Background

Vitamin D deficiency is common in pregnancy. Vitamin D plays an important role in the developing brain, and deficiency may impair childhood behavioral development.

Objectives

This study examined the relationship between gestational 25(OH)D concentrations and childhood behavior in the Environmental influences on Child Health Outcomes (ECHO) Program.

Methods

Mother-child dyads from ECHO cohorts with data available on prenatal (first trimester through delivery) or cord blood 25(OH)D and childhood behavioral outcomes were included. Behavior was assessed using the Strengths and Difficulties Questionnaire or the Child Behavior Checklist, and data were harmonized using a crosswalk conversion. Linear mixed-effects models examined associations of 25(OH)D with total, internalizing, and externalizing problem scores while adjusting for important confounders, including age, sex, and socioeconomic and lifestyle factors. The effect modification by maternal race was also assessed.

Results

Early (1.5-5 y) and middle childhood (6-13 y) outcomes were examined in 1688 and 1480 dyads, respectively. Approximately 45% were vitamin D deficient [25(OH)D < 20 ng/mL], with Black women overrepresented in this group. In fully adjusted models, 25(OH)D concentrations in prenatal or cord blood were negatively associated with externalizing behavior T-scores in middle childhood [-0.73 (95% CI: -1.36, -0.10) per 10 ng/mL increase in gestational 25(OH)D]. We found no evidence of effect modification by race. In a sensitivity analysis restricted to those with 25(OH)D assessed in prenatal maternal samples, 25(OH)D was negatively associated with externalizing and total behavioral problems in early childhood.

Conclusions

This study confirmed a high prevalence of vitamin D deficiency in pregnancy, particularly among Black women, and revealed evidence of an association between lower gestational 25(OH)D and childhood behavioral problems. Associations were more apparent in analyses restricted to prenatal rather than cord blood samples. Interventions to correct vitamin D deficiency during pregnancy should be explored as a strategy to improve childhood behavioral outcomes.

Prenatal antidepressant exposure has been associated with increased risk for neurodevelopmental disorders in childhood, including autism spectrum disorder (ASD). The current study utilized multi-cohort data from the Environmental influences on Child Health Outcomes (ECHO) program (N = 3129) to test for this association, and determine whether the association remained after adjusting for maternal prenatal depression and other potential confounders. Antidepressants and a subset of selective serotonin reuptake inhibitors (SSRIs) were examined in relation to binary (e.g., diagnostic) and continuous measures of ASD and ASD related traits (e.g., social difficulties, behavior problems) in children 1.5 to 12 years of age. Child sex was tested as an effect modifier. While prenatal antidepressant exposure was associated with ASD related traits in univariate analyses, these associations were statistically non-significant in models that adjusted for prenatal maternal depression and other maternal and child characteristics. Sex assigned at birth was not an effect modifier for the prenatal antidepressant and child ASD relationship. Overall, we found no association between prenatal antidepressant exposures and ASD diagnoses or traits. Discontinuation of antidepressants in pregnancy does not appear to be warranted on the basis of increased risk for offspring ASD.