Umbilical cord blood testosterone and childhood internalizing and externalizing behavior: a prospective study.

Monique Robinson,Jeffrey A Keelan,Peter Jacoby,Andrew J O Whitehouse,Eugen Mattes,Michael G Sawyer,Martha Hickey

doi:10.1371/journal.pone.0059991

Abstract

Antenatal testosterone exposure influences fetal neurodevelopment and gender-role behavior in postnatal life and may contribute to differences in developmental psychopathology during childhood. We prospectively measured the associations between umbilical cord blood testosterone levels at birth and childhood behavioral development in both males and females from a large population based sample. The study comprised 430 females and 429 males from the Western Australian Pregnancy Cohort (Raine) Study where umbilical cord blood had been collected. Total testosterone concentrations were determined by mass spectrometry and bioavailable testosterone (BioT) levels were calculated. At two, five, eight and ten years of age, the participants completed the Child Behavior Checklist (CBCL). Linear regression models were used to analyse the relationship between BioT concentrations (in quartiles) and CBCL scores (total, internalizing, externalizing and selected syndrome). Boys had higher mean CBCL T-scores than girls across all ages of follow-up. There was no significant relationship between cord blood BioT quartiles and CBCL total, internalizing and externalizing T-scores at age two or five to ten combined. In the syndrome score analyses, higher BioT quartiles were associated with significantly lower scores for attention problems for boys at age five, eight and ten, and greater withdrawal symptoms in pre-school girls (age five). We did not identify a consistent relationship between antenatal testosterone exposure and total, internalizing or externalizing behavioral difficulties in childhood. Higher umbilical cord BioT levels were associated with lower scores for attention problems in boys up to 10 years and more withdrawn behavior in 5-year-old girls; however, these findings were not consistent across ages and require further investigation in a larger sample.

Highlights

Both animal and human studies have reported that fetal androgen exposure during pregnancy can influence the postnatal development of sexually differentiated behaviors, with greater testosterone exposure thought to predispose to more masculine behaviors, such as aggression
Another small study (n = 34) of females affected by congenital adrenal hyperplasia (CAH), an endocrine disorder characterised by the overproduction of fetal adrenal androgens, found increased expression of autistic traits compared with relatives unaffected by CAH [3]
In the random effects model presenting the Child Behavior Checklist (CBCL) outcomes from age five to ten years combined (Table 3), we did not find a significant association between bioavailable testosterone (BioT) quartile and CBCL T-scores

Summary

Introduction

Both animal and human studies have reported that fetal androgen exposure during pregnancy can influence the postnatal development of sexually differentiated behaviors, with greater testosterone exposure thought to predispose to more masculine behaviors, such as aggression. In a small cohort of 88 preschool girls, evidence of higher antenatal testosterone exposure measured by digit ratio was found to be associated with an increased risk for hyperactivity and poorer social functioning- behavioral problems usually more common in boys [8]. Another small study (n = 34) of females affected by congenital adrenal hyperplasia (CAH), an endocrine disorder characterised by the overproduction of fetal adrenal androgens, found increased expression of autistic traits (again, usually more common in boys than girls) compared with relatives unaffected by CAH [3]

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