Maternal thyroid function in early pregnancy and child attention-deficit hyperactivity disorder: an individual-participant meta-analysis

Levie, Deborah; Korevaar, Tim I. M.; Mulder, Tessa A.; Bath, Sarah C.; Dineva, Mariana; Lopez-Espinosa, Maria-José; Basterrechea, Mikel; Santa Marina, Loreto; Rebagliato, Marisa; Sunyer Deu, Jordi; Rayman, Margaret P.; Tiemeier, Henning; Peeters, Robin P.; Guxens Junyent, Mònica

doi:http://dx.doi.org/10.1089/thy.2018.0794

Maternal thyroid function in early pregnancy and child attention-deficit hyperactivity disorder: an individual-participant meta-analysis

Citation

Levie D, Korevaar TIM, Mulder TA, Bath SC, Dineva M, Lopez-Espinosa MJ, Basterrechea M, Santa-Marina L, Rebagliato M, Sunyer J, Rayman MP, Tiemeier H, Peeters RP, Guxens M. Maternal thyroid function in early pregnancy and child attention-deficit hyperactivity disorder: an individual-participant meta-analysis. Thyroid. 2019; 29(9):1316-26. DOI: 10.1089/thy.2018.0794

Abstract

Background: Thyroid hormone is essential for optimal fetal brain development. Evidence suggests that both low and high maternal thyroid hormone availability may have adverse effects on child neurodevelopmental outcomes, but the effect on behavioral problems remains unclear. We studied the association of maternal thyrotropin (TSH) and free thyroxine (fT4) concentrations during the first 18 weeks of pregnancy with child attention-deficit hyperactivity disorder (ADHD). Methods: A total of 7669 mother-child pairs with data on maternal thyroid function and child ADHD were selected from three prospective population-based birth cohorts: INfancia y Medio Ambiente (INMA; N = 1073, Spain), Generation R (N = 3812, The Netherlands), and Avon Longitudinal Study of Parents and Children (ALSPAC; N = 2784, United Kingdom). Exclusion criteria were multiple pregnancy, fertility treatment, usage of medication affecting the thyroid, and pre-existing thyroid disease. We used logistic regression models to study the association of maternal thyroid function with the primary outcome, ADHD, assessed via the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria by parents and/or teachers at a median child age of 4.5 to 7.6 years, and with the secondary outcome, an ADHD symptom score above the 90th percentile. Effect modification by gestational age and sex was tested with interaction terms and stratified analyses. Results: Overall, 233 (3%) children met the criteria for ADHD. When analyzed continuously, neither fT4 nor TSH was associated with a higher risk of ADHD (odds ratio [OR] 1.1, 95% confidence interval [CI 1.0-1.3], p = 0.060 and OR 0.9 [CI 0.9-1.1], p = 0.385, respectively) or with high symptom scores. When investigating effect modification by gestational age, a higher fT4 was associated with symptoms above the 90th percentile but only in the first trimester (for fT4 per 1 SD: OR 1.2 [CI 1.0-1.4], p = 0.027). However, these differential effects by gestational age were not consistent. No significant effect modification by sex was observed. Conclusions: We found no clear evidence of an association between maternal thyroid function and child ADHD.