Emily S. Barrett

Psychosocial Stress and Pregnancy Outcome

This article is intended to help clinicians better understand the ever-expanding body of research on whether psychosocial stress (both acute and chronic) is linked to 2 major adverse pregnancy outcomes: preterm birth and low birth weight. We summarize the existing literature and then review assessment tools commonly used to diagnose various types of psychosocial stress, with attention to how and when assessments should be made. After discussing the physiologic mechanisms hypothesized to underlie these relationships, we examine the range of existing interventions aimed at reducing psychosocial stress and review their efficacy at improving birth outcomes. Future directions for prevention of adverse pregnancy outcomes are discussed and suggest that an entirely new approach may be necessary.

Overconfidence in wargames: experimental evidence on expectations, aggression, gender and testosterone

Summary Overconfidence has long been noted by historians and political scientists as a major cause of war. However, the origins of such overconfidence, and sources of variation, remain poorly understood. Mounting empirical studies now show that mentally healthy people tend to exhibit psychological biases that encourage optimism, collectively known as ‘positive illusions’. Positive illusions are thought to have been adaptive in our evolutionary past because they served to cope with adversity, harden resolve, or bluff opponents. Today, however, positive illusions may contribute to costly conflicts and wars. Testosterone has been proposed as a proximate mediator of positive illusions, given its role in promoting dominance and challenge behaviour, particularly in men. To date, no studies have attempted to link overconfidence, decisions about war, gender, and testosterone. Here we report that, in experimental wargames: (i) people are overconfident about their expectations of success; (ii) those who are more overconfident are more likely to attack; (iii) overconfidence and attacks are more pronounced among males than females; and (iv) testosterone is related to expectations of success, but not within gender, so its influence on overconfidence cannot be distinguished from any other gender specific factor. Overall, these results constitute the first empirical support of recent theoretical work linking overconfidence and war.

Prenatal phthalate exposures and neurobehavioral development scores in boys and girls at 6-10 years of age.

Background: There is concern over potential neurobehavioral effects of prenatal phthalate exposures, but available data are inconsistent. Objectives: We examined associations between prenatal urinary concentrations of phthalate metabolites and neurobehavioral scores among children. Methods: We measured phthalate metabolite concentrations in urine samples from 153 pregnant participants in the Study for Future Families, a multicenter cohort study. Mothers completed the Child Behavior Checklist when the children were 6–10 years of age. We estimated overall and sex-specific associations between phthalate concentrations and behavior using adjusted multiple regression interaction models. Results: In boys, concentrations of monoisobutyl phthalate were associated with higher scores for inattention (β = 0.27; 95% CI: 0.04, 0.50), rule-breaking behavior (β = 0.20; 95% CI: 0.01, 0.38), aggression (β = 0.34; 95% CI: 0.09, 0.59), and conduct problems (β = 0.39; 95% CI: 0.20, 0.58), whereas the molar sum of di(2-ethylhexyl) phthalate metabolites was associated with higher scores for somatic problems (β = 0.15; 95% CI: 0.03, 0.28). Higher monobenzyl phthalate concentrations were associated with higher scores for oppositional behavior (β = 0.16; 95% CI: 0.01, 0.32) and conduct problems (β = 0.21; 95% CI: 0.06, 0.37) in boys, but with reduced anxiety scores in girls (β = –0.20; 95% CI: –0.39, –0.01). In general, the associations reported above were close to the null among girls. Model coefficients represent the difference in the square root–transformed outcome score associated with a 1-unit increase in log-transformed metabolites. Conclusions: Our results suggest associations between exposure to certain phthalates in late pregnancy and behavioral problems in boys. Given the few studies on this topic and methodological and population differences among studies, additional research is warranted. Citation: Kobrosly RW, Evans S, Miodovnik A, Barrett ES, Thurston SW, Calafat AM, Swan SH. 2014. Prenatal phthalate exposures and neurobehavioral development scores in boys and girls at 6–10 years of age. Environ Health Perspect 122:521–528; http://dx.doi.org/10.1289/ehp.1307063

Anogenital distance is related to ovarian follicular number in young Spanish women: a cross-sectional study.

BackgroundIn animals, anogenital distance (AGD) at birth reflects androgen levels during pregnancy and predicts adult AGD. Little is known about AGD in relation to female reproductive characteristics in humans, a question this study was designed to explore.MethodsWe used multiple linear and logistic regression analyses to model the relationships between adult female reproductive system characteristics (e.g. ovarian morphology, menstrual cycle) and two measures of AGD [anus-fourchette (AGDAF) and anus-clitoris (AGDAC)] in 100 college-age volunteers in Spain. Ovarian morphology was classified as having < 6 or ≥ 6 follicles per ovary.ResultsBoth AGD measures were positively associated with ovarian follicle number, with AGDAF being more strongly associated. Women in the upper tertile of the AGDAF and AGDAC distributions were more likely to have ≥ 6 ovarian follicles [OR: 6.0 (95% CI 2.0, 17.6) and 3.0 (95% CI 1.1, 8.6), respectively] compared to women in the lowest tertile.ConclusionsIncreased follicular recruitment has been related to excess androgen exposure in utero in toxicological studies. Our results suggest that the androgenic environment during early fetal life may influence reproductive system development, including AGD, in human females.

Prenatal bisphenol A exposure and maternally reported behavior in boys and girls.

Prenatal exposure to gonadal hormones plays a major role in the normal development of the male and female brain and sexually dimorphic behaviors. Hormone-dependent differences in brain structure and function suggest that exposure to exogenous endocrine disrupting chemicals may be associated with sex-specific alterations in behavior. Bisphenol A (BPA) is an environmental chemical that has been shown to alter estrogen, androgen, and thyroid hormone signaling pathways. Epidemiological and experimental studies suggest associations between prenatal exposure to BPA and child behavior, however data are inconsistent, and few studies have examined school age children. We examined BPA concentration in spot urine samples from women at mean 27 weeks of pregnancy in relation to child behavior assessed at age 6-10 years using the parent-completed Child Behavior Checklist (CBCL). We report associations between maternal BPA urinary concentrations and several CBCL scores in 153 children (77 boys and 76 girls). We observed a significant interaction between maternal urinary BPA and sex for several behaviors (externalizing, aggression, Anxiety Disorder, Oppositional/Defiant Disorder and Conduct Disorder traits), but no significant associations between BPA and scores on any CBCL scales. However in analyses restricted to children of mothers with detectable prenatal urinary BPA (n=125), BPA was associated with moderately increased internalizing and externalizing behaviors, withdrawn/depressed behavior, somatic problems, and Oppositional/Defiant Disorder traits in boys. In addition we observed a significant interaction between BPA and sex for several behaviors (externalizing, withdrawn/depressed, rule-breaking, Oppositional/Defiant Disorder traits, and Conduct Disorder traits). These results suggest that prenatal exposure to BPA may be related to increased behavior problems in school age boys, but not girls.

Prenatal exposure to stressful life events is associated with masculinized anogenital distance (AGD) in female infants

In animal models, prenatal stress programs reproductive development in the resulting offspring, however little is known about effects in humans. Anogenital distance (AGD) is a commonly used, sexually dimorphic biomarker of prenatal androgen exposure in many species. In rodents, prenatally stressed males have shorter AGD than controls (suggesting lower prenatal androgen exposure), whereas prenatally stressed females have longer AGD than controls (suggesting greater prenatal androgen exposure). Our objective was to investigate the relationship between stressful life events in pregnancy and infant AGD. In a prospective cohort study, pregnant women and their partners reported exposure to stressful life events during pregnancy. Pregnancies in which the couple reported 4+ life events were considered highly stressed. After birth (average 16.5 months), trained examiners measured AGD in the infants (137 males, 136 females). After adjusting for age, body size and other covariates, females born to couples reporting high stress had significantly longer (i.e. more masculine) AGD than females born to couples reporting low stress (p=0.015). Among males, high stress was weakly, but not significantly, associated with shorter AGD. Our results suggest prenatal stress may masculinize some aspects of female reproductive development in humans. More sensitive measures of prenatal stress and additional measures of reproductive development are needed to better understand these relationships and clarify mechanisms.

Socioeconomic factors and phthalate metabolite concentrations among United States women of reproductive age.

INTRODUCTION Relatively little is known about the socioeconomic correlates of phthalate metabolite urine concentrations among the general population, exposures of increasing public health concern, particularly for women of reproductive age. METHODS We pooled data from the 2001-2008 cycles of the National Health and Nutrition Examination Survey to examine the associations between phthalate metabolite concentrations (including the molar sum of four di-2-ethylhexyl phthalate (DEHP) metabolites, the molar sum of two dibutyl phthalate (DBP) metabolites, and metabolites of benzylbutyl phthalate (BzBP) and diethyl phthalate (DEP)) with socioeconomic indicators (including ethnicity, education, income, and food security status) among women 20 to 39 years age. We also derived a socioeconomic status summary measure using factor analysis and investigated its associations with metabolite concentrations. RESULTS In fully adjusted models, the lowest quartile of overall socioeconomic status was associated with 1.83 (95% CI=1.54-2.17) times the concentrations of mono-benzyl phthalate (MBzP), and 0.72 (95% CI=0.54-0.98) times the concentrations of (molar sum) DEHP metabolites compared with the highest quartile of overall socioeconomic status. This latter association was driven primarily by educational attainment. All Non-White ethnicities combined had 1.24 (95% CI=1.09-1.40) times the concentrations of (molar sum) DBP metabolites, 1.32 (95% CI=1.12-1.56) times the mono-ethyl phthalate (MEP) concentrations, and 0.82 (95% CI=0.71-0.96) the concentrations of MBzP of Non-Hispanic Whites. CONCLUSIONS Biomarkers of phthalate exposure vary with socioeconomic factors in women of reproductive age in the United States. Given the public health concern surrounding phthalate exposure, more research is needed to elucidate the reasons for these differences.

Phthalate exposure and reproductive hormone concentrations in pregnancy

Some phthalate chemicals can affect hormone physiology in utero, resulting in adverse reproductive health outcomes in animal models. It is unknown whether these exposures are related to circulating maternal hormone concentrations during pregnancy. We used multivariate linear regression to estimate associations between phthalate metabolite concentrations and concurrent serum-free and total testosterone and estradiol (E2) levels in 180 pregnant women in the Study for Future Families. We also examined associations between prenatal serum hormone concentrations and anogenital outcome in infants. All analyses were adjusted for appropriate confounding variables. Total testosterone, free testosterone, and E2 concentrations ranged from 8 to 406 ng/dl, 0.03 to 1.2 ng/dl, and 529 to 40 600 pg/ml respectively. We observed an inverse association between log-sum di-2-ethylhexyl phthalate (DEHP) metabolite concentrations and lower log-total testosterone concentrations (-0.15, 95% CI -0.26, -0.04) and log-free testosterone (-0.15, 95% CI -0.27, -0.03). This relationship persisted regardless of fetal sex. Similarly, we observed an inverse association between log monobutyl phthalate (MBP) concentrations and log-total and -free testosterone concentrations in women carrying male fetuses. Monoethyl phthalate (MEP) concentrations were positively associated with log-total and -free testosterone concentrations in women carrying male fetuses (0.09, 95% CI 0.003, 0.17 and 0.10, 95% CI 0.01, 0.19 respectively). Prenatal hormone concentrations were not significantly associated with infant anogenital outcomes. Our preliminary data suggest that DEHP metabolite, MBP, and MEP exposures during pregnancy are associated with prenatal sex steroid hormone concentrations, but sex steroid hormone concentrations were not associated with infant reproductive outcomes.

Marriage and motherhood are associated with lower testosterone concentrations in women

Testosterone has been hypothesized to modulate the trade-off between mating and parenting effort in males. Indeed, evidence from humans and other pair-bonded species suggests that fathers and men in committed relationships have lower testosterone levels than single men and men with no children. To date, only one published study has examined testosterone in relation to motherhood, finding that mothers of young children have lower testosterone than non-mothers. Here, we examine this question in 195 reproductive-age Norwegian women. Testosterone was measured in morning serum samples taken during the early follicular phase of the menstrual cycle, and marital and maternal status were assessed by questionnaire. Mothers of young children (age ≤3) had 14% lower testosterone than childless women and 19% lower testosterone than women who only had children over age 3. Among mothers, age of the youngest child strongly predicted testosterone levels. There was a trend towards lower testosterone among married women compared to unmarried women. All analyses controlled for body mass index (BMI), age, type of testosterone assay, and time of serum sample collection. This is the first study to look at testosterone concentrations in relation to marriage and motherhood in Western women, and it suggests that testosterone may differ with marital and maternal status in women, providing further corroboration of previous findings in both sexes.

Anogenital distance and penile width measurements in The Infant Development and the Environment Study (TIDES): methods and predictors

BACKGROUND Anogenital distance (AGD) is an androgen responsive anatomic measurement that may have significant utility in clinical and epidemiological research studies. We describe development of standardized measurement methods and predictors of AGD outcomes. METHODS We examined infants born to 758 participants in The Infant Development and the Environment Study (TIDES cohort) in four clinical centers in 2011-2013. We developed and implemented a detailed training protocol that incorporated multiple quality control (QC) measures. In males, we measured anoscrotal distance (AGDAS), anopenile distance (AGDAP), and penile width (PW) and in females, anofourchette distance (AGDAF,) and anoclitoral distance (AGDAC). A single examiner obtained three repetitions of all measurements, and a second examiner obtained independent measurements for 14% of infants. We used the intra-rater ICC to assess within-examiner variability and the inter-rater ICC to assess between-examiner variability. We used multivariable linear regression to examine predictors of AGD outcomes including: gestational age at birth, birth weight, gestational age, several measures of body size, race, maternal age, and study center. RESULTS In the full TIDES cohort, including 758 mothers and children, significant predictors of AGD and PW included: age at exam, gestational age at birth, weight-for-length Z-score, maternal age and study center. In 371 males, the mean (SD) AGDAS, AGDAP, and PW were 24.7 (4.5), 49.6 (5.9), and 10.8 (1.3) mm, respectively. In 387 females, the mean (SD) AGDAF and AGDAC were 16.0 (3.2) mm and 36.7 (3.8) mm, respectively. The intra-examiner ICC and inter-examiner ICC averaged over all subjects and examiners were between 0.89-0.92 and 0.69-0.84 respectively. CONCLUSIONS Our study confirms that with appropriate training and quality control measures, AGD and PW measurements can be performed reliably and accurately in male and female infants. In order for reliable interpretation, these measurements should be adjusted for appropriate covariates in epidemiologic analysis.