Maternal Thyroid Function in Early Pregnancy Affects Child Brain Morphology

Medical visualization taken from human scanned data showing heart and brain development from the embryonic period at week 6 to the fetal period at week 16. From left to right, this composited image shows each stage of organ development from weeks 6-10 as well as week 16. At week 6 a heart tube has developed from mesodermal tissues, and the final stage of heart development is formed at week 10, meaning that the heart has two atria, two ventricles, and the blood vessels necessary for circulation. The nervous system is formed from a structure called the neural tube, which begins to form around the 25th day after conception. Once the neural tube closes, the more specific regions and structures in the brain begin to form and fall into place. Neural circuits, or connections between neurons that communicate information throughout the brain, are formed in the fetal period. All structures continue to develop, and the functionality within the brain is strengthened. The age where the brain reaches adult weight varies within the teenage years, and the brain is fully developed around the age of 25.
The association of TSH with child brain morphology differed according to gestational age at evaluation of thyroid function.

Both low and high maternal thyroid stimulating hormone (TSH) levels, particularly in early pregnancy, may be associated with a smaller volume of total grey matter and cortical grey matter in children age 9 to 12 years, according to study results published in The Lancet Diabetes & Endocrinology.

Epidemiologic studies have reported that maternal hypothyroidism is negatively associated with adverse neurodevelopmental outcomes in offspring, including low IQ, autism, schizophrenia, and attention-deficit hyperactivity disorder. In addition, there are studies reporting a relationship between maternal thyroid dysfunction might and brain morphology.

The goal of this study was to assess the impact of maternal thyroid function on child brain morphology and to explore whether this association is dependent on the timing of thyroid assessment during gestation.

The prospective cohort study was part of the Generation R Study, a population-based prospective cohort in Rotterdam, The Netherlands, that followed patients from early fetal life onward. The study included pregnant women with an expected delivery date between April 1, 2002, and January 1, 2006, with available thyroid function tests during early or mid-pregnancy (≤18 weeks of gestation). They included only mother-child pairs with available brain magnetic resonance imaging (MRI) data for the child at age 10 years.

Of 7069 women enrolled during early or midpregnancy, 1981 mother-child pairs were assessed. The study identified an inverted U-shaped association of maternal TSH with total grey matter volume (P =.007) and with cortical grey matter volume (P =.022) as assessed by offspring MRI scans.

Related Articles

The association of TSH with child total grey matter volume (P =.053) and cortical grey matter volume (P =.086) differed according to gestational age at evaluation of thyroid function. The association between maternal TSH and grey matter volume was most evident at 8 weeks gestation, while the association between TSH and child brain morphology was much less pronounced if thyroid function tests were done after the first 14 weeks of pregnancy.

The researchers acknowledged several limitations of the study, including lack of longitudinal thyroid function measurements over the course of pregnancy, possible selection bias, and limited data on pubertal status, which might affect brain morphology.

“[O]ur study shows that both a low and a high maternal thyroid function are negatively associated with child total grey matter volume and cortical grey matter volume as assessed by MRI. We show that these effects are more evident in early pregnancy with a suggested effect threshold around the 14th week of pregnancy,” concluded the researchers.

Follow @EndoAdvisor


Jansen TA, Korevaar TIM, Mulder TA, et al. Maternal thyroid function during pregnancy and child brain morphology: a time window-specific analysis of a prospective cohort [published online June 28, 2019]. Lancet Diabetes Endocrinol. doi:10.1016/S2213-8587(19)30153-6