; mice were terminated on the 16th day. Fetal weights were acquired with a Denver analytical balance. Serum levels of sFlt-1 and PlGF were measured using enzyme-linked immunosorbent assay (ELISA). The data were statistically analyzed via analysis of variance (ANOVA). On average, fetal birth weight was 0.7150 g in the normal group, 0.4936 g in the PE group, and 0.6768 g in the PE with rVEGF121 injection group. ANOVA showed significant growth restriction in the PE group (P=0.006), confirming the use of anti Qa-2 as a suitable PE model. Kidney histopathology results, sFlt-1 levels, and PlGF levels also demonstrated that anti Qa-2 consistently conferred hallmarks of PE in mice. Vascular endothelial growth factor (VEGF) injection prevented fetal growth restriction; comparable fetal weights were observed between the PE model with VEGF treatment and the normal group (P=0.610) but differed from the untreated PE group (P=0.021). Injection of rVEGF121 has the potential to prevent fetal growth restriction in a newly proposed PE mouse model.

  13. Neurobehavioral determinants of nutritional security in fetal growth-restricted individuals.

    PubMed

    Portella, André Krumel; Silveira, Patrícia Pelufo

    2014-12-01

    Fetal growth restriction results from a failure to achieve a higher growth potential and has been associated with many maternal conditions, such as chronic diseases (infections, hypertension, and some cases of diabetes and obesity), exposures (tobacco smoke, drugs), and malnutrition. This early adversity induces a series of adaptive physiological responses aimed at improving survival, but imposing increased risk for developing chronic nontransmittable diseases (obesity, type II diabetes, cardiovascular disease) in the long term. Recently, mounting evidence has shown that fetal growth impairment is related to altered feeding behavior and preferences through the life course. When living in countries undergoing nutritional transition, in which individuals experience the coexistence of underweight and overweight problems (the "double burden of malnutrition"), fetal growth-restricted children can be simultaneously growth restricted and overweight-a double burden of malnutrition at the individual level. Considering food preferences as an important aspect of nutrition security, we will summarize the putative neurobiological mechanisms at the core of the relationship between fetal growth and nutrition security over the life course and the evidence linking early life adversity to later food preferences.

  14. Isolated fetal choroid plexus cysts: not an indication for genetic diagnosis?

    PubMed

    Sohn, C; Gast, A S; Krapfl, E

    1997-01-01

    Offering invasive prenatal cytogenetic testing in cases of isolated choroid plexus cysts is controversial. To give a contribution to this discussion we recorded prospectively the course of 41 fetuses with cysts of the choroid plexus diagnosed in 4,326 pregnancies sonographically scanned in our center between January 1994 and August 1995. The fetuses were all in the 13th to 24th week of gestation, with an average of 19.3 weeks. Only 1 of these fetuses (with large bilateral choroid plexus cysts) had further sonographically visible malformations (renal and cardiac anomalies, malposition of the hands). 34 fetuses had bilateral and 7 one-sided plexus cysts. 38 of the 41 patients decided on invasive diagnosis; karyotyping was successful in all these cases. The complete follow-up until 5 days after birth is known in 38 fetuses, including 3 without genetic diagnosis. A chromosomal aberration was detectable only in 1 fetus (trisomy 18, this fetus had the additional malformations described above), the other fetuses all displaying neither chromosomal nor morphological abnormalities. All fetuses, excluding 1 (the pregnancy was terminated due to trisomy 18) were re-examined before the 25th week of gestation, plexus cysts only still being visible in 3 fetuses. By the 30th week of gestation in these 3 fetuses the cysts had also disappeared. Furthermore, 20 pregnancies with confirmed trisomy 18 diagnosed between 1990 and 1996 were analyzed retrospectively. In 19 cases heart defects had been detected by prenatal ultrasound, cervical hygroma being less common (6 cases) and other malformations still rarer. Choroid plexus cysts had, however, been seen only in the 1 case described above. There was no case of isolated choroid plexus cysts in this group. From our data and current literature we conclude that isolated choroid plexus cysts are not an absolute indication for fetal karyotyping. In our opinion a detailed ultrasound assessment to seek for further malformations in a specialized

  15. The relationship between gestational weight gain and fetal growth: time to take stock?

    PubMed

    O'Higgins, Amy C; Doolan, Anne; Mullaney, Laura; Daly, Niamh; McCartney, Daniel; Turner, Michael J

    2014-07-01

    The aim of this article is to review the current evidence on gestational weight gain (GWG). Maternal obesity has emerged as one of the great challenges in modern obstetrics as it is becoming increasingly common and is associated with increased maternal and fetal complications. There has been an upsurge of interest in GWG with an emphasis on the relationship between excessive GWG and increased fetal growth. Recent recommendations from the Institute of Medicine in the USA have revised downwards the weight gain recommendations in pregnancy for obese mothers. We believe that it is time to take stock again about the advice that pregnant women are given about GWG and their lifestyle before, during, and after pregnancy. The epidemiological links between excessive GWG and aberrant fetal growth are weak, particularly in obese women. There is little evidence that intervention studies decrease excessive GWG or improve intrauterine fetal growth. Indeed, there is a potential risk that inappropriate interventions during the course of pregnancy may lead to fetal malnutrition that may have adverse clinical consequences, both in the short- and long-term. It may be more appropriate to shift the focus of attention from monitoring maternal weight to increasing physical activity levels and improving nutritional intakes.

  16. [Cervical vertebrae: Mandibular growth dynamism indicators?].

    PubMed

    Raberin, Monique; Cozor, Ilinca; Gobert-Jacquart, Stéphanie

    2012-03-01

    A study of mandibular growth maturation was performed on a population of 103 patients during orthodontic treatment (69 girls and 34 boys) from 11 to 16 years, having initially a Class II skeletal discrepancy. The relationship between wrist maturation indices and the cervical vertebrae maturation was studied by Lamparski classification. Significant correlations were found between Björk stages, MP3=, MP3 cap and MP3 U and respectively Lamparski stages as CVS 2, CVS 3-4 and CVS 5-6. This retrospective longitudinal study identified three mandibular variables at three different maturation stages according to Björk classification and to the six stages of Lamparski classification. The relationships between these different maturation stages and a quantitative mandibular response permit to estimate optimal time for our orthodontic therapy. The results indicate a significant increase in mandibular length between CVS 4 and CVS 5, suggesting the persistence of a condylar response to a stimulation therapy after CVS3 or CVS 4 stages (MP3 cap). Mandibular growth seems to continue after MP3 U stage or CVS 5 stage. © EDP Sciences, SFODF, 2012.

  17. Mother's educational level and fetal growth: the genesis of health inequalities.

    PubMed

    Silva, Lindsay M; Jansen, Pauline W; Steegers, Eric A P; Jaddoe, Vincent W V; Arends, Lidia R; Tiemeier, Henning; Verhulst, Frank C; Moll, Henriëtte A; Hofman, Albert; Mackenbach, Johan P; Raat, Hein

    2010-10-01

    Women of low socio-economic status (SES) give birth to lighter babies. It is unknown from which moment during pregnancy socio-economic differences in fetal weight can be observed, whether low SES equally affects different fetal-growth components, or what the effect of low SES is after taking into account mediating factors. In 3545 pregnant women participating in the Generation R Study, we studied the association of maternal educational level (high, mid-high, mid-low and low) as a measure of SES with fetal weight, head circumference, abdominal circumference and femur length. We did this before and after adjusting for potential mediators, including maternal height, pre-pregnancy body mass index and smoking. In fetuses of low-educated women relative to those of high-educated women, fetal growth was slower, leading to a lower fetal weight that was observable from late pregnancy onwards. In these fetuses, growth of the head [-0.16 mm/week; 95% confidence interval (CI): -0.25 to -0.07; P = 0.0004], abdomen (-0.10 mm/week; 95% CI: -0.21 to 0.01; P = 0.08) and femur (-0.03 mm/week; 95% CI: -0.05 to -0.006; P = 0.01) were all slower; from mid-pregnancy onwards, head circumference was smaller, and from late pregnancy onwards, femur length was also smaller. The negative effect of low education was greatest for head circumference (difference in standard deviation score in late pregnancy: -0.26; 95% CI: -0.36 to -0.15; P < 0.0001). This effect persevered even after adjustment for the potential mediators (adjusted difference: -0.14; 95% CI: -0.25 to -0.03; P = 0.01). Low maternal education is associated with a slower fetal growth and this effect appears stronger for growth of the head than for other body parts.

  18. Ethnic differences in fetal size and growth in a multi-ethnic population.

    PubMed

    Sletner, Line; Rasmussen, Svein; Jenum, Anne Karen; Nakstad, Britt; Jensen, Odd Harald Rognerud; Vangen, Siri

    2015-09-01

    Impaired or excessive fetal growth is associated with adverse short- and long-term health outcomes that differ between ethnic groups. We explored ethnic differences in fetal size and growth from mid pregnancy until birth. Data are from the multi-ethnic STORK-Groruddalen study, a population-based, prospective cohort of 823 pregnant women and their offspring in Oslo, Norway. Measures were z-scores of estimated fetal weight (EFW), head circumference (HC), abdominal circumference (AC) and femur length (FL), in gestational week 24, 32 and 37, measured by ultrasound, and similar measures at birth. Differences in fetal size and growth were assessed using separate Linear Mixed Models including all four time points, with ethnic Europeans as reference. In week 24 South Asian fetuses had smaller AC, but larger FL than Europeans, and slightly lower EFW (-0.17 SD (-0.33, -0.01), p=0.04). Middle East/North African fetuses also had larger FL, but similar AC, and hence slightly higher EFW (0.18 (0.003, 0.36), p=0.05). Both groups had slower growth of AC, FL and EFW from this time until birth, and had -0.61 SD (-0.73, -0.49) and -0.28 SD (-0.41, -0.15) lower birth weight respectively. Ethnic East Asians, on the other hand, were smaller throughout pregnancy and had -0.58 SD (-0.82, -0.34) lower birth weight. Significant ethnic differences remained after adjusting for maternal factors. We observed ethnic differences in fetal size and body proportions already in gestational week 24, and in fetal growth from this time until birth, which were only partly explained by key maternal factors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Effects of hyperthyroidism on expression of vascular endothelial growth factor (VEGF) and apoptosis in fetal adrenal glands.

    PubMed

    Karaca, T; Hulya Uz, Y; Karabacak, R; Karaboga, I; Demirtas, S; Cagatay Cicek, A

    2015-11-26

    This study investigated the expression of vascular endothelial growth factor (VEGF), vascular density, and apoptosis in fetal rat adrenal glands with hyperthyroidism in late gestation. Twelve mature female Wistar albino rats with the same biological and physiological features were used for this study. Rats were divided into two groups: control and hyperthyroidism. Hyperthyroidism was induced by daily subcutaneous injections of L-thyroxine (250 μg/kg) before pregnancy for 21 days and during pregnancy. Rats in the control and hyperthyroidism groups were caged according to the number of male rats. Zero day of pregnancy (Day 0) was indicated when the animals were observed to have microscopic sperm in vaginal smears. Pregnant rats were sacrificed on the 20th day of pregnancy; blood from each animal was collected to determine the concentrations of maternal adrenocorticotropic hormone and thyroxine. Rat fetuses were then quickly removed from the uterus, and the adrenal glands of the fetuses were dissected. VEGF expression, vascular density, and apoptosis were analyzed in fetal rat adrenal glands. Maternal serum levels of the adrenocorticotropic hormone and free thyroxine were significantly higher in the hyperthyroidism group than in the control group. Immunohistochemistry revealed that the number of VEGF positive cells and vessel density significantly increased in the hyperthyroidism rat fetal adrenal group compared with the control group. Hyperthyroidism did not change the fetal and placental weights and the number of fetuses. This study demonstrates that hyperthyroidism may have an effect on the development of rat adrenal glands mediated by VEGF expression, angiogenesis, and apoptosis.

  20. Effects of Hyperthyroidism on Expression of Vascular Endothelial Growth Factor (VEGF) and Apoptosis in Fetal Adrenal Glands

    PubMed Central

    Hulya Uz, Y.; Karabacak, R.; Karaboga, I.; Demirtas, S.; Cagatay Cicek, A.

    2015-01-01

    This study investigated the expression of vascular endothelial growth factor (VEGF), vascular density, and apoptosis in fetal rat adrenal glands with hyperthyroidism in late gestation. Twelve mature female Wistar albino rats with the same biological and physiological features were used for this study. Rats were divided into two groups: control and hyperthyroidism. Hyperthyroidism was induced by daily subcutaneous injections of L-thyroxine (250 µg/kg) before pregnancy for 21 days and during pregnancy. Rats in the control and hyperthyroidism groups were caged according to the number of male rats. Zero day of pregnancy (Day 0) was indicated when the animals were observed to have microscopic sperm in vaginal smears. Pregnant rats were sacrificed on the 20th day of pregnancy; blood from each animal was collected to determine the concentrations of maternal adrenocorticotropic hormone and thyroxine. Rat fetuses were then quickly removed from the uterus, and the adrenal glands of the fetuses were dissected. VEGF expression, vascular density, and apoptosis were analyzed in fetal rat adrenal glands. Maternal serum levels of the ACTH and free thyroxine were significantly higher in the hyperthyroidism group than in the control group. Immunohistochemistry revealed that the number of VEGF positive cells and vessel density significantly increased in the hyperthyroidism rat fetal adrenal group compared with the control group. Hyperthyroidism did not change the fetal and placental weights and the number of fetuses. This study demonstrates that hyperthyroidism may have an effect on the development of rat adrenal glands mediated by VEGF expression, angiogenesis, and apoptosis. PMID:26708182

  1. Noninvasive monitoring of fetal growth and development in the Siberian polecat (Mustela eversmanni)

    USGS Publications Warehouse

    Wimsatt, Jeffrey; Johnson, Jay D.; Wrigley, Robert H.; Biggins, Dean E.; Godbey, Jerry L.

    1998-01-01

    The Siberian polecat (Mustela eversmanni) is the preferred species to assess procedures and establish normative values for application in the related and endangered black-footed ferret (Mustela nigripes). This study was undertaken to physically, ultrasonographically, and radiographically evaluate fetal development in a spontaneously breeding captive Siberian polecat population. Ultrasonographically, fetal sac enlargement allowed presumptive preg nancy detection as early as 12 days of gestation, the fetal pole was the first definitive sign of pregnancy at about 18 days of gestation, when the fetal heart beat also appeared, and definitive pregnancy detection by ultrasound was essentially 100% accurate after 18 days. The estimation of fetal number by ultrasound was less reliable than by radiography, as it is in other litter-bearing species. Crown-rump growth, organ differentiation, and calcification patterns resembled those of domestic carnivores except that comparable developmental stages in polecats occurred at dispro portionately later times, suggesting that young Siberian polecats are delivered in a less developed state. Careful palpation permitted detection of pregnancy after day 17 but with less certainty than with ultrasound. Radiographic evaluation was insensitive and of limited value for pregnancy detection until near term. Litter number and fetal detail were difficult to assess until ossification could be observed, 3-6 days before parturition.

  2. Effects of prenatal methamphetamine exposure on fetal growth and drug withdrawal symptoms in infants born at term.

    PubMed

    Smith, Lynne; Yonekura, M Lynn; Wallace, Toni; Berman, Nancy; Kuo, Jennifer; Berkowitz, Carol

    2003-02-01

    To determine fetal growth and the incidence of withdrawal symptoms in term infants exposed to methamphetamine in utero, we retrospectively identified neonates whose mothers used methamphetamine during pregnancy and matched them to unexposed newborns. Exclusion criteria included multiple and preterm gestations. Although there were no differences in infant growth parameters between the methamphetamine-exposed and methamphetamine-unexposed neonates, methamphetamine exposure throughout gestation was associated with decreased growth relative to infants exposed only for the first two trimesters. In addition, there were significantly more small for gestational age infants in the methamphetamine group compared with the unexposed group. Methamphetamine-exposed infants whose mothers smoked had significantly decreased growth relative to infants exposed to methamphetamine alone. Withdrawal symptoms (as determined by a previously reported scoring system) requiring pharmacologic intervention were observed in 4% of methamphetamine-exposed infants. These preliminary findings indicate that methamphetamine use is associated with growth restriction in infants born at term.

  3. Epidermal growth factor acts as a corticotropin-releasing factor in chronically catheterized fetal lambs.

    PubMed Central

    Polk, D H; Ervin, M G; Padbury, J F; Lam, R W; Reviczky, A L; Fisher, D A

    1987-01-01

    Epidermal growth factor (EGF) has been reported to stimulate adrenocorticotropin hormone (ACTH), growth hormone and prolactin secretion from pituitary tissue in vitro, and in large doses evokes ACTH secretion in adult sheep in vivo. In order to assess a possible role for EGF in the pituitary hyperfunction characteristic of the in utero fetus, we measured changes in plasma immunoreactive ACTH concentrations after acute administration of saline, purified mouse EGF or synthetic ovine corticotropin releasing factor (CRF) to chronically catheterized fetal sheep. Both CRF and EGF were associated with increases in plasma immunoreactive ACTH concentrations. Peak values 60 min after 10-micrograms injections of either EGF or CRF increased from baseline ACTH values of 61 +/- 11 pg/ml to 191 +/- 37 and 178 +/- 25 pg/ml, respectively. Dose-response studies indicate that at low doses (less than 20 micrograms) EGF is as potent a stimulus for ACTH release as CRF. EGF infusion was not associated with detectable changes in circulating CRF, catecholamines, arginine vasopressin levels, or plasma growth hormone concentrations. We speculate that EGF may be important in the regulation of pituitary function in the developing mammalian fetus. PMID:3029180

  4. Abolition of fetal breathing movements by spinal cord transection leads to reductions in fetal lung liquid volume, lung growth, and IGF-II gene expression.

    PubMed

    Harding, R; Hooper, S B; Han, V K

    1993-08-01

    Fetal breathing movements (FBM) are considered necessary for normal growth and structural maturation of the fetal lung, but the underlying mechanisms are unclear. The small fluctuations in lung dimensions caused by FBM have been proposed as a stimulus to lung growth, but it is equally possible that FBM act by maintaining the basal level of lung luminal volume, which is an established determinant of fetal lung growth. Our aim, therefore, was to determine the effects of abolishing FBM, while retaining the integrity of the diaphragm, on the volume and rate of production of fetal lung liquid, gene expression for IGF-II, and fetal lung growth. FBM were abolished in seven fetal sheep by high spinal cord transection at 114 +/- 1.2 d of gestation; seven intact fetuses served as controls. At 119 to 124, 125 to 130, and 131 to 136 d, we measured the volume and secretion rate of lung liquid by dye dilution. At these three age ranges, the lungs of cord-transfected fetuses contained 27 to 53% less lung liquid than controls (p = 0.004), and their rates of secretion were 65 to 138% greater (p = 0.001). At postmortem (135 +/- 0.1 d), the lungs of the cord transected fetuses contained less DNA per kg body weight and tended to be lighter and to contain less protein than controls. IGF-II gene expression in the lungs of cord-transected fetuses was significantly less than that in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. [Relationship of fetal total bile acid and the change of fetal pancreas endocrine secretion and its impact on fetal growth and development in intrahepatic cholestasis of pregnancy].

    PubMed

    Cheng, Xian-ying; Zhang, Li-juan; Lin, Li; Liu, Jia; Ding, Yi-ling

    2009-01-01

    To investigate the relationship of fetal total bile acid (TBA) concentration with the change of fetal pancreas endocrine secretion and its impact on fetal growth and development in intrahepatic cholestasis of pregnancy (ICP). The concentrations of TBA, insulin, glucagon and glucose in the cord blood were measured in 30 fetuses with maternal ICP (case group) and 30 fetuses of normogravidas (control group) after elective cesarean section during the same period in the Department of Obstetrics of Xiangya Second Hospital of Central South University from March 2007 to February 2008. The cord blood TBA concentration was investigated by enzyme method and the concentrations of insulin and glucagon were investigated by radioimmunoassay. The glucose was measured by oxidase-superoxide method. The neonatal weight, length and the ponderal index (PI) were measured after parturition. (1) The cord blood insulin concentration (9.0 +/- 3.3) mU/L and the ratio of insulin over glucagon 0.048 +/- 0.028 in the case group was significantly lower than that of controls (10.1 +/- 3.7) mU/L, 0.050 +/- 0.020 (P < 0.05). The concentrations of TBA (10.3 +/- 3.8) miromol/L and glucagon (235 +/- 57) ng/L in case group were obviously higher than that in controls (4.1 +/- 1.3) micromol/L, (205 +/-34) ng/L (P < 0.05). But no difference was shown in the glucose concentration in cord blood between the case and control groups [(3.4 +/- 1.1) mmol/L vs. (3.6 +/- 1.2) mmol/L, P > 0.05]. (2) The neonatal weight and length in case group were significantly lower than that of control [(3163 +/- 478) g vs. (3498 +/- 393) g, (46.5 +/- 2.3) cm vs. (49.3 +/- 1.9) cm, P < 0.01]; while the Ponderal index in case group was significantly higher than that of control group (3.13 +/- 0.23 vs. 2.92 +/- 0.29, P < 0.01). (3) The cord blood TBA concentration respectively showed a linear relationship with the cord blood insulin concentration, the cord blood glucagon concentration and the ratio of insulin over glucagon in the

  6. Late but not early gestational maternal growth hormone treatment increases fetal adiposity in overnourished adolescent sheep.

    PubMed

    Wallace, Jacqueline M; Matsuzaki, Masatoshi; Milne, John; Aitken, Raymond

    2006-08-01

    In the overnourished adolescent sheep, maternal tissue synthesis is promoted at the expense of placental growth and leads to a major decrease in lamb birth weight at term. Maternal growth hormone (GH) concentrations are attenuated in these pregnancies, and it was recently demonstrated that exogenous GH administration throughout the period of placental proliferation stimulates uteroplacental and fetal development by Day 81 of gestation. The present study aimed to determine whether these effects persist to term and to establish whether GH affects fetal growth and body composition by increasing placental size or by altering maternal metabolism. Adolescent recipient ewes were implanted with singleton embryos on Day 4 postestrus. Three groups of ewes offered a high dietary intake were injected twice daily with recombinant bovine GH from Days 35 to 65 of gestation (high intake plus early GH) or from Days 95 to 125 of gestation (high intake plus late GH) or remained untreated (high intake only). A fourth moderate-intake group acted as optimally nourished controls. Pregnancies were terminated at Day 130 of gestation (6 per group) or were allowed to progress to term (8-10 per group). GH administration elevated maternal plasma concentrations of GH, insulin, glucose, and nonesterified fatty acids during the defined treatment windows, while urea concentrations were decreased. At Day 130, GH treatment had reduced the maternal adiposity score, percentage of fat in the carcass, and internal fat depots and leptin concentrations, predominantly in the high-intake plus late GH group. Placental weight was lower in high-intake vs. control dams but independent of GH treatment. In contrast, fetal weight was elevated by late GH treatment, and these fetuses had higher relative carcass fat content, perirenal fat mass, and liver glycogen concentrations than all other groups. Expression of leptin mRNA in fetal perirenal fat and fetal plasma leptin concentrations were not significantly altered

  7. 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

  8. Fetal growth trajectory and risk for eczema in a Saudi population.

    PubMed

    AlMakoshi, Amel; Ellahi, Awaiss; Sallout, Bala; Devereux, Graham; Turner, Steve

    2015-12-01

    Recent studies in Western cohorts have identified associations between increasing fetal abdominal circumference (AC) during mid-pregnancy and increased risk for eczema and atopy. We sought to replicate these findings in a Saudi population where antenatal environmental exposures are different compared with Western countries. A Saudi birth cohort was recruited to relate maternal dietary intake and fetal growth to wheeze, eczema, and rhinitis in the first 2 yrs. Fetal size was determined from routine ultrasound scan measurements in the second and third trimesters and birthweight was noted. Parent-reported outcomes during the first 2 yrs were acquired by telephone-administered questionnaire. There were 1076 mothers recruited. AC was determined in 562 for the second, in 632 for the third, and in 281 for both second and third trimesters. A history of eczema was determined in 814 children at 2 yrs of age. There was an inverse relationship between change in abdominal circumference between the second and third trimesters for eczema (OR 0.66 per z score increase in AC [95% CI 0.49, 0.89]), and the quartile with the greatest faltering growth were at increased risk compared with other groups (p ≤ 0.045). Change in fetal size between the third trimester and birth was not associated with altered eczema risk. There were no associations between fetal growth and wheeze at the age of 2 yrs. Our findings contrast observations made in Western populations but nonetheless suggest that factors associated with changing fetal growth trajectory in the second half of pregnancy are also relevant to atopy development on the global setting. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. 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

  10. Maternal psychiatric disease and epigenetic evidence suggest a common biology for poor fetal growth.

    PubMed

    Ciesielski, Timothy H; Marsit, Carmen J; Williams, Scott M

    2015-08-25

    We sought to identify and characterize predictors of poor fetal growth among variables extracted from perinatal medical records to gain insight into potential etiologic mechanisms. In this process we reevaluated a previously observed association between poor fetal growth and maternal psychiatric disease. We evaluated 449 deliveries of >36 weeks gestation that occurred between 9/2008 and 9/2010 at the Women and Infants Hospital in Providence Rhode Island. This study group was oversampled for Small-for-Gestational-Age (SGA) infants and excluded Large-for-Gestational-Age (LGA) infants. We assessed the associations between recorded clinical variables and impaired fetal growth: SGA or Intrauterine Growth Restriction (IUGR) diagnosis. After validating the previously observed association between maternal psychiatric disease and impaired fetal growth we addressed weaknesses in the prior studies by explicitly considering antidepressant use and the timing of symptoms with respect to pregnancy. We then evaluated DNA methylation levels at 27 candidate loci in placenta from a subset of these deliveries (n = 197) to examine if epigenetic variation could provide insight into the mechanisms that cause this co-morbidity. Infants of mothers with prenatal psychiatric disease (Depression, Anxiety, OCD/Panic) had increased odds of poor fetal growth (ORadjusted = 3.36, 95%CI: 1.38-8.14). This relationship was similar among those who were treated with antidepressants (ORadjusted = 3.69, 95%CI: 1.31-10.45) and among those who were not (ORadjusted = 3.19, 95%CI: 1.30-7.83). Among those with a history of psychiatric disease but no active disease in pregnancy the ORadjusted was 0.45 (95%CI: 0.09-2.35). A locus near the transcription start site of the leptin receptor (cg21655790) had methylation levels that were decreased in the presence of: 1) SGA/IUGR, and 2) active but not resolved psychiatric disease (among mothers not on antidepressants). These results validate and

  11. Hyperoncotic enhancement of pulmonary growth after fetal tracheal occlusion: a comparison between dextran and albumin.

    PubMed

    Chang, Robert; Komura, Makoto; Andreoli, Steven; Klingenberg, Markus; Jennings, Russell; Wilson, Jay; Fauza, Dario

    2004-03-01

    This study was aimed at comparing albumin and dextran as intrapulmonary hyperoncotic enhancers of fetal lung growth after tracheal occlusion. Fetal lambs (n = 27) were divided proportionally into 5 groups: group I consisted of sham-operated controls; group II underwent tracheal occlusion (TO); groups III, IV, and V underwent TO and intratracheal infusion of 60 mL of either saline, 6% dextran-70, or 25% albumin, respectively. Multiple fetal lung analyses were performed near term. Statistical analysis was by 1-way analysis of variance (ANOVA) and post-hoc analyses by the Bonferroni correction for multiple comparisons (P <.05). The lung volume-to-body weight ratio was significantly higher in groups IV and V than in all other groups with no differences between groups II and III, nor between groups IV and V. Airspace fraction was not significantly different among the groups, nor was there any evidence of alveolar cellular damage. Type-II pneumocyte density was higher in group I than in groups II, IV, and V, with no differences among the latter 3 groups. Lung liquid biochemical profile was normal in all groups. Albumin is as effective as dextran as an intrapulmonary hyperoncotic booster of lung growth acceleration after fetal tracheal occlusion, with no lasting effects on its fetal lung liquid levels. As a naturally occurring oncotic agent, albumin may be a safer option in the clinical application of this therapeutic concept.

  12. Predictiveness of sonographic fetal weight estimation as a function of prior probability of intrauterine growth retardation.

    PubMed

    Simon, N V; Levisky, J S; Shearer, D M; Morris, K C; Hansberry, P A

    1988-06-01

    We evaluated the predictiveness of sonographically estimated fetal weight as a function of the estimation of probability of having intrauterine growth retardation (IUGR) before obtaining an ultrasound scan (prior probability). The value of the estimated fetal weight resided more in its high specificity than in its sensitivity, hence in its ability to confirm that the fetus is normal. The predictiveness of the method was further enhanced when the fetal weight estimation was placed in the context of the prior probability of IUGR. In particular, the positive predictive value of the test as well as the likelihood of having a growth-retarded infant in spite of an estimated fetal weight within the normal range were considerably higher as the prior probability of IUGR increased. Since the obstetrician using all available evidence is likely to form a rather good estimate of the possibility of IUGR before ordering a scan, this improvement in the predictiveness of estimated fetal weight through a Bayesian approach can be advantageously applied to ultrasound analysis and can effectively support clinical decision making.

  13. [Fetal magnetocardiography].

    PubMed

    van Leeuwen, P

    1997-09-01

    demonstrate the potential of the method in the examination of the fetal conductive system, arrhythmias, congential defects, growth, development of the autonomic system, acidosis and distress. Furthermore, first results in pathological cases indicate that it may become a valuable tool in prenatal diagnostics. Improvements in instrumentation as well as prospective multicenter studies with larger numbers of appropriate subjects are required to determine whether magnetocardiography will establish itself as a new tool in clinical fetal, surveillance.

  14. Fetal akinesia.

    PubMed

    Hammond, E; Donnenfeld, A E

    1995-03-01

    Normal fetal growth and development during pregnancy is highly dependent upon adequate fetal movement. Limitation of movement, regardless of the underlying cause, can result in a particular pattern of abnormal fetal morphogenesis. This phenotype is termed the fetal akinesia deformation sequence (FADS). The etiology of fetal akinesia may be generally classified into one of five categories: neuropathy, myopathy, restrictive dermopathy, teratogen exposure, or restricted movement due to intrauterine constraint. In this article, the differential diagnosis of fetal akinesia is systematically reviewed and information regarding prenatal diagnosis, prognosis, perinatal management, and recurrence risks are discussed.

  15. Physically demanding work, fetal growth and the risk of adverse birth outcomes. The Generation R Study.

    PubMed

    Snijder, Claudia A; Brand, Teus; Jaddoe, Vincent; Hofman, Albert; Mackenbach, Johan P; Steegers, Eric A P; Burdorf, Alex

    2012-08-01

    Work-related risk factors, such as long work hours, and physically demanding work have been suggested to adversely influence pregnancy outcome. The authors aimed to examine associations between various aspects of physically demanding work with fetal growth in different trimesters during pregnancy and the risks of adverse birth outcomes. Associations between physically demanding work and fetal growth were studied in 4680 pregnant women participating in a population-based prospective cohort study from early pregnancy onwards in The Netherlands (2002-2006). Mothers who filled out a questionnaire during mid-pregnancy (response 77% of enrolment) were included if they conducted paid employment and had a spontaneously conceived singleton live born pregnancy. Questions on physical workload were obtained from the Dutch Musculoskeletal Questionnaire and concerned questions on lifting, long periods of standing or walking, night shifts and working hours. Fetal growth characteristics were repeatedly measured by ultrasound and were used in combination with measurements at birth. There were no consistent significant associations between physically demanding work nor working hours in relation to small for gestational age, low birth weight or preterm delivery. Women exposed to long periods of standing had lower growth rates for fetal head circumference (HC), resulting in a reduction of approximately 1 cm (3%) of the average HC at birth. Compared with women working <25 h/week, women working 25-39 h/week and >40 h/week had lower growth rates for both fetal weight and HC, resulting in a difference of approximately 1 cm in HC at birth and a difference of 148-198 g in birth weight. Long periods of standing and long working hours per week during pregnancy seem to negatively influence intrauterine growth.

  16. Factors associated with ultrasound-aided detection of suboptimal fetal growth in a malaria-endemic area in Papua New Guinea.

    PubMed

    Unger, Holger Werner; Ome-Kaius, Maria; Karl, Stephan; Singirok, Dupain; Siba, Peter; Walker, Jane; Wangnapi, Regina Alice; Mueller, Ivo; Rogerson, Stephen John

    2015-04-03

    Fetal growth restriction (FGR) is associated with increased infant mortality rates and ill-health in adulthood. Evaluation of fetal growth requires ultrasound. As a result, ultrasound-assisted evaluations of causes of FGR in malaria-endemic developing countries are rare. We aimed to determine factors associated with indicators of abnormal fetal growth in rural lowland Papua New Guinea (PNG). Weights and growth of 671 ultrasound-dated singleton pregnancies (<25 gestational weeks) were prospectively monitored using estimated fetal weights and birthweights. Maternal nutritional status and haemoglobin levels were assessed at enrolment, and participants were screened for malaria on several occasions. FGR was suspected upon detection of an estimated fetal weight or birthweight <10(th) centile (small-for-gestational age) and/or low fetal weight gain, defined as a change in weight z-score in the first quartile. Factors associated with fetal weight and fetal weight gain were additionally assessed by evaluating differences in weight z-scores and change in weight z-scores. Log-binomial and linear mixed effect models were used to determine factors associated with indicators of FGR. SGA and low weight gain were detected in 48.3% and 37.0% of pregnancies, respectively. Of participants, 13.8%, 21.2%, and 22.8% had a low mid-upper arm circumference (MUAC, <22 cms), short stature (<150 cms) and anaemia (haemoglobin <90 g/L) at first antenatal visit. 24.0% (161/671) of women had at least one malaria infection detected in peripheral blood. A low MUAC (adjusted risk ratio [aRR] 1.51, 95% CI 1.29, 1.76, P < 0.001), short stature (aRR 1.27, 95% CI 1.04, 1.55, P = 0.009), and anaemia (aRR 1.27, 95% CI 1.06, 1.51, P = 0.009) were associated with SGA, and a low body mass index was associated with low fetal weight gain (aRR 2.10, 95% CI 1.62, 2.71, P < 0.001). Additionally, recent receipt of intermittent preventive treatment in pregnancy was associated with increased weight

  17. [Consequences of smoking on fetal development and risk of intra-uterine growth retardation or in utero fetal death].

    PubMed

    Collet, M; Beillard, C

    2005-04-01

    Active and passive smoking constitutes one of the most serious public health problems due to the deleterious effect on the expected infant and the mother. These effects are dose dependent as illustrated by intra-uterine growth retardation, where the effect worsens with duration of smoking during pregnancy, and also by other conditions such as abrutio placentae or placenta praevia, premature rupture of the membranes and preterm birth, where the risk is multiplied by two (or even three)! In utero death is the ultimate sanction. Studies on the consequences of maternal smoking on fetal development have demonstrated the cardiovascular effect (CO and nicotine) and the respiratory effect (CO) which can be aggravated after birth by passive smoking. Teratogenic and cancerogenic effects have also been clearly demonstrated. Maternal smoking would also affect fetal brain development with negative effects on the major neurotransmitter systems (domaminergic, serotinergic, noradrenergic) and on the development of key structures such as the prefrontal cortex, certain limbic structures including the hippocampus and other structures implicated in motor function such as the ventral striatum. These development anomalies of the brain could give rise, after birth, to psychological, behavioral, attention and cognitive disorders, further arguments in favor of an effective anti-smoking policy including appropriate care for smoking pregnant mothers in both hospital and outpatient settings.

  18. Assessment of Fetal Autonomic Nervous System Activity by Fetal Magnetocardiography: Comparison of Normal Pregnancy and Intrauterine Growth Restriction

    PubMed Central

    Fukushima, Akimune; Nakai, Kenji; Kanasugi, Tomonobu; Terata, Miyuki; Sugiyama, Toru

    2011-01-01

    Objective. To clarify the developmental activity of the autonomic nervous system (ANS) of the normal fetus and intrauterine growth restriction (IUGR) cases using fetal magnetocardiography (FMCG). Subjects and Methods. Normal pregnancy (n = 35) and IUGR (n = 12) cases at 28–39 and 32–37 weeks of gestation, respectively, were included in this study. The R-R interval variability was used to calculate the coefficient of variance (CVRR) and low frequency/high frequency (LF/HF) ratio. Results. The value of CVRR in the normal pregnancy group displayed a slight increasing trend with gestational age. However, no such trend was observed in the IUGR group. In contrast, the LF/HF ratio in both the normal pregnancy group and the IUGR group clearly increased over the gestational period; the normal group showing statistical significance. Conclusion. The development of fetal ANS activity in IUGR cases might differ from that observed in the normal pregnancy group, and this may facilitate early detection of IUGR. PMID:21547087

  19. IFPA Meeting 2011 workshop report II: Angiogenic signaling and regulation of fetal endothelial function; placental and fetal circulation and growth; spiral artery remodeling.

    PubMed

    Bulmer, J N; Burton, G J; Collins, S; Cotechini, T; Crocker, I P; Croy, B A; Cvitic, S; Desforges, M; Deshpande, R; Gasperowicz, M; Groten, T; Haugen, G; Hiden, U; Host, A J; Jirkovská, M; Kiserud, T; König, J; Leach, L; Murthi, P; Pijnenborg, R; Sadekova, O N; Salafia, C M; Schlabritz-Loutsevitch, N; Stanek, J; Wallace, A E; Westermeier, F; Zhang, J; Lash, G E

    2012-02-01

    Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2011 there were twelve themed workshops, three of which are summarized in this report. These workshops related to vascular systems and circulation in the mother, placenta and fetus, and were divided in to 1) angiogenic signaling and regulation of fetal endothelial function; 2) placental and fetal circulation and growth; 3) spiral artery remodeling.

  20. Placental Vitamin D-Binding Protein Expression in Human Idiopathic Fetal Growth Restriction

    PubMed Central

    Wookey, Alice F.; Chollangi, Tejasvy; Yong, Hannah E. J.

    2017-01-01

    Vitamin D-binding protein is a multifunctional serum protein with multiple actions related to normal health. Vitamin D-binding protein transports vitamin D and influences the metabolism of this key hormone but it also has additional immunomodulatory and actin-clearing properties. We investigated whether vitamin D-binding protein expression is altered in fetal growth restriction-associated placental dysfunction. Protein was extracted from 35 placentae derived from 17 healthy control subjects and 18 gestation-matched subjects with fetal growth restriction (FGR). FGR subjects were further subdivided as idiopathic (n = 9) and nonidiopathic (n = 9). Vitamin D-binding protein and 25(OH) vitamin D were measured by ELISA and normalized to protein concentration. The results showed significantly reduced levels of placental vitamin D-binding protein (control versus FGR, p < 0.05, Student's t-test) that were strongly associated with idiopathic fetal growth restriction (p < 0.01, Kruskal-Wallis), whereas levels of vitamin D-binding protein were not associated with placental 25(OH) vitamin D stores (p = 0.295, Pearson's correlation). As such, vitamin D-binding protein may be a factor in unexplained placental dysfunction associated with idiopathic fetal growth restriction and may potentially serve as a biomarker of this disease. PMID:28293436

  1. Paternal Low Protein Diet Programs Preimplantation Embryo Gene Expression, Fetal Growth and Skeletal Development in Mice.

    PubMed

    Watkins, Adam J; Sirovica, Slobodan; Stokes, Ben; Isaacs, Mark; Addison, Owen; Martin, Richard A

    2017-02-08

    Defining the mechanisms underlying the programming of early life growth is fundamental for improving adult health and wellbeing. While the association between maternal diet, offspring growth and adult disease risk is well-established, the effect of father's diet on offspring development are largely unknown. Therefore, we fed male mice an imbalanced low protein diet (LPD) to determine the impact on post-fertilisation development and fetal growth. We observed that in preimplantation embryos derived from LPD fed males, expression of multiple genes within the central metabolic AMPK pathway was reduced. In late gestation, paternal LPD programmed increased fetal weight, however, placental weight was reduced, resulting in an elevated fetal:placental weight ratio. Analysis of gene expression patterns revealed increased levels of transporters for calcium, amino acids and glucose within LPD placentas. Furthermore, placental expression of the epigenetic regulators Dnmt1 and Dnmt3L were increased also, coinciding with altered patterns of maternal and paternal imprinted genes. More strikingly, we observed fetal skeletal development was perturbed in response to paternal LPD. Here, while offspring of LPD fed males possessed larger skeletons, their bones comprised lower volumes of high mineral density in combination with reduced maturity of bone apatite. These data offer new insight in the underlying programming mechanisms linking poor paternal diet at the time of conception with the development and growth of his offspring.

  2. 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.

  3. Relationship between arterial and venous Doppler and perinatal outcome in fetal growth restriction.

    PubMed

    Baschat, A A; Gembruch, U; Reiss, I; Gortner, L; Weiner, C P; Harman, C R

    2000-10-01

    fetuses with abnormal venous flows. The only statistically significant relation between Doppler indices and outcome was the association between abnormal ductus venosus flow and fetal death (r2 = 0.24, P < 0.05). Growth restricted fetuses with abnormal venous flow have worse perinatal outcome compared to those where flow abnormality is confined to the umbilical or middle cerebral artery. In fetuses with low middle cerebral artery pulsatility, venous Doppler allows detection of further deterioration. While abnormal venous flows can be significantly associated with fetal demise, gestational age at delivery significantly impacts on all short-term outcomes.

  4. Comparison between Urinary Oestrogen Assay and Serial Ultrasonic Cephalometry in Assessment of Fetal Growth Retardation

    PubMed Central

    Campbell, Stuart; Kurjak, Asim

    1972-01-01

    Urinary oestrogen assay and serial ultrasonic cephalometry were performed on 284 patients who were considered on clinical grounds to be at risk of having a growth-retarded fetus. It was found that ultrasonic cephalometry was significantly better than oestrogens in diagnosing the small-for-dates baby, but that there was no significant difference between the two methods in predicting perinatal asphyxia. Of the 14 stillbirths, three were in the normal ultrasonic growth rate group and five had normal oestrogen excretion. Both methods were found to be of value in the diagnosis of fetal growth-retardation, although cephalometry would seem to have some advantages, especially in distinguishing between fetal growth-retardation and mistaken maturity. PMID:4673993

  5. Variation in Excessive Fetal Growth across Levels of Prenatal Care among Women with Gestational Diabetes.

    PubMed

    Hale, Nathan L; Probst, Janice C; Liu, Jihong; Bennett, Kevin J; Martin, Amy Brock; Glover, Saundra

    2011-10-01

    Examine the association between prenatal care and excessive fetal growth outcomes among mothers with gestational diabetes mellitus (GDM). We conducted a retrospective analysis of 2004-2007 singleton live births to South Carolina women, limited to those for whom both birth certificate and hospital discharge data were available (N = 179 957). Gestational diabetes mellitus was identified from birth certificate and/or hospital discharge claims. Measures of excessive fetal growth were large for gestational age (90th and 95th percentiles) and macrosomia (birth weight > 4500 g). The Adequacy of Prenatal Care Utilization index was used to measure prenatal care. Gestational diabetes mellitus was recorded for 6.9% of women in the study population. Women with GDM were more likely than other women to have an infant with excessive fetal growth, regardless of the level of prenatal care; however, there was a significant interaction between GDM status and levels of prenatal care. All women with GDM had increased odds for large infant outcomes. However, those receiving inadequate prenatal care were markedly more likely to experience excessive fetal growth outcomes (odds ratio = 1.38, confidence interval = 1.15-1.66) than women also with GDM and intermediate/adequate prenatal care. Similar patterns were noted for large for gestational age (95th) and macrosomia (total birth weight ≥ 4500 g). Observed associations suggest a link between inadequate prenatal care and a higher risk for excessive fetal growth among women with GDM. Further research is needed to clarify the nature of the association and suggest ways to get high-risk women into care sooner.

  6. Maternal fish consumption, fetal growth and the risks of neonatal complications: the Generation R Study.

    PubMed

    Heppe, Denise H M; Steegers, Eric A P; Timmermans, Sarah; Breeijen, Hanneke den; Tiemeier, Henning; Hofman, Albert; Jaddoe, Vincent W V

    2011-03-01

    Maternal fish consumption during pregnancy has been suggested to affect birth outcomes. Previous studies mainly focused on birth outcomes and did not study fetal growth during pregnancy. In a prospective cohort study from early pregnancy onwards in The Netherlands, we assessed the associations of first-trimester maternal total-fish, lean-fish, fatty-fish and shellfish consumption with fetal growth characteristics in the second and third trimesters, growth characteristics at birth and the risks of neonatal complications, including pre-term birth, low birth weight and small for gestational age. In total, 3380 mothers completed a 293-item semi-quantitative FFQ to obtain information about fish consumption during the first trimester of pregnancy. Head circumference, femur length and fetal weight were estimated in the second and third trimesters by ultrasound. Information about birth anthropometrics and neonatal complications was available from hospital and midwife registries. Maternal older age, higher educational level, folic acid supplement use, alcohol use and not smoking were associated with higher fish consumption (P < 0·01). After adjustment, we observed no consistent associations of maternal total-fish consumption or specific consumption of lean fish, fatty fish or shellfish with fetal growth characteristics in the second and third trimesters and at birth. Likewise, total-fish consumption or specific consumption of any type of fish was not consistently associated with the risks of neonatal complications. These findings suggest that in a population with a relatively low fish intake, consumption of lean fish, fatty fish or shellfish in the first trimester is not associated with fetal growth or the risks of neonatal complications.

  7. Maternal uterine natural killer cells nurture fetal growth: in medio stat virtus.

    PubMed

    Colucci, Francesco; Kieckbusch, Jens

    2015-02-01

    Much research in reproductive immunology is preoccupied with maternal tolerance of the semi-allogeneic fetus. This inevitably leads to the assumption that the maternal immune system should be suppressed, similarly to the immunosuppression needed to avoid rejection of an allograft. However, the parallels with transplantation immunology are misleading, and we discuss how interactions between variable immune system genes expressed on maternal natural killer (NK) cells and on the fetal trophoblast modulate fetal growth. Exaggerated suppression or activation of maternal NK cells associates with both extremes of birth weight. Copyright © 2015. Published by Elsevier Ltd.

  8. Temporal pattern of accelerated lung growth after tracheal occlusion in the fetal rabbit.

    PubMed Central

    De Paepe, M. E.; Johnson, B. D.; Papadakis, K.; Sueishi, K.; Luks, F. I.

    1998-01-01

    Tracheal occlusion in utero is a potent stimulus of fetal lung growth. We describe the early growth mechanics of fetal lungs and type II pneumocytes after tracheal ligation (TL). Fetal rabbits underwent TL at 24 days gestational age (DGA; late pseudoglandular stage; term = 31 to 33 days) and were sacrificed at time intervals ranging from 1 to 5 days after TL. Lung growth was measured by stereological volumetry and bromodeoxyuridine (BrdU) pulse labeling. Pneumocyte II population kinetics were analyzed using a combination of anti-surfactant protein A and BrdU immunohistochemistry and computer-assisted morphometry. Nonoperated littermates served as controls. TL resulted in dramatically enhanced lung growth (lung weight/body weight was 5.00 +/- 0.81% in TL versus 2.52 +/- 0.13% in controls at 29 DGA; P < 0.001, unpaired Student's t-test). Post-TL lung growth was characterized by a 3-day lag-phase typified by relative stagnation of growth, followed by distension of airspaces, increased cell proliferation, and accelerated architectural and cellular maturation by postligation days 4 and 5. During the proliferation phase, the replicative activity of type II cells was markedly increased (type II cell BrdU labeling index was 10.0 +/- 4.1% in TL versus 1.1 +/- 0.3% for controls at 29 DGA; P < 0.02), but their numerical density decreased (3.0 +/- 0.5 x 10(-3)/microm2 in TL versus 4.5 +/- 0.3 x 10(-3)/microm2 in controls at 29 DGA; P < 0.02), suggesting accelerated terminal differentiation to type I cells. In conclusion, post-TL lung development is characterized by a well defined temporal pattern of lung growth and maturation. The rabbit model lends itself well to study the regulatory mechanisms underlying accelerated fetal lung growth after TL. Images Figure 2 Figure 4 Figure 6 Figure 8 Figure 9 PMID:9422535

  9. The roles of placental growth hormone and placental lactogen in the regulation of human fetal growth and development.

    PubMed

    Handwerger, S; Freemark, M

    2000-04-01

    The human growth hormone (hGH)/human placental lactogen (hPL) gene family, which consists of two GH and three PL genes, is important in the regulation of maternal and fetal metabolism and the growth and development of the fetus. During pregnancy, pituitary GH (hGH-N) expression in the mother is suppressed; and hGH-V, a GH variant expressed by the placenta, becomes the predominant GH in the mother. hPL, which is the product of the hPL-A and hPL-B genes, is secreted into both the maternal and fetal circulations after the sixth week of pregnancy. hGH-V and hPL act in concert in the mother to stimulate insulin-like growth factor (IGF) production and modulate intermediary metabolism, resulting in an increase in the availability of glucose and amino acids to the fetus. In the fetus, hPL acts via lactogenic receptors and possibly a unique PL receptor to modulate embryonic development, regulate intermediary metabolism and stimulate the production of IGFs, insulin, adrenocortical hormones and pulmonary surfactant. hGH-N, which is expressed by the fetal pituitary, has little or no physiological actions in the fetus until late in pregnancy due to the lack of functional GH receptors on fetal tissues. hGH-V, which is also a potent somatogenic hormone, is not released into the fetus. Taken together, studies of the hGH/hPL gene family during pregnancy reveal a complex interaction of the hormones with one another and with other growth factors. Additional investigations are necessary to clarify the relative roles of the family members in the regulation of fetal growth and development and the factors that modulate the expression of the genes.

  10. MCT8 expression in human fetal cerebral cortex is reduced in severe intrauterine growth restriction.

    PubMed

    Chan, Shiao Y; Hancox, Laura A; Martín-Santos, Azucena; Loubière, Laurence S; Walter, Merlin N M; González, Ana-Maria; Cox, Phillip M; Logan, Ann; McCabe, Christopher J; Franklyn, Jayne A; Kilby, Mark D

    2014-02-01

    The importance of the thyroid hormone (TH) transporter, monocarboxylate transporter 8 (MCT8), to human neurodevelopment is highlighted by findings of severe global neurological impairment in subjects with MCT8 (SLC16A2) mutations. Intrauterine growth restriction (IUGR), usually due to uteroplacental failure, is associated with milder neurodevelopmental deficits, which have been partly attributed to dysregulated TH action in utero secondary to reduced circulating fetal TH concentrations and decreased cerebral thyroid hormone receptor expression. We postulate that altered MCT8 expression is implicated in this pathophysiology; therefore, in this study, we sought to quantify changes in cortical MCT8 expression with IUGR. First, MCT8 immunohistochemistry was performed on occipital and parietal cerebral cortex sections obtained from appropriately grown for gestational age (AGA) human fetuses between 19 weeks of gestation and term. Secondly, MCT8 immunostaining in the occipital cortex of stillborn IUGR human fetuses at 24-28 weeks of gestation was objectively compared with that in the occipital cortex of gestationally matched AGA fetuses. Fetuses demonstrated widespread MCT8 expression in neurons within the cortical plate and subplate, in the ventricular and subventricular zones, in the epithelium of the choroid plexus and ependyma, and in microvessel wall. When complicated by IUGR, fetuses showed a significant fivefold reduction in the percentage area of cortical plate immunostained for MCT8 compared with AGA fetuses (P<0.05), but there was no significant difference in the proportion of subplate microvessels immunostained. Cortical MCT8 expression was negatively correlated with the severity of IUGR indicated by the brain:liver weight ratios (r(2)=0.28; P<0.05) at post-mortem. Our results support the hypothesis that a reduction in MCT8 expression in the IUGR fetal brain could further compromise TH-dependent brain development.

  11. MCT8 expression in human fetal cerebral cortex is reduced in severe intrauterine growth restriction

    PubMed Central

    Chan, Shiao Y; Hancox, Laura A; Martín-Santos, Azucena; Loubière, Laurence S; Walter, Merlin N M; González, Ana-Maria; Cox, Phillip M; Logan, Ann; McCabe, Christopher J; Franklyn, Jayne A; Kilby, Mark D

    2014-01-01

    The importance of the thyroid hormone (TH) transporter, monocarboxylate transporter 8 (MCT8), to human neurodevelopment is highlighted by findings of severe global neurological impairment in subjects with MCT8 (SLC16A2) mutations. Intrauterine growth restriction (IUGR), usually due to uteroplacental failure, is associated with milder neurodevelopmental deficits, which have been partly attributed to dysregulated TH action in utero secondary to reduced circulating fetal TH concentrations and decreased cerebral thyroid hormone receptor expression. We postulate that altered MCT8 expression is implicated in this pathophysiology; therefore, in this study, we sought to quantify changes in cortical MCT8 expression with IUGR. First, MCT8 immunohistochemistry was performed on occipital and parietal cerebral cortex sections obtained from appropriately grown for gestational age (AGA) human fetuses between 19 weeks of gestation and term. Secondly, MCT8 immunostaining in the occipital cortex of stillborn IUGR human fetuses at 24–28 weeks of gestation was objectively compared with that in the occipital cortex of gestationally matched AGA fetuses. Fetuses demonstrated widespread MCT8 expression in neurons within the cortical plate and subplate, in the ventricular and subventricular zones, in the epithelium of the choroid plexus and ependyma, and in microvessel wall. When complicated by IUGR, fetuses showed a significant fivefold reduction in the percentage area of cortical plate immunostained for MCT8 compared with AGA fetuses (P<0.05), but there was no significant difference in the proportion of subplate microvessels immunostained. Cortical MCT8 expression was negatively correlated with the severity of IUGR indicated by the brain:liver weight ratios (r2=0.28; P<0.05) at post-mortem. Our results support the hypothesis that a reduction in MCT8 expression in the IUGR fetal brain could further compromise TH-dependent brain development. PMID:24204008

  12. RNA Sequencing Exposes Adaptive and Immune Responses to Intrauterine Growth Restriction in Fetal Sheep Islets.

    PubMed

    Kelly, Amy C; Bidwell, Christopher A; McCarthy, Fiona M; Taska, David J; Anderson, Miranda J; Camacho, Leticia E; Limesand, Sean W

    2017-04-01

    The risk of type 2 diabetes is increased in children and adults who exhibited fetal growth restriction. Placental insufficiency and intrauterine growth restriction (IUGR) are common obstetrical complications associated with fetal hypoglycemia and hypoxia that reduce the β-cell mass and insulin secretion. In the present study, we have defined the underlying mechanisms of reduced growth and proliferation, impaired metabolism, and defective insulin secretion previously established as complications in islets from IUGR fetuses. In an IUGR sheep model that recapitulates human IUGR, high-throughput RNA sequencing showed the transcriptome of islets isolated from IUGR and control sheep fetuses and identified the transcripts that underlie β-cell dysfunction. Functional analysis expanded mechanisms involved in reduced proliferation and dysregulated metabolism that include specific cell cycle regulators and growth factors and mitochondrial, antioxidant, and exocytotic genes. These data also identified immune responses, wnt signaling, adaptive stress responses, and the proteasome as mechanisms of β-cell dysfunction. The reduction of immune-related gene expression did not reflect a change in macrophage density within IUGR islets. The present study reports the islet transcriptome in fetal sheep and established processes that limit insulin secretion and β-cell growth in fetuses with IUGR, which could explain the susceptibility to premature islet failure in adulthood. Islet dysfunction formed by intrauterine growth restriction increases the risk for diabetes. Copyright © 2017 Endocrine Society.

  13. Correlation between Maternal Characteristics during Early Pregnancy, Fetal Growth Rate and Newborn Weight in Healthy Pregnancies.

    PubMed

    Caradeux, Javier; Serra, Ramón; Palmeiro, Yasna; Correa, Paula J; Valenzuela, Ignacio; Olguin, Jaime; Montenegro, Lazaro; Nien, Jyh Kae; Osorio, Eduardo; Illanes, Sebastián

    2016-01-01

    The objective of this study was to evaluate the association between maternal characteristics in early pregnancy and fetal growth (FG) and birth weight (BW). A prospective cohort study was performed in unselected pregnant women who attended an ultrasound evaluation at 11-14 weeks of pregnancy. Medical history, biochemical blood tests, biophysical variables and fetal weight at 20-25 and 30-36 weeks as well as the BW were assessed. Bivariate and multivariate linear models were constructed. In all, 543 patients with normal pregnancy and labor were selected. The multiple regression analysis showed a statistically significant association between maternal body mass index (BMI) in early pregnancy and the uterine artery pulsatility index (UtAPI) in the first trimester with BW (p < 0.0008) and with the ratio of fetal growth between the second and third trimesters (p < 0.0001). No correlation was found between these variables and first trimester levels of hemoglobin or glycemia. Maternal first trimester BMI and UtAPI correlate with the rate of intrauterine FG and with the BW. This evidence highlights the influence of maternal first trimester variables on fetuses with normal growth and the potential role of these variables in fetal programming. © 2016 S. Karger AG, Basel.

  14. Misoprostol versus Foley catheter insertion for induction of labor in pregnancies affected by fetal growth restriction.

    PubMed

    Chavakula, Pearlin R; Benjamin, Santosh J; Abraham, Anuja; Londhe, Vaibhav; Jeyaseelan, Visalakshi; Mathews, Jiji E

    2015-05-01

    To compare 25μg of vaginal misoprostol with a Foley catheter for induction of labor (IOL) for fetal growth restriction. A randomized controlled trial was conducted in a tertiary center in South India. Women with fetal growth restriction (n=100) were randomized to be induced with three doses of vaginal misoprostol (25μg) every 6hours or with an intracervical Foley catheter, inserted 12hours before rupture of membranes, and oxytocin if needed. The primary outcome was uterine tachysystole with fetal cardiotocography abnormalities. Secondary outcomes pertained to effectiveness, complications, and patient satisfaction. One woman in the misoprostol group and none in the Foley catheter group had uterine tachysystole. The duration of labor from IOL to delivery was similar in both groups (P=0.416). More women in the misoprostol group had a vaginal delivery within 12hours (26.1% versus 5.6%; P=0.005). Women induced with misoprostol were less likely to deliver by lower-segment cesarean delivery (15.2% versus 29.6%; P=0.168) and to require oxytocin augmentation (60.9% versus 85.2%; P=0.007). Complications were few in both group. Few women had uterine tachysystole with cardiotocography abnormalities. Vaginal misoprostol at 25μg was more effective than a Foley catheter for IOL in fetal growth restriction. Clinical Trials Registry India:CTRI/2014/02/004411. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  15. 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.

  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.

  17. 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.

  18. Population versus Customized Fetal Growth Norms and Adverse Outcomes in an Intrapartum Cohort

    PubMed Central

    Costantine, Maged M.; Lai, Yinglei; Bloom, Steven L.; Spong, Catherine Y.; Varner, Michael W.; Rouse, Dwight J.; Ramin, Susan M.; Caritis, Steve N.; Peaceman, Alan M.; Sorokin, Yoram; Sciscione, Anthony; Mercer, Brian M.; Thorp, John M.; Malone, Fergal D.; Harper, Margaret; Iams, Jay D.

    2013-01-01

    Objective To compare population versus customized fetal growth norms in identifying neonates at risk for adverse outcomes (APO) associated with small for gestational age (SGA). Study Design Secondary analysis of an intrapartum fetal pulse oximetry trial in nulliparous women at term. Birthweight percentiles were calculated using ethnicity- & gender-specific population norms and customized norms (Gardosi). Results 508 (9.9%) and 584 (11.3%) neonates were SGA by population (SGApop) and customized (SGAcust) norms. SGApop infants were significantly associated with a composite adverse neonatal outcome, neonatal intensive care admission, low fetal oxygen saturation and reduced risk of cesarean delivery; while both SGApop and SGAcust were associated with a 5-minute Apgar score < 4. The ability of customized and population birthweight percentiles in predicting APO was poor (12 out of 14 APOs had AUC <0.6). Conclusion In this intrapartum cohort, neither customized nor normalized-population norms adequately identify neonates at risk of APO related to SGA. PMID:22893556

  19. 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

  20. Antenatal betamethasone and fetal growth in prematurely born children: implications for temperament traits at the age of 2 years.

    PubMed

    Pesonen, Anu-Katriina; Räikkönen, Katri; Lano, Aulikki; Peltoniemi, Outi; Hallman, Mikko; Kari, M Anneli

    2009-01-01

    We explored whether repeated dose of antenatal betamethasone and variation in intrauterine growth of prematurely born children predict temperament characteristics at the age of 2 years. The patients (n = 142) were prematurely born children (mean gestational age: 31.0 weeks; range: 24.6-35.0 weeks) who participated in a randomized and blinded trial testing the effects of a repeated dose of antenatal betamethasone in imminent preterm birth. Fetal growth was estimated as weight, length, and head circumference in SDs according to Finnish growth charts. Parents assessed their toddlers' temperament with 201 items of the Early Childhood Temperament Questionnaire (mean child corrected age: 2.1 years). No significant main effects of repeated betamethasone on toddler temperament existed. However, a significant interaction between study group and duration of exposure to betamethasone emerged; those exposed to a repeated dose for >24 hours before delivery were more impulsive. One-SD increases in weight, length, and head circumference at birth were associated with 0.14- to 0.19-SD lower levels of negative affectivity (fearfulness, anger proneness, and sadness); 1-SD increases in length, weight, and head circumference at birth were associated with 0.14- to 0.18-SD higher levels of effortful control (self-regulation). Repeated antenatal betamethasone did not induce alterations in toddler temperament. The results, however, suggest that a longer duration of exposure is associated with higher impulsivity scores. Regardless of betamethasone exposure, slower fetal growth exerted influences on temperament. Our findings indicate prenatal programming of psychological development and imply that more attention is needed to support the development of infants born at the lower end of the fetal growth distribution.

  1. 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

  2. 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.

  3. Lung-derived growth factors: possible paracrine effectors of fetal lung development

    SciTech Connect

    Montes, A.M.

    1985-01-01

    A potential role for paracrine secretions in lung organogenesis has been hypothesized (Alescio and Piperno, 1957). These studies present direct support for the paracrine model by demonstrating the presence of locally produced mitogenic/maturational factors in fetal rat lung tissue. Conditioned serum free medium (CSFM) from nineteen-day fetal rat lung cultures was shown to contain several bioactive peptides as detected by /sup 3/H-Thymidine incorporation into chick embryo and rat lung fibroblasts, as well as /sup 14/C-choline incorporation into surfactant in mixed cell cultures. Using ion-exchange chromatography and Sephadex gel filtration, a partially purified mitogen, 11-III, was obtained. The partially purified 11-III stimulates mitosis in chick embryo fibroblasts and post-natal rat lung fibroblasts. Multiplication in fetal rat lung fibroblasts cultures is stimulated only when these are pre-incubated with a competence factor or unprocessed CSFM. This suggests the existence of an endogenously produced competence factor important in the regulation of fetal lung growth. Preparation 11-III does not possess surfactant stimulating activity as assessed by /sup 3/H-choline incorporation into lipids in predominantly type-II cell cultures. These data demonstrate the presence of a maturational/mitogenic factor, influencing type-II mixed cell cultures. In addition, 11-III had been shown to play an autocrine role stimulating the proliferation of fetal lung fibroblasts. Finally, these data suggest the existence of a local produced competence factor.

  4. Embryonic growth discordance and early fetal loss: the STORK multiple pregnancy cohort and systematic review.

    PubMed

    D'Antonio, F; Khalil, A; Mantovani, E; Thilaganathan, B

    2013-10-01

    Is there an association between discordance in embryonic growth and fetal loss at the time of the 11-14-week scan in twin pregnancies? Regardless of the chorionicity, crown rump length (CRL) discordance at 7(+0)-9(+6) weeks is predictive of subsequent single fetal demise in the first trimester. Previous small studies have reported a variable association between discordance in embryonic growth and subsequent fetal loss. Retrospective study of all twin pregnancies of known chorionicity from a large regional cohort over a 10-year period. A total of 1356 twin pregnancies (288 monochorionic and 1068 dichorionic) were included in the study. Women presenting to the early pregnancy unit were included in the study. Logistic regression, ROC curve and Kaplan-Meier analyses were performed to evaluate the association between CRL discordance at 7(+0)-9(+6) weeks and spontaneous single fetal loss diagnosed at the 11-14-week scan. A systematic review was also performed using MEDLINE, EMBASE, Cinahl and the Cochrane Library in order to explore the relationship between early growth discordance and single fetal loss in twin pregnancies. There were 111 (8.2%) single fetal losses diagnosed at 11-14 weeks in this cohort. At multivariate analysis, CRL discordance percentile [odds ratio (OR) 1.20; 95% confidence interval (CI), 1.12-1.63, P < 0.0001] and CRL <5th centile of at least one twin (OR, 2.21; 95% CI 1.23-4.24, P = 0.023), but not chorionicity (P = 0.486) or maternal age (P = 0.283) was independently associated with the loss of one fetus at the 11-14-week scan. The predictive accuracy of CRL discordance for single fetal loss was high (AUC = 0.93; 95% CI = 0.91-0.94). A significant association was found between the increase in the degree of embryonic discordance and the likelihood of early fetal loss (P < 0.0001). Only a high-risk population was analysed. Therefore, the patients studied were not a representative sample from the population of women pregnant with twins. Twin

  5. 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

  6. Fetal growth and risk of stillbirth: a population-based case-control study.

    PubMed

    Bukowski, Radek; Hansen, Nellie I; Willinger, Marian; Reddy, Uma M; Parker, Corette B; Pinar, Halit; Silver, Robert M; Dudley, Donald J; Stoll, Barbara J; Saade, George R; Koch, Matthew A; Rowland Hogue, Carol J; Varner, Michael W; Conway, Deborah L; Coustan, Donald; Goldenberg, Robert L

    2014-04-01

    Stillbirth is strongly related to impaired fetal growth. However, the relationship between fetal growth and stillbirth is difficult to determine because of uncertainty in the timing of death and confounding characteristics affecting normal fetal growth. We conducted a population-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in five geographic areas in the US. Fetal growth abnormalities were categorized as small for gestational age (SGA) (<10th percentile) or large for gestational age (LGA) (>90th percentile) at death (stillbirth) or delivery (live birth) using population, ultrasound, and individualized norms. Gestational age at death was determined using an algorithm that considered the time-of-death interval, postmortem examination, and reliability of the gestational age estimate. Data were weighted to account for the sampling design and differential participation rates in various subgroups. Among 527 singleton stillbirths and 1,821 singleton live births studied, stillbirth was associated with SGA based on population, ultrasound, and individualized norms (odds ratio [OR] [95% CI]: 3.0 [2.2 to 4.0]; 4.7 [3.7 to 5.9]; 4.6 [3.6 to 5.9], respectively). LGA was also associated with increased risk of stillbirth using ultrasound and individualized norms (OR [95% CI]: 3.5 [2.4 to 5.0]; 2.3 [1.7 to 3.1], respectively), but not population norms (OR [95% CI]: 0.6 [0.4 to 1.0]). The associations were stronger with more severe SGA and LGA (<5th and >95th percentile). Analyses adjusted for stillbirth risk factors, subset analyses excluding potential confounders, and analyses in preterm and term pregnancies showed similar patterns of association. In this study 70% of cases and 63% of controls agreed to participate. Analysis weights accounted for differences between consenting and non-consenting women. Some of the characteristics used for individualized fetal growth estimates were missing and were replaced with reference

  7. Fetal Growth and Risk of Stillbirth: A Population-Based Case–Control Study

    PubMed Central

    Bukowski, Radek; Hansen, Nellie I.; Willinger, Marian; Reddy, Uma M.; Parker, Corette B.; Pinar, Halit; Silver, Robert M.; Dudley, Donald J.; Stoll, Barbara J.; Saade, George R.; Koch, Matthew A.; Rowland Hogue, Carol J.; Varner, Michael W.; Conway, Deborah L.; Coustan, Donald; Goldenberg, Robert L.

    2014-01-01

    Background Stillbirth is strongly related to impaired fetal growth. However, the relationship between fetal growth and stillbirth is difficult to determine because of uncertainty in the timing of death and confounding characteristics affecting normal fetal growth. Methods and Findings We conducted a population-based case–control study of all stillbirths and a representative sample of live births in 59 hospitals in five geographic areas in the US. Fetal growth abnormalities were categorized as small for gestational age (SGA) (<10th percentile) or large for gestational age (LGA) (>90th percentile) at death (stillbirth) or delivery (live birth) using population, ultrasound, and individualized norms. Gestational age at death was determined using an algorithm that considered the time-of-death interval, postmortem examination, and reliability of the gestational age estimate. Data were weighted to account for the sampling design and differential participation rates in various subgroups. Among 527 singleton stillbirths and 1,821 singleton live births studied, stillbirth was associated with SGA based on population, ultrasound, and individualized norms (odds ratio [OR] [95% CI]: 3.0 [2.2 to 4.0]; 4.7 [3.7 to 5.9]; 4.6 [3.6 to 5.9], respectively). LGA was also associated with increased risk of stillbirth using ultrasound and individualized norms (OR [95% CI]: 3.5 [2.4 to 5.0]; 2.3 [1.7 to 3.1], respectively), but not population norms (OR [95% CI]: 0.6 [0.4 to 1.0]). The associations were stronger with more severe SGA and LGA (<5th and >95th percentile). Analyses adjusted for stillbirth risk factors, subset analyses excluding potential confounders, and analyses in preterm and term pregnancies showed similar patterns of association. In this study 70% of cases and 63% of controls agreed to participate. Analysis weights accounted for differences between consenting and non-consenting women. Some of the characteristics used for individualized fetal growth estimates were missing

  8. Is cerebroplacental ratio a marker of impaired fetal growth velocity and adverse pregnancy outcome?

    PubMed

    Khalil, Asma; Morales-Rosello, José; Khan, Naila; Nath, Mintu; Agarwal, Priya; Bhide, Amar; Papageorghiou, Aris; Thilaganathan, Basky

    2017-06-01

    The cerebroplacental ratio has been proposed as a marker of failure to reach growth potential near term. Low cerebroplacental ratio, regardless of the fetal size, is independently associated with the need for operative delivery for presumed fetal compromise and with neonatal unit admission at term. The main aim of this study was to evaluate whether the cerebroplacental ratio at term is a marker of reduced fetal growth rate. The secondary aim was to investigate the relationship between a low cerebroplacental ratio at term, reduced fetal growth velocity, and adverse pregnancy outcome. This was a retrospective cohort study of singleton pregnancies in a tertiary referral center. The abdominal circumference was measured at 20-24 weeks' gestation and both abdominal circumference and fetal Dopplers recorded at or beyond 35 weeks, within 2 weeks of delivery. Abdominal circumference and birthweight values were converted into Z scores and centiles, respectively, and fetal Doppler parameters into multiples of median, adjusting for gestational age. Abdominal circumference growth velocity was quantified using the difference in the abdominal circumference Z score, comparing the scan at or beyond 35 weeks with the scan at 20-24 weeks. Both univariable and multivariable logistic regression analyses were performed to investigate the association between low cerebroplacental ratio and the low abdominal circumference growth velocity (in the lowest decile) and to identify and adjust for potential confounders. As a sensitivity analysis, we refitted the model excluding the data on pregnancies with small-for-gestational-age neonates. The study included 7944 pregnancies. Low cerebroplacental ratio multiples of median was significantly associated with both low abdominal circumference growth velocity (adjusted odds ratio, 2.10; 95% confidence interval, 1.71-2.57, P <0.001) and small for gestational age (adjusted odds ratio, 3.60; 95% confidence interval, 3.04-4.25, P < .001). After the

  9. Fetal deficiency of lin28 programs life-long aberrations in growth and glucose metabolism.

    PubMed

    Shinoda, Gen; Shyh-Chang, Ng; Soysa, T Yvanka de; Zhu, Hao; Seligson, Marc T; Shah, Samar P; Abo-Sido, Nora; Yabuuchi, Akiko; Hagan, John P; Gregory, Richard I; Asara, John M; Cantley, Lewis C; Moss, Eric G; Daley, George Q

    2013-08-01

    LIN28A/B are RNA binding proteins implicated by genetic association studies in human growth and glucose metabolism. Mice with ectopic over-expression of Lin28a have shown related phenotypes. Here, we describe the first comprehensive analysis of the physiologic consequences of Lin28a and Lin28b deficiency in knockout (KO) mice. Lin28a/b-deficiency led to dwarfism starting at different ages, and compound gene deletions showed a cumulative dosage effect on organismal growth. Conditional gene deletion at specific developmental stages revealed that fetal but neither neonatal nor adult deficiency resulted in growth defects and aberrations in glucose metabolism. Tissue-specific KO mice implicated skeletal muscle-deficiency in the abnormal programming of adult growth and metabolism. The effects of Lin28b KO could be rescued by Tsc1 haplo-insufficiency in skeletal muscles. Our data implicate fetal expression of Lin28a/b in the regulation of life-long effects on metabolism and growth, and demonstrate that fetal Lin28b acts at least in part via mTORC1 signaling. Copyright © 2013 AlphaMed Press.

  10. Fetal deficiency of Lin28 programs life-long aberrations in growth and glucose metabolism

    PubMed Central

    Shinoda, Gen; Shyh-Chang, Ng; de Soysa, T. Yvanka; Zhu, Hao; Seligson, Marc T.; Shah, Samar P.; Abo-Sido, Nora; Yabuuchi, Akiko; Hagan, John P.; Gregory, Richard I.; Asara, John M.; Cantley, Lewis C.; Moss, Eric G.; Daley, George Q.

    2013-01-01

    LIN28A/B are RNA binding proteins implicated by genetic association studies in human growth and glucose metabolism. Mice with ectopic over-expression of Lin28a have shown related phenotypes. Here we describe the first comprehensive analysis of the physiologic consequences of Lin28a and Lin28b deficiency in knockout (KO) mice. Lin28a/b-deficiency led to dwarfism starting at different ages, and compound gene deletions showed a cumulative dosage effect on organismal growth. Conditional gene deletion at specific developmental stages revealed that fetal but neither neonatal nor adult deficiency resulted in growth defects and aberrations in glucose metabolism. Tissue-specific KO mice implicated skeletal muscle-deficiency in the abnormal programming of adult growth and metabolism. The effects of Lin28b KO can be rescued by Tsc1 haplo-insufficiency in skeletal muscles. Our data implicate fetal expression of Lin28a/b in the regulation of life-long effects on metabolism and growth, and demonstrate that fetal Lin28b acts at least in part via mTORC1 signaling. PMID:23666760

  11. Sildenafil citrate rescues fetal growth in the catechol-O-methyl transferase knockout mouse model.

    PubMed

    Stanley, Joanna L; Andersson, Irene J; Poudel, Rajan; Rueda-Clausen, Christian F; Sibley, Colin P; Davidge, Sandra T; Baker, Philip N

    2012-05-01

    Preeclampsia and fetal growth restriction are responsible for the majority of maternal and perinatal morbidity and mortality associated with complicated pregnancies. Although their etiologies are complex and multifactorial, both are associated with increased uterine artery resistance. Sildenafil citrate is able to rescue the dysfunction observed ex vivo in uterine arteries of women with preeclampsia. The ability of sildenafil citrate to increase uterine artery vasodilation, thereby decreasing uterine artery resistance and, hence, ameliorated preeclampsia and fetal growth restriction, was tested in a mouse model of preeclampsia, the catechol-O-methyl transferase knockout mouse (COMT(-/-)). COMT(-/-) and C57BL/6J mice were treated (0.2 mg/mL in drinking water, n=6-12) from gestational day 12.5 to 18.5. Measures of pup growth, including body weight, crown/rump length, and abdominal circumference, were reduced in COMT(-/-) mice; this was normalized after treatment with Sildenafil. COMT(-/-) mice also demonstrated abnormal umbilical Doppler waveforms, including reverse arterial blood flow velocity. This was normalized after treatment with Sildenafil. Abnormal uterine artery Doppler waveforms were not demonstrated in COMT(-/-) mice, although ex vivo responses of uterine arteries to phenylephrine were increased; moreover, treatment with Sildenafil did improve ex vivo sensitivity to an endothelium-dependent vasodilator. The data presented here demonstrate that Sildenafil can rescue pup growth and improve abnormal umbilical Doppler waveforms, providing support for a potential new therapeutic strategy targeting fetal growth restriction.

  12. Transcriptomic regulations in oligodendroglial and microglial cells related to brain damage following fetal growth restriction.

    PubMed

    Rideau Batista Novais, Aline; Pham, Hoa; Van de Looij, Yohan; Bernal, Miguel; Mairesse, Jerome; Zana-Taieb, Elodie; Colella, Marina; Jarreau, Pierre-Henri; Pansiot, Julien; Dumont, Florent; Sizonenko, Stéphane; Gressens, Pierre; Charriaut-Marlangue, Christiane; Tanter, Mickael; Demene, Charlie; Vaiman, Daniel; Baud, Olivier

    2016-12-01

    Fetal growth restriction (FGR) is a major complication of human pregnancy, frequently resulting from placental vascular diseases and prenatal malnutrition, and is associated with adverse neurocognitive outcomes throughout life. However, the mechanisms linking poor fetal growth and neurocognitive impairment are unclear. Here, we aimed to correlate changes in gene expression induced by FGR in rats and abnormal cerebral white matter maturation, brain microstructure, and cortical connectivity in vivo. We investigated a model of FGR induced by low-protein-diet malnutrition between embryonic day 0 and birth using an interdisciplinary approach combining advanced brain imaging, in vivo connectivity, microarray analysis of sorted oligodendroglial and microglial cells and histology. We show that myelination and brain function are both significantly altered in our model of FGR. These alterations, detected first in the white matter on magnetic resonance imaging significantly reduced cortical connectivity as assessed by ultrafast ultrasound imaging. Fetal growth retardation was found associated with white matter dysmaturation as shown by the immunohistochemical profiles and microarrays analyses. Strikingly, transcriptomic and gene network analyses reveal not only a myelination deficit in growth-restricted pups, but also the extensive deregulation of genes controlling neuroinflammation and the cell cycle in both oligodendrocytes and microglia. Our findings shed new light on the cellular and gene regulatory mechanisms mediating brain structural and functional defects in malnutrition-induced FGR, and suggest, for the first time, a neuroinflammatory basis for the poor neurocognitive outcome observed in growth-restricted human infants. GLIA 2016;64:2306-2320.

  13. Synaptic development and neuronal myelination are altered with growth restriction in fetal guinea pigs.

    PubMed

    Piorkowska, Karolina; Thompson, Jennifer; Nygard, Karen; Matushewski, Brad; Hammond, Robert; Richardson, Bryan

    2014-01-01

    This study examines aberrant synaptogenesis and myelination of neuronal connections as possible links to neurological sequelae in growth-restricted fetuses. Pregnant guinea pig sows were subjected to uterine blood flow restriction or sham surgeries at midgestation. The animals underwent necropsy at term with fetuses grouped according to body weight and brain-to-liver weight ratios as follows: appropriate for gestational age (n = 12); asymmetrically fetal growth restricted (aFGR; n = 8); symmetrically fetal growth restricted (sFGR; n = 8), and large for gestational age (n = 8). Fetal brains were perfusion fixed and paraffin embedded to determine immunoreactivity for synaptophysin and synaptopodin as markers of synaptic development and maturation, respectively, and for myelin basic protein as a marker for myelination, which was further assessed using Luxol fast blue staining. The most pertinent findings were that growth-restricted guinea pig fetuses exhibited reduced synaptogenesis and synaptic maturation as well as reduced myelination, which were primarily seen in subareas of the hippocampus and associated efferent tracts. These neurodevelopmental changes were more pronounced in the sFGR compared to the aFGR animals. Accordingly, altered hippocampal development involving synaptogenesis and myelination may represent a mechanism by which cognitive deficits manifest in human growth-restricted offspring in later life. © 2014 S. Karger AG, Basel.

  14. Fetal and childhood growth patterns associated with bone mass in school-age children: the Generation R Study.

    PubMed

    Heppe, Denise Hm; Medina-Gomez, Carolina; de Jongste, Johan C; Raat, Hein; Steegers, Eric Ap; Hofman, Albert; Rivadeneira, Fernando; Jaddoe, Vincent Wv

    2014-12-01

    Low birth weight is associated with lower bone accrual in children and peak bone mass in adults. We assessed how different patterns of longitudinal fetal and early childhood growth influence bone properties at school age. In 5431 children participating in a population-based prospective cohort study, we measured fetal growth by ultrasound at 20 and 30 weeks gestation, and childhood growth at birth, 1, 2, 3, and 4 years of age. We analyzed these growth measurements in relation to total body (less head) BMD measured by DXA at age 6. We used conditional growth modeling; a technique which takes into account correlation between repeatedly measured growth measures. Our results showed that estimated fetal weight gain, femur length growth between 20 and 30 weeks of gestation, femur length growth between 30 weeks and birth, as well as all height and weight growth measurements from birth to 4 years of age were all positively associated with BMC, bone area (BA), and BMD (all p < 0.01). Fetal femur length growth between 30 weeks and birth was positively associated with BMC and BA (both p < 0.001), but not with BMD. Overall, childhood growth measurements exerted a larger influence on bone measures than fetal growth measures. The strongest effect estimate was observed during the first year of life. Children born small (<10th percentile) for gestational age (SGA) had lower BMC and BA, but not BMD, than children born appropriate for gestational age (AGA), whereas children born large (>90th percentile) for gestational age (LGA) had higher BMC and BA (all p < 0.001). These differences were no longer present in children showing subsequent accelerated and decelerated infant growth, respectively. We conclude that both fetal and childhood growth patterns are associated with bone mineral accrual, showing the strongest effect estimates in infancy. Compensatory infant growth counteracts the adverse consequences of fetal growth restriction on bone development. © 2014 American

  15. 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

  16. 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

    2015-12-23

    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.

  17. Differences in cortical development assessed by fetal MRI in late-onset intrauterine growth restriction.

    PubMed

    Egaña-Ugrinovic, Gabriela; Sanz-Cortes, Magdalena; Figueras, Francesc; Bargalló, Nuria; Gratacós, Eduard

    2013-08-01

    The objective of the study was to evaluate cortical development parameters by magnetic resonance imaging (MRI) in late-onset intrauterine growth-restricted (IUGR) fetuses and normally grown fetuses. A total of 52 IUGR and 50 control fetuses were imaged using a 3T MRI scanner at 37 weeks of gestational age. T2 half-Fourier acquisition single-shot turbo spin-echo anatomical acquisitions were obtained in 3 planes. Cortical sulcation (fissures depth corrected by biparietal diameter), brain volumetry, and asymmetry indices were assessed by means of manual delineation and compared between cases and controls. Late-onset IUGR fetuses had significantly deeper measurements in the left insula (late-onset IUGR: 0.293 vs control: 0.267; P = .02) and right insula (0.379 vs 0.318; P < .01) and the left cingulate fissure (0.096 vs 0.087; P = .03) and significantly lower intracranial (441.25 cm(3) vs 515.82 cm(3); P < .01), brain (276.47 cm(3) vs 312.07 cm(3); P < .01), and left opercular volumes (2.52 cm(3) vs 3.02 cm(3); P < .01). IUGR fetuses showed significantly higher right insular asymmetry indices. Late-onset IUGR fetuses had a different pattern of cortical development assessed by MRI, supporting the existence of in utero brain reorganization. Cortical development could be useful to define fetal brain imaging-phenotypes characteristic of IUGR. Copyright © 2013 Mosby, Inc. All rights reserved.

  18. Wheat growth monitoring with radar vegetation indices

    USDA-ARS?s Scientific Manuscript database

    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...

  19. Fetal growth and air pollution - A study on ultrasound and birth measures.

    PubMed

    Malmqvist, Ebba; Liew, Zeyan; Källén, Karin; Rignell-Hydbom, Anna; Rittner, Ralf; Rylander, Lars; Ritz, Beate

    2017-01-01

    Air pollution has been suggested to affect fetal growth, but more data is needed to assess the timing of exposure effects by using ultrasound measures. It is also important to study effects in low exposure areas to assess eventual thresholds of effects. The MAPSS (Maternal Air Pollution in Southern Sweden) cohort consists of linked registry data for around 48,000 pregnancies from an ultrasound database, birth registry and exposure data based on residential addresses. Measures of air pollution exposure were obtained through dispersion modelling with input data from an emissions database (NOx) with high resolution (100-500m grids). Air pollution effects were assessed with linear regressions for the following endpoints; biparietal diameter, femur length, abdominal diameter and estimated fetal weight measured in late pregnancy and birth weight and head circumference measured at birth. We estimated negative effects for NOx; in the adjusted analyses the decrease of abdominal diameter and femur length were -0.10 (-0.17, -0.03) and -0.13 (-0.17, -0.01)mm, respectively, per 10µg/m(3) increment of NOx. We also estimated an effect of NOx-exposures on birth weight by reducing birth weight by 9g per 10µg/m(3) increment of NOx. We estimated small but statistically significant effects of air pollution on late fetal and birth size and reduced fetal growth late in pregnancy in a geographic area with levels below current WHO air quality guidelines.

  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.

  1. 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.

  2. Association of prenatal lipid-based nutritional supplementation with fetal growth in rural Gambia.

    PubMed

    Johnson, William; Darboe, Momodou K; Sosseh, Fatou; Nshe, Patrick; Prentice, Andrew M; Moore, Sophie E

    2017-04-01

    Prenatal supplementation with protein-energy (PE) and/or multiple-micronutrients (MMNs) may improve fetal growth, but trials of lipid-based nutritional supplements (LNSs) have reported inconsistent results. We conducted a post-hoc analysis of non-primary outcomes in a trial in Gambia, with the aim to test the associations of LNS with fetal growth and explore how efficacy varies depending on nutritional status. The sample comprised 620 pregnant women in an individually randomized, partially blinded trial with four arms: (a) iron and folic acid (FeFol) tablet (usual care, referent group), (b) MMN tablet, (c) PE LNS, and (d) PE + MMN LNS. Analysis of variance examined unadjusted differences in fetal biometry z-scores at 20 and 30 weeks and neonatal anthropometry z-scores, while regression tested for modification of intervention-outcome associations by season and maternal height, body mass index, and weight gain. Despite evidence of between-arm differences in some fetal biometry, z-scores at birth were not greater in the intervention arms than the FeFol arm (e.g., birth weight z-scores: FeFol -0.71, MMN -0.63, PE -0.64, PE + MMN -0.62; group-wise p = .796). In regression analyses, intervention associations with birth weight and head circumference were modified by maternal weight gain between booking and 30 weeks gestation (e.g., PE + MMN associations with birth weight were +0.462 z-scores (95% CI [0.097, 0.826]) in the highest quartile of weight gain but -0.099 z-scores (-0.459, 0.260) in the lowest). In conclusion, we found no strong evidence that a prenatal LNS intervention was associated with better fetal growth in the whole sample.

  3. Should we use customized fetal growth percentiles in urban Canada?

    PubMed

    Melamed, Nir; Ray, Joel G; Shah, Prakesh S; Berger, Howard; Kingdom, John C

    2014-02-01

    An increasingly common challenge in antenatal care of the small for gestational age (SGA) fetus is the distinction between the constitutionally (physiologically) small fetus and the fetus affected by pathological intrauterine growth restriction (IUGR). We discuss here the rationale and the evidence for the use of customized growth percentiles for the purpose of distinguishing between the fetus with true IUGR and the fetus with constitutional SGA. We also provide estimates of the potential effects of adopting ethnicity-specific birth weight curves on the rates of SGA and large for gestational age status in multi-ethnic metropolitan cities in North America and Europe, such as the City of Toronto. Using customized growth percentiles would result in a considerable decline in the rate of a false-positive diagnosis of SGA among visible minorities, and improve the detection rate of true large for gestational age fetuses among these groups.

  4. Dietary fat impacts fetal growth and metabolism: uptake of chylomicron remnant core lipids by the placenta.

    PubMed

    Rebholz, Sandra L; Burke, Katie T; Yang, Qing; Tso, Patrick; Woollett, Laura A

    2011-08-01

    The fetus requires significant energy for growth and development. Although glucose is a major source of energy for the fetus, other maternal nutrients also appear to promote growth. Thus, the goal of these studies was to determine whether triglyceride-rich remnants are taken up by the placenta and whether maternal dietary lipids, independently of adiposity, can impact fetal growth. To accomplish our first goal, chylomicron particles were duallly labeled with cholesteryl ester and triglycerides. The placenta took up remnant particles/core lipids at rates greater than adipose tissue and skeletal muscle but less than the liver. Although the placenta expresses apoE receptors, uptake of chylomicron remnants and/or core lipids can occur independently of apoE. To determine the impact of dietary lipid on fetal growth, independent of maternal adiposity, females were fed high-fat diets (HFD) for 1 mo; there was no change in adiposity or leptin levels prior to or during pregnancy of dams fed HFD. Fetal masses were greater in dams fed HFD, and mRNA levels of proteins involved in fatty acid oxidation (CPT I, PPARα), but not glucose oxidation (pyruvate kinase) or other regulatory processes (HNF-4α, LXR), were increased with maternal dietary fat. There was also no change in mRNA levels of proteins involved in placental glucose and fatty acid transport, and GLUT1 protein levels in microvillous membranes were similar in placentas of dams fed either diet. Thus, the ability of the placenta to take up chylomicron remnant core lipids likely contributes to accelerated fetal growth in females fed high fat diets.

  5. 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.

  6. Placental leptin in normal, diabetic and fetal growth-retarded pregnancies.

    PubMed

    Lea, R G; Howe, D; Hannah, L T; Bonneau, O; Hunter, L; Hoggard, N

    2000-08-01

    Leptin expression in third trimester placenta (p) and leptin concentrations in umbilical cord blood (cb) were investigated in normal pregnancies [n = 10 (p), 31 (cb)] and abnormal pregnancies complicated with (i) maternal insulin-dependent diabetes [IDDM: n = 3 (p), 13 (cb)], (ii) gestational diabetes [GD: n = 2 (p), 10 (cb)] and (iii) fetal growth retardation [FGR: n = 5 (p), 5 (cb)]. By in-situ hybridization and immunohistochemistry, placental leptin mRNA and protein were co-localized to the syncytiotrophoblast and villous vascular endothelial cells. Leptin receptor was immunolocalized to the syncytiotrophoblast. Relative to controls, the FGR group was characterized by low concentrations of placental and cord blood leptin. In a twin pregnancy, the normal-sized infant exhibited more placental and cord blood leptin than its growth-retarded twin. In contrast, both diabetic groups exhibited high concentrations of placental leptin mRNA and protein. The IDDM group exhibited the highest concentrations of leptin in cord blood. No change was observed in the expression of the leptin receptor in either the growth-retarded or diabetic pregnancies. In conclusion, the localization of placental leptin suggests that it may be released into both maternal and fetal blood. Furthermore, in fetal growth-retarded and diabetic pregnancies, the changes in leptin expression in the placenta and in leptin concentrations in umbilical cord blood appear to be related.

  7. [Value of 3D-4D sonography in fetal and gynecological ultrasound examination: principles and indications].

    PubMed

    Levaillant, Jm

    2006-12-01

    Three-dimensional ultrasound has become an essential tool for visualization of fetal structures in the past few years. The recent improvements in transducers and signal processing provide new information, particularly in obstetrics and gynecology sonography. The present paper will present the most recent advances in volume acquisition and presentation modes followed by results of fetal organ visualization in normal and abnormal cases as well as applications in gynecology.

  8. Fetal Echocardiography and Pulsed-wave Doppler Ultrasound in a Rabbit Model of Intrauterine Growth Restriction

    PubMed Central

    Hodges, Ryan; Endo, Masayuki; La Gerche, Andre; Eixarch, Elisenda; DeKoninck, Philip; Ferferieva, Vessilina; D'hooge, Jan; Wallace, Euan M.; Deprest, Jan

    2013-01-01

    Fetal intrauterine growth restriction (IUGR) results in abnormal cardiac function that is apparent antenatally due to advances in fetoplacental Doppler ultrasound and fetal echocardiography. Increasingly, these imaging modalities are being employed clinically to examine cardiac function and assess wellbeing in utero, thereby guiding timing of birth decisions. Here, we used a rabbit model of IUGR that allows analysis of cardiac function in a clinically relevant way. Using isoflurane induced anesthesia, IUGR is surgically created at gestational age day 25 by performing a laparotomy, exposing the bicornuate uterus and then ligating 40-50% of uteroplacental vessels supplying each gestational sac in a single uterine horn. The other horn in the rabbit bicornuate uterus serves as internal control fetuses. Then, after recovery at gestational age day 30 (full term), the same rabbit undergoes examination of fetal cardiac function. Anesthesia is induced with ketamine and xylazine intramuscularly, then maintained by a continuous intravenous infusion of ketamine and xylazine to minimize iatrogenic effects on fetal cardiac function. A repeat laparotomy is performed to expose each gestational sac and a microultrasound examination (VisualSonics VEVO 2100) of fetal cardiac function is performed. Placental insufficiency is evident by a raised pulsatility index or an absent or reversed end diastolic flow of the umbilical artery Doppler waveform. The ductus venosus and middle cerebral artery Doppler is then examined. Fetal echocardiography is performed by recording B mode, M mode and flow velocity waveforms in lateral and apical views. Offline calculations determine standard M-mode cardiac variables, tricuspid and mitral annular plane systolic excursion, speckle tracking and strain analysis, modified myocardial performance index and vascular flow velocity waveforms of interest. This small animal model of IUGR therefore affords examination of in utero cardiac function that is

  9. 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

  10. 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.

  11. 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

  12. Maternal caffeine intake from coffee and tea, fetal growth, and the risks of adverse birth outcomes: the Generation R Study.

    PubMed

    Bakker, Rachel; Steegers, Eric A P; Obradov, Aleksandra; Raat, Hein; Hofman, Albert; Jaddoe, Vincent W V

    2010-06-01

    Caffeine is a widely used and accepted pharmacologically active substance. The effect of caffeine intake during pregnancy on fetal growth and development is still unclear. We examined the associations of maternal caffeine intake, on the basis of coffee and tea consumption, with fetal growth characteristics measured in each trimester of pregnancy and the risks of adverse birth outcomes. Associations were studied in 7346 pregnant women participating in a population-based prospective cohort study from early pregnancy onward in the Netherlands (2001-2005). Caffeine intake in the first, second, and third trimesters was on the basis of coffee and tea consumption and was assessed by questionnaires. Fetal growth characteristics were repeatedly measured by ultrasound. Information about birth outcomes was obtained from hospital records. We observed no consistent associations of caffeine intake with fetal head circumference or estimated fetal weight in any trimester. Higher caffeine intake was associated with smaller first-trimester crown-rump length, second- and third-trimester femur length, and birth length (P for trend <0.05). Offspring of mothers who consumed > or =6 caffeine units/d tended to have increased risks of small-for-gestational-age infants at birth. Our results suggest that caffeine intake of > or =6 units/d during pregnancy is associated with impaired fetal length growth. Caffeine exposure might preferentially adversely affect fetal skeletal growth. Further studies are needed to assess these associations in non-European populations and to assess the postnatal consequences.

  13. Sonographic Evaluation of Fetal Adrenal Gland in Gestational Diabetes: Relation to Fetal Growth and Maternal Biochemical Markers.

    PubMed

    Garcia-Flores, Jose; Cruceyra, Mireia; Cañamares, Marina; Garicano, Ainhoa; Espada, Mercedes; Nieto, Olga; Tamarit, Ines; Sainz de la Cuesta, Ricardo

    2017-05-01

    To relate measurements and volume of the fetal adrenal gland in third trimester ultrasound in diabetic pregnancies (1) to birth weight; (2) to other sonographic markers of diabetic fetopathy (expected fetal weight, sectional area, and fractional volume in fetal limbs); and (3) to maternal biochemical markers of diabetes (HbA1c, leptin). Fetal adrenal gland measurements were obtained between 32 and 34 weeks. The gland length, width, depth, and volume (by Virtual Organ Computer-Aided Analysis [VOCAL]) were measured for total gland and fetal zone. Fetal total and fat sectional area and fractional volume were obtained in arm and thigh. A maternal blood sample was obtained. Univariate and multivariate models were used to assess the associations. Thirty-nine diabetic pregnancies were included. Birth weight related significantly to total and fetal zone adrenal depth, and total adrenal volume in third trimester. Total adrenal length and corrected adrenal gland volume also showed a significant correlation to birth weight percentile in univariate and multivariate models. Total adrenal volume associated significantly to total and fat areas and volumes in fetal limbs. Both maternal leptin and HbA1c levels found a significant positive relation to fetal total adrenal volume and corrected adrenal gland volume. Total adrenal gland volume showed a significant association to maternal HbA1c level in multivariate model. An enlargement of the fetal adrenal gland may be observed in gestational diabetes, not only related to birth weight, but also to distinctive features of diabetic pregnancies, such as fat tissue fetal deposits or maternal biochemical markers. © 2017 by the American Institute of Ultrasound in Medicine.

  14. Craniofacial growth in fetal Tarsius bancanus: brains, eyes and nasal septa

    PubMed Central

    Jeffery, Nathan; Davies, Karen; Köckenberger, Walter; Williams, Steve

    2007-01-01

    The tarsier skull has been of particular interest in studies of primate taxonomy and functional morphology for several decades. Despite this, there remains no comprehensive data on how the tarsier skull develops, especially in relation to the soft-tissues of the head. Here we have documented for the first time fetal development of the skull and brain as well as the nasal septum and eyes in T. bancanus. We have also tested for the possible influence of these tissues in shaping skull architecture. Nineteen post-mortem specimens were imaged using high-resolution magnetic resonance imaging and magnetic resonance microscopy. Landmarks and volume data were collected and analysed. Findings demonstrated massive increases of brain size and eye size as well as flattening of the midline cranial base, facial projection and orbital margin frontation. Little evidence was found to support the notion that growth of the brain or nasal septum physically drives the observed changes of the skull. However, increases in the size of the eyes relative to skull size were associated with orbital margin frontation. With the possible exception of the results for eye size, the findings indicate that rather than forcing change the soft-tissues form a framework that physically constrains the morphogenetic template of the skeletal elements. This suggests, for example, that the degree of cranial base angulation seen in adulthood is not directly determined by brain expansion bending the basicranium, but by brain enlargement limiting the extent of cranial base flattening (retroflexion) in the fetus. PMID:17451471

  15. 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

  16. Fetal window of vulnerability to airborne polycyclic aromatic hydrocarbons on proportional intrauterine growth restriction.

    PubMed

    Choi, Hyunok; Wang, Lu; Lin, Xihong; Spengler, John D; Perera, Frederica P

    2012-01-01

    Although the entire duration of fetal development is generally considered a highly susceptible period, it is of public health interest to determine a narrower window of heightened vulnerability to polycyclic aromatic hydrocarbons (PAHs) in humans. We posited that exposure to PAHs during the first trimester impairs fetal growth more severely than a similar level of exposure during the subsequent trimesters. In a group of healthy, non-smoking pregnant women with no known risks of adverse birth outcomes, personal exposure to eight airborne PAHs was monitored once during the second trimester for the entire cohort (n = 344), and once each trimester within a subset (n = 77). Both air monitoring and self-reported PAH exposure data were used in order to statistically estimate PAH exposure during the entire gestational period for each individual newborn. One natural-log unit increase in prenatal exposure to the eight summed PAHs during the first trimester was associated with the largest decrement in the Fetal Growth Ratio (FGR) (-3%, 95% Confidence Interval (CI), -5 to -0%), birthweight (-105 g, 95% CI, -188 to -22 g), and birth length (-0.78 cm, 95% CI, -1.30 to -0.26 cm), compared to the unit effects of PAHs during the subsequent trimesters, after accounting for confounders. Furthermore, a unit exposure during the first trimester was associated with the largest elevation in Cephalization Index (head to weight ratio) (3 μm/g, 95% CI, 1 to 5 μm/g). PAH exposure was not associated with evidence of asymmetric growth restriction in this cohort. PAH exposure appears to exert the greatest adverse effect on fetal growth during the first trimester. The present data support the need for the protection of pregnant women and the embryo/fetus, particularly during the earliest stage of pregnancy.

  17. Melanocortin 1 receptor function: shifting gears from determining skin and nevus phenotype to fetal growth.

    PubMed

    Gruis, Nelleke A; van Doorn, Remco

    2012-08-01

    Variants in the MC1R gene influence skin pigmentation and thereby modulate risk of melanoma and basal and squamous cell carcinoma. In this issue, Kinsler et al. report an association between the MC1R genotype and the development of congenital melanocytic nevi. Further, higher birth weight was observed in carriers of MC1R variants, suggesting a role for the melanocortin network in fetal growth.

  18. 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

  19. Stimulation of DNA and Collagen Synthesis by Autologous Growth Factor in Cultured Fetal Rat Calvaria

    NASA Astrophysics Data System (ADS)

    Canalis, Ernesto; Peck, William A.; Raisz, Lawrence G.

    1980-11-01

    Conditioned medium derived from organ or cell cultures prepared from 19- to 21-day fetal rat calvaria stimulated the incorporation of [3H]proline into collagen and of [3H]thymidine into DNA in organ cultures of the same tissue. Addition of cortisol enhanced the effect on collagen but not on DNA synthesis. These effects appeared to be due to a nondialyzable and heat-stable growth factor.

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

    PubMed Central

    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

  1. Maternal Lipids as Strong Determinants of Fetal Environment and Growth in Pregnancies With Gestational Diabetes Mellitus

    PubMed Central

    Schaefer-Graf, Ute M.; Graf, Kristof; Kulbacka, Irina; Kjos, Siri L.; Dudenhausen, Joachim; Vetter, Klaus; Herrera, Emilio

    2008-01-01

    OBJECTIVE—To determine the contribution of maternal glucose and lipids to intrauterine metabolic environment and fetal growth in pregnancies with gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS—In 150 pregnancies, serum triglycerides (TGs), cholesterol, free fatty acids (FFAs), glycerol, insulin, and glucose were determined in maternal serum and cord blood during the 3rd trimester. Maternal glucose values came from oral glucose tolerance testing and glucose profiles. Measurements of fetal abdominal circumference (AC) were performed simultaneously with maternal blood sampling and birth weight, and BMI and neonatal fat mass were obtained following delivery. RESULTS—Maternal TGs and FFAs correlated with fetal AC size (at 28 weeks: triglycerides, P = 0.001; FFAs, P = 0.02), and at delivery they correlated with all neonatal anthropometric measures (FFA: birth weight, P = 0.002; BMI, P = 0.001; fat mass, P = 0.01). After adjustment for confounding variables, maternal FFAs and TGs at delivery remained the only parameters independently related to newborns large for gestational age (LGA) (P = 0.008 and P = 0.04, respectively). Maternal FFA levels were higher in mothers with LGA newborns than in those with appropriate for gestational age (AGA) newborns (362.8 ± 101.7 vs. 252.4 ± 10.1, P = 0.002). Maternal levels of TGs, FFAs, and glycerol at delivery correlated with those in cord blood (P = 0.003, P = 0.004, and P = 0.005, respectively). Fetal triglyceride and cholesterol levels were negatively correlated with newborn birth weight (P = 0.001), BMI (P = 0.004), and fat mass (P = 0.001). TGs were significantly higher in small for gestational age (SGA) newborns compared with AGA or LGA newborns, while insulin-to-glucose ratio and FFAs were the highest in LGA newborns. CONCLUSIONS—In well-controlled GDM pregnancies, maternal lipids are strong predictors for fetal lipids and fetal growth. Infants with abnormal growth seem to be exposed to a distinct

  2. Estimating wheat growth with radar vegetation indices

    USDA-ARS?s Scientific Manuscript database

    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. 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. © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  4. 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

  5. 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

  6. 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

  7. Non-occupational exposure to paint fumes during pregnancy and fetal growth in a general population.

    PubMed

    Sørensen, Mette; Andersen, Anne-Marie N; Raaschou-Nielsen, Ole

    2010-05-01

    Occupational exposure to organic solvents during pregnancy has been associated with reduced fetal growth. Though organic solvents in the form of paint fumes are also found in the home environment, no studies have investigated the effect of such exposure in a general population. We studied associations between residential exposure to paint fumes during pregnancy and fetal growth within the Danish National Birth Cohort which consecutively recruited pregnant women from 1996 to 2002 from all over Denmark. Around the 30th pregnancy week, 19,000 mothers were interviewed about use of paint in their residence during pregnancy. The mothers were also asked about smoking habits and alcohol consumption during pregnancy, pre-pregnancy weight, height, parity and occupation. Information on birth weight and gestational age was obtained from national registers. We found that 45% of the mothers had been exposed to paint fumes in their residence during pregnancy. We found a statistically significant inverse relationship between exposure to paint fumes and the risk of being small for gestational age. There were no statistically significant associations between exposure to paint fumes and birth weight and risk of preterm birth after adjustment for potential confounders. Our results suggest that there are no causal relationship between non-occupational exposure to paint fumes in the residence during pregnancy and fetal growth.

  8. Maternal smoking, alcohol drinking, caffeine consumption, and fetal growth: results from a prospective study.

    PubMed

    Shu, X O; Hatch, M C; Mills, J; Clemens, J; Susser, M

    1995-03-01

    In a prospective study of 712 pregnancies, we examined associations between maternal smoking, alcohol, and caffeine consumption and fetal growth. We interviewed patients at entry into care [12.9 +/- 4.3 (standard deviation) weeks], and at 28 and 36 weeks of gestation. We found the expected reductions in adjusted birthweight among women who smoked throughout pregnancy: 168 gm [95% confidence limits (CL) = -326, -10] for low/moderate amounts (< or = 15 cigarettes per day); 288 gm (95% CL = -491, -84) for heavy smoking (> 15 cigarettes per day). We also found a decrease in birthweight (-179 gm; 95% CL = -364, 7) among smokers who reported quiting early in pregnancy. First trimester alcohol consumption (average: four drinks per week) was associated with a 155-gm reduction in fetal growth (95% CL = -324, 15), even after adjustment for number of cigarettes smoked. The association, observed with all types of alcohol consumption, was stronger among smokers (-270 gm) but was also present in nonsmokers (-115 gm). Caffeine consumption showed no relation to fetal growth, even among heavy consumers, although they were relatively few. This study implicates heavy maternal smoking at any point in pregnancy, including solely in the early months, and possibly moderate alcohol drinking as causes of low birthweight.

  9. 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.

  10. [Early diagnosis of intra-uterine growth restriction by ultrasonographic estimation of fetal weight].

    PubMed

    Martins, Maria Marta; Tedesco, José Júlio de Azevedo

    2005-01-01

    Aiming to reduce the perinatal and late morbidity and lethality through opportune prenatal intervention, this study proposed to sequentially evaluate the echographic fetal weight at the 25th and 27th weeks of gestation, establishing cut-off values for echographic fetal weight useful in the diagnosis of small-for-gestational-age at this gestation time, and developing a mathematical model able to recognize the probability of a newborn small-for- gestational-age. Eighty-five newborns were evaluated, 35 small and 50 adequate for gestational age. The mothers who underwent prenatal care at our Institution were healthy or presented chronic arterial hypertension as the only disease, no history of addictions, gemellarity or malformed fetuses. All mothers performed ultrasonographic exams at the 25th and 27th weeks for estimation of the fetal weight. The exams were able to detect the inadequate development of those fetuses small-for-gestational-age group. The cut-off values for echographic fetal weight were established as 775 grams and 1015 grams for the 25th and 27th weeks, respectively. A mathematical model was developed, capable of quantifying the probability of newborns exhibiting insufficient intra-uterine growth, being small-for-gestational-age.

  11. Large fetal congenital cystic adenomatoid malformations: growth trends and patient survival.

    PubMed

    Kunisaki, Shaun M; Barnewolt, Carol E; Estroff, Judy A; Ward, Valerie L; Nemes, Luanne P; Fauza, Dario O; Jennings, Russell W

    2007-02-01

    The prognosis for fetuses with large congenital cystic adenomatoid malformations (CCAMs) remains uncertain. This study examined the natural history of large fetal CCAMs managed expectantly at a major referral center. A 5-year retrospective review was conducted on fetuses diagnosed with a thoracic lesion (n = 59). Large CCAMs were identified on prenatal imaging and followed longitudinally. Perinatal outcomes were assessed. Twelve (20.3%) fetuses had large CCAMs in the absence of other congenital anomalies. Peak CCAM size occurred at 25.3 +/- 3.6 weeks' gestation. Serial magnetic resonance volumetry demonstrated a trend toward decreasing CCAM mass volume relative to thoracic cavity volume over time. Overall, 6 patients, including 3 with signs of early hydrops, showed a marked regression of their lesions relative to estimated fetal weight. Five fetuses required an emergent intervention postnatally, including extracorporeal membrane oxygenation support (n = 1), cyst aspiration (n = 1), and lung resection (n = 5). Overall survival was 75%, with severe hydrops before 30 weeks seen in all 3 deaths. Large fetal CCAMs tend to peak in size at 25 weeks' gestation and are characterized by in utero diminution relative to overall fetal growth. The prognosis for most fetuses with large CCAMs remains quite favorable under careful perinatal management.

  12. Paternal MHC expression on mouse trophoblast affects uterine vascularization and fetal growth.

    PubMed

    Madeja, Zofia; Yadi, Hakim; Apps, Richard; Boulenouar, Selma; Roper, Stephen J; Gardner, Lucy; Moffett, Ashley; Colucci, Francesco; Hemberger, Myriam

    2011-03-08

    The mammalian fetus represents a semiallograft within the maternal uterus yet is not rejected. This situation is particularly pronounced in species with a hemochorial type of placentation, such as humans and rodents, where maternal tissues and blood are in direct contact with fetal trophoblast and thus potentially with paternal antigens. The main polymorphic antigens responsible for graft rejection are MHC antigens. In humans the trophoblast cells invading into the decidua have a unique pattern of MHC class I expression characterized by both classical (HLA-C) and nonclassical (HLA-G and HLA-E) molecules. Whether such an unusual MHC repertoire on the surface of trophoblast is a conserved feature between species with hemochorial placentation has not been resolved. Here we demonstrate, using a range of methods, that C57BL/6 mouse trophoblast predominantly expresses only one MHC class I antigen, H2-K, at the cell surface of giant cells but lacks expression of nonclassical MHC molecules. Antigenic disparity between parental MHCs affects trophoblast-induced transformation of the uterine vasculature and, consequently, placental and fetal gowth. Maternal uterine blood vessels were more dilated, allowing for increased blood supply, in certain combinations of maternal and paternal MHC haplotypes, and these allogeneic fetuses and placentas were heavier at term compared with syngeneic controls. Thus, maternal-fetal immune interactions are instrumental to optimize reproductive success. This cross-talk has important implications for human disorders of pregnancy, such as preeclampsia and fetal growth restriction.

  13. In Utero Programming of Later Adiposity: The Role of Fetal Growth Restriction

    PubMed Central

    Sarr, Ousseynou; Yang, Kaiping; Regnault, Timothy R. H.

    2012-01-01

    Intrauterine growth restriction (IUGR) is strongly associated with obesity in adult life. The mechanisms contributing to the onset of IUGR-associated adult obesity have been studied in animal models and humans, where changes in fetal adipose tissue development, hormone levels and epigenome have been identified as principal areas of alteration leading to later life obesity. Following an adverse in utero development, IUGR fetuses display increased lipogenic and adipogenic capacity in adipocytes, hypoleptinemia, altered glucocorticoid signalling, and chromatin remodelling, which subsequently all contribute to an increased later life obesity risk. Data suggest that many of these changes result from an enhanced activity of the adipose master transcription factor regulator, peroxisome proliferator-activated receptor-γ (PPARγ) and its coregulators, increased lipogenic fatty acid synthase (FAS) expression and activity, and upregulation of glycolysis in fetal adipose tissue. Increased expression of fetal hypothalamic neuropeptide Y (NPY), altered hypothalamic leptin receptor expression and partitioning, reduced adipose noradrenergic sympathetic innervations, enhanced adipose glucocorticoid action, and modifications in methylation status in the promoter of hepatic and adipose adipogenic and lipogenic genes in the fetus also contribute to obesity following IUGR. Therefore, interventions that inhibit these fetal developmental changes will be beneficial for modulation of adult body fat accumulation. PMID:23251802

  14. High Fat Diet Induced Developmental Defects in the Mouse: Oocyte Meiotic Aneuploidy and Fetal Growth Retardation/Brain Defects

    PubMed Central

    Purcell, Scott H.; Chi, Maggie; Jimenez, Patricia T.; Grindler, Natalia; Schedl, Tim; Moley, Kelle H.

    2012-01-01

    Background Maternal obesity is associated with poor outcomes across the reproductive spectrum including infertility, increased time to pregnancy, early pregnancy loss, fetal loss, congenital abnormalities and neonatal conditions. Furthermore, the proportion of reproductive-aged woman that are obese in the population is increasing sharply. From current studies it is not clear if the origin of the reproductive complications is attributable to problems that arise in the oocyte or the uterine environment. Methodology/Principal Findings We examined the developmental basis of the reproductive phenotypes in obese animals by employing a high fat diet mouse model of obesity. We analyzed very early embryonic and fetal phenotypes, which can be parsed into three abnormal developmental processes that occur in obese mothers. The first is oocyte meiotic aneuploidy that then leads to early embryonic loss. The second is an abnormal process distinct from meiotic aneuploidy that also leads to early embryonic loss. The third is fetal growth retardation and brain developmental abnormalities, which based on embryo transfer experiments are not due to the obese uterine environment but instead must be from a defect that arises prior to the blastocyst stage. Conclusions/Significance Our results suggest that reproductive complications in obese females are, at least in part, from oocyte maternal effects. This conclusion is consistent with IVF studies where the increased pregnancy failure rate in obese women returns to the normal rate if donor oocytes are used instead of autologous oocytes. We postulate that preconceptional weight gain adversely affects pregnancy outcomes and fetal development. In light of our findings, preconceptional counseling may be indicated as the preferable, earlier target for intervention in obese women desiring pregnancy and healthy outcomes. PMID:23152876

  15. Fetal organ growth in response to oesophageal infusion of amniotic fluid, colostrum, milk or gastrin-releasing peptide: a study in fetal sheep.

    PubMed

    Trahair, J F; Sangild, P T

    2000-01-01

    The hypothesis of the present study was that the infusion of the biological fluids to which the developing gut is normally exposed (i.e. amniotic fluid, colostrum, milk) and a single growth factor (gastrin-releasing peptide), which is found in high concentrations in fetal fluids and milk, could ameliorate the altered growth induced by the elimination of swallowed input secondary to ligation of the oesophagus. At 108-110 days of gestation the fetal oesophagus was ligated and a catheter inserted towards the stomach (32 fetuses). At 117-119 days of gestation saline (n = 5), amniotic fluid (n = 5), colostral whey (n = 5), milk whey (n = 5) or gastrin-releasing peptide (3.6 nmol day(-1), n = 6), was infused for 7 days (4 x 20 mL day(-1)), or no infusion was given (ligated group, n = 6). A further 15 fetuses were not ligated (normal group, n = 15). All fetuses had carotid artery and/or jugular vein catheters implanted. At 124-126 days of gestation the fetus was delivered and fetal body and organ weights recorded. Analysing the results by ANOVA, there were no effects of either ligation alone or infusion after ligation on fetal weight, crown-rump length, or weight relative to bodyweight of heart, adrenal, pancreas, large intestine and cecum. There were significant differences between the infusion groups for lungs, kidney, pancreas, total gut, abomasum, small intestine, spleen, chest and neck thymus, and mesenteric lymph nodes. Ligation alone significantly reduced small intestinal growth and increased kidney and spleen growth. Colostrum infusion enhanced growth of most organs. Gastrin-releasing peptide significantly increased growth of all the immune organs studied. It was concluded that at an age when premature delivery could be encountered, the fetal gut is capable of significant adaptive growth, to varying degrees, depending on the enteral diet. Growth effects in organs distant to the gut suggest that either gastrointestinal uptake and transport of growth factors or

  16. Effect of maternal dietary energy types on placenta nutrient transporter gene expressions and intrauterine fetal growth in rats.

    PubMed

    Lin, Yan; Zhuo, Yong; Fang, Zheng-feng; Che, Lian-qiang; Wu, De

    2012-10-01

    The objectives of this study were to investigate the effects of maternal dietary energy types on the mRNA expressions of the placental nutrient transporter and intrauterine fetal growth and to examine whether altered intrauterine fetal growth could be associated with different gene expressions relating to fetal energy metabolism and DNA methylation. Seventy-two 3-mo-old rats were allocated to one of four groups: low fat/low fiber (L-L), low fat/high fiber, high fat/low fiber (H-L), or high fat/high fiber. Rats were fed the treatment diets 4 wk before mating and continued in pregnancy until sample collections were obtained on days 13.5 and 17.5 of pregnancy. The fetal weight in the L-L group was significantly lower than that in the H-L group (P < 0.05). The placental nutrient transporter mRNA expressions of glucose transporter-3 (Slc2a3) and cationic amino acid transporter-1 (Slc7a1) in the L-L group with a decreased fetal weight were downregulated compared with that in the H-L group with an increased fetal weight. However, placental Slc2a1 and the system A amino acid transporter gene Slc38a4 mRNA expressions were adaptively upregulated by the L-L diet with a decreased fetal weight (P < 0.05). For the placental imprinted gene Igf-2 and H19 expressions, lower Igf-2 and higher H19 expressions were associated with the decreased fetal growth in the L-L group compared with the H-L group with an increased fetal weight. Different fetal growth was associated with different DNA methyltransferase-1 and methyltransferase-3a expressions (P > 0.05) and energy metabolism-related genes. Collectively, these results demonstrated that intrauterine fetal growth could be affected by different energy intake types through placenta nutrient transporter gene expressions, and different fetal growths were associated with altered fetal genes related to DNA methylation and energy metabolism. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Timing of Gestational Weight Gain on Fetal Growth and Infant Size at Birth in Vietnam

    PubMed Central

    Young, Melissa F.; Hong Nguyen, Phuong; Addo, O. Yaw; Pham, Hoa; Nguyen, Son; Martorell, Reynaldo; Ramakrishnan, Usha

    2017-01-01

    Objective To examine the importance of timing of gestational weight gain during three time periods: 1: ≤ 20 weeks gestation), 2: 21–29 weeks) and 3: ≥ 30 weeks) on fetal growth and infant birth size. Methods Study uses secondary data from the PRECONCEPT randomized controlled trial in Thai Nguyen province, Vietnam (n = 1436). Prospective data were collected on women starting pre-pregnancy through delivery. Maternal conditional weight gain (CWG) was defined as window-specific weight gains, uncorrelated with pre-pregnancy body mass index and all prior body weights. Fetal biometry, was assessed by ultrasound measurements of head and abdomen circumferences, biparietal diameter, and femoral length throughout pregnancy. Birth size outcomes included weight and length, and head, abdomen and mid upper arm circumferences as well as small for gestational age (SGA). Adjusted generalized linear and logistic models were used to examine associations. Results Overall, three-quarters of women gained below the Institute of Medicine guidelines, and these women were 2.5 times more likely to give birth to a SGA infant. Maternal CWG in the first window (≤ 20 weeks), followed by 21–29 weeks, had the greatest association on all parameters of fetal growth (except abdomen circumference) and infant size at birth. For birth weight, a 1 SD increase CWG in the first 20 weeks had 3 times the influence compared to later CWG (≥ 30 weeks) (111 g vs. 39 g) and was associated with a 43% reduction in SGA risk (OR (95% CI): 0.57 (0.46–0.70). Conclusion There is a need to target women before or early in pregnancy to ensure adequate nutrition to maximize impact on fetal growth and birth size. Trial Registration ClinicalTrials.gov, NCT01665378 PMID:28114316

  18. Anthropometry of fetal growth in rural Malawi in relation to maternal malaria and HIV status

    PubMed Central

    Kalanda, B; van Buuren, S; Verhoeff, F; Brabin, B

    2005-01-01

    Objective: To describe fetal growth centiles in relation to maternal malaria and HIV status, using cross sectional measurements at birth. Design: A cross sectional study of pregnant women and their babies. Data on maternal socioeconomic status and current pregnancy, including HIV status and newborn anthropometry, were collected. Malaria parasitaemia was assessed in maternal peripheral and placental blood, fetal haemoglobin was measured in cord blood, and maternal HIV status was determined. Setting: Two district hospitals in rural southern Malawi, between March 1993 and July 1994. Outcome variables: Newborn weight, length, Rohrer's ponderal index. Results: Maternal HIV (adjusted odds ratio (AOR) 1.76 (95% confidence interval 1.04 to 2.98)) and first pregnancy (AOR 1.83 (1.10 to 3.05)) were independently associated with low weight for age. Placental or peripheral parasitaemia at delivery (AOR 1.73 (1.02 to 2.88)) and primigravidae (AOR 2.13 (1.27 to 3.59)) were independently associated with low length for age. Maternal malaria at delivery and primiparity were associated with reduced newborn weight and length but not with disproportionate growth. Maternal HIV infection was associated only with reduced birth weight. The malaria and parity effect occurred throughout gestational weeks 30–40, but the HIV effect primarily after 38 weeks gestation. Conclusion: Fetal growth retardation in weight and length commonly occurs in this highly malarious area and is present from 30 weeks gestation. A maternal HIV effect on fetal weight occurred after 38 weeks gestation. PMID:15724042

  19. Relation of fetal growth to adult lung function in south India

    PubMed Central

    Stein, C. E.; Kumaran, K.; Fall, C. H.; Shaheen, S. O.; Osmond, C.; Barker, D. J.

    1997-01-01

    BACKGROUND: Follow up studies in Britain have shown that low rates of fetal growth are followed by reduced lung function in adult life, independent of smoking and social class. It is suggested that fetal adaptations to undernutrition in utero result in permanent changes in lung structure, which in turn lead to chronic airflow obstruction. India has high rates of intrauterine growth retardation, but no study has examined the association between fetal growth and adult lung function in Indian people. We have related size at birth to lung function in an urban Indian population aged 38-59 years. METHODS: Two hundred and eighty six men and women born in one hospital in Mysore City, South India, during 1934-1953 were traced by a house-to-house survey of the city. Their mean forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were measured using a turbine spirometer. These measurements were linked to their size at birth, recorded at the time. RESULTS: In both men and women mean FEV1 fell with decreasing birthweight. Adjusted for age and height, it fell by 0.09 litres with each pound (454 g) decrease in birthweight in men (95% confidence interval (CI) 0.01 to 0.16) and by 0.06 (95% CI -0.01 to 0.13) in women. Likewise, mean FVC fell by 0.11 litres (95% CI 0.02 to 0.19) with each pound decrease in birthweight in men, and by 0.08 litres (95% CI 0.002 to 0.16) in women. FEV1 and FVC were lower in men who smoked, but the associations with size at birth were independent of smoking. Small head circumference at birth was associated with a low FEV1/FVC ratio in men which may reflect restriction in airway growth in early gestation. CONCLUSION: This is further evidence that adult lung function is "programmed" in fetal life. Smoking may be particularly detrimental to the lung function of populations already disadvantaged by poor rates of fetal growth. 


 PMID:9404378

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

    PubMed Central

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

    2015-01-01

    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

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

    PubMed

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

    2013-01-01

    The origin of embryos including those created through assisted reproductive technologies might 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 immunologically detect Ki67 (a marker of proliferating cells) and 5-methyl cytosine followed by image analysis, and determine mRNA expression for three DNA methyltransferases. Fetal length and labeling index (proportion of proliferating cells) in maternal caruncles (maternal placenta) and fetal membranes (fetal placenta) were less (P < 0.001) in NAT-ET, IVF, and IVA than in NAT. In fetal membranes, expression of 5-methyl cytosine was greater (P < 0.02) in IVF and IVA than in NAT. In maternal caruncles, mRNA expression for DNMT1 was greater (P < 0.01) in IVA compared with the other groups, but DNMT3A expression was less (P < 0.04) in NAT-ET and IVA than in NAT. In fetal membranes, expression of mRNA for DNMT3A was greater (P < 0.01) in IVA compared with the other groups, and was similar in NAT, NAT-ET, and IVF groups. Thus, embryo origin might have specific effects on growth and function of ovine uteroplacental 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 assisted reproductive technologies.

  2. [Factors associated with false diagnosis of fetal growth restriction].

    PubMed

    Mendes, Renata Franco Pimentel; Martinelli, Silvio; Bittar, Roberto Eduardo; Francisco, Rossana Pulcineli Vieira; Zugaib, Marcelo

    2014-06-01

    The aim of this study was to analize and describe some characteristics related to a false diagnosis of intrauterine growth restriction (IUGR). We retrospectively included 48 pregnant women referred to our service with a suspected diagnosis of IUGR that was not confirmed after birth and we compared them to another group with confirmed IUGR. We then analyzed the characteristics of the false-positive results. The results of the study were divided into continuous and categorical variables for analysis. The χ2test or Fisher exact test was applied to compare proportions. The level of significance was set at p<0.05 for all tests. In our sample, pregnant women with a false diagnosis of IUGR had the following characteristics: they were referred earlier (mean gestational age of 32.8 weeks); were submitted to 2 to 6 ultrasound examinations before been registered in our service; in 25% of cases ultrasound examination was performed before 12 weeks; in 66.7% of cases the symphysis-fundal height measurement was normal; in 52.1% of cases they had at least 1 sonographic exam above the 10th percentile; on average, the last ultrasound examination (performed on average at 36 weeks) was above the 18th percentile; the women were submitted to a mean number of 5 ultrasound examinations and to a mean number of 4.6 vitality exams. The false diagnosis of IUGR involves high hospital costs and higher demand for specialists. The symphysis-fundal height measurement must be valued, and the diagnosis of IUGR must be confirmed with ultrasonography in the last weeks of pregnancy before any obstetric management is taken.

  3. Allometric studies on growth and development of the human placenta: growth of tissue compartments and diffusive conductances in relation to placental volume and fetal mass.

    PubMed

    Mayhew, Terry M

    2006-06-01

    Correlations between placental size and fetal mass during gestation fail to account for changes in composition that accompany placental growth and maturation. This study uses stereological data on the sizes of different tissue compartments in human placentas from 10 weeks of gestation to term and relates them to placental volume and to fetal mass by means of allometric analysis. In addition, tissue dimensions are used to calculate a physiological transport measure (diffusive conductance) for the villous membrane. Histological sections randomly sampled from placentas and analysed stereologically provided estimates of structural quantities (volumes, exchange surface areas, lengths, numbers of nuclei, diffusion distances). These data were combined with a physicochemical quantity (Krogh's diffusion coefficient) in order to estimate oxygen diffusive conductances for the villous membrane and its two components (trophoblast and stroma). Allometric relationships between these quantities and placental volume or fetal mass were obtained by linear regression analyses after log-transformation. Placental tissues had different growth trajectories: most grew more rapidly than placental volume and all grew more slowly than fetal mass. Diffusion distances were inversely related to placental and fetal size. Differential growth impacted on diffusive conductances, which, again, did not improve commensurately with placental volume but did match exactly growth of the fetus. Findings show that successful integration between supply and demand can be achieved by differential tissue growth. Allometric analysis of results from recent studies on the murine placenta suggest further that diffusive conductances may also be matched to fetal mass during gestation and to fetal mass at term across species.

  4. The consequences of fetal growth restriction on brain structure and neurodevelopmental outcome.

    PubMed

    Miller, Suzanne L; Huppi, Petra S; Mallard, Carina

    2016-02-15

    Fetal growth restriction (FGR) is a significant complication of pregnancy describing a fetus that does not grow to full potential due to pathological compromise. FGR affects 3-9% of pregnancies in high-income countries, and is a leading cause of perinatal mortality and morbidity. Placental insufficiency is the principal cause of FGR, resulting in chronic fetal hypoxia. This hypoxia induces a fetal adaptive response of cardiac output redistribution to favour vital organs, including the brain, and is in consequence called brain sparing. Despite this, it is now apparent that brain sparing does not ensure normal brain development in growth-restricted fetuses. In this review we have brought together available evidence from human and experimental animal studies to describe the complex changes in brain structure and function that occur as a consequence of FGR. In both humans and animals, neurodevelopmental outcomes are influenced by the timing of the onset of FGR, the severity of FGR, and gestational age at delivery. FGR is broadly associated with reduced total brain volume and altered cortical volume and structure, decreased total number of cells and myelination deficits. Brain connectivity is also impaired, evidenced by neuronal migration deficits, reduced dendritic processes, and less efficient networks with decreased long-range connections. Subsequent to these structural alterations, short- and long-term functional consequences have been described in school children who had FGR, most commonly including problems in motor skills, cognition, memory and neuropsychological dysfunctions. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  5. 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

  6. Developmental indices of nutritionally induced placental growth restriction in the adolescent sheep.

    PubMed

    Lea, Richard G; Hannah, Lisa T; Redmer, Dale A; Aitken, Raymond P; Milne, John S; Fowler, Paul A; Murray, Joanne F; Wallace, Jacqueline M

    2005-04-01

    Most intrauterine growth restriction cases are associated with reduced placental growth. Overfeeding adolescent ewes undergoing singleton pregnancies restricts placental growth and reduces lamb birth weight. We used this sheep model of adolescent pregnancy to investigate whether placental growth restriction is associated with altered placental cell proliferation and/or apoptosis at d 81 of pregnancy, equivalent to the apex in placental growth. Adolescent ewes with singleton pregnancies were offered a high or moderate level of a complete diet designed to induce restricted or normal placental size at term, respectively. Bromodeoxyuridine (Brd-U) was administered to H and M ewes 1 h before slaughter. Placental tissues were examined for a) Brd-U (immunohistochemistry) and b) apoptosis regulatory genes by in situ hybridization, Northern analyses (bax, mcl-1), immunohistochemistry, and Western analyses (bax). Quantification was carried out by image analysis. Total placentome weights were equivalent between groups. Brd-U predominantly localized to the trophectoderm and was significantly lower in the H group. Bax and mcl-1 mRNA were localized to the maternal-fetal interface. Bax protein was significantly increased in the H group and predominant in the uninuclear fetal trophectoderm. These observations indicate that reduced placental size at term may be due to reduced placental cell proliferation and possibly increased apoptosis occurring much earlier in gestation.

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

    PubMed

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

    2014-10-01

    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. 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. 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 shows a tendency of a smaller head circumference during childhood. 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 reduced growth during childhood. This study is the first to link prenatal Pb exposure to poorer growth in school-age children. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. 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

  9. The influence of maternal undernutrition in ovine twin pregnancy on fetal growth and Doppler flow-velocity waveforms.

    PubMed

    Newnham, J P; Kelly, R W; Patterson, L; James, I

    1991-11-01

    The effects on placental blood flow velocity of maternal undernutrition during mid pregnancy were investigated in 38 twin bearing pregnant sheep by Doppler analysis of umbilical and uteroplacental arterial waveforms. Mid pregnancy undernutrition resulted in fetal growth restriction manifest at term gestation by reduced mean birth weight. Arterial waveform systolic/diastolic ratios from the umbilical and uteroplacental arterial circulations were not influenced by maternal nutrition either during the dietary deprivation or during a subsequent period of dietary supplementation. An effect of heart rate on systolic/diastolic ratios could not be demonstrated. The results indicate that the fetus responds to mid pregnancy maternal undernutrition with restricted growth but without alterations in systolic/diastolic ratios in umbilical or uteroplacental arterial waveforms.

  10. Anthropometric protocols for the construction of new international fetal and newborn growth standards: the INTERGROWTH-21st Project

    PubMed Central

    Ismail, L Cheikh; Knight, HE; Bhutta, Z; Chumlea, WC

    2014-01-01

    The primary aim of the INTERGROWTH-21st Project is to construct new, prescriptive standards describing optimal fetal and preterm postnatal growth. The anthropometric measurements include the head circumference, recumbent length and weight of the infants, and the stature and weight of the parents. In such a large, international, multicentre project, it is critical that all study sites follow standardised protocols to ensure maximal validity of the growth and nutrition indicators used. This paper describes, in detail, the selection of anthropometric personnel, equipment, and measurement and calibration protocols used to construct the new standards. Implementing these protocols at each study site ensures that the anthropometric data are of the highest quality to construct the international standards. PMID:23841804

  11. Chronically Increased Amino Acids Improve Insulin Secretion, Pancreatic Vascularity, and Islet Size in Growth-Restricted Fetal Sheep.

    PubMed

    Brown, Laura D; Davis, Melissa; Wai, Sandra; Wesolowski, Stephanie R; Hay, William W; Limesand, Sean W; Rozance, Paul J

    2016-10-01

    Placental insufficiency is associated with reduced supply of amino acids to the fetus and leads to intrauterine growth restriction (IUGR). IUGR fetuses are characterized by lower glucose-stimulated insulin secretion, smaller pancreatic islets with less β-cells, and impaired pancreatic vascularity. To test whether supplemental amino acids infused into the IUGR fetus could improve these complications of IUGR we used acute (hours) and chronic (11 d) direct fetal amino acid infusions into a sheep model of placental insufficiency and IUGR near the end of gestation. IUGR fetuses had attenuated acute amino acid-stimulated insulin secretion compared with control fetuses. These results were confirmed in isolated IUGR pancreatic islets. After the chronic fetal amino acid infusion, fetal glucose-stimulated insulin secretion and islet size were restored to control values. These changes were associated with normalization of fetal pancreatic vascularity and higher fetal pancreatic vascular endothelial growth factor A protein concentrations. These results demonstrate that decreased fetal amino acid supply contributes to the pathogenesis of pancreatic islet defects in IUGR. Moreover, the results show that pancreatic islets in IUGR fetuses retain their ability to respond to increased amino acids near the end of gestation after chronic fetal growth restriction.

  12. 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…

  13. [Premature rupture of fetal membranes at term: an indication for induced labor with prostaglandins?].

    PubMed

    Lettau, R; Hege, G; Steldinger, R

    1995-01-01

    Premature rupture of membranes (PROM) at term is thought to be related to an increased infection risk for mother and child. A prospective study was conducted to evaluate the efficacy of prostaglandins for induction of labour in 433 cases of PROM presenting after 35 completed weeks of gestation. Intracervical gel or vaginal pessaries were given in dependence on the Bishop-score. Course of delivery and fetal outcome were analysed. In 57.3% single application was sufficient to induce the delivery. Only 1.8% of cases did not respond. 21% of patients were delivered within six hours of the first application and 89.6% during the first 24 hours. The rate of cesarean section was 15.5%. Fetal distress caused by uterine hyperstimulation was observed in 9.9% and required intrapartum tocolysis. A fetal acidosis (pH < 7.15) was present in 4.1%. The neonatal infective morbidity was 0.4%. Severe maternal complications were not observed. We conclude that use of prostaglandins for induction of labour in case of PROM at term seems to be a recommendable measure. In primiparous women or in the presence of an unfavorable cervix-score shorter duration to delivery diminishes the risk of fetal infection.

  14. 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…

  15. The effect of maternal hyperoxygenation on fetal circulatory system in normal growth and IUGR fetuses. What we can learn from this impact.

    PubMed

    Khatib, Nizar; Thaler, Israel; Beloosesky, Ron; Dabaja, Hanin; Ganem, Nadir; Abecassis, Philippe; Ginsberg, Yuval; Weiner, Zeev

    2017-03-21

    The objectives of study were to assess and compare the effects of maternal hyperoxygenation on fetal circulation, in fetuses with intrauterine growth retardation and normal fetal growth. Twelve singleton pregnant women with normal fetal growth and 12 singleton pregnant women with intrauterine growth restriction were recruited. Mean gestational age of 35.2 ± 3.5 and 34.7 ± 3.9 weeks, respectively. Doppler blood flow velocity waveforms were obtained from the middle cerebral artery, umbilical, main and proximal right pulmonary arteries. Pulsatility indices were calculated for all the vessels. Peak systolic velocity was determined for the middle cerebral artery. Following baseline measurements; each woman received 70% humidified oxygen for 10 min. Doppler measurements were then repeated. The pulsatility index in the middle cerebral artery increased significantly from 1.5 ± 0.27 to 1.88 ± 0.48, respectively (p = .006) in the high-risk group. However, it did not change significantly in the low-risk group. Hyperoxygenation caused a significant decrease in pulsatility indices in the pulmonary arteries for both groups. Hyperoxygenation interrupts the relative brain-sparing effect in the intrauterine growth retardation group, but it did not significantly change the pulsatility index of the middle cerebral artery in fetuses with adequate weight. The pulsatility index in the pulmonary arteries decreased significantly following hyperoxygenation.

  16. Fetal growth according to different reference ranges in twin pregnancies with placental insufficiency

    PubMed Central

    Nakano, Julianny Cavalheiro Nery; Liao, Adolfo Wenjaw; de Lourdes Brizot, Maria; Miyadahira, Mariana; Francisco, Rossana Pulcineli Vieira; Zugaib, Marcelo

    2015-01-01

    The aim of this study was to compare different fetal growth curves in twin pregnancies with severe placental insufficiency. A retrospective cross-sectional analysis of 47 twin pregnancies with absent or reverse end diastolic flow in the umbilical artery of one fetus was performed. Pregnancies with major fetal abnormalities, twin-twin transfusion or three or more fetuses were not included. The estimated fetal weight zeta-scores were calculated for both fetuses (abnormal Doppler and co-twin) according to the following criteria: Hadlock, Liao and Araújo. The abdominal circumference zeta-scores were calculated according to Hadlock, Liao, Araújo, Ong and Stirrup. The mean estimates of the zeta-score values were calculated using generalized estimating equation regression analysis. The mean gestational age at inclusion was 27.4±4.7 weeks. The fetal sex and the interaction Doppler findings × criteria correlated significantly with the zeta-score values (p<0.001 for both variables). The estimated fetal weight mean zeta-scores (standard error) according to each criteria were as follows: Hadlock - abnormal Doppler: -2.98 (0.18), co-twin: -1.16 (0.15); Liao - abnormal Doppler: -2.89 (0.24), co-twin: -0.58 (0.19); and Araújo - abnormal Doppler: -3.05 (0.29), co-twin: -0.75 (0.18). Values for abdominal circumference were as follows: Hadlock - abnormal Doppler: -3.14 (0.26), co-twin: -1.13 (0.19); Liao - abnormal Doppler: -2.63 (0.27), co-twin: -0.42 (0.19); Araújo - abnormal Doppler: -2.44 (0.22), co-twin: -0.71 (0.14); Ong - abnormal Doppler: -3.36 (0.34), co-twin: -1.48 (0.23); and Stirrup AD -- -2.36 (0.14), co-twin: -1.18 (0.10). Sex- and plurality-specific charts should be used in the evaluation of fetal growth in twin pregnancies with placental insufficiency. PMID:26735222

  17. Chronic ethanol exposure and folic acid supplementation: fetal growth and folate status in the maternal and fetal guinea pig.

    PubMed

    Hewitt, Amy J; Knuff, Amber L; Jefkins, Matthew J; Collier, Christine P; Reynolds, James N; Brien, James F

    2011-05-01

    Chronic ethanol exposure (CEE) can produce developmental abnormalities in the CNS of the embryo and developing fetus. Folic acid (FA) is an important nutrient during pregnancy and low folate status exacerbates ethanol-induced teratogenicity. This study tested the hypotheses that (1) CEE depletes folate stores in the mother and fetus; and (2) maternal FA supplementation maintains folate stores. CEE decreased fetal body, brain, hippocampus weights, and brain to body weight ratio but not hippocampus to body weight ratio. These effects of CEE were not mitigated by maternal FA administration. The FA regimen prevented the CEE-induced decrease of term fetal liver folate. However, it did not affect maternal liver folate or fetal RBC folate at term, and did not mitigate the nutritional deficit-induced decrease of term fetal hippocampus folate. This study suggests that maternal FA supplementation may have differential effects on folate status in the mother and the fetus. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Growth trajectories of the human fetal brain tissues estimated from 3D reconstructed in utero MRI.

    PubMed

    Scott, Julia A; Habas, Piotr A; Kim, Kio; Rajagopalan, Vidya; Hamzelou, Kia S; Corbett-Detig, James M; Barkovich, A James; Glenn, Orit A; Studholme, Colin

    2011-08-01

    In the latter half of gestation (20-40 gestational weeks), human brain growth accelerates in conjunction with cortical folding and the deceleration of ventricular zone progenitor cell proliferation. These processes are reflected in changes in the volume of respective fetal tissue zones. Thus far, growth trajectories of the fetal tissue zones have been extracted primarily from 2D measurements on histological sections and magnetic resonance imaging (MRI). In this study, the volumes of major fetal zones-cortical plate (CP), subplate and intermediate zone (SP+IZ), germinal matrix (GMAT), deep gray nuclei (DG), and ventricles (VENT)--are calculated from automatic segmentation of motion-corrected, 3D reconstructed MRI. We analyzed 48 T2-weighted MRI scans from 39 normally developing fetuses in utero between 20.57 and 31.14 gestational weeks (GW). The supratentorial volume (STV) increased linearly at a rate of 15.22% per week. The SP+IZ (14.75% per week) and DG (15.56% per week) volumes increased at similar rates. The CP increased at a greater relative rate (18.00% per week), while the VENT (9.18% per week) changed more slowly. Therefore, CP increased as a fraction of STV and the VENT fraction declined. The total GMAT volume slightly increased then decreased after 25 GW. We did not detect volumetric sexual dimorphisms or total hemispheric volume asymmetries, which may emerge later in gestation. Further application of the automated fetal brain segmentation to later gestational ages will bridge the gap between volumetric studies of premature brain development and normal brain development in utero. Published by Elsevier Ltd.

  19. Growth trajectories of the human fetal brain tissues estimated from 3D reconstructed in utero MRI

    PubMed Central

    Scott, Julia A.; Habas, Piotr A.; Kim, Kio; Rajagopalan, Vidya; Hamzelou, Kia S.; Corbett-Detig, James M.; Barkovich, A. James; Glenn, Orit A.; Studholme, Colin

    2012-01-01

    In the latter half of gestation (20 to 40 gestational weeks), human brain growth accelerates in conjunction with cortical folding and the deceleration of ventricular zone progenitor cell proliferation. These processes are reflected in changes in the volume of respective fetal tissue zones. Thus far, growth trajectories of the fetal tissue zones have been extracted primarily from 2D measurements on histological sections and magnetic resonance imaging (MRI). In this study, the volumes of major fetal zones—cortical plate (CP), subplate and intermediate zone (SP+IZ), germinal matrix (GMAT), deep gray nuclei (DG), and ventricles (VENT)—are calculated from automatic segmentation of motion-corrected, 3D reconstructed MRI. We analyzed 48 T2-weighted MRI scans from 39 normally developing fetuses in utero between 20.57 and 31.14 gestational weeks (GW). The supratentorial volume (STV) increased linearly at a rate of 15.22% per week. The SP+IZ (14.75% per week) and DG (15.56% per week) volumes increased at similar rates. The CP increased at a greater relative rate (18.00% per week), while the VENT (9.18% per week) changed more slowly. Therefore, CP increased as a fraction of STV and the VENT fraction declined. The total GMAT volume slightly increased then decreased after 25 GW. We did not detect volumetric sexual dimorphisms or total hemispheric volume asymmetries, which may emerge later in gestation. Further application of the automated fetal brain segmentation to later gestational ages will bridge the gap between volumetric studies of premature brain development and normal brain development in utero. PMID:21530634

  20. 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

  1. Prenatal air pollution exposure and ultrasound measures of fetal growth in Los Angeles, California.

    PubMed

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

    2014-04-01

    Few previous studies examined the impact of prenatal air pollution exposures on fetal development based on ultrasound measures during pregnancy. 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 <10μm 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. 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 0.2-0.3mm. For women residing within 5km of a monitoring station, we estimated biparietal diameter reductions of 0.9-1.0mm 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. Prenatal exposure to traffic-derived pollution was negatively associated with fetal head size measured as biparietal diameter in late pregnancy. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. How to monitor pregnancies complicated by fetal growth restriction and delivery before 32 weeks: post-hoc analysis of TRUFFLE study.

    PubMed

    Ganzevoort, W; Mensing Van Charante, N; Thilaganathan, B; Prefumo, F; Arabin, B; Bilardo, C M; Brezinka, C; Derks, J B; Diemert, A; Duvekot, J J; Ferrazzi, E; Frusca, T; Hecher, K; Marlow, N; Martinelli, P; Ostermayer, E; Papageorghiou, A T; Schlembach, D; Schneider, K T M; Todros, T; Valcamonico, A; Visser, G H A; Van Wassenaer-Leemhuis, A; Lees, C C; Wolf, H

    2017-06-01

    In the recent TRUFFLE study, it appeared that, in pregnancies complicated by fetal growth restriction (FGR) between 26 and 32 weeks' gestation, monitoring of the fetal ductus venosus (DV) waveform combined with computed cardiotocography (CTG) to determine timing of delivery increased the chance of infant survival without neurological impairment. However, concerns with the interpretation were raised, as DV monitoring appeared to be associated with a non-significant increase in fetal death, and some infants were delivered after 32 weeks, at which time the study protocol no longer applied. This secondary sensitivity analysis of the TRUFFLE study focuses on women who delivered before 32 completed weeks' gestation and analyzes in detail the cases of fetal death. Monitoring data of 317 pregnancies with FGR that delivered before 32 weeks were analyzed, excluding those with absent outcome data or inevitable perinatal death. Women were allocated randomly to one of three groups of indication for delivery according to the following monitoring strategies: (1) reduced fetal heart rate short-term variation (STV) on CTG; (2) early changes in fetal DV waveform; and (3) late changes in fetal DV waveform. Primary outcome was 2-year survival without neurological impairment. The association of the last monitoring data before delivery and infant outcome was assessed by multivariable analysis. Two-year survival without neurological impairment occurred more often in the two DV groups (both 83%) than in the CTG-STV group (77%), however, the difference was not statistically significant (P = 0.21). Among the surviving infants in the DV groups, 93% were free of neurological impairment vs 85% of surviving infants in the CTG-STV group (P = 0.049). All fetal deaths (n = 7) occurred in the groups with DV monitoring. Of the monitoring parameters obtained shortly before fetal death in these seven cases, an abnormal CTG was observed in only one case. Multivariable regression analysis of

  3. Effect of short-term maternal fasting in the third trimester on uterine, umbilical, and fetal middle cerebral artery Doppler indices.

    PubMed

    Abd-El-Aal, Diaa-Eldeen M; Shahin, Ahmed Y; Hamed, Hossam O

    2009-10-01

    To assess the effect of short-term maternal fasting on uterine, umbilical, and middle cerebral artery Doppler indices, and on maternal serum glucose levels and fetal behavior. Maternal serum glucose levels, fetal biophysical profiles, and uterine, umbilical, and middle cerebral artery Doppler indices were assessed in 110 healthy women in the third trimester of pregnancy after fasting for 10-12 hours and 2 hours after a balanced meal. Maternal serum glucose levels, nonstress test results, fetal breathing movements, and biophysical profile improved after a meal compared with after fasting for 10-12 hours. Uterine, umbilical, and middle cerebral artery Doppler indices were not significantly different after fasting and after a meal. Short-term maternal fasting during the third trimester of pregnancy has no effect on uterine, umbilical, or fetal cerebral artery Doppler indices, and has a transient but significant effect on maternal serum glucose levels and fetal behavior.

  4. Maternal vitamin D status and calcium intake interact to affect fetal skeletal growth in utero in pregnant adolescents.

    PubMed

    Young, Bridget E; McNanley, Thomas J; Cooper, Elizabeth M; McIntyre, Allison W; Witter, Frank; Harris, Z Leah; O'Brien, Kimberly O

    2012-05-01

    Maternal calcium intake and vitamin D status may affect fetal bone development. This study was designed to examine relations between maternal calcium intake, 25-hydroxyvitamin D [25(OH)D] status, and fetal bone growth across pregnancy. This was a prospective longitudinal design. Maternal 25(OH)D, parathyroid hormone, and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were determined at midgestation (∼26 wk) and at delivery in 171 adolescents (≤ 18 y). Dietary recalls and fetal sonograms were performed up to 3 times across gestation, and fetal femur and humerus z scores were generated. Fetal femur and humerus z scores and neonatal birth length were significantly greater (P < 0.03) in adolescents consuming ≥ 1050 mg than in those consuming <1050 mg Ca/d. Maternal 25(OH)D > 50 nmol/L was significantly positively associated with fetal femur and humerus z scores (P < 0.01). When maternal smoking, height, race, weight gain, and gestational age were controlled for, these relations remained significant. Interactions between calcium intake and 25(OH)D were evident. Calcium intake was associated with fetal femur z scores and birth length only when maternal 25(OH)D was ≤ 50 nmol/L (P < 0.05). Similarly, maternal 25(OH)D was associated with fetal femur and humerus z scores only when maternal calcium intake was <1050 mg/d (P < 0.03). Optimal calcium intake and adequate maternal vitamin D status are both needed to maximize fetal bone growth. Interactions between these nutrients were evident when either calcium or vitamin D status was limited. Improving maternal calcium intake and/or vitamin D status during pregnancy may have a positive effect on fetal skeletal development in pregnant adolescents.

  5. Fetal growth and childhood acute lymphoblastic leukemia: findings from the childhood leukemia international consortium.

    PubMed

    Milne, Elizabeth; Greenop, Kathryn R; Metayer, Catherine; Schüz, Joachim; Petridou, Eleni; Pombo-de-Oliveira, Maria S; Infante-Rivard, Claire; Roman, Eve; Dockerty, John D; Spector, Logan G; Koifman, Sérgio; Orsi, Laurent; Rudant, Jérémie; Dessypris, Nick; Simpson, Jill; Lightfoot, Tracy; Kaatsch, Peter; Baka, Margarita; Faro, Alessandra; Armstrong, Bruce K; Clavel, Jacqueline; Buffler, Patricia A

    2013-12-15

    Positive associations have been reported between the measures of accelerated fetal growth and risk of childhood acute lymphoblastic leukemia (ALL). We investigated this association by pooling individual-level data from 12 case-control studies participating in the Childhood Leukemia International Consortium. Two measures of fetal growth-weight-for-gestational-age and proportion of optimal birth weight (POBW)-were analysed. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression, and combined in fixed effects meta-analyses. Pooled analyses of all data were also undertaken using multivariable logistic regression. Subgroup analyses were undertaken when possible. Data on weight for gestational age were available for 7,348 cases and 12,489 controls from all 12 studies and POBW data were available for 1,680 cases and 3,139 controls from three studies. The summary ORs from the meta-analyses were 1.24 (95% CI: 1.13, 1.36) for children who were large for gestational age relative to appropriate for gestational age, and 1.16 (95% CI: 1.09, 1.24) for a one-standard deviation increase in POBW. The pooled analyses produced similar results. The summary and pooled ORs for small-for-gestational-age children were 0.83 (95% CI: 0.75, 0.92) and 0.86 (95% CI: 0.77, 0.95), respectively. Results were consistent across subgroups defined by sex, ethnicity and immunophenotype, and when the analysis was restricted to children who did not have high birth weight. The evidence that accelerated fetal growth is associated with a modest increased risk of childhood ALL is strong and consistent with known biological mechanisms involving insulin-like growth factors. © 2013 UICC.

  6. Fetal Growth and Childhood Acute Lymphoblastic Leukemia: Findings from the Childhood Leukemia International Consortium (CLIC)

    PubMed Central

    Milne, Elizabeth; Greenop, Kathryn R.; Metayer, Catherine; Schüz, Joachim; Petridou, Eleni; Pombo-de-Oliveira, Maria S.; Infante-Rivard, Claire; Roman, Eve; Dockerty, John D.; Spector, Logan G.; Koifman, Sérgio; Orsi, Laurent; Rudant, Jérémie; Dessypris, Nick; Simpson, Jill; Lightfoot, Tracy; Kaatsch, Peter; Baka, Margarita; Faro, Alessandra; Armstrong, Bruce K.; Clavel, Jacqueline; Buffler, Patricia A.

    2013-01-01

    Positive associations have been reported between measures of accelerated fetal growth and risk of childhood acute lymphoblastic leukemia (ALL). We investigated this association by pooling individual-level data from 12 case-control studies participating in the Childhood Leukemia International Consortium. Two measures of fetal growth – weight-for-gestational-age and proportion of optimal birth weight (POBW) – were analysed. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression, and combined in fixed effects meta-analyses. Pooled analyses of all data were also undertaken using multivariable logistic regression. Subgroup analyses were undertaken when possible. Data on weight for gestational age were available for 7,348 cases and 12,489 controls from all 12 studies and POBW data were available for 1,680 cases and 3,139 controls from three studies. The summary ORs from the meta-analyses were 1.24 (95% CI 1.13, 1.36) for children who were large for gestational age relative to appropriate for gestational age, and 1.16 (95% CI: 1.09, 1.24) for a one standard deviation increase in POBW. The pooled analyses produced similar results. The summary and pooled ORs for small-for-gestational-age children were 0.83 (95% CI: 0.75, 0.92) and 0.86 (95% CI 0.77, 0.95) respectively. Results were consistent across subgroups defined by sex, ethnicity and immunophenotype, and when the analysis was restricted to children who did not have high birth weight. The evidence that accelerated fetal growth is associated with a modest increased risk of childhood ALL is strong and consistent with known biological mechanisms involving insulin like growth factors. PMID:23754574

  7. Postnatal growth restriction and gene expression changes in a mouse model of fetal alcohol syndrome.

    PubMed

    Kaminen-Ahola, Nina; Ahola, Arttu; Flatscher-Bader, Traute; Wilkins, Sarah J; Anderson, Greg J; Whitelaw, Emma; Chong, Suyinn

    2010-10-01

    Growth restriction, craniofacial dysmorphology, and central nervous system defects are the main diagnostic features of fetal alcohol syndrome. Studies in humans and mice have reported that the growth restriction can be prenatal or postnatal, but the underlying mechanisms remain unknown.We recently described a mouse model of moderate gestational ethanol exposure that produces measurable phenotypes in line with fetal alcohol syndrome (e.g., craniofacial changes and growth restriction in adolescent mice). In this study, we characterize in detail the growth restriction phenotype by measuring body weight at gestational day 16.5, cross-fostering from birth to weaning, and by extending our observations into adulthood. Furthermore, in an attempt to unravel the molecular events contributing to the growth phenotype, we have compared gene expression patterns in the liver and kidney of nonfostered, ethanol-exposed and control mice at postnatal day 28.We find that the ethanol-induced growth phenotype is not detectable prior to birth, but is present at weaning, even in mice that have been cross-fostered to unexposed dams. This finding suggests a postnatal growth restriction phenotype that is not due to deficient postpartum care by dams that drank ethanol, but rather a physiologic result of ethanol exposure in utero. We also find that, despite some catch-up growth after 5 weeks of age, the effect extends into adulthood, which is consistent with longitudinal studies in humans.Genome-wide gene expression analysis revealed interesting ethanol-induced changes in the liver, including genes involved in the metabolism of exogenous and endogenous compounds, iron homeostasis, and lipid metabolism.

  8. Endocrine regulation of fetal skeletal muscle growth: impact on future metabolic health.

    PubMed

    Brown, Laura D

    2014-05-01

    Establishing sufficient skeletal muscle mass is essential for lifelong metabolic health. The intrauterine environment is a major determinant of the muscle mass that is present during the life course of an individual, because muscle fiber number is set at the time of birth. Thus, a compromised intrauterine environment from maternal nutrient restriction or placental insufficiency that restricts muscle fiber number can have permanent effects on the amount of muscle an individual will live with. Reduced muscle mass due to fewer muscle fibers persists even after compensatory or 'catch-up' postnatal growth occurs. Furthermore, muscle hypertrophy can only partially compensate for this limitation in fiber number. Compelling associations link low birth weight and decreased muscle mass to future insulin resistance, which can drive the development of the metabolic syndrome and type 2 diabetes, and the risk of cardiovascular events later in life. There are gaps in knowledge about the origins of reduced muscle growth at the cellular level and how these patterns are set during fetal development. By understanding the nutrient and endocrine regulation of fetal skeletal muscle growth and development, we can direct research efforts toward improving muscle growth early in life to prevent the development of chronic metabolic diseases later in life.

  9. Endocrine regulation of fetal skeletal muscle growth: impact on future metabolic health

    PubMed Central

    Brown, Laura D.

    2014-01-01

    Establishing sufficient skeletal muscle mass is essential for lifelong metabolic health. The intrauterine environment is a major determinant of the muscle mass that is present for the life course of an individual, because muscle fiber number is set at the time of birth. Thus, a compromised intrauterine environment from maternal nutrient restriction or placental insufficiency that restricts development of muscle fiber number can have permanent effects on the amount of muscle an individual will live with. Reduced muscle mass due to fewer muscle fibers persists even after compensatory or “catch up” postnatal growth occurs. Furthermore, muscle hypertrophy can only partially compensate for this limitation in fiber number. Compelling associations link low birth weight and decreased muscle mass to future insulin resistance, which can drive the development of the metabolic syndrome and type 2 diabetes, and risk for cardiovascular events later in life. There are gaps in knowledge about the origins of reduced muscle growth at the cellular level and how these patterns are set during fetal development. By understanding the nutrient and endocrine regulation of fetal skeletal muscle growth and development, we can direct research efforts towards improving muscle growth early in life in order to prevent the development of chronic metabolic disease later in life. PMID:24532817

  10. 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

  11. 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

  12. 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.

  13. Congenital Heart Defects and Measures of Fetal Growth in Newborns with Down Syndrome or 22q11.2 Deletion Syndrome.

    PubMed

    Matthiesen, Niels B; Agergaard, Peter; Henriksen, Tine B; Bach, Cathrine C; Gaynor, J William; Hjortdal, Vibeke; Østergaard, John R

    2016-08-01

    To estimate the association between congenital heart defects (CHD) and indices of fetal growth in Down and 22q11.2 deletion syndromes. We established 2 Danish nationwide cohorts of newborn singletons with either Down syndrome (n = 670) or 22q11.2 deletion syndrome (n = 155), born 1997-2011. In both cohorts, we analyzed the association between CHD, CHD severity, and indices of fetal growth by multivariable linear regression adjusted for potential confounders. We report mean differences in gestational age specific z-scores compared with newborns without CHD. Down syndrome and 22q11.2 deletion syndrome were both associated with lower mean birth weight and head circumference z-scores. We found no association between CHD or CHD severity and indices of fetal growth. In Down syndrome, the association between any CHD and the mean difference in head circumference z-score was 0.03 (95% CI -0.12, 0.18), and the estimate regarding birth weight z-score was 0.09 (95% CI -0.08, 0.25). The corresponding estimates in 22q11.2 deletion syndrome were 0.00 (95% CI -0.33, 0.32) and -0.09 (95% CI -0.45, 0.26). We found no association between CHD and fetal growth measures in newborns with Down syndrome or 22q11.2 deletion syndrome. Thus, in certain subtypes of CHD, the contribution of genetic factors to prenatal growth impairment may be more important than circulatory disturbances. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. 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.

  15. Effects of protein energy supplementation during pregnancy on fetal growth: a review of the literature focusing on contextual factors.

    PubMed

    Liberato, Selma C; Singh, Gurmeet; Mulholland, Kim

    2013-01-01

    Maternal diet during pregnancy is one of the most important factors associated with adequate fetal growth. There are many complications associated with fetal growth restriction that lead to lifelong effects. The aim of this review was to describe the studies examining the effects of protein energy supplementation during pregnancy on fetal growth focusing on the contextual differences. Relevant articles published between 2007 and 2012 were identified through systematic electronic searches of the PubMed, Science Direct, and EBSCO database and the examination of the bibliographies of retrieved articles. The search aimed to identify studies examining pregnant women receiving protein and/or energy during pregnancy and to assess fetal growth measures. Data of effectiveness and practical aspects of protein energy supplementation during pregnancy were extracted and compiled. Twenty studies (11 randomized controlled trials, 8 controlled before and after, and 1 prospective study) were included in this review. Positive outcomes in infants and women cannot be expected if the supplementation is not needed. Therefore, it is essential to correctly select women who will benefit from dietary intervention programs during pregnancy. However, there is currently no consensus on the most effective method of identifying these women. The content of protein in the supplements considering total diet is also an important determinant of fetal growth. Balanced protein energy supplementation (containing up to 20% of energy as protein) given to pregnant women with energy or protein deficit appears to improve fetal growth, increase birth weight (by 95-324 g) and height (by 4.6-6.1 mm), and decrease the percentage of low birth weight (by 6%). Supplements with excess protein (>20% of energy as protein) provided to women with a diet already containing adequate protein may conversely impair fetal growth. There is also no consensus on the best time to start supplementation. Strong quality studies

  16. Expression of the fetal hematopoiesis regulator FEV indicates leukemias of prenatal origin.

    PubMed

    Liu, T-H; Tang, Y-J; Huang, Y; Wang, L; Guo, X-L; Mi, J-Q; Liu, L-G; Zhu, H; Zhang, Y; Chen, L; Liu, X; Zhang, L-H; Ye, Q-J; Li, B-S; Tang, J-Y; Ford, A; Enver, T; Liu, F; Chen, G-Q; Hong, D-L

    2017-05-01

    The origin of cancers is associated with etiology as well as therapeutics. Several studies reveal that malignancies in children can originate in utero. However, a diagnostic approach to distinguish between cancers initiated pre- or postnatally is absent. Here we identified a transcriptional factor FEV (fifth Ewing variant) that was expressed in fetal hematopoietic cells and became silent after birth. We characterized that FEV was essential for the self-renewal of hematopoietic stem cells (HSCs). We next found that FEV was expressed in most infant leukemia samples, but seldom in adult samples, in accord with the known prenatal origins of the former. We further determined the majority of pediatric acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML) were FEV positive. Moreover, FEV knockdown markedly impaired the leukemia-propagating ability of leukemic stem cells. We therefore identified FEV is unique to fetal HSCs and stably expressed in leukemic cells of prenatal origin. It may also provide a tractable therapeutic target.

  17. 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.

  18. Hyperoncotic enhancement of fetal pulmonary growth after tracheal occlusion: an alveolar and capillary morphometric analysis.

    PubMed

    Kunisaki, Shaun M; Chang, Robert W; Andreoli, Steven; Lewicke, Sara; Peña-Peterson, Snow; Jennings, Russell W; Fauza, Dario O

    2006-07-01

    Previous work has shown that intrapulmonary delivery of oncotic agents enhance overall lung growth after late gestational fetal tracheal occlusion (TO). This study was a post hoc analysis aimed at determining whether actual alveolar and capillary hyperplasias are maximized in this setting. Twenty-one near term fetal lambs were evenly divided into 4 groups: group I comprised sham-operated controls; group II had TO alone; and groups III and IV underwent TO and intratracheal infusion of equal amounts of either saline or 25% albumin, respectively. Approximately 2 weeks thereafter, their lungs were examined by detailed alveolar and capillary morphometry before birth. Statistical analysis included analysis of variance and the Bonferroni correction for multiple comparisons (P < .05). Total alveolar and capillary numbers, as well as total alveolar surface area, were significantly higher in group IV and lower in group I compared with all other groups, with no differences between groups II and III. Alveolar capillary load was normal in all groups. Intrapulmonary delivery of concentrated albumin safely enhances short-term alveolar and capillary hyperplasia in a late gestational model of fetal TO. This therapeutic concept may allow for TO to be effective and predictable when performed late in gestation.

  19. The effect of androgen excess on maternal metabolism, placental function and fetal growth in obese dams.

    PubMed

    Fornes, Romina; Maliqueo, Manuel; Hu, Min; Hadi, Laila; Jimenez-Andrade, Juan M; Ebefors, Kerstin; Nyström, Jenny; Labrie, Fernand; Jansson, Thomas; Benrick, Anna; Stener-Victorin, Elisabet

    2017-08-14

    Pregnant women with polycystic ovary syndrome (PCOS) are often overweight or obese. To study the effects of maternal androgen excess in obese dams on metabolism, placental function and fetal growth, female C57Bl6J mice were fed a control (CD) or a high fat/high sucrose (HF/HS) diet for 4-10 weeks, and then mated. On gestational day (GD) 15.5-17.5, dams were injected with dihydrotestosterone (CD-DHT, HF/HS-DHT) or a vehicle (CD-Veh, HF/HS-Veh). HF/HS dams had higher fat content, both before mating and on GD18.5, with no difference in glucose homeostasis, whereas the insulin sensitivity was higher in DHT-exposed dams. Compared to the CD groups, the livers from HF/HS dams weighed more on GD18.5, the triglyceride content was higher, and there was a dysregulation of liver enzymes related to lipogenesis and higher mRNA expression of Fitm1. Fetuses from HF/HS-Veh dams had lower liver triglyceride content and mRNA expression of Srebf1c. Maternal DHT exposure, regardless of diet, decreased fetal liver Pparg mRNA expression and increased placental androgen receptor protein expression. Maternal diet-induced obesity, together with androgen excess, affects maternal and fetal liver function as demonstrated by increased triglyceride content and dysfunctional expression of enzymes and transcription factors involved in de novo lipogenesis and fat storage.

  20. Increased hepatic glucose production in fetal sheep with intrauterine growth restriction is not suppressed by insulin.

    PubMed

    Thorn, Stephanie R; Brown, Laura D; Rozance, Paul J; Hay, William W; Friedman, Jacob E

    2013-01-01

    Intrauterine growth restriction (IUGR) increases the risk for metabolic disease and diabetes, although the developmental origins of this remain unclear. We measured glucose metabolism during basal and insulin clamp periods in a fetal sheep model of placental insufficiency and IUGR. Compared with control fetuses (CON), fetuses with IUGR had increased basal glucose production rates and hepatic PEPCK and glucose-6-phosphatase expression, which were not suppressed by insulin. In contrast, insulin significantly increased peripheral glucose utilization rates in CON and IUGR fetuses. Insulin robustly activated AKT, GSK3β, and forkhead box class O (FOXO)1 in CON and IUGR fetal livers. IUGR livers, however, had increased basal FOXO1 phosphorylation, nuclear FOXO1 expression, and Jun NH(2)-terminal kinase activation during hyperinsulinemia. Expression of peroxisome proliferator-activated receptor γ coactivator 1α and hepatocyte nuclear factor-4α were increased in IUGR livers during basal and insulin periods. Cortisol and norepinephrine concentrations were positively correlated with glucose production rates. Isolated IUGR hepatocytes maintained increased glucose production in culture. In summary, fetal sheep with IUGR have increased hepatic glucose production, which is not suppressed by insulin despite insulin sensitivity for peripheral glucose utilization. These data are consistent with a novel mechanism involving persistent transcriptional activation in the liver that seems to be unique in the fetus with IUGR.

  1. 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

  2. Cognitive ability in adolescents born small for gestational age: Associations with fetal growth velocity, head circumference and postnatal growth.

    PubMed

    Jensen, Rikke Beck; Juul, Anders; Larsen, Torben; Mortensen, Erik Lykke; Greisen, Gorm

    2015-12-01

    Small size at birth may be associated with impaired cognitive ability later in life. The aim of this study was to examine the effect of being born small for gestational age (SGA), with or without intrauterine growth restriction (IUGR) on cognitive ability in late adolescence. A follow-up study of a former cohort included 123 participants (52 males); 47 born SGA and 76 born appropriate for gestational age (AGA). Fetal growth velocity (FGV) was determined by serial ultrasound measurements during the third trimester. A control group matched for age and birthplace was included. The original Wechsler Adult Intelligence Scale (WAIS) was administered, and verbal, performance and full-scale Intelligence Quotient (IQ) scores were calculated. There was no difference in IQ between adolescents born SGA and AGA. FGV or IUGR during the third trimester did not influence cognitive ability in late adolescence. Full-scale IQ was positively related to head circumference (HC) in adolescence (B: 1.30, 95% CI: 0.32-2.28, p=0.01). HC at birth and three months was positively associated with full-scale IQ. Catch-up growth in the group of SGA children was associated with a significantly increased height, larger HC, increased levels of insulin-like growth factor-I (IGF-I) and increased full-scale IQ compared to those born SGA without catch-up growth. SGA and IUGR may not be harmful for adult cognitive ability, at least not in individuals born at near-term. However, known risk factors of impaired fetal growth may explain the link between early growth and cognitive ability in adulthood. Copyright © 2015. Published by Elsevier Ireland Ltd.

  3. High‐altitude ancestry protects against hypoxia‐associated reductions in fetal growth

    PubMed Central

    Julian, Colleen Glyde; Vargas, Enrique; Armaza, J Fernando; Wilson, Megan J; Niermeyer, Susan; Moore, Lorna G

    2007-01-01

    Objective The chronic hypoxia of high‐altitude (⩾2500 m) residence has been shown to decrease birth weight in all populations studied to date. However, multigenerational high‐altitude populations appear protected relative to newcomer groups. This study aimed to determine whether such protection exists independently of other factors known to influence fetal growth and whether admixed populations (ie, people having both high‐ and low‐altitude ancestry) show an intermediate level of protection. Design 3551 medical records from consecutive deliveries to Andean, European or Mestizo (ie, admixed) women at low, intermediate or high altitudes in Bolivia were evaluated for maternal characteristics influencing fetal growth as measured by birth weight and the frequency of small for gestational age births (SGA or ⩽10th percentile birth weight for gestational age and sex). Two‐way analysis of variance and χ2 tests were used to compare maternal and infant characteristics. The effects of ancestry or altitude on SGA and birth weight were assessed using logistic or linear regression models, respectively. Results Altitude decreased birth weight and increased SGA in all ancestry groups. Andean infants weighed more and were less often SGA than Mestizo or European infants at high altitude (13%, 16% and 33% respectively, p<0.01). After accounting for the influences of maternal hypertensive complications of pregnancy, parity, body weight, and number of prenatal visits, European relative to Andean ancestry increased the frequency of SGA at high altitude nearly fivefold. Conclusions Andean relative to European ancestry protects against altitude‐associated reductions in fetal growth. The intermediate protection seen in the admixed (Mestizo) group is consistent with the influence of genetic or other Andean‐specific protective characteristics. PMID:17329275

  4. Impact of bariatric surgery on fetal growth restriction: experience of a perinatal and bariatric surgery center.

    PubMed

    Chevrot, Audrey; Kayem, Gilles; Coupaye, Muriel; Lesage, Ninon; Msika, Simon; Mandelbrot, Laurent

    2016-05-01

    Bariatric surgery is known to improve some pregnancy outcomes, but there is concern that it may increase the risk of small for gestational age. To assess the impact of bariatric surgery on pregnancy outcomes and specifically of the type of bariatric surgery on the risk of fetal growth restriction. A single-center retrospective case-control study. The study group comprised all deliveries in women who had undergone bariatric surgery. To investigate the effects of weight loss on pregnancy outcomes, we compared the study group with a control group matched for presurgery body mass index. Secondly, to assess the specific impact of the type of surgery on the incidence of fetal growth restriction in utero, we distinguished subgroups with restrictive and malabsorptive bariatric surgery, and compared outcomes for each of these subgroups with a second control group, matched for prepregnancy body mass index. Among 139 patients operated, 58 had a malabsorptive procedure (gastric bypass) and 81 a purely restrictive procedure (72 a gastric banding and 9 a sleeve gastrectomy). Compared with controls matched for presurgery body mass index, the study group had a decreased rate of gestational diabetes (12% vs 23%, P = .02) and large for gestational age >90th percentile (11% vs 22%, P = .01) but an increased rate of small for gestational age <10th percentile. The incidence of small for gestational age was higher after gastric bypass (29%) than it was after restrictive surgery (9%) or in controls matched for prepregnancy body mass index (6%) (P < .01 between bypass and controls). In multivariable analysis, after adjustment for other risk factors, gastric bypass remained strongly associated with small for gestational age (adjusted odds ratio, 7.16; 95% confidence interval, 2.74-18.72). Malabsorptive bariatric surgery was associated with an increased risk of fetal growth restriction. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Pregnancy outcome and placental findings in pregnancies complicated by fetal growth restriction with and without preeclampsia.

    PubMed

    Kovo, Michal; Schreiber, Letizia; Elyashiv, Osnat; Ben-Haroush, Avi; Abraham, Golan; Bar, Jacob

    2015-03-01

    To compare pregnancy outcome and placental pathology in pregnancies complicated by fetal growth restriction (FGR) with and without preeclampsia. Labor, fetal/neonatal outcome, and placental pathology parameters from neonates with a birth weight below the 10 th percentile (FGR), born between 24 and 42 weeks of gestation, were reviewed. Results were compared between pregnancies complicated with preeclampsia (hypertensive FGR [H-FGR]) to those without preeclampsia (normotensive FGR [N-FGR]). Composite neonatal outcome, defined as 1 or more of early complication (respiratory distress, necrotizing enterocolitis, sepsis, transfusion, ventilation, seizure, hypoxic-ischemic encephalopathy, phototherapy, or death), Apgar score ≤ 7 at 5 minutes, and days of hospitalization, were compared between the groups. Placental lesions, classified as lesions related to maternal vascular supply, lesions consistent with fetal thrombo-occlusive disease and inflammatory lesions, maternal inflammatory response, and fetal inflammatory response, were also compared. Women in the H-FGR group (n = 72) were older, with higher body mass index (BMI) and higher rate of preterm labor (<34 weeks) than in the N-FGR group (n = 270), P < .001 for all. Composite neonatal outcome was worse in the H-FGR than in the N-FGR group, 50% versus 15.5%, P < .001. Higher rate of maternal placental vascular lesions was detected in H-FGR compared with N-FGR, 82% versus 57.7%, P < .001. Using a stepwise logistic regression model, maternal BMI (1.13 odds ratio [OR], confidence interval [CI] 1.035-1.227, P = .006) and neonatal birth weight (0.996 OR, CI 0.995-0.998, P < .001) were independently associated with worse neonatal outcome. Worse neonatal outcome and more maternal placental vascular lesions in pregnancy complicated by FGR with preeclampsia versus FGR without preeclampsia suggest different pathophysiology in these entities. © The Author(s) 2014.

  6. Amniotic fluid derived mesenchymal stromal cells augment fetal lung growth in a nitrofen explant model.

    PubMed

    Di Bernardo, Julie; Maiden, Michael M; Hershenson, Marc B; Kunisaki, Shaun M

    2014-06-01

    Recent experimental work suggests the therapeutic role of mesenchymal stromal cells (MSCs) during lung morphogenesis. The purpose of this study was to investigate the potential paracrine effects of amniotic fluid-derived MSCs (AF-MSCs) on fetal lung growth in a nitrofen explant model. Pregnant Sprague-Dawley dams were gavage fed nitrofen on gestational day 9.5 (E9.5). E14.5 lung explants were subsequently harvested and cultured ex vivo for three days on filter membranes in conditioned media from rat AF-MSCs isolated from control (AF-Ctr) or nitrofen-exposed (AF-Nitro) dams. The lungs were analyzed morphometrically and by quantitative gene expression. Although there were no significant differences in total lung surface area among hypoplastic lungs, there were significant increases in terminal budding among E14.5+3 nitrofen explants exposed to AF-Ctr compared to explants exposed to medium alone (58.8±8.4 vs. 39.0±10.0 terminal buds, respectively; p<0.05). In contrast, lungs cultured in AF-Nitro medium failed to augment terminal budding. Nitrofen explants exposed to AF-Ctr showed significant upregulation of surfactant protein C to levels observed in normal fetal lungs. AF-MSCs can augment branching morphogenesis and lung epithelial maturation in a fetal explant model of pulmonary hypoplasia. Cell therapy using donor-derived AF-MSCs may represent a novel strategy for the treatment of fetal congenital diaphragmatic hernia. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. The effect of placenta previa on fetal growth and pregnancy outcome, in correlation with placental pathology.

    PubMed

    Weiner, E; Miremberg, H; Grinstein, E; Mizrachi, Y; Schreiber, L; Bar, J; Kovo, M

    2016-12-01

    To compare the clinical characteristics and placental histopathology between pregnancies complicated by placenta previa and controls. Between 2009 and 2015, cesarean deliveries (CDs) of 119 pregnancies with placenta previa were identified from which maternal outcomes, neonatal outcomes and placental pathology were reviewed. Results were compared with CDs matched for maternal age and pregnancy complications (control group, n=119). Placental lesions were classified into maternal and fetal vascular supply lesions and inflammatory response. Composite neonatal outcome was defined as one or more of early neonatal complications. Small-for-gestational age (SGA) was defined as birth weight ⩽10th percentile. Placentas from the previa group had higher rates of weights <10th percentile (P<0.001) and of maternal and fetal vascular supply lesions (P<0.001, for both). Higher rate of SGA (P=0.003) and worse composite neonatal outcome (P<0.001) were also observed in the previa group as compared with controls. After controlling for potential confounding bias using multivariable logistic regression models, placenta previa remained statistically significantly associated with placental maternal (adjusted odds ratio (aOR) 2.48, 95% confidence interval (CI) 1.2-4.9, P=0.009) and fetal (aOR 7.05, 95% CI 2.4-20.2, P<0.001) vascular supply lesions, SGA (aOR 10, 95% CI 2.3-44.2, P=0.002) and adverse neonatal outcome (aOR 6.87, 95% CI 2.9-11.8, P<0.001). More placental vascular supply lesions, higher rate of SGA and worse neonatal outcome characterized pregnancies with placenta previa in the current study. These findings may suggest that abnormal placentation is accompanied by suboptimal implantation that interferes with fetal growth.

  8. Antenatal taurine supplementation for improving brain ultrastructure in fetal rats with intrauterine growth restriction.

    PubMed

    Liu, J; Liu, L; Chen, H

    2011-05-05

    Changes in brain ultrastructure of fetal rats with intrauterine growth restriction (IUGR) were explored and the effects of antenatal taurine supplementation on their brain ultrastructure were determined. Fifteen pregnant rats were randomly divided into three groups: control group, IUGR model group and IUGR group given antenatal taurine supplements. Taurine was added to the diet of the taurine group at a dose of 300 mg/kg/d from 12 days after conception until natural delivery. Transmission electron microscopy was used to observe ultrastructural changes in the brains of the newborn rats. At the same time, brain cellular apoptosis was detected using TUNEL, and the changes in protein expression of neuron specific enolase and glial fibrillary acidic protein were analyzed using immunohistochemistry. The results showed that: 1) The average body weight and cerebral weight were significantly lower in the IUGR group than in the control group (p<0.01) and both of them were less so after taurine was supplemented (p<0.01). 2) Transmission electron microscopy revealed that brain cortex structures were sparse IUGR rats, showing many scattered apoptotic cells, decreased numbers of synapses, lower glial cell proliferation, and fewer neurons, more sparsely arranged, while these factors were significantly improved with taurine supplementation. 3) The results of TUNEL showed that the counts of apoptotic brain cells in IUGR groups were significantly increased from those in control groups and that taurine could significantly decrease brain cell apoptosis (p<0.001). 4) The results of immunohistochemistry showed that antenatal taurine-supplementation could significantly increase the counts of neuron specific enolase and glial fibrillary acidic protein immunoreactive cells in fetal rats with IUGR (p<0.001). It can be concluded that it IUGR has a significant detrimental influence on the development of fetal rat brains, and antenatal supplement of taurine can significantly improve the IUGR

  9. Relationship between nutritionally-mediated placental growth restriction and fetal growth, body composition and endocrine status during late gestation in adolescent sheep.

    PubMed

    Wallace, J M; Bourke, D A; Aitken, R P; Palmer, R M; Da Silva, P; Cruickshank, M A

    2000-01-01

    The aim was to investigate the consequences of nutritionally-mediated placental growth restriction on fetal organ growth, conformation, body composition and endocrine status during late gestation. Embryos recovered from superovulated adult ewes inseminated by a single sire were transferred in singleton to the uterus of peripubertal adolescent recipients. Post-transfer, adolescent dams were offered a high (H) or moderate (M) level of a complete diet to promote rapid or moderate maternal growth rates, respectively (n=7 per group). After day 100 of gestation the feed intake of the M dams was adjusted weekly to maintain body condition score. Liveweight gain during the first 100 days of gestation was 301+/-24 and 90+/-4.6 g/day for the H and M groups, respectively. Maternal plasma concentrations of insulin, IGF-I and urea were significantly higher and non-esterified fatty acid concentrations significantly lower in H compared with M dams prior to slaughter on day 128 of gestation. At this stage of gestation, total placentome weight was 50 per cent lower in H compared with M groups (P< 0.001) and was associated with a 37 per cent reduction in fetal weight (P< 0.01). All variables of fetal conformation and absolute fetal organ weights, with the exception of the adrenal glands, were lower (P< 0. 05) in the fetuses from H intake dams. However, relative fetal organ weights expressed as g/kg fetal body weight, with the exception of the gut, were not influenced by maternal dietary intake. Furthermore, fetal weight but not maternal nutritional group were predictive of individual organ weight for all organs dissected. Together these results imply that growth restriction in the fetuses derived from H intake dams was largely symmetrical. Fetal plasma concentrations of insulin, IGF-I and glucose were attenuated (P< 0.05) in fetuses from H compared with M groups. The lower fetal body weight in the former group was associated with a reduction in absolute but not relative crude protein

  10. Reference charts of gestation-specific tissue Doppler imaging indices of systolic and diastolic functions in the normal fetal heart.

    PubMed

    Chan, Louis Yik-si; Fok, Wing Yee; Wong, John Tai-hung; Yu, Cheuk Man; Leung, Tse Ngong; Lau, Tze Kin

    2005-10-01

    Assessment of fetal cardiac function is difficult because of limited accessibility. Tissue Doppler imaging (TDI) is a promising technique in assessing diastolic function in adults. There has been sparseness concerning the use of TDI in assessing fetal cardiac function. The aim of this study was to construct reference charts of TDI indices of systolic and diastolic functions of the normal fetal heart. Ventricular myocardial velocities at the left ventricular (LV) wall, right ventricular (RV) wall, and interventricular septum (IVS) were assessed by TDI in 302 subjects. From 19 to 37 weeks of gestation, peak myocardial velocities during early diastole (Em) increased from 3.3 to 7.2, 3.9 to 8.3, and 3.2 to 5.0 m/s at the LV wall, RV wall, and IVS, respectively. Peak myocardial velocities during atrial contraction (Am) also increased throughout gestation, but the magnitude of increase was smaller (6.3 to 7.9, 7.7 to 10.6, and 5.5 to 5.9 m/s for the LV wall, RV wall, and IVS, respectively). As a consequence, the Em/Am ratio increased from 0.51 to 0.61 at midtrimester to 0.76 to 0.91 at term. Similar to Em, peak myocardial velocities during systole (Sm) also increased by almost 2 times from 18 to 37 weeks of gestation (3.8 to 6.0, 4.2 to 7.6, and 3.3 to 5.6 for the LV wall, RV wall, and IVS, respectively). Reference charts of gestation-specific Em, Am, Em/Am ratio, Sm, and E/Em were constructed accordingly. In midtrimester, fetal diastolic function is predominantly contributed by atrial contraction. As gestation advances, ventricular relaxation becomes increasingly mature. Reference charts for TDI indices were constructed, these will allow identification of fetuses with an abnormal diastolic function.

  11. 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

  12. Retarded fetal growth patterns and early neonatal mortality in a Mexico City population.

    PubMed

    Balcazar, H; Haas, J D

    1991-01-01

    The study reported here classified 9,660 newborn infants delivered at a maternal and child health center in Mexico City by length of gestation, presence or absence of growth retardation, and (in the case of growth-retarded infants) proportionate or disproportionate growth retardation in terms of the infants' weight and length. It was found that preterm infants (delivered before 38 weeks of gestation) had nine times the early neonatal mortality of term infants, irrespective of growth retardation patterns. Also, the type of fetal growth retardation involved (proportionate or disproportionate) in those cases where such retardation was present was found to have an impact on early neonatal mortality. That is, preterm and term infants classified as having proportionate growth retardation respectively exhibited 1.5 and 9.5 times the early neonatal mortality of preterm and term infants with disproportionate growth retardation. Among other things, these findings suggest a need for assessing types of growth retardation as well as etiologic factors when evaluating mortality risk in newborns.

  13. Utero-placental perfusion Doppler indices in growth restricted fetuses: effect of sildenafil citrate.

    PubMed

    El-Sayed, Mohamed Adel; Saleh, Said Abdel-Aty; Maher, Mohammad Ahmed; Khidre, Asmaa Mohamed

    2017-03-27

    To assess efficacy and tolerability of sildenafil citrate on utero-placental blood flow and fetal growth in pregnancies complicated by fetal growth restriction (FGR). From March 2015, a randomized controlled trial of 54 patients at 24 weeks or more complicated by FGR and abnormal Doppler indices were randomly allocated 1:1 into an intervention arm (receive sildenafil citrate, 50 mg) or a control arm (receive placebo). The primary outcomes were changes occurred in the Doppler parameters 2 h following drug administration. Baseline characteristics were similar between groups. Significant difference was observed in the Delta uterine and umbilical Doppler indices among sildenafil group as compared to placebo group (p < 0.001). Middle cerebral Doppler indices, however, decreased significantly after sildenafil, which could be the result of shifting more blood to improve the utero-placental perfusion. No difference regarding Delta cerebro-placental ratio among both groups (p = 0.979). Sildenafil was also associated with pregnancy prolongation (p = .0001), increased gestational age at delivery (p = .004), improved neonatal weight (p = .0001), and less admission to neonatal intensive care unit (p = .03). No adverse effects reported in both treatment arms. Sildenafil citrate, by its vasodilator effect, can improve utero-placental blood flow in pregnancies complicated by FGR and abnormal Doppler. gov Registry: NCT02362399.

  14. Posttraumatic growth following pregnancy termination for fetal abnormality: the predictive role of coping strategies and perinatal grief.

    PubMed

    Lafarge, Caroline; Mitchell, Kathryn; Fox, Pauline

    2017-09-01

    Research about termination for fetal abnormality (TFA) suggests that it is a traumatic event with potential negative psychological consequences. However, evidence also indicates that following traumatic events individuals may experience growth. Although TFA's negative psychological outcomes are well documented, little is known of the potential for growth following this event. Therefore, the study's objectives were to measure posttraumatic growth (PTG) post-TFA, examine the relationship between PTG, perinatal grief and coping, and determine the predictors of PTG. An online, retrospective survey was conducted with 161 women. Eligible participants were women over 18 who had undergone TFA. Participants were recruited from a support organisation. They completed the Brief COPE, Short Perinatal Grief Scale and Posttraumatic Growth Inventory. Data were analysed using regression analyses. Moderate levels of PTG were observed for "relating to others," "personal strengths" and "appreciation of life." "Positive reframing" was a significant predictor of PTG. Despite using mainly "adaptive" coping strategies, women's grief levels were high. "Adaptive" coping strategies such as, "positive reframing" are relevant to TFA. They may act as protective factors against distress and as foundations for growth, implicating that interventions such as Cognitive Behavioural Therapy, which aim to reframe women's experience, may be beneficial.

  15. 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

  16. [Magnetocardiography--a possible supplementary method for early detection of fetal distress in high-risk pregnancies].

    PubMed

    Schiermeier, S; van Leeuwen, P; Lange, S; Hatzmann, W

    2005-02-01

    Ever since the first report on fetal magnetocardiography by Kariniemi in 1974 numerous studies have examined cardiac activity in healthy fetuses using this technique. Recently there has been an increase in reports on the identification of fetal pathological states, in particular in the diagnosis of fetal arrhythmias, using magnetocardiography. Other possible applications of this non-invasive method include the assessment of intrauterine growth retardation and fetal stress. In a patient with gestational hypertension and asymmetric growth retardation without pathological ultrasound findings, fetal magnetocardiography showed a reduced beat-to-beat heart rate variability indicating signs of fetal stress. On the day following the magnetocardiographic recording, fetal Doppler ultrasonography findings indicated an incipient brain sparing effect. The fetal growth retardation was reflected in the duration of the fetal cardiac time intervals. We conclude that fetal magnetocardiography non-invasively enables the timely identification of pathological fetal conditions.

  17. Effects of perfluorooctane sulfuric acid on placental PRL-family hormone production and fetal growth retardation in mice.

    PubMed

    Lee, Chae Kwan; Kang, Sung Goo; Lee, Jong Tae; Lee, Soo-Woong; Kim, Jeong Ho; Kim, Dae Hwan; Son, Byung Chul; Kim, Kun Hyung; Suh, Chun Hui; Kim, Se Yeong; Park, Yeong Beom

    2015-02-05

    Perfluorooctane sulfuric acid (PFOS) is a persistent organic pollutant, causes fetal growth retardation but the mechanism is still unclear. This study focused on PFOS-induced toxicity such as placental trophoblast cell histopathological changes, endocrine function (i.e., prolactin (PRL)-family hormone production) and subsequent fetal growth retardation in mice. Maternal body weight gain, placental and fetal weights were significantly decreased in proportion to PFOS dosage. Placental efficiency (fetal weight/placental weight) was significantly reduced dose-dependently. Necrotic changes were observed in PFOS-treated placental tissues, and the area of injury increased dose-dependently. Finally, mRNA levels and maternal serum concentrations of the PRL-family hormones (mPL-II, mPLP-Cα, mPLP-K) were significantly reduced dose-dependently. In addition, the changing pattern between PRL-family hormone concentrations and fetal body weight was positively correlated. These results suggest that gestational PFOS treatment induces placental histopathological changes and disruption of endocrine function, finally may lead to fetal growth retardation in mice.

  18. Maternal protein restriction and fetal growth: lack of evidence of a role for homocysteine in fetal programming.

    PubMed

    Langley-Evans, Simon C; Lilley, Christina; McMullen, Sarah

    2006-09-01

    The disease-programming effects of a maternal low-protein (MLP) diet in rat pregnancy have been suggested to be attributable of hyperhomocysteinaemia. The aim of the present study was to determine whether MLP feeding impacted upon maternal and day 20 fetal homocysteine concentrations, with ensuing effects upon oxidant/antioxidant status. Sixty-four pregnant rats were fed either MLP diet or control diet before termination of pregnancy at days 4, 10, 18 or 20 gestation (full-term gestation 22 d). Maternal plasma homocysteine concentrations were similar in control and MLP-fed dams at all points in gestation. Fetal plasma homocysteine was similarly unaffected by MLP feeding at day 20 gestation. Activities of superoxide dismutase and glutathione peroxidase were similar in livers of mothers and fetuses in the two groups. Whilst catalase activity was not influenced by diet in maternal liver, MLP exposure increased catalase activity in fetal liver at day 20. Oxidative injury (protein carbonyl concentration) was lower in the livers of MLP-fed animals at day 18 gestation (P<0.05), but significantly greater at day 20. Hepatic expression of methionine synthase was similar in control and MLP-fed dams at all stages of gestation. Expression of DNA methyltransferase 1 in fetal liver was altered by maternal diet in a sex- and gestational age-specific manner. In conclusion, MLP feeding does not impact upon maternal or fetal homocysteine concentrations prior to day 20 gestation in the rat. There was no evidence of increased oxidative injury in fetal tissue that might explain the long-term programming effects of the diet.

  19. Low PAPP-A in the first trimester is associated with reduced fetal growth rate prior to gestational week 20.

    PubMed

    Salvig, J D; Kirkegaard, I; Winding, T N; Henriksen, T B; Tørring, N; Uldbjerg, N

    2010-06-01

    To evaluate the association between maternal pregnancy-associated plasma protein-A (PAPP-A) and fetal growth from the first to the second trimester. A prospective cohort study including 8347 pregnant women attending prenatal care at Aarhus University Hospital were conducted. PAPP-A was measured during 8 to 14 gestational weeks. Fetal growth between the two scans in the first and second trimesters was estimated by (GA(20)- GA(12))/Days(calendar), where GA(12) reflects gestational age in days calculated from crown-rump length at a 12-week scan, GA(20) reflects gestational age in days calculated from biparietal diameter at a 20-week scan, and Days(calendar) reflects the number of calendar days between the two scans. Fetal growth rate from the first to the second trimester was correlated with PAPP-A, with a regression coefficient of 0.009 (95% CI, 0.007-0.012, P < 0.001). PAPP-A below 0.30 MoM was associated with a fetal growth rate below the tenth centile, with an adjusted OR of 2.05 (95% CI, 1.24-3.38). Low levels of PAPP-A are associated not only with low birth weight at term but also with slower fetal growth prior to 20 weeks of gestation.

  20. Growth and fertilization of porcine fetal oocytes grafted under the renal capsules of nude mice.

    PubMed

    Kaneko, Hiroyuki; Kikuchi, Kazuhiro; Noguchi, Junko

    2016-10-15

    indicate that porcine fetal ovaries during the late pregnancy period are able to grow and produce oocytes with fertilization ability after being grafted into nude mice. The presence of primordial follicles is likely to be associated with the ability of fetal ovaries to produce antral follicles after xenografting.

  1. Is There Hope for Renal Growth on Imaging Studies Following Ureteral Reimplant for Boys With Fetal Hydronephrosis and Urinary Reflux?

    PubMed Central

    Wang, Ming-Hsien

    2015-01-01

    Reflux nephropathy is thought to be the etiology for renal maldevelopment. We present two boys with fetal hydronephrosis and sterile vesicoureteral reflux (VUR). There was lack of renal growth of the refluxing renal units on surveillance renal ultrasound. Parents elected to undergo open ureteral reimplants. Post-surgical ultrasounds demonstrated improved renal growth. PMID:26793522

  2. Maternal stressors during prolonged antepartum hospitalization following transfer for maternal-fetal indications.

    PubMed

    Doyle, Nora M; Monga, Manju; Kerr, Marcia; Hollier, Lisa M

    2004-01-01

    Our objective was to identify stressors in women requiring prolonged hospitalization following maternal-fetal transfer to a tertiary care center. Using a modified version of the previously validated Antepartum Hospital Stressors Inventory (AHSI), all women transferred to our university-based maternal-fetal service between May 2000 and June 2002 and hospitalized for greater than 1 month completed a semi-structured interview. The AHSI uses Likert scales to evaluate environment, health factors, communication with health care providers, family separation, self-image, and emotional and family status issues as stressors. Nine consecutive women met inclusion criteria and all agreed to participate. Median maternal age was 27 years (range 19 to 33), and gestational age at transfer was 25 weeks (range 20 to 31). Parity ranged from 0 to 3 and educational level ranged from grade 2 to graduate degrees. The women were from Caucasian, Hispanic, and Asian racial-ethnic backgrounds; all were married. Median distance from transferring hospital was 20 miles (range 10 to 275 miles). All patients reported separation from family, sleeping alone, anxiety about the pregnancy and the baby's health, boredom, and eating hospital meals as the greatest stressors. Stress was relieved in all women by ultrasounds, family members staying in the room, cable television, and internet access. Routine beauty maintenance, massage, physical therapy, and continued contact with referring physician were also cited as stress alleviators. Following maternal-fetal transfer, prolonged antepartum hospitalization is associated with stress that may be alleviated by access to the outside world via television and the internet, liberal visitation, access to health and beauty maintenance, and ongoing contact with the referring physician.

  3. Maternal oxygen delivery is not related to altitude- and ancestry-associated differences in human fetal growth

    PubMed Central

    Zamudio, Stacy; Postigo, Lucrecia; Illsley, Nicholas P; Rodriguez, Carmelo; Heredia, Gladys; Brimacombe, Michael; Echalar, Lourdes; Torricos, Tatiana; Tellez, Wilma; Maldonado, Ivan; Balanza, Elfride; Alvarez, Tatiana; Ameller, Julio; Vargas, Enrique

    2007-01-01

    Fetal growth is reduced at high altitude, but the decrease is less among long-resident populations. We hypothesized that greater maternal uteroplacental O2 delivery would explain increased fetal growth in Andean natives versus European migrants to high altitude. O2 delivery was measured with ultrasound, Doppler and haematological techniques. Participants (n= 180) were pregnant women of self-professed European or Andean ancestry living at 3600 m or 400 m in Bolivia. Ancestry was quantified using ancestry-informative single nucleotide polymorphims. The altitude-associated decrement in birth weight was 418 g in European versus 236 g in Andean women (P < 0.005). Altitude was associated with decreased uterine artery diameter, volumetric blood flow and O2 delivery regardless of ancestry. But the hypothesis was rejected as O2 delivery was similar between ancestry groups at their respective altitudes of residence. Instead, Andean neonates were larger and heavier per unit of O2 delivery, regardless of altitude (P < 0.001). European admixture among Andeans was negatively correlated with birth weight at both altitudes (P < 0.01), but admixture was not related to any of the O2 transport variables. Genetically mediated differences in maternal O2 delivery are thus unlikely to explain the Andean advantage in fetal growth. Of the other independent variables, only placental weight and gestational age explained significant variation in birth weight. Thus greater placental efficiency in O2 and nutrient transport, and/or greater fetal efficiency in substrate utilization may contribute to ancestry- and altitude-related differences in fetal growth. Uterine artery O2 delivery in these pregnancies was 99 ± 3 ml min−1, ∼5-fold greater than near-term fetal O2 consumption. Deficits in maternal O2 transport in third trimester normal pregnancy are unlikely to be causally associated with variation in fetal growth. PMID:17510190

  4. Newborn adiposity measured by plethysmography is not predicted by late gestation two-dimensional ultrasound measures of fetal growth.

    PubMed

    Moyer-Mileur, Laurie J; Slater, Hillarie; Thomson, J Anne; Mihalopoulos, Nicole; Byrne, Jan; Varner, Michael W

    2009-09-01

    Noninvasive measures of fetal and neonatal body composition may provide early identification of children at risk for obesity. Air displacement plethysmography provides a safe, precise measure of adiposity and has recently been validated in infants. Therefore, we explored relationships between term newborn percent body fat (%BF) measured by air displacement plethysmography to 2-dimensional ultrasound (2-D US) biometric measures of fetal growth and maternal and umbilical cord endocrine activity. A total of 47 mother/infant pairs were studied. Fetal biometrics by 2-D US and maternal blood samples were collected during late gestation (35 wk postmenstrual age); infants were measured within 72 h of birth. Fetal biometrics included biparietal diameter, femur length, head circumference, abdominal circumference (AC), and estimated fetal weight (EFW). Serum insulin, insulin-like growth factor (IGF) 1, IGF binding protein-3, and leptin concentrations were measured in umbilical cord and maternal serum. The mean %BF determined by plethysmography was 10.9 +/- 4.8%. EFW and fetal AC had the largest correlations with newborn %BF (R(2) = 0.14 and 0.10, respectively; P < 0.05); however, stepwise linear regression modeling did not identify any fetal biometric parameters as a significant predictor of newborn %BF. Newborn mid-thigh circumference (MTC; cm) and ponderal index (PI; weight, kg/length, cm(3)) explained 21.8 and 14.4% of the variability in %BF, respectively, and gave the best stepwise linear regression model (%BF = 0.446 MTC + 0.347 PI -29.692; P < 0.001). We conclude that fetal growth biometrics determined by 2-D US do not provide a reliable assessment of %BF in term infants.

  5. Fetal growth parameters and birth weight: their relationship to neonatal body composition

    PubMed Central

    Lee, W; Balasubramaniam, M; Deter, RL; Hassan, SS; Gotsch, F; Kusanovic, JP; Goncalves, LF; Romero, R

    2013-01-01

    Objectives The main goal was to investigate the relationship between prenatal sonographic parameters and birth weight in predicting neonatal body composition. Methods Standard fetal biometry and soft tissue parameters were assessed prospectively in third-trimester pregnancies using three-dimensional ultrasonography. Growth parameters included biparietal diameter (BIPARIETAL DIAMETER (BPD), head circumference (HC), abdominal circumference (AC), mid-thigh circumference and femoral diaphysis length (FDL). Soft tissue parameters included fractional arm volume (AVol) and fractional thigh volume (TVol) that were derived from 50% of the humeral or femoral diaphysis lengths, respectively. Percentage of neonatal body fat (%BF) was determined within 48 h of delivery using a pediatric air displacement plethysmography system based on principles of whole-body densitometry. Correlation and stepwise multiple linear regression analyses were performed with potential prenatal predictors and %BF as the outcome variable. Results Eighty-seven neonates were studies with a mean ± SD %BF of 10.6 ± 4.6%. TVol had the greatest correlation with newborn %BF of all single-parameter models. This parameter alone explained 46.1% of the variability in %BF and the best stepwise multiple linear regression model was: %BF = 0.129 (TVol) – 1.03933 (P<0.001). Birth weight similarly explained 44.7% of the variation in %BF. AC and estimated fetal weight (EFW) accounted for only 24.8% and 30.4% of the variance in %BF, respectively. Skeletal growth parameters, such as FDL (14.2%), HC (7.9%) and BPD (4.0%), contributed the least towards explaining the variance in %BF. Conclusions During the late third trimester of pregnancy %BF is most highly correlated with TVol. Similar to actual birth weight, this soft tissue parameter accounts for a significant improvement in explaining the variation in neonatal %BF compared with fetal AC or EFW alone. PMID:19253324

  6. Positive intrapulmonary oncotic pressure enhances short-term lung growth acceleration after fetal tracheal occlusion.

    PubMed

    Dzakovic, Alexander; Kaviani, Amir; Jennings, Russell W; Wilson, Jay M; Fauza, Dario O

    2002-07-01

    This study was aimed at determining whether positive oncotic pressure induced in the fetal lung liquid could safely maximize accelerated lung growth after tracheal occlusion. Fetal lambs (n = 21) were divided into 4 groups: group I (n = 5) consisted of sham-operated controls; group II (n = 5) underwent simple tracheal occlusion (TO); group III (n = 5) received TO and 60 mL of saline injected into the trachea; and group IV (n = 6) underwent TO and intratracheal infusion of 60 mL of iso-osmotic, 6% Dextran 70. All fetuses were delivered near term, at a mean of 15.9 +/- 1 days postoperatively. Their lungs were studied by standard morphometric techniques, and the basic chemical profile of the lung liquid was analyzed. Statistical comparisons were by 1-way analysis of variance (ANOVA) and post-hoc analyses by the Bonferroni correction for multiple comparisons, with P values less than.05 considered significant. The lung volume-to-body-weight ratio (LV:BW) was significantly different among groups. Pairwise comparisons of LV:BW showed that it was higher in group IV than in all other groups, but there was no difference between groups II and III. Airspace fraction was not significantly different among groups, and histologic appearance was normal in all lung samples. There were no differences in lung liquid osmolarity, pH level, and electrolyte concentrations. Positive intrapulmonary oncotic pressure by an isosmotic agent boosts short-term lung growth acceleration after fetal tracheal occlusion with no evidence of cell damage. Copyright 2002, Elsevier Science (USA). All rights reserved.

  7. 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

  8. Fetal alcohol exposure and mammary tumorigenesis in offspring: role of the estrogen and insulin-like growth factor systems.

    PubMed

    Cohick, Wendie S; Crismale-Gann, Catina; Stires, Hillary; Katz, Tiffany A

    2015-01-01

    Fetal alcohol spectrum disorders affect a significant number of live births each year, indicating that alcohol consumption during pregnancy is an important public health issue. Environmental exposures and lifestyle choices during pregnancy may affect the offspring's risk of disease in adulthood, leading to the idea that a woman's risk of breast cancer may be pre-programmed prior to birth. Exposure of pregnant rats to alcohol increases tumorigenesis in the adult offspring in response to mammary carcinogens. The estrogen and insulin-like growth factor (IGF-I) axes occupy central roles in normal mammary gland development and breast cancer. 17-β estradiol (E2) and IGF-I synergize to regulate formation of terminal end buds and ductal elongation during pubertal development. The intracellular signaling pathways mediated by the estrogen and IGF-I receptors cross-talk at multiple levels through both genomic and non-genomic mechanisms. Several components of the E2 and IGF-I systems are altered in early development in rat offspring exposed to alcohol in utero, therefore, these changes may play a role in the enhanced susceptibility to mammary carcinogens observed in adulthood. Alcohol exposure in utero induces a number of epigenetic alterations in non-mammary tissues in the offspring and other adverse in utero exposures induce epigenetic modifications in the mammary gland. Future studies will determine if fetal alcohol exposure can induce epigenetic modifications in genes that regulate E2/IGF action at key phases of mammary development, ultimately leading to changes in susceptibility to carcinogens.

  9. Sildenafil citrate treatment enhances amino acid availability in the conceptus and fetal growth in an ovine model of intrauterine growth restriction.

    PubMed

    Satterfield, M Carey; Bazer, Fuller W; Spencer, Thomas E; Wu, Guoyao

    2010-02-01

    Adequate placental blood flow is essential for the optimal delivery of nutrients from mother to fetus for conceptus growth. Restricted fetal development results from pathophysiological and environmental factors that alter utero-placental blood flow, placental function, and, therefore, nutrient availability in the fetus. To test this hypothesis, 0, 75, or 150 mg/d sildenafil citrate (Viagra) was administered subcutaneously from d 28 to 115 of gestation to either nutrient-restricted [50% of NRC requirements) or adequately-fed ewes (100% of NRC requirements). On d 115, maternal, fetal, and placental tissues and fluids were collected. Concentrations of total amino acids and polyamines in uterine venous and arterial sera, amniotic and allantoic fluids, and fetal umbilical venous serum were lower (P < 0.05) in nutrient-restricted ewes than in adequately fed ewes, as were the ratios of total amino acids in fetal umbilical venous serum to uterine arterial serum. Sildenafil citrate dose-dependently increased (P < 0.05) total amino acids and polyamines in amniotic fluid, allantoic fluid, and fetal serum without affecting values in maternal serum. Fetal weight was lower (P < 0.05) in nutrient-restricted ewes on d 115. Sildenafil citrate treatment dose-dependently increased (P < 0.05) fetal weight in both nutrient-restricted and adequately fed ewes. This study supports the hypothesis that long-term sildenafil citrate treatment enhances fetal growth, at least in part, by increasing the availability of amino acids in the conceptus. These findings may lead to the clinical use of sildenafil citrate in human pregnancies suspected to be at risk for intrauterine fetal growth retardation.

  10. Aquaporins in Fetal Development.

    PubMed

    Martínez, Nora; Damiano, Alicia E

    2017-01-01

    Water homeostasis during fetal development is of crucial physiologic importance. The successful formation and development of the placenta is critical to maintain normal fetal growth and homeostasis. The expression of several aquaporins (AQPs ) was found from blastocyst stages to term placenta and fetal membranes. Therefore, AQPs are proposed to play important roles in normal pregnancy, fetal growth, and homeostasis of amniotic fluid volume, and water handling in other organs. However, the functional importance of AQPs in fetal development remains to be elucidated.

  11. First-trimester fetal growth restriction and the occurrence of miscarriage in rural Bangladesh: A prospective cohort study

    PubMed Central

    Rashid, Harunor; Ma, Enbo; Ferdous, Farzana; Ekström, Eva-Charlotte

    2017-01-01

    Fetal growth restriction in early pregnancy increases the risk of adverse pregnancy outcome, which has a significant social and psychological impact on women. There is limited information related to community-based study to evaluate early indicators related to miscarriage. The aim of this study is to examine the relationship between fetal growth restriction, measured by ultrasound crown-rump length (CRL), and subsequent occurrence of miscarriage in pregnant women in rural Bangladesh. The study was conducted within the Maternal and Infant Nutrition Interventions Trial in Matlab (MINIMat study), Bangladesh. A total of 4436 pregnant women were enrolled in the study when they were at less than 14 gestational weeks. The expected CRL was determined based on an established growth curve of gestational age and CRL, and deviation from this curve of CRL was expressed as a z-score. After identifying related covariates, the multiple Poisson regression model was used to determine the independent contribution from the CRL to miscarriage. A total of 3058 singleton pregnant women were included in analyses, with 92 miscarriages and 2966 continued pregnancies. The occurrence of miscarriages was significantly higher in the smaller categories of CRL z-score after adjustments for maternal age, parity, early pregnancy BMI, gestational age at CRL measurement and socioeconomic status (adjusted relative risk [95% confidence interval]: 1.03 [1.02–1.05] for less than -2 z-score). In a rural Bangladesh population, smaller than expected CRL for the gestational age was related to subsequent miscarriage. Ultrasound biometry information together with careful clinical assessment should provide much needed attention and care for pregnant women. PMID:28732073

  12. Cell dynamics in fetal intestinal epithelium: implications for intestinal growth and morphogenesis

    PubMed Central

    Grosse, Ann S.; Pressprich, Mark F.; Curley, Lauren B.; Hamilton, Kara L.; Margolis, Ben; Hildebrand, Jeffrey D.; Gumucio, Deborah L.

    2011-01-01

    The cellular mechanisms that drive growth and remodeling of the early intestinal epithelium are poorly understood. Current dogma suggests that the murine fetal intestinal epithelium is stratified, that villi are formed by an epithelial remodeling process involving the de novo formation of apical surface at secondary lumina, and that radial intercalation of the stratified cells constitutes a major intestinal lengthening mechanism. Here, we investigate cell polarity, cell cycle dynamics and cell shape in the fetal murine intestine between E12.5 and E14.5. We show that, contrary to previous assumptions, this epithelium is pseudostratified. Furthermore, epithelial nuclei exhibit interkinetic nuclear migration, a process wherein nuclei move in concert with the cell cycle, from the basal side (where DNA is synthesized) to the apical surface (where mitosis takes place); such nuclear movements were previously misinterpreted as the radial intercalation of cells. We further demonstrate that growth of epithelial girth between E12.5 and E14.5 is driven by microtubule- and actinomyosin-dependent apicobasal elongation, rather than by progressive epithelial stratification as was previously thought. Finally, we show that the actin-binding protein Shroom3 is crucial for the maintenance of the single-layered pseudostratified epithelium. In mice lacking Shroom3, the epithelium is disorganized and temporarily stratified during villus emergence. These results favor an alternative model of intestinal morphogenesis in which the epithelium remains single layered and apicobasally polarized throughout early intestinal development. PMID:21880782

  13. Dietary interventions for fetal growth restriction - therapeutic potential of dietary nitrate supplementation in pregnancy.

    PubMed

    Cottrell, Elizabeth; Tropea, Teresa; Ormesher, Laura; Greenwood, Susan; Wareing, Mark; Johnstone, Edward; Myers, Jenny; Sibley, Colin

    2017-08-01

    Fetal growth restriction (FGR) affects around 5% of pregnancies and is associated with significant short- and long-term adverse outcomes. A number of factors can increase the risk of FGR, one of which is poor maternal diet. In terms of pathology, both clinically and in many experimental models of FGR, impaired uteroplacental vascular function is implicated, leading to a reduction in the delivery of oxygen and nutrients to the developing fetus. Whilst mechanisms underpinning impaired uteroplacental vascular function are not fully understood, interventions aimed at enhancing nitric oxide (NO) bioavailability remain a key area of interest in obstetric research. In addition to endogenous NO production from the amino acid l-arginine, via nitric oxide synthase (NOS) enzymes, research in recent years has established that significant NO can be derived from dietary nitrate, via the 'alternative NO pathway'. Dietary nitrate, abundant in green leafy vegetables and beetroot, can increase NO bioactivity, conferring beneficial effects on cardiovascular function and blood flow. Given the beneficial effects of dietary nitrate supplementation to date in non-pregnant humans and animals, current investigations aim to assess the therapeutic potential of this approach in pregnancy to enhance NO bioactivity, improve uteroplacental vascular function and increase fetal growth. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

  14. Birth weight and fetal growth in infants born to female hairdressers and their sisters.

    PubMed

    Axmon, A; Rylander, L

    2009-03-01

    To investigate birth weight and fetal growth in female hairdressers, while controlling for intergenerational effects and effects related to childhood exposures. A cohort of women who had attended vocational schools for hairdressers were compared to their sisters with respect to birth weight and fetal growth (measured as small for gestational age (SGA) or large for gestational age (LGA), respectively) in their infants. In total, 6223 infants born to 3137 hairdressers and 8388 infants born to 3952 hairdressers' sisters were studied. Among the infants born to the hairdressers' sisters, the distribution of birth weights were wider than that among the infants born to the hairdressers. This was also reflected in that hairdresser cohort affiliation tended to be protective against both SGA (odds ratio 0.80; 95% confidence interval 0.49 to 1.31) and LGA (0.77; 0.54 to 1.09). For LGA, this effect was even more pronounced among women who had actually worked as hairdressers during at least one pregnancy (0.60; 0.39 to 0.92). The infants born to these women also had a significantly lower mean birth weight (3387 g vs 3419 g; p = 0.033). The results from the present study suggest that infants born to hairdressers have a decreased risk of being LGA. This is most likely not caused by a shift in birth weight distribution or abnormal glucose metabolism.

  15. New computerized fetal heart rate analysis for surveillance of intrauterine growth restriction.

    PubMed

    Huhn, E A; Lobmaier, S; Fischer, T; Schneider, R; Bauer, A; Schneider, K T; Schmidt, G

    2011-05-01

    Decreased fetal heart rate variability is associated with higher perinatal morbidity and mortality in intrauterine growth restriction (IUGR). This study used a new method [phase-rectified signal averaging (PRSA)] to calculate acceleration- and deceleration-related fluctuations of the fetal heart rate. Cardiotocograms from 74 growth-restricted and 161 normal fetuses were included. Both groups were matched for gestational age. The transformed PRSA signal was quantified by the acceleration-related parameter-averaged acceleration capacity (AAC) and compared to the standard short-term variation (STV). Mann-Whitney test and receiver operator characteristic (ROC) curves were used for statistical analysis. For AAC, the median values of the IUGR group and control group were 1.97 bpm [interquartile range (IQR): 1.66-2.23] and 2.49 bpm (IQR: 2.24-2.72), respectively. For STV, these values were 5.44 ms (IQR: 4.49-7.38) and 7.79 ms (IQR: 6.35-9.66), respectively. The area under the ROC curve was 81.4% for AAC and 70.5% for STV. The results of AAC are in both groups comparable to STV. Longitudinal studies are needed to investigate the association of AAC with the clinical outcome of the newborn. Copyright © 2011 John Wiley & Sons, Ltd.

  16. The effect of extremely low frequency electromagnetic fields on pregnancy and fetal growth, and development.

    PubMed

    Mahram, Manoochehr; Ghazavi, Mohammad

    2013-04-01

    Exposure to electromagnetic fields (EMFs) and its effects at different frequencies on living beings has been investigated for decades. However, there are fewer studies that have been conducted on humans, thus this study aims to determine the effect of extremely low frequency (ELF) -EMFs on pregnancy, fetal growth and development in humans. In this epidemiologic analytical cohort study, cases included pregnant women and their newborns. There were 222 women exposed to ELF-EMFs from high voltage electricity towers and cables during pregnancy and 158 women who had no exposure during pregnancy. Data that included pregnancy duration, neonatal birth weight, length, head circumference, gender and congenital malformations were collected through direct questions, measurements and referral to the registered data of related hospital or health center documents. Collected data was analyzed by SPSS-16. P < 0.05 was considered significant. No significant difference was found in pregnancy duration and preterm labor, neonatal birth weight, length, head circumference and congenital malformations in the two studied groups. Although the results of this study have shown no significant effects of ELF-EMFs on human pregnancy, fetal growth and development, taking precautionary measures to reduce exposure to EMFs by pregnant women seems logical. Conducting similar studies is strongly recommended.

  17. Transamniotic fetal feeding. II. A model of intrauterine growth retardation using the relationship of "natural runting" to uterine position.

    PubMed

    Flake, A W; Villa, R L; Adzick, N S; Harrison, M R

    1987-09-01

    Intrauterine growth retardation (IUGR) is a leading cause of perinatal morbidity and mortality. Most IUGR is the result of inadequate transfer of nutrients from mother to fetus. Transamniotic fetal feeding (TAFF) has been proposed as a method of treating IUGR in which nutrients, infused into the amniotic fluid, would be swallowed, absorbed, and utilized by the growth retarded fetus. To study this hypothesis, we have developed a rabbit model for IUGR and TAFF. We studied the effects of maternal nutritional deprivation, uterine artery ligation, and fetal position in the uterine horn on fetal body and organ growth in 96 rabbit litters. Nutritional deprivation (n = 28) and vascular interruption (n = 34) yielded inconsistent results with high fetal mortality. We were surprised to find that fetal growth was directly and consistently related to position in the uterine horn. There is a highly significant difference (P less than .0001) in weight between siblings in the no. 1 and no. 3 positions in the rabbit uterine horn at 30 days gestation that is not present at 23 days. This "natural" runting resembles human IUGR, which occurs during the last trimester of pregnancy and shows relative brain sparing. This model, in combination with our previously reported technique for TAFF, will make possible a controlled study of the efficacy of TAFF in the treatment of IUGR.

  18. A normative spatiotemporal MRI atlas of the fetal brain for automatic segmentation and analysis of early brain growth.

    PubMed

    Gholipour, Ali; Rollins, Caitlin K; Velasco-Annis, Clemente; Ouaalam, Abdelhakim; Akhondi-Asl, Alireza; Afacan, Onur; Ortinau, Cynthia M; Clancy, Sean; Limperopoulos, Catherine; Yang, Edward; Estroff, Judy A; Warfield, Simon K

    2017-03-28

    Longitudinal characterization of early brain growth in-utero has been limited by a number of challenges in fetal imaging, the rapid change in size, shape and volume of the developing brain, and the consequent lack of suitable algorithms for fetal brain image analysis. There is a need for an improved digital brain atlas of the spatiotemporal maturation of the fetal brain extending over the key developmental periods. We have developed an algorithm for construction of an unbiased four-dimensional atlas of the developing fetal brain by integrating symmetric diffeomorphic deformable registration in space with kernel regression in age. We applied this new algorithm to construct a spatiotemporal atlas from MRI of 81 normal fetuses scanned between 19 and 39 weeks of gestation and labeled the structures of the developing brain. We evaluated the use of this atlas and additional individual fetal brain MRI atlases for completely automatic multi-atlas segmentation of fetal brain MRI. The atlas is available online as a reference for anatomy and for registration and segmentation, to aid in connectivity analysis, and for groupwise and longitudinal analysis of early brain growth.

  19. 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.

  20. 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

  1. Influence of intrauterine growth restriction on airway development in fetal and postnatal sheep.

    PubMed

    Wignarajah, Dharshini; Cock, Megan L; Pinkerton, Kent E; Harding, Richard

    2002-06-01

    Epidemiologic studies suggest that intrauterine growth restriction (IUGR) can lead to impaired lung function, yet little information exists on the effects of IUGR on airway development. Our objectives were to characterize morphometrically effects of IUGR on airway structure in the fetus and to determine whether alterations persist into postnatal life. We used two groups of sheep, each with appropriate controls; a fetal group was subjected to IUGR by restriction of placental function from 120 to 140 d (term approximately 147 d), and a postnatal group, killed 8 wk after birth, was subjected to IUGR from 120 d to birth at term. In both fetuses and postnatal lambs, IUGR did not alter lung weight relative to body weight. In IUGR fetuses, the luminal areas and basement membrane perimeters of the trachea and larger bronchi (generations 0-8, trachea = 0) were smaller than in controls. Airway wall areas, relative to basement membrane perimeters, were reduced in IUGR fetuses compared with controls, largely due to reduced areas of cartilage and epithelium. At 8 wk after birth, there were no significant differences in airway dimensions between IUGR and control lambs. However, the number of profiles of bronchial submucosal glands, relative to basement membrane perimeters, was lower in IUGR lambs than in controls and the area of epithelial mucin was increased. We conclude that restriction of fetal growth during late gestation impairs the growth of bronchial walls that could affect airway compliance in the immediate postnatal period. Although airway growth deficits are reversed by 8 wk, alterations in mucus elements persist.

  2. Relationships among Polycyclic Aromatic Hydrocarbon–DNA Adducts, Proximity to the World Trade Center, and Effects on Fetal Growth

    PubMed Central

    Perera, Frederica P.; Tang, Deliang; Rauh, Virginia; Lester, Kristin; Tsai, Wei Yann; Tu, Yi Hsuan; Weiss, Lisa; Hoepner, Lori; King, Jeffrey; Del Priore, Giuseppe; Lederman, Sally Ann

    2005-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are toxic pollutants released by the World Trade Center (WTC) fires and various urban combustion sources. Benzo[a]pyrene (BaP) is a representative member of the class of PAHs. PAH–DNA adducts, or BaP–DNA adducts as their proxy, provide a measure of chemical-specific genetic damage that has been associated with increased risk of adverse birth outcomes and cancer. To learn whether PAHs from the WTC disaster increased levels of genetic damage in pregnant women and their newborns, we analyzed BaP–DNA adducts in maternal (n = 170) and umbilical cord blood (n = 203) obtained at delivery from nonsmoking women who were pregnant on 11 September 2001 and were enrolled at delivery at three downtown Manhattan hospitals. The mean adduct levels in cord and maternal blood were highest among newborns and mothers who resided within 1 mi of the WTC site during the month after 11 September, intermediate among those who worked but did not live within this area, and lowest in those who neither worked nor lived within 1 mi (reference group). Among newborns of mothers living within 1 mi of the WTC site during this period, levels of cord blood adducts were inversely correlated with linear distance from the WTC site (p = 0.02). To learn whether PAHs from the WTC disaster may have affected birth outcomes, we analyzed the relationship between these outcomes and DNA adducts in umbilical cord blood, excluding preterm births to reduce variability. There were no independent fetal growth effects of either PAH–DNA adducts or environmental tobacco smoke (ETS), but adducts in combination with in utero exposure to ETS were associated with decreased fetal growth. Specifically, a doubling of adducts among ETS-exposed subjects corresponded to an estimated average 276-g (8%) reduction in birth weight (p = 0.03) and a 1.3-cm (3%) reduction in head circumference (p = 0.04). The findings suggest that exposure to elevated levels of PAHs, indicated by PAH

  3. 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.

  4. Statistical considerations for the development of prescriptive fetal and newborn growth standards in the INTERGROWTH-21st Project.

    PubMed

    Altman, D G; Ohuma, E O

    2013-09-01

    The INTERGROWTH-21(st) Project has in its mandate to develop prescriptive standards for fetal, neonatal and preterm post-neonatal growth. The project comprises three components: the Fetal Growth Longitudinal Study (FGLS), the Preterm Postnatal Follow-up Study (PPFS), and the Newborn Cross-Sectional Study (NCSS). We consider here the statistical aspects of the three components as they relate to the construction of these standards, in particular the sample size, and outline the principles that will guide the planned main analyses. © 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.

  5. A computational model of the fetal circulation to quantify blood redistribution in intrauterine growth restriction.

    PubMed

    Garcia-Canadilla, Patricia; Rudenick, Paula A; Crispi, Fatima; Cruz-Lemini, Monica; Palau, Georgina; Camara, Oscar; Gratacos, Eduard; Bijnens, Bart H; Bijens, Bart H

    2014-06-01

    Intrauterine growth restriction (IUGR) due to placental insufficiency is associated with blood flow redistribution in order to maintain delivery of oxygenated blood to the brain. Given that, in the fetus the aortic isthmus (AoI) is a key arterial connection between the cerebral and placental circulations, quantifying AoI blood flow has been proposed to assess this brain sparing effect in clinical practice. While numerous clinical studies have studied this parameter, fundamental understanding of its determinant factors and its quantitative relation with other aspects of haemodynamic remodeling has been limited. Computational models of the cardiovascular circulation have been proposed for exactly this purpose since they allow both for studying the contributions from isolated parameters as well as estimating properties that cannot be directly assessed from clinical measurements. Therefore, a computational model of the fetal circulation was developed, including the key elements related to fetal blood redistribution and using measured cardiac outflow profiles to allow personalization. The model was first calibrated using patient-specific Doppler data from a healthy fetus. Next, in order to understand the contributions of the main parameters determining blood redistribution, AoI and middle cerebral artery (MCA) flow changes were studied by variation of cerebral and peripheral-placental resistances. Finally, to study how this affects an individual fetus, the model was fitted to three IUGR cases with different degrees of severity. In conclusion, the proposed computational model provides a good approximation to assess blood flow changes in the fetal circulation. The results support that while MCA flow is mainly determined by a fall in brain resistance, the AoI is influenced by a balance between increased peripheral-placental and decreased cerebral resistances. Personalizing the model allows for quantifying the balance between cerebral and peripheral-placental remodeling

  6. A Computational Model of the Fetal Circulation to Quantify Blood Redistribution in Intrauterine Growth Restriction

    PubMed Central

    Garcia-Canadilla, Patricia; Rudenick, Paula A.; Crispi, Fatima; Cruz-Lemini, Monica; Palau, Georgina; Camara, Oscar; Gratacos, Eduard; Bijens, Bart H.

    2014-01-01

    Intrauterine growth restriction (IUGR) due to placental insufficiency is associated with blood flow redistribution in order to maintain delivery of oxygenated blood to the brain. Given that, in the fetus the aortic isthmus (AoI) is a key arterial connection between the cerebral and placental circulations, quantifying AoI blood flow has been proposed to assess this brain sparing effect in clinical practice. While numerous clinical studies have studied this parameter, fundamental understanding of its determinant factors and its quantitative relation with other aspects of haemodynamic remodeling has been limited. Computational models of the cardiovascular circulation have been proposed for exactly this purpose since they allow both for studying the contributions from isolated parameters as well as estimating properties that cannot be directly assessed from clinical measurements. Therefore, a computational model of the fetal circulation was developed, including the key elements related to fetal blood redistribution and using measured cardiac outflow profiles to allow personalization. The model was first calibrated using patient-specific Doppler data from a healthy fetus. Next, in order to understand the contributions of the main parameters determining blood redistribution, AoI and middle cerebral artery (MCA) flow changes were studied by variation of cerebral and peripheral-placental resistances. Finally, to study how this affects an individual fetus, the model was fitted to three IUGR cases with different degrees of severity. In conclusion, the proposed computational model provides a good approximation to assess blood flow changes in the fetal circulation. The results support that while MCA flow is mainly determined by a fall in brain resistance, the AoI is influenced by a balance between increased peripheral-placental and decreased cerebral resistances. Personalizing the model allows for quantifying the balance between cerebral and peripheral-placental remodeling

  7. Average acceleration and deceleration capacity of fetal heart rate in normal pregnancy and in pregnancies complicated by fetal growth restriction.

    PubMed

    Graatsma, E M; Mulder, E J H; Vasak, B; Lobmaier, S M; Pildner von Steinburg, S; Schneider, K T M; Schmidt, G; Visser, G H A

    2012-12-01

    To study fetal heart rate (FHR), its short term variability (STV), average acceleration capacity (AAC), and average deceleration capacity (ADC) throughout uncomplicated gestation, and to perform a preliminary comparison of these FHR parameters between small-for dates (SFD) and control fetuses. Prospective observational study of 7 h FHR-recordings obtained with a fetal-ECG monitor in the second half of uncomplicated pregnancies (n = 90) and pregnancies complicated by fetal SFD (n = 30). FHR and STV were calculated according to established analysis. True beat-to-beat FHR, recorded at 1 ms accuracy, was used to calculate AAC and ADC using Phase Rectified Signal Averaging (PRSA). Mean values of FHR, STV, AAC, and ADC derived from recordings in SFD fetuses were compared with the reference curves. Compared with the control group the mean z-scores for STV, AAC, and ADC in SFD fetuses were lower by 1.0 SD, 1.5 SD, and 1.7 SD, respectively (p < 0.0001 for all comparisons). In SFD fetuses, both the AAC and ADC z-scores were lower than the STV z-scores (p < 0.02 and p < 0.002, respectively). Analysis of the AAC and ADC as recorded with a high resolution fECG recorder may differentiate better between normal and SFD fetuses than STV.

  8. Mild Gestational Hyperglycemia in Rat Induces Fetal Overgrowth and Modulates Placental Growth Factors and Nutrient Transporters Expression

    PubMed Central

    Cisse, Ouma; Fajardy, Isabelle; Dickes-Coopman, Anne; Moitrot, Emmanuelle; Montel, Valérie; Deloof, Sylvie; Rousseaux, Jean; Vieau, Didier; Laborie, Christine

    2013-01-01

    Mild gestational hyperglycemia is often associated with fetal overgrowth that can predispose the offspring to metabolic diseases later in life. We hypothesized that unfavorable intrauterine environment may compromise the development of placenta and contribute to fetal overgrowth. Therefore, we developed a rat model and investigated the effects of maternal dysglycemia on fetal growth and placental gene expression. Female rats were treated with single injection of nicotinamide plus streptozotocin (N-STZ) 1-week before mating and were studied at gestational day 21. N-STZ pregnant females displayed impaired glucose tolerance that is associated with a lower insulin secretion. Moderate hyperglycemia induced fetal overgrowth in 40% of newborns, from pregnancies with 10 to 14 pups. The incidence of macrosomia was less than 5% in the N-STZ pregnancies when the litter size exceeds 15 newborns. We found that placental mass and the labyrinthine layer were increased in macrosomic placentas. The expression of genes involved in placental development and nutrient transfer was down regulated in the N-STZ placentas of macrosomic and normosomic pups from pregnancies with 10 to 14 ones. However, we observed that lipoprotein lipase 1 (LPL1) gene expression was significantly increased in the N-STZ placentas of macrosomic pups. In pregnancies with 15 pups or more, the expression of IGFs and glucose transporter genes was also modulated in the control placentas with no additional effect in the N-STZ ones. These data suggest that placental gene expression is modulated by gestational conditions that might disrupt the fetal growth. We described here a new model of maternal glucose intolerance that results in fetal overgrowth. We proposed that over-expression of LPL1 in the placenta may contribute to the increased fetal growth in the N-STZ pregnancies. N-STZ model offers the opportunity to determinate whether these neonatal outcomes may contribute to developmental programming of metabolic

  9. Prenatal mercury contamination: relationship with maternal seafood consumption during pregnancy and fetal growth in the 'EDEN mother-child' cohort

    PubMed Central

    Drouillet-Pinard, Peggy; Huel, Guy; Slama, Rémy; Forhan, Anne; Sahuquillo, Josiane; Goua, Valérie; Thiébaugeorges, Olivier; Foliguet, Bernard; Magnin, Guillaume; Kaminski, Monique; Cordier, Sylvaine; Charles, Marie-Aline

    2010-01-01

    SUMMARY Background Maternal seafood intake is of great health interest since it constitutes an important source of n-3 fatty acids, but provides also an important pathway for fetal exposure to mercury (Hg). Objectives To determine associations between Hg contamination and both maternal seafood consumption and fetal growth in French pregnant women. Design Pregnant women included in the “EDEN mother-child” cohort study answered food frequency questionnaires on their usual diet in the year before and during the last three months of pregnancy, from which frequencies of seafood intake were evaluated. Total hair-Hg level was determined for the first 691 included women. Associations between Hg level, seafood intake and several neonatal measurements were studied using linear regressions adjusted for confounding variables. Results The median Hg level for mothers was 0.52 μg/g. Maternal seafood intake was associated with Hg level (r=0.33, p<0.0001). There was no association between Hg level and fetal growth in the whole sample of women, except for an early negative relation with biparietal diameter. A positive association was found between seafood intake and fetal growth in overweight women only which remained unchanged after adjustment for Hg level (birthweight: +101g for a difference of 1SD in seafood consumption, p=0.008). Conclusions Although seafood intake was associated with Hg contamination in French pregnant women, the contamination level was low. There was no consistent association between Hg level and fetal growth. Taking into account Hg level did not modify associations between seafood intake and fetal growth. PMID:20487582

  10. Fetal growth and premature delivery in pregnant women on antiepileptic drugs.

    PubMed

    Hernández-Díaz, Sonia; McElrath, Thomas F; Pennell, Page B; Hauser, W Allen; Yerby, Mark; Holmes, Lewis B

    2017-09-01

    To evaluate the effects of epilepsy and antiepileptic drugs (AEDs) used during pregnancy on fetal growth and preterm delivery. This study included singleton liveborn infants born to women enrolled in the North American Antiepileptic Drug Pregnancy Registry between 1997 and 2016. Data were collected prospectively through telephone interviews. The prevalence of preterm birth (<37 weeks) and small for gestational age status (SGA) among infants exposed prenatally to AEDs when used by women with epilepsy (WWE) or women without epilepsy (WWOE) was compared with that among infants unexposed to AEDs and born to WWOE. Multivariate log-binomial regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). The study population included infants born to 6,777 AED-WWE, 696 AED-WWOE, and 486 no-AED-WWOE. The risk of prematurity was 6.2% for no-AED-WWOE, 9.3% for AED-WWE (RR = 1.5, 95% CI = 1.0-2.1), and 10.5% for AED-WWOE (RR = 1.5, 95% CI = 1.0-2.4). Prenatal exposure to AEDs in WWE and WWOE was associated with a mean lower birth weight of 110 and 136g, respectively, as compared to no-AED-WWOE. The prevalence of SGA was 5.0% for no-AED-WWOE, 10.9% for AED-WWE (RR = 2.0, 95% CI = 1.3-3.0), and 11.0% for AED-WWOE (RR = 1.9, 95% CI = 1.2-2.9). Within users of AEDs in monotherapy, the prevalence of SGA ranged from 7.3% for lamotrigine to 18.5% for topiramate. Women on AEDs during pregnancy, whether for epilepsy or for other neuropsychiatric indications, are at a higher risk of delivering prematurely and giving birth to SGA newborns. The risk may vary by drug. Ann Neurol 2017;82:457-465. © 2017 American Neurological Association.

  11. Experimental bone defect healing with xenogenic demineralized bone matrix and bovine fetal growth plate as a new xenograft: radiological, histopathological and biomechanical evaluation.

    PubMed

    Bigham, A S; Dehghani, S N; Shafiei, Z; Nezhad, S Torabi

    2009-02-01

    The following study was designed to evaluate xenogenic bovine demineralized bone matrix (DBM) and new xenograft (Bovine fetal growth plate) effects on bone healing process. Twenty male White New Zealand rabbits were used in this study. In group I (n = 10) the defect was filled by xenogenic DBM and in group II (n = 10) the defect was filled by a segment of bovine fetal growth plate and was fixed by cercelage wire. Radiological, histopathological, and biomechanical evaluations were performed blindly and results scored and analyzed statistically. Statistical tests did not support significant differences between two groups radiographically (P > 0.05). There was a significant difference for union at the 28th postoperative radiologically (P < 0.05). Xenograft was superior to DBM group at the 28th postoperative day for radiological union (P < 0.03). Histopathological and biomechanical evaluation revealed no significant differences between two groups. In conclusion, the results of this study indicate that satisfactory healing occurred in rabbit radius defect filled with xenogenic bovine DBM and xenogenic bovine fetal growth plate. Complications were not identified and healing was faster in two grafting groups.

  12. The association between low 50 g glucose challenge test result and fetal growth restriction.

    PubMed

    Melamed, Nir; Hiersch, Liran; Peled, Yoav; Hod, Moshe; Wiznitzer, Arnon; Yogev, Yariv

    2013-07-01

    To determine whether a low-GCT result is predictive of low birthweight and to identify the lower GCT threshold for prediction of fetal growth restriction. A retrospective cohort study of 12,899 women who underwent a GCT (24-28 weeks). Women with a low-GCT result (<10th percentile (70 mg/dL) were compared to women with normal-GCT result (70-140 mg/dL). ROC analysis was used to determine the optimal lower GCT threshold for the prediction of growth restriction. Women in the low GCT had significant lower rates of cesarean delivery (18.7% versus 22.5%), shoulder dystocia (0.0% versus 0.3%), mean birthweight (3096 ± 576 versus 3163 ± 545) and birthweight percentile (49.1 ± 27.0 versus 53.1 ± 26.7) and significant higher rates of birthweight <2500 g (11.3% versus 8.5%), below the 10th percentile (8.3% versus 6.5%) and 3rd percentile (2.3% versus 1.4%). Low GCT was independently associated with an increased risk for birthweight <2500 g (OR = 1.6, 1.2-2.0), birthweight <10th percentile (OR = 1.3, 1.1-1.6), birthweight <3rd percentile (OR = 1.7, 1.2-2.5) and neonatal hypoglycemia (OR = 1.4, 1.02-2.0). The optimal GCT threshold for the prediction of birthweight <10th percentile was 88.5 mg/dL (sensitivity 48.5%, specificity 58.1%). Low-GCT result is independently associated with low birthweight and can be used in combination with additional factors for the prediction of fetal growth restriction.

  13. Cumulative effects of prenatal-exposure to exogenous chemicals and psychosocial stress on fetal growth: Systematic-review of the human and animal evidence.

    PubMed

    Vesterinen, Hanna M; Morello-Frosch, Rachel; Sen, Saunak; Zeise, Lauren; Woodruff, Tracey J

    2017-01-01

    Adverse effects of prenatal stress or environmental chemical exposures on fetal growth are well described, yet their combined effect remains unclear. To conduct a systematic review on the combined impact and interaction of prenatal exposure to stress and chemicals on developmental outcomes. We used the first three steps of the Navigation Guide systematic review. We wrote a protocol, performed a robust literature search to identify relevant animal and human studies and extracted data on developmental outcomes. For the most common outcome (fetal growth), we evaluated risk of bias, calculated effect sizes for main effects of individual and combined exposures, and performed a random effects meta-analysis of those studies reporting on odds of low birthweight (LBW) by smoking and socioeconomic status (SES). We identified 17 human- and 22 animal-studies of combined chemical and stress exposures and fetal growth. Human studies tended to have a lower risk of bias across nine domains. Generally, we found stronger effects for chemicals than stress, and these exposures were associated with reduced fetal growth in the low-stress group and the association was often greater in high stress groups, with limited evidence of effect modification. We found smoking associated with significantly increased odds of LBW, with a greater effect for high stress (low SES; OR 4.75 (2.46-9.16)) compared to low stress (high SES; OR 1.95 (95% CI 1.53-2.48)). Animal studies generally had a high risk of bias with no significant combined effect or effect modification. We found that despite concern for the combined effects of environmental chemicals and stress, this is still an under-studied topic, though limited available human studies indicate chemical exposures exert stronger effects than stress, and this effect is generally larger in the presence of stress.

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

    PubMed

    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

    2016-04-01

    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. 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. 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)]. 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). Our results suggested that elevated maternal THM exposure may adversely affect fetal growth. 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.

  15. First-trimester adiponectin and subsequent development of preeclampsia or fetal growth restriction.

    PubMed

    Valdés, Enrique R; Lattes, Karinna A; Muñoz, Hernán S; Barja, Pilar Y; Papapietro, Karin V

    2011-01-01

    The evidence regarding the utility of assessing first-trimester adiponectin (ApN) serum levels in early prediction of preeclampsia (PE) and fetal growth restriction (FGR) is contradictory. This study aims to determine the role of maternal serum ApN levels as an early predictor of PE and FGR. A prospective case-control study among a pregnant population who attended their 11- to 14-week ultrasound scan at the University of Chile's Clinical Hospital's Fetal Medicine Unit. We included patients who developed PE or FGR (10 cases per group) and 35 healthy controls. We determined ApN levels in blood samples from these 55 patients using a commercial ELISA kit and assessed the relationship of ApN levels with variables like development of PE, FGR, weight at birth and maternal BMI. There were no significant differences among first-trimester ApN serum levels in the groups. Average concentrations were 8, 6.8 and 10.8 ng/ml for the control, PE and FGR groups, respectively. In our study, maternal serum ApN levels were not useful in predicting subsequent development of PE and FGR. However, maternal serum ApN concentration adjusted by BMI was significantly higher during the first trimester in women who later developed FGR. Copyright © 2011 S. Karger AG, Basel.

  16. Fetal cardiac size in normal, intrauterine growth retarded, and diabetic pregnancies.

    PubMed

    Veille, J C; Hanson, R; Sivakoff, M; Hoen, H; Ben-Ami, M

    1993-07-01

    A total of 177 M-mode echocardiography studies were done on three groups of fetuses at different gestational ages: group I, normally grown fetuses; group II, intrauterine growth-retarded fetuses (IUGR); and group III, fetuses of diabetic mothers. Adjusted for gestational age and for fetal weight, the hearts of fetuses with IUGR were found to have an increased minor axis dimension due to free wall hypertrophy. No ventricular dilation was found in this group. Furthermore, IUGR fetuses have a larger heart proportionally to their body weight, raising the possibility of a "sparing effect" in this particular group. The hearts of fetuses of diabetic mothers were also found to have a significantly larger cardiac size than that of a group of normally grown fetuses. The increase was secondary to free wall hypertrophy, interventricular septal hypertrophy, and right ventricular dilation. This study confirms previous reports about fetal diabetic cardiomegaly and documents the contribution of the different cardiac components to this increase in size. The free wall hypertrophy found in these two groups may occur by different processes, which needs to be further investigated.

  17. A progesterone-brown fat axis is involved in regulating fetal growth.

    PubMed

    McIlvride, Saraid; Mushtaq, Aleena; Papacleovoulou, Georgia; Hurling, Chloe; Steel, Jennifer; Jansen, Eugène; Abu-Hayyeh, Shadi; Williamson, Catherine

    2017-09-06

    Pregnancy is associated with profound maternal metabolic changes, necessary for the growth and development of the fetus, mediated by reproductive signals acting on metabolic organs. However, the role of brown adipose tissue (BAT) in regulating gestational metabolism is unknown. We show that BAT phenotype is lost in murine pregnancy, while there is a gain of white adipose tissue (WAT)-like features. This is characterised by reduced thermogenic capacity and mitochondrial content, accompanied by increased levels of markers of WAT and lipid accumulation. Surgical ablation of BAT prior to conception caused maternal and fetal hyperlipidemia, and consequently larger fetuses. We show that BAT phenotype is altered from day 5 of gestation, implicating early pregnancy factors, which was confirmed by reduced expression of BAT markers in progesterone challenged oophorectomised mice. Moreover, in vitro data using primary BAT cultures show a direct impact of progesterone on expression of Ucp1. These data demonstrate that progesterone mediates a phenotypic change in BAT, which contributes to the gestational metabolic environment, and thus overall fetal size.

  18. Levels of neopterin and C-reactive protein in pregnant women with fetal growth restriction.

    PubMed

    Erkenekli, K; Keskin, U; Uysal, B; Kurt, Y G; Sadir, S; Çayci, T; Ergün, A; Erkaya, S; Danişman, N; Uygur, D

    2015-04-01

    The aim of this study was to evaluate whether pregnant women with fetal growth restriction (FGR) have higher plasma neopterin and C-reactive protein (CRP) concentrations compared with those with uncomplicated pregnancy. A total of 34 pregnant women with FGR and 62 patients with uncomplicated pregnancy were included. Neopterin and CRP levels were measured at the time of diagnosis. The primary outcome of this study was to compare the neopterin and CRP levels in pregnant women with FGR and those with uncomplicated pregnancies. The secondary outcome of our study was to evaluate the correlation between fetal birth weight and maternal neopterin levels. The serum neopterin levels were significantly elevated in pregnant women with FGR (22.71 ± 7.70 vs 19.15 ± 8.32). However, CRP was not elevated in pregnant women with FGR (7.47 ± 7.59 vs 5.29 ± 3.58). These findings support the hypothesis that pregnancy with FGR is associated with a marked increase in macrophage activation and the natural immune system.