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Prenatal sex hormones and behavioral outcomes in children.

ABSTRACT: Abnormal sex hormone levels in utero have been associated with child behavioral problems, but it is unclear if normal variation in prenatal sex hormones is associated with subsequent behavior in childhood. We assessed maternal sex hormones, including serum estrone (E1), estradiol (E2), estriol (E3), free testosterone (FT), and total testosterone (TT), during early pregnancy (gestational week 6-21 (mean = 11.1)) and evaluated child behavior at ages 4-5 using the Behavioral Assessment System for Children (BASC-2) and Social Responsiveness Scale (SRS-2) in 404 mother/child pairs (211 girls, 193 boys) within The Infant Development and Environment Study, a multi-site pregnancy cohort study. Associations between hormones and composite scores were evaluated using multiple linear regressions in both sexes combined, and separate models assessed effect modification by sex with the addition of interaction terms. A 10-fold increase in maternal FT or TT was associated in both sexes with a 4.3-point (95 % CI: 0.5, 8.2) or 4.4-point (0.8, 8.0) higher BASC-2 internalizing composite T score, respectively. In addition, a 10-fold increase in FT or TT was associated with a 3.8-point (0.04, 7.5) or 4.0-point (0.5, 7.5) higher behavioral symptoms index composite score. In models evaluating effect modification by sex, a 10-fold increase in E1 was associated with a 4.3-point (1.2, 7.4) decrease in adaptive skills composite score in girls only (interaction p = 0.04). We observed associations between testosterone and internalizing behaviors and behavioral symptoms index in both sexes, as well as a female-specific association between E1 and adaptive skills. Sex hormones during pregnancy may play a key role in influencing later-life behavior, and additional studies should further examine different periods of susceptibility to hormonal signals.

SUBMITTER: Day DB

PROVIDER: S-EPMC7759302 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Prenatal sex hormones and behavioral outcomes in children.

Day Drew B DB Collett Brent R BR Barrett Emily S ES Bush Nicole R NR Swan Shanna H SH Wang Christina C Sathyanarayana Sheela S

Psychoneuroendocrinology 20191224

Abnormal sex hormone levels in utero have been associated with child behavioral problems, but it is unclear if normal variation in prenatal sex hormones is associated with subsequent behavior in childhood. We assessed maternal sex hormones, including serum estrone (E1), estradiol (E2), estriol (E3), free testosterone (FT), and total testosterone (TT), during early pregnancy (gestational week 6-21 (mean = 11.1)) and evaluated child behavior at ages 4-5 using the Behavioral Assessment System for C ...[more]

PMID: 31901731

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Project description:Despite accumulating evidence from animal models demonstrating that prenatal alcohol exposure (PAE) results in life-long neuroendocrine dysregulation, very little is known on this topic among humans with fetal alcohol spectrum disorders (FASD). We expected that alterations in gonadal hormones might interfere with the typical development of white matter (WM) myelination, and in a sex-dependent manner, in human adolescents with FASD. In order to investigate this hypothesis, we used diffusion tensor imaging (DTI) to assess: 1) whether or not sex moderates the impact of PAE on WM microstructure; and 2) how gonadal hormones relate to alterations in WM microstructure in children and adolescents affected by PAE.61 youth (9 to 16 yrs.; 49% girls; 50% PAE) participated as part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD). DTI scans and passive drool samples were obtained to examine neurodevelopmental associations with testosterone (T) and dehydroepiandrosterone (DHEA) levels in boys and girls, and estradiol (E2) and progesterone (P) levels in girls. Tract-based spatial statistics were utilized to generate fractional anisotropy (FA) and mean diffusivity (MD) for 9 a priori WM regions of interest (ROIs).As predicted, alterations in FA were observed in adolescents with PAE relative to controls, and these differences varied by sex. Girls with PAE exhibited lower FA (Inferior fronto-occipital and Uncinate fasciculi) while boys with PAE exhibited higher FA (Callosal body, Cingulum, Corticospinal tract, Optic radiation, Superior longitudinal fasciculus) relative to age-matched controls. When gonadal hormone levels were examined in relation to DTI measures, additional group differences in FA were revealed, demonstrating that neuroendocrine factors are associated with PAE-related brain alterations.These findings provide human evidence that PAE relates to sex-specific differences in WM microstructure, and underlying alterations in gonadal hormone function may, in part, contribute to these effects. Determining PAE-effects on neuroendocrine function among humans is an essential first step towards developing novel clinical (e.g., assessment or intervention) tools that target hormone systems to improve on-going brain development among children and adolescents with FASD.

Project description:BackgroundRecent studies have suggested an association between prenatal paracetamol exposure and adverse neurodevelopmental outcomes in children. However, these findings may be confounded by unmeasured factors related to maternal use of paracetamol and child outcomes.ObjectiveTo examine the association between duration and timing of prenatal paracetamol exposure on parent-reported communication skills, behaviour, and temperament in preschool-aged children, with focus on the role of unmeasured confounding.MethodsWe used data from the Norwegian Mother and Child Cohort Study. Linear and generalised linear models with inverse probability weights and robust standard errors were used to quantify the association between prenatal paracetamol exposure and continuous and categorical outcomes.ResultsOf the 32 934 children included in our study, 8374 (25.4%), 4961 (15.1%), and 1791 (5.4%) were prenatally exposed to paracetamol in one, two, and three trimesters, respectively. Children exposed to paracetamol in two trimesters scored lower on shyness compared with unexposed children (β -0.62, 95% confidence interval [CI] -1.05, -0.19). Children exposed to paracetamol in three trimesters had a moderate increased risk of internalising behaviour problems (relative risk (RR) 1.36, 95% CI 1.02, 1.80) and borderline externalising behaviour problems (RR 1.22, 95% CI 0.93, 1.60) compared with unexposed children. Children exposed to paracetamol in 2nd/3rd trimester scored lower on shyness (β -0.32, 95% CI -0.66, 0.02) compared with unexposed children. Sensitivity analyses indicated that unmeasured confounders play an important role and may potentially bias the effect estimates away from the null.ConclusionsTiming of exposure and short-term use of paracetamol during pregnancy do not seem to pose any substantial risk of the outcomes examined. Although we found an association between paracetamol use in multiple trimesters and lower shyness and greater internalising behaviour in preschool-aged children, we cannot rule out chance or unmeasured confounding as possible explanations for these findings.

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Prenatal sex hormones and behavioral outcomes in children.

Publications

Prenatal sex hormones and behavioral outcomes in children.

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