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Maternal distress, DNA methylation, and fetal programing of stress physiology in Brazilian mother-infant pairs.

ABSTRACT: Maternal prenatal psychosocial stress is associated with adverse hypothalamic-pituitary-adrenal axis (HPAA) function among infants. Although the biological mechanisms influencing this process remain unknown, altered DNA methylation is considered to be one potential mechanism. We investigated associations between maternal prenatal psychological distress, infant salivary DNA methylation, and stress physiology at 12 months. Mother's distress was measured via depression and anxiety in early and late pregnancy in a cohort of 80 pregnant adolescents. Maternal hair cortisol was collected during pregnancy. Saliva samples were collected from infants at 12 months to quantify DNA methylation of three stress-related genes (FKBP5, NR3C1, OXTR) (n = 62) and diurnal cortisol (n = 29). Multivariable linear regression was used to test for associations between prenatal psychological distress, and infant DNA methylation and cortisol. Hair cortisol concentrations in late pregnancy were negatively associated with two sites of FKBP5 (site 1: B = -22.33, p = .003; site 2: B = -15.60, p = .012). Infants of mothers with elevated anxiety symptoms in late pregnancy had lower levels of OXTR2 CpG2 methylation (B = -2.17, p = .03) and higher evening salivary cortisol (B = 0.41, p = .03). Furthermore, OXTR2 methylation was inversely associated with evening cortisol (B = -0.14, p-value ≤ .001). Our results are, to our knowledge, the first evidence that the methylation of the oxytocin receptor may contribute to the regulation of HPAA during infancy.

SUBMITTER: Wiley KS

PROVIDER: S-EPMC9792831 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Maternal distress, DNA methylation, and fetal programing of stress physiology in Brazilian mother-infant pairs.

Wiley Kyle S KS Camilo Caroline C Gouveia Gisele G Euclydes Verônica V Panter-Brick Catherine C Matijasevich Alicia A Ferraro Alexandre Archanjo AA Fracolli Lislaine Aparecida LA Chiesa Anna Maria AM Miguel Euripedes Constantino EC Polanczyk Guilherme V GV Brentani Helena H

Developmental psychobiology 20230101 1

Maternal prenatal psychosocial stress is associated with adverse hypothalamic-pituitary-adrenal axis (HPAA) function among infants. Although the biological mechanisms influencing this process remain unknown, altered DNA methylation is considered to be one potential mechanism. We investigated associations between maternal prenatal psychological distress, infant salivary DNA methylation, and stress physiology at 12 months. Mother's distress was measured via depression and anxiety in early and late ...[more]

PMID: 36567654

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Project description:Background and aimsInfant adverse birth outcomes have been suggested to contribute to neonatal morbidity and mortality and may cause long-term health consequences. Although evidence suggests maternal prepregnancy body mass index (BMI) categories associate with some birth outcomes, there is no consensus on these associations. We aimed to examine the associations of maternal prepregnancy BMI categories with a wide range of adverse birth outcomes.MethodsData were from a population-based retrospective cohort study of 9,282,486 eligible mother-infant pairs in the U.S. between 2016 and 2018. Maternal prepregnancy BMI was classified as: underweight (<18.5 kg/m2); normal weight (18.5-24.9 kg/m2); overweight (25.0-29.9 kg/m2); obesity grade 1 (30-34.9 kg/m2); obesity grade 2 (35.0-39.9 kg/m2); and obesity grade 3 (≥40 kg/m2). A total of six birth outcomes of the newborn included preterm birth, low birthweight, macrosomia, small for gestational age (SGA), large for gestational age (LGA), and low Apgar score (5-min score <7).ResultsMaternal prepregnancy overweight and obesity increased the likelihood of infant preterm birth, with odds ratios (ORs) (95% CIs) of 1.04 (1.04-1.05) for overweight, 1.18 (1.17-1.19) for obesity grade 1, 1.31 (1.29-1.32) for obesity grade 2, and 1.47 (1.45-1.48) for obesity grade 3, and also for prepregnancy underweight (OR = 1.32, 95% CI = 1.30-1.34) after adjusting for all potential covariates. Prepregnancy overweight and obesity were associated with higher odds of macrosomia, with ORs (95% CIs) of 1.53 (1.52-1.54) for overweight, 1.92 (1.90-1.93) for obesity grade 1, 2.33 (2.31-2.35) for obesity grade 2, and 2.87 (2.84-2.90) for obesity grade 3. Prepregnancy overweight and obesity was associated with higher odds of LGA, with ORs (95% CIs) of 1.58 (1.57-1.59) for overweight, 2.05 (2.03-2.06) for obesity grade 1, 2.54 (2.52-2.56) for obesity grade 2, and 3.17 (3.14-3.21) for obesity grade 3. Prepregnancy overweight and obesity were also associated with higher odds of low Apgar score, with ORs (95% CIs) of 1.12 (1.11-1.14) for overweight, 1.21 (1.19-1.23) for obesity grade 1, 1.34 (1.31-1.36) for obesity grade 2, and 1.55 (1.51-1.58) for obesity grade 3.ConclusionOur findings suggest maintaining or obtaining a healthy body weight for prepregnancy women could substantially reduce the likelihood of important infant adverse birth outcomes.

Project description:BackgroundMany 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. The causal mechanisms and the relative contributions of maternal and fetal genetic effects behind these observed associations are unresolved.Methods and findingsBased on 10,734 mother-infant duos of European ancestry from the UK, Northern Europe, Australia, and North America, we constructed haplotype genetic scores using single-nucleotide polymorphisms (SNPs) known to be associated with adult height, body mass index (BMI), blood pressure (BP), fasting plasma glucose (FPG), and type 2 diabetes (T2D). Using these scores as genetic instruments, we estimated the maternal and fetal genetic effects underlying the observed associations between maternal phenotypes and pregnancy outcomes. We also used infant-specific birth weight genetic scores as instrument and examined the effects of fetal growth on pregnancy outcomes, maternal BP, and glucose levels during pregnancy. The maternal nontransmitted haplotype score for height was significantly associated with gestational duration (p = 2.2 × 10-4). Both maternal and paternal transmitted height haplotype scores were highly significantly associated with birth weight and length (p < 1 × 10-17). The maternal transmitted BMI scores were associated with birth weight with a significant maternal effect (p = 1.6 × 10-4). Both maternal and paternal transmitted BP scores were negatively associated with birth weight with a significant fetal effect (p = 9.4 × 10-3), whereas BP alleles were significantly associated with gestational duration and preterm birth through maternal effects (p = 3.3 × 10-2 and p = 4.5 × 10-3, respectively). The nontransmitted haplotype score for FPG was strongly associated with birth weight (p = 4.7 × 10-6); however, the glucose-increasing alleles in the fetus were associated with reduced birth weight through a fetal effect (p = 2.2 × 10-3). The haplotype scores for T2D were associated with birth weight in a similar way but with a weaker maternal effect (p = 6.4 × 10-3) and a stronger fetal effect (p = 1.3 × 10-5). The paternal transmitted birth weight score was significantly associated with reduced gestational duration (p = 1.8 × 10-4) and increased maternal systolic BP during pregnancy (p = 2.2 × 10-2). The major limitations of the study include missing and heterogenous phenotype data in some data sets and different instrumental strength of genetic scores for different phenotypic traits.ConclusionsWe found that both maternal height and fetal growth are important factors in shaping the duration of gestation: genetically elevated maternal height is associated with longer gestational duration, whereas alleles that increase fetal growth are associated with shorter gestational duration. Fetal growth is influenced by both maternal and fetal effects and can reciprocally influence maternal phenotypes: taller maternal stature, higher maternal BMI, and higher maternal blood glucose are associated with larger birth size through maternal effects; in the fetus, the height- and metabolic-risk-increasing alleles are associated with increased and decreased birth size, respectively; alleles raising birth weight in the fetus are associated with shorter gestational duration and higher maternal BP. These maternal and fetal genetic effects may 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.

Dataset Information

Maternal distress, DNA methylation, and fetal programing of stress physiology in Brazilian mother-infant pairs.

Publications

Maternal distress, DNA methylation, and fetal programing of stress physiology in Brazilian mother-infant pairs.

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