Umbilical Cord Blood Testosterone and Childhood Internalizing and Externalizing Behavior: A Prospective Study

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umbilical cord BioT levels were associated with lower scores for attention problems in boys up to 10 years and more withdrawn behavior in 5-year-old girls; however, these findings were not consistent across ages and require further investigation in a larger sample.

Emotional and behavioral adjustment in 4 to 11-year-old boys and girls with classic congenital adrenal hyperplasia and unaffected siblings

“…as assessed with the SDQ. This implication of the present study concurs with a prior study showing no strong or consistent relationships between umbilical cord blood testosterone and emotional or behavioral problems in typically-developing young children (Robinson et al, 2013) and also concurs with prior research showing no differences in emotional or behavioral problems between children and adolescents with CAH and their unaffected relatives (Berenbaum et al, 2004). Moreover, on average, both girls with CAH and unaffected sisters in the current study showed increased externalizing and psychosocial problems in comparison with girls in the general population, suggesting that social influences, such as familial processes or social stigma, play a stronger role than endocrine influences in the development of psychological difficulties in these children.…”

Adult digit ratio (2D:4D) is not related to umbilical cord androgen or estrogen concentrations, their ratios or net bioactivity

“…We have recently reported that higher cord testosterone concentrations are associated with behavioural problems in early childhood. Attention difficulties in males and withdrawal symptoms in females were both negatively related to cord blood testosterone levels [39]. Together, these data suggest that umbilical cord blood is a valid method for examining early-life sex steroid exposure.…”

“…First, Lutchmaya and colleagues analysed males and females together, and although sex was controlled in the analyses, there is emerging evidence that males and females respond differently to circulating sex steroid concentrations [53], as evidenced by different associations identified for males and females [19,25,27,39,55]. Therefore, males and females should be separated in association analyses.…”

“…However, there is increasing recognition from experimental studies that the effect of prenatal sex steroid exposure on postnatal development is not restricted to early fetal development and that sex steroid levels in the final trimester also contribute to fetal development [41,56]. Furthermore, evidence from studies examining relationships between umbilical cord sex steroids and subsequent development [10,19,22,23,39,55], indicate that these sex steroid concentrations are informative markers for childhood development. Currently, umbilical cord blood is the only practical means of assessing fetal sex steroid concentrations during uncomplicated pregnancies [16,18,44].…”

Effects of Prenatal Leydig Cell Function on the Ratio of the Second to Fourth Digit Lengths in School-Aged Children

“…On the other hand, umbilical cord blood is obtained immediately after delivery, and its hormone levels are broadly considered to reflect the hormonal environment of the fetus at late gestation [ 9 , 10 ]. Previous studies have been performed using cord blood to investigate the relationship between fetal hormonal exposure and human development [ 11 – 13 ].…”