scholarly journals Haplotype genetic score analysis in 10,734 mother/infant pairs reveals complex maternal and fetal genetic effects underlying the associations between maternal phenotypes, birth outcomes and adult phenotypes

2019 ◽  
Author(s):  
Jing Chen ◽  
Jonas Bacelis ◽  
Pol Sole Navais ◽  
Amit Srivastava ◽  
Julius Juodakis ◽  
...  
Keyword(s):  
Birth Weight ◽  
Birth Outcomes ◽  
Fetal Growth ◽  
Late Onset ◽  
Genetic Effects ◽  
European Ancestry ◽  
Birth Size ◽  
Maternal Height ◽  
Genetic Score ◽  
Gestational Duration

ABSTRACTMany maternal traits are associated with a neonate’s gestational duration, birth weight and birth length. These birth outcomes are subsequently associated with late onset health conditions. Based on 10,734 mother/infant duos of European ancestry, we constructed haplotype genetic scores to dissect the maternal and fetal genetic effects underlying these observed associations. We showed that maternal height and fetal growth jointly affect the duration of gestation – maternal height positively influences the gestational duration, while faster fetal growth reduces gestational duration. Fetal growth is influenced by both maternal and fetal effects and can reciprocally influence maternal phenotypes: tall maternal stature and higher blood glucose causally increase birth size; in the fetus, the height and metabolic risk increasing alleles can lead to increased and decreased birth size respectively; birth weight-raising alleles in fetus may reduce gestational duration and increase maternal blood pressure. These maternal and fetal genetic effects can largely explain the observed associations between the studied maternal phenotypes and birth outcomes as well as the life-course associations between these birth outcomes and adult phenotypes.

scholarly journals Genome-wide association study of offspring birth weight in 86,577 women highlights maternal genetic effects that are independent of fetal genetics

2015 ◽  
Author(s):  
Robin N Beaumont ◽  
Nicole M Warrington ◽  
Alana Cavadino ◽  
Jessica Tyrrell ◽  
Michael Nodzenski ◽  
...  
Keyword(s):  
Birth Weight ◽  
Fetal Growth ◽  
Association Studies ◽  
Genetic Effects ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Maternal Genotype ◽  
Maternal Determinants ◽  
Gestational Duration

AbstractGenome-wide association studies (GWAS) of birth weight have focused on fetal genetics, while relatively little is known about how maternal genetic variation influences fetal growth. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth.We meta-analysed GWAS data on up to 8.7 million SNPs in up to 86,577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects.Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9 and CYP3A7) showed evidence of association with offspring birth weight at P<5x10-8. The SEM analyses showed at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration.The identified associations indicate effects of maternal glucose, cytochrome P450 activity and gestational duration, and potential effects of maternal blood pressure and immune function on fetal growth. Further characterization of these associations, for example in mechanistic and causal analyses, will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.

scholarly journals Prenatal maternal stress and birth outcomes in rural Ghana: sex-specific associations

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Kenneth Ayuurebobi Ae-Ngibise ◽  
Blair J. Wylie ◽  
Ellen Boamah-Kaali ◽  
Darby W. Jack ◽  
Felix Boakye Oppong ◽  
...  
Keyword(s):  
Birth Weight ◽  
Birth Outcomes ◽  
Fetal Growth ◽  
Head Circumference ◽  
Maternal Stress ◽  
Birth Outcome ◽  
Sub Saharan Africa ◽  
Adverse Birth Outcome ◽  
Prenatal Maternal Stress ◽  
Rural Ghana

Abstract Background In developed countries, prenatal maternal stress has been associated with poor fetal growth, however this has not been evaluated in rural sub-Saharan Africa. We evaluated the effect of prenatal maternal stress on fetal growth and birth outcomes in rural Ghana. Methods Leveraging a prospective, rural Ghanaian birth cohort, we ascertained prenatal maternal negative life events, categorized scores as 0-2 (low stress; referent), 3-5 (moderate), and > 5 (high) among 353 pregnant women in the Kintampo North Municipality and Kintampo South District located within the middle belt of Ghana. We employed linear regression to determine associations between prenatal maternal stress and infant birth weight, head circumference, and length. We additionally examined associations between prenatal maternal stress and adverse birth outcome, including low birth weight, small for gestational age, or stillbirth. Effect modification by infant sex was examined. Results In all children, high prenatal maternal stress was associated with reduced birth length (β = − 0.91, p = 0.04; p-value for trend = 0.04). Among girls, moderate and high prenatal maternal stress was associated with reduced birth weight (β = − 0.16, p = 0.02; β = − 0.18, p = 0.04 respectively; p-value for trend = 0.04) and head circumference (β = − 0.66, p = 0.05; β = − 1.02, p = 0.01 respectively; p-value for trend = 0.01). In girls, high prenatal stress increased odds of any adverse birth outcome (OR 2.41, 95% CI 1.01-5.75; p for interaction = 0.04). Sex-specific analyses did not demonstrate significant effects in boys. Conclusions All infants, but especially girls, were vulnerable to effects of prenatal maternal stress on birth outcomes. Understanding risk factors for impaired fetal growth may help develop preventative public health strategies. Trial registration NCT01335490 (prospective registration). Date of Registration: April 14, 2011. Status of Registration: Completed.

scholarly journals Genetics of early growth traits

2020 ◽  
Vol 29 (R1) ◽  
pp. R66-R72
Author(s):  
Diana L Cousminer ◽  
Rachel M Freathy
Keyword(s):  
Birth Weight ◽  
Health Outcomes ◽  
Fetal Growth ◽  
Association Studies ◽  
Later Life ◽  
Early Growth ◽  
Mr Studies ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Genetic Contributions

Abstract In recent years, genome-wide association studies have shed light on the genetics of early growth and its links with later-life health outcomes. Large-scale datasets and meta-analyses, combined with recently developed analytical methods, have enabled dissection of the maternal and fetal genetic contributions to variation in birth weight. Additionally, longitudinal approaches have shown differences between the genetic contributions to infant, childhood and adult adiposity. In contrast, studies of adult height loci have shown strong associations with early body length and childhood height. Early growth-associated loci provide useful tools for causal analyses: Mendelian randomization (MR) studies have provided evidence that early BMI and height are causally related to a number of adult health outcomes. We advise caution in the design and interpretation of MR studies of birth weight investigating effects of fetal growth on later-life cardiometabolic disease because birth weight is only a crude indicator of fetal growth, and the choice of genetic instrument (maternal or fetal) will greatly influence the interpretation of the results. Most genetic studies of early growth have to date centered on European-ancestry participants and outcomes measured at a single time-point, so key priorities for future studies of early growth genetics are aggregation of large samples of diverse ancestries and longitudinal studies of growth trajectories.

scholarly journals Prediction of late-onset fetal growth restriction using a combined first- and second-trimester screening model in South Chinese infants: a retrospective study

2019 ◽  
Author(s):  
Haiqing Zheng ◽  
Yan Feng ◽  
Jiexin Zhang ◽  
Kuanrong Li ◽  
Huiying Liang ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Birth Weight ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Detection Rate ◽  
Prediction Models ◽  
Late Onset ◽  
Growth Restriction ◽  
Abdominal Circumference ◽  
Second Trimester

Abstract Background Prediction models for early and late fetal growth restriction (FGR) have been established in many high-income countries. However, prediction models for late FGR in China are limited. This study aimed to develop a simple combined first- and second-trimester prediction model for screening late-onset FGR in South Chinese infants.Methods This retrospective study included 2258 women who had singleton pregnancies and received routine ultrasound scans. Late-onset FGR was defined as a birth weight < the 10th percentile plus abnormal Doppler indices and/or a birth weight below the 3rd percentile after 32 weeks, regardless of the Doppler status. Multivariate logistic regression was used to develop a prediction model.Results Ninety-three fetuses were identified as late-onset FGR. The significant predictors for late-onset FGR were maternal age, height, weight, and medical history; the second-trimester head circumference (HC)/abdominal circumference (AC) ratio; and the estimated fetal weight (EFW). This model achieved a detection rate (DR) of 52.6% for late-onset FGR at a 10% false positive rate (FPR) (area under the curve (AUC): 0.80, 95%CI 0.76-0.85).Conclusions A multivariate model combining first- and second-trimester default tests can detect 52.6% of cases of late-onset FGR. Further studies with more screening markers are needed to improve the detection rate.

scholarly journals Prediction of late-onset fetal growth restriction using a combined first- and second-trimester screening model in South Chinese infants: a retrospective study

2020 ◽  
Author(s):  
Haiqing Zheng ◽  
Yan Feng ◽  
Jiexin Zhang ◽  
Kuanrong Li ◽  
Huiying Liang ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Birth Weight ◽  
Prediction Model ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Detection Rate ◽  
Prediction Models ◽  
Late Onset ◽  
Validation Dataset ◽  
Second Trimester

Abstract Background: Prediction models for early and late fetal growth restriction (FGR) have been established in many high-income countries. However, prediction models for late FGR in China are limited. This study aimed to develop a simple combined first- and second-trimester prediction model for screening late-onset FGR in South Chinese infants. Methods: This retrospective study included 2258 women who had singleton pregnancies and received routine ultrasound scans as training dataset. A validation dataset including 565 pregnant women was used to evaluate the model in order to enable an unbiased estimation. Late-onset FGR was defined as a birth weight < the 10th percentile plus abnormal Doppler indices and/or a birth weight below the 3rd percentile after 32 weeks, regardless of the Doppler status. Multivariate logistic regression was used to develop a prediction model. The model included the a priori risk (maternal characteristics), the second-trimester head circumference (HC/AC) / abdomen circumference (HC) ratio and estimated fetal weight (EFW). Results: Ninety-three fetuses were identified as late-onset FGR. The significant predictors for late-onset FGR were maternal age, height, weight, and medical history; the second-trimester HC/ AC ratio; and the EFW. This model achieved a detection rate (DR) of 52.6% for late-onset FGR at a 10% false positive rate (FPR) (area under the curve (AUC): 0.80, 95%CI 0.76-0.85). The AUC of the validation dataset was 0.65 (95%CI 0.54-0.78). Conclusions: A multivariate model combining first- and second-trimester default tests can detect 52.6% of cases of late-onset FGR at a 10% FPR. Further studies with more screening markers are needed to improve the detection rate.

FACTORS AFFECTING BIRTH WEIGHT

PEDIATRICS ◽  
1989 ◽  
Vol 84 (3) ◽  
pp. A90-A90
Author(s):  
Student
Keyword(s):  
Birth Weight ◽  
Pregnant Women ◽  
Fetal Growth ◽  
Research Group ◽  
Maternal Smoking ◽  
Low Birthweight ◽  
District General Hospital ◽  
Maternal Height ◽  
Socioeconomic Conditions ◽  
Factors Affecting

Maternal smoking, stress, and poor socioeconomic conditions during pregnancy have been linked with low birthweight babies. Is there any way of deciding which of these related potential causes is the most important? In an attempt to do that a research group. . . studied over 1500 pregnant women delivering at a district general hospital in inner London. They showed that the most important influence on fetal growth was smoking, which was associated with a 5% reduction in birth weight after adjustment for maternal height and parity, gestation, and the baby's sex. Of over 40 socioeconomic and psychosocial factors examined, only four were significantly related to a reduction in birth weight, and these became non-significant after adjustment for smoking. The authors conclude that any effects of stress and poor environment on fetal growth are small compared with the effect of smoking.

scholarly journals Sexual Dimorphism in the Growth Hormone and Insulin-Like Growth Factor Axis at Birth

2003 ◽  
Vol 88 (8) ◽  
pp. 3708-3714 ◽  
Author(s):  
Michael P. P. Geary ◽  
P. Jane Pringle ◽  
Charles H. Rodeck ◽  
John C. P. Kingdom ◽  
Peter C. Hindmarsh
Keyword(s):  
Birth Weight ◽  
Head Circumference ◽  
Mode Of Delivery ◽  
Plasma Concentrations ◽  
Birth Size ◽  
Maternal Height ◽  
Cord Plasma ◽  
Igf I ◽  
Plasma Gh ◽  
Igfbp 3

In rodents and humans there is a sexually dimorphic pattern of GH secretion that influences the serum concentration of IGF-I. Pattern differences can be identified in children, but it is not known how early this difference is established. We studied the plasma concentrations of IGF-I, IGF-II, IGF-binding protein-3 (BP-3), and GH in cord blood taken from the offspring of 1650 singleton Caucasian pregnancies born at term and related these values to birth weight, length, and head circumference. Pregnancies complicated by preterm delivery, antepartum hemorrhage, pregnancy-induced hypertension, preeclampsia, or gestational diabetes and where cigarette smoking continued were excluded, resulting in a cohort of 987. Cord plasma concentrations of IGF-I, IGF-II, and IGFBP-3 were influenced by factors influencing birth size: gestational age at delivery, mode of delivery, maternal height, and parity of the mother. Plasma GH concentrations were inversely related to the plasma concentrations of IGF-I and IGFBP-3; 10.2% of the variability in cord plasma IGF-I concentration and 2.7% for IGFBP-3 was explained by sex of the offspring and parity. None of the factors, apart from maternal height, influenced cord serum IGF-II concentrations (adjusted r2 = 1%). Sex of the baby, mode of delivery, and parity influenced cord serum GH concentrations (adjusted r2 = 2.6%). Birth weight, length, and head circumference measurements were greater in males than females (P &lt; 0.001). Mean cord plasma concentrations of IGF-I (males, 66.4 ± 1.2 μg/liter; females, 74.5 ± 1.3 μg/liter; P &lt; 0.001) and IGFBP-3 (males, 910 ± 13 μg/liter; females 978 ± 13 μg/liter; P &lt; 0.001) were significantly lower in males than females. Cord plasma GH concentrations were higher in males than females (males, 30.0 ± 1.2 mU/liter; females, 26.9 ± 1.1 mU/liter; P = 0.05), but no difference was noted between the sexes for IGF-II (males, 508 ± 6 μg/liter; females, 519 ± 6 μg/liter; P = NS). After adjustment for gestational age, parity, and maternal height, cord plasma concentrations of IGF-I and IGFBP-3 along with sex explained 38.0% of the variability in birth weight, 25.0% in birth length, and 22.7% in head circumference. These data demonstrate that in a group of singleton Caucasian babies born at term, cord plasma IGF-I, IGFBP-3, and GH concentrations relate to birth size, with evidence for sexual dimorphism in the GH-IGF axis.

scholarly journals High-end arteriolar resistance limits uterine artery blood flow and restricts fetal growth in preeclampsia and gestational hypertension at high altitude

2011 ◽  
Vol 300 (5) ◽  
pp. R1221-R1229 ◽  
Author(s):  
Vaughn A. Browne ◽  
Lilian Toledo-Jaldin ◽  
R. Daniela Davila ◽  
Luis P. Lopez ◽  
Henry Yamashiro ◽  
...  
Keyword(s):  
Blood Flow ◽  
Birth Weight ◽  
High Altitude ◽  
Fetal Growth ◽  
Early Onset ◽  
Uterine Artery ◽  
Late Onset ◽  
Gestational Hypertension ◽  
Arterial Blood Flow ◽  
Arteriolar Resistance

The reduction in infant birth weight and increased frequency of preeclampsia (PE) in high-altitude residents have been attributed to greater placental hypoxia, smaller uterine artery (UA) diameter, and lower UA blood flow (QUA). This cross-sectional case-control study determined UA, common iliac (CI), and external iliac (EI) arterial blood flow in Andeans residing at 3,600–4,100 m, who were either nonpregnant (NP, n = 23), or experiencing normotensive pregnancies (NORM; n = 155), preeclampsia (PE, n = 20), or gestational hypertension (GH, n = 12). Pregnancy enlarged UA diameter to ∼0.62 cm in all groups, but indices of end-arteriolar vascular resistance were higher in PE or GH than in NORM. QUAwas lower in early-onset (≤34 wk) PE or GH than in NORM, but was normal in late-onset (>34 wk) illness. Left QUAwas consistently greater than right in NORM, but the pattern reversed in PE. Although QCIand QEIwere higher in PE and GH than NORM, the fraction of QCIdistributed to the UA was reduced 2- to 3-fold. Women with early-onset PE delivered preterm, and 43% had stillborn small for gestational age (SGA) babies. Those with GH and late-onset PE delivered at term but had higher frequencies of SGA babies (GH=50%, PE=46% vs. NORM=15%, both P < 0.01). Birth weight was strongly associated with reduced QUA( R2= 0.80, P < 0.01), as were disease severity and adverse fetal outcomes. We concluded that high end-arteriolar resistance, not smaller UA diameter, limited QUAand restricted fetal growth in PE and GH. These are, to our knowledge, the first quantitative measurements of QUAand pelvic blood flow in early- vs. late-onset PE in high-altitude residents.

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