Urinary Iodine Concentrations in Pregnant Women and Offspring Brain Morphology

Background: Severe maternal iodine deficiency during pregnancy leads to marked intellectual disability in the offspring. Although recent studies showed that even mild-to-moderate maternal iodine deficiency is associated with lower intelligence quotient and attention deficit hyperactivity disorder in offspring, the underlying neurobiological mechanism of these associations remains unknown. The aim of this study was to investigate the association of maternal iodine excretion during pregnancy with offspring brain morphology during pre-adolescence. Methods: This study was embedded within Generation R, a prospective population-based birth cohort in Rotterdam, the Netherlands. We included 990 mother-child pairs with data on urinary iodine concentration (UIC) and creatinine during pregnancy. The UIC was assessed at <18 and/or 18-25 weeks of gestation and offspring brain imaging data were acquired with magnetic resonance imaging (MRI) at age 10 years. We used linear regression to study the association of the iodine-to-creatinine ratio (UI/Creat) with offspring brain MRI outcomes. Results: Maternal UI/Creat during pregnancy was not consistently associated with offspring brain morphology. A low UI/Creat (<150 μg/g) during pregnancy was nominally associated with smaller total gray matter volume, but this did not survive correction for multiple testing. Also, we could not identify a linear association between continuous iodine excretion and offspring brain morphology. Instead, our results suggest a curvilinear association between UI/Creat and brain morphology. In sensitivity analyses using the World Health Organization categorization for UIC values, both low and high UI/Creat were associated with smaller total gray matter volume. Conclusions: The current study provides some but no conclusive evidence for an association of maternal iodine excretion during pregnancy with offspring brain morphology. Our results suggest that the exact definition of the reference group is important because of potential non-linear associations, which could be leveraged in future studies.