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Fetal Genotype and Maternal Glucose Have Independent and Additive Effects on Birth Weight.

ABSTRACT: Maternal glycemia is a key determinant of birth weight, but recent large-scale genome-wide association studies demonstrated an important contribution of fetal genetics. It is not known whether fetal genotype modifies the impact of maternal glycemia or whether it acts through insulin-mediated growth. We tested the effects of maternal fasting plasma glucose (FPG) and a fetal genetic score for birth weight on birth weight and fetal insulin in 2,051 European mother-child pairs from the Exeter Family Study of Childhood Health (EFSOCH) and the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. The fetal genetic score influenced birth weight independently of maternal FPG and impacted growth at all levels of maternal glycemia. For mothers with FPG in the top tertile, the frequency of large for gestational age (birth weight ?90th centile) was 31.1% for offspring with the highest tertile genetic score and only 14.0% for those with the lowest tertile genetic score. Unlike maternal glucose, the fetal genetic score was not associated with cord insulin or C-peptide. Similar results were seen for HAPO participants of non-European ancestry (n = 2,842 pairs). This work demonstrates that for any level of maternal FPG, fetal genetics has a major impact on fetal growth and acts predominantly through independent mechanisms.

SUBMITTER: Hughes AE

PROVIDER: S-EPMC5910006 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Fetal Genotype and Maternal Glucose Have Independent and Additive Effects on Birth Weight.

Hughes Alice E AE Nodzenski Michael M Beaumont Robin N RN Talbot Octavious O Shields Beverley M BM Scholtens Denise M DM Knight Bridget A BA Lowe William L WL Hattersley Andrew T AT Freathy Rachel M RM

Diabetes 20180220 5

Maternal glycemia is a key determinant of birth weight, but recent large-scale genome-wide association studies demonstrated an important contribution of fetal genetics. It is not known whether fetal genotype modifies the impact of maternal glycemia or whether it acts through insulin-mediated growth. We tested the effects of maternal fasting plasma glucose (FPG) and a fetal genetic score for birth weight on birth weight and fetal insulin in 2,051 European mother-child pairs from the Exeter Family ...[more]

PMID: 29463506

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Project description:Many studies have shown that neonates of smoking mothers have a lower birth weight, but several issues remain poorly studied, e.g., the effects of giving up smoking or the combined effects of smoking and maternal obesity. Therefore, we evaluated a prospective cohort of 912 mothers in a single pregnancy, recruited in Poland, in 2015-2016. In the cohort, we recorded 72 (7.9%) newborns with birth weight <10th percentile, 21 (2.3%) fetal growth restriction (FGR) cases, and 60 (6.6%) low birth weight (LBW, <2500 g) newborns. In the cohort, 168 (18.4%) women smoked before pregnancy; the mean number of cigarettes/day was 10.8 (1-30), and the mean number of years of cigarette smoking was 8.5 (1-25). Among smokers, 57 (6.3%) women smoked in the first trimester. Adjusted odds ratio (AOR) of newborn outcomes (with 95% confidence intervals, CI) was calculated in multi-dimensional logistic regressions. Compared to participants who had never smoked, smoking before pregnancy was associated with a higher odds ratio of birth weight <10th percentile (AOR = 1.93, CI: 1.08-3.44, p = 0.027), but the result for LBW (AOR = 2.76, CI: 1.05-7.26, p = 0.039) and FGR (AOR = 1.13, CI: 0.38-3.36, p = 0.822) had the wider confidence interval or was insignificant. Effects of smoking cessation before pregnancy were statistically insignificant for the studied outcomes. Smoking in the first trimester was associated with a higher risk of birth weight <10th percentile (AOR = 4.68, CI: 2.28-9.62, p < 0.001), LBW (AOR = 6.42, CI: 1.84-22.36, p = 0.004), and FGR (AOR = 3.60, CI: 0.96-13.49, p = 0.057). Smoking cessation in the second/third trimester was associated with a higher odds ratio of birth weight <10th percentile (AOR = 4.54, CI: 1.58-13.02, p = 0.005), FGR (AOR = 3.36, CI: 0.6-18.74, p = 0.167), and LBW (AOR = 2.14, CI: 0.62-7.36), p = 0.229), to a similar degree to smoking in the first trimester. The odds ratios were higher in the subgroup of pre-pregnancy body mass index ?25 kg/m2 for the risk of birth weight <10th percentile (AOR = 6.39, CI: 2.01-20.34, p = 0.002) and FGR (AOR = 6.25, CI: 0.86-45.59, p = 0.071). The length of cigarette smoking time was also the risk factor for studied outcomes. Conclusions: Smoking in the first trimester increased the studied risks, and the coexistence of excessive maternal weight increased the effects. Smoking cessation during the second/third trimester did not have a protective effect.

Project description:Fetal alcohol-related growth restriction persists through infancy, but its impact later in life is less clear. Animal studies have demonstrated important roles for maternal nutrition in fetal alcohol spectrum disorders, but the impact of prenatal maternal body composition has not been studied in humans. This study examined the effects of prenatal alcohol exposure on longitudinal growth from birth through young adulthood and the degree to which maternal weight and body mass index (BMI) moderate these effects.Nearly 480 mothers were recruited at their first prenatal clinic visit to overrepresent moderate-to-heavy use of alcohol during pregnancy, including a 5% random sample of low-level drinkers and abstainers. They were interviewed at every prenatal visit about their alcohol consumption using a timeline follow-back approach. Their children were examined for weight, length/height, and head circumference at birth, 6.5 and 13 months, and 7.5, 14, and 19 years.In multiple regression models with repeated measures (adjusted for confounders), prenatal alcohol exposure was associated with longitudinal reductions in weight, height, and weight-for-length/BMI that were largely determined at birth. At low-to-moderate levels of exposure, these effects were more severe in infancy than in later childhood. By contrast, effects persisted among children whose mothers drank at least monthly and among those born to women with alcohol abuse and/or dependence who had consumed ? 4 drinks/occasion. In addition, effects on weight, height, and head circumference were markedly stronger among children born to mothers with lower prepregnancy weight.These findings confirm prior studies demonstrating alcohol-related reductions in weight, height, weight-for-height/BMI, and head circumference that persist through young adulthood. Stronger effects were seen among children born to mothers with smaller prepregnancy weight, which may have been because of attainment of higher blood alcohol concentrations in smaller mothers for a given amount of alcohol intake or to increased vulnerability in infants born to women with poorer nutrition.

Project description:Birth weight is considered not only to undermine future growth, but also to induce lifelong diseases; the aim of this study is to explore the relationship between birth weight and adult bone mass. We performed multivariable regression analyses to assess the association of birth weight with bone parameters measured by dual-energy X-ray absorptiometry (DXA) and by quantitative ultrasound (QUS), independently. We also implemented a systemic Mendelian randomization (MR) analysis to explore the causal association between them with both fetal-specific and maternal-specific instrumental variables. In the observational analyses, we found that higher birth weight could increase the adult bone area (lumbar spine, β-coefficient= 0.17, P < 2.00 × 10-16; lateral spine, β-coefficient = 0.02, P = 0.04), decrease bone mineral content-adjusted bone area (BMCadjArea) (lumbar spine, β-coefficient= - 0.01, P = 2.27 × 10-14; lateral spine, β-coefficient = - 0.05, P = 0.001), and decrease adult bone mineral density (BMD) (lumbar spine, β-coefficient = - 0.04, P = 0.007; lateral spine; β-coefficient = - 0.03, P = 0.02; heel, β-coefficient = - 0.06, P < 2.00 × 10-16), and we observed that the effect of birth weight on bone size was larger than that on BMC. In MR analyses, the higher fetal-specific genetically determined birth weight was identified to be associated with higher bone area (lumbar spine; β-coefficient = 0.15, P = 1.26 × 10-6, total hip, β-coefficient = 0.15, P = 0.005; intertrochanteric area, β-coefficient = 0.13, P = 0.0009; trochanter area, β-coefficient = 0.11, P = 0.03) but lower BMD (lumbar spine, β-coefficient = - 0.10, P = 0.01; lateral spine, β-coefficient = - 0.12, P = 0.0003, and heel β-coefficient = - 0.11, P = 3.33 × 10-13). In addition, we found that the higher maternal-specific genetically determined offspring birth weight was associated with lower offspring adult heel BMD (β-coefficient = - 0.001, P = 0.04). The observational analyses suggested that higher birth weight was associated with the increased adult bone area but decreased BMD. By leveraging the genetic instrumental variables with maternal- and fetal-specific effects on birth weight, the observed relationship could be reflected by both the direct fetal and indirect maternal genetic effects.

Project description:BACKGROUND:Higher birth weight is an important adverse outcome associated with hyperglycemia in pregnancy. Recent studies suggest that phthalate exposure is associated with elevated glucose levels in pregnant women, with implications for higher birth weight in the offspring. No study to date has investigated the association between prenatal phthalate exposure on infant high birth weight accounting for the range of pregnancy glucose levels. METHODS:A total of 350 women participating in an ongoing pregnancy cohort had data available on urinary phthalate metabolite concentrations at up to four time points across pregnancy. Urinary phthalate metabolites were averaged across pregnancy and log-transformed, specific gravity-adjusted and analyzed in quartiles. Birth weight was examined continuously (in grams), as well as dichotomized as large for gestational age (>90th percentile). Glucose levels were assessed based on Results from 50-g glucose challenge tests as a part of screening for gestational diabetes conducted at 24-28 weeks gestation, and grouped into 3 categories <120?mg/dL, 120-<140?mg/dL and ?140?mg/dL. Multivariable linear regression was performed, adjusting for potential confounders in the overall population and stratified by pregnancy glucose levels. RESULTS:Approximately 20% of infants born to women with glucose levels ?140?mg/dL were large for gestational age. Average mono-ethyl phthalate (MEP) concentrations were higher among women who had glucose levels ?140?mg/dL (geometric mean 140.9??g/L; 95% CI: 91.6-216.8); however, higher MEP concentrations were not associated with higher birth weight. When stratified by maternal glucose levels, there was a suggestive association between higher concentrations of mono-(3-carboxypropyl) phthalate (MCPP) and higher birth weight among women with glucose levels ?140?mg/dL (adj. birth weight: 569.2?g; 95% CI: 14.1, 1178.2). CONCLUSIONS:Higher urinary phthalate metabolite concentrations were not significantly associated with higher birth weight. Counter to our hypothesis, women with higher glucose levels and higher urinary phthalate metabolites did not deliver babies with higher birth weight.

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Fetal Genotype and Maternal Glucose Have Independent and Additive Effects on Birth Weight.

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Fetal Genotype and Maternal Glucose Have Independent and Additive Effects on Birth Weight.

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