Effects of Maternal Hypothyroidism on Offspring Hippocampus and Memory

Background: Rodents with gestational thyroid-hormone (TH) deficiencies and children with congenital hypothyroidism show abnormal hippocampal development. Given that the human hippocampus starts to develop early in gestation, we asked if children born to women with hypothyroidism during pregnancy also show hippocampal abnormalities and if this is related to the severity of maternal TH insufficiency and current memory functioning. We additionally sought to determine whether effects were more prominent in anterior or posterior hippocampal subsections given these support different memory functions and have different developmental trajectories. We hypothesized that these children would have smaller than normal hippocampal volumes than controls and show memory deficits on both standardized tests and indices of everyday memory functioning. Methods: We studied 54 children aged 9 to 12 years: 30 controls and 24 HYPO cases-offspring from women diagnosed with hypothyroidism prior to or during pregnancy and treated with l-thyroxine. All children received a thorough assessment of memory functions and an MRI scan. For each child, right and left hippocampi were manually traced, and volumes of right and left hippocampi and anterior and posterior segments were determined. Results: HYPO cases showed significantly smaller right and left hippocampal volumes than controls, particularly in right posterior and left anterior segments. In HYPO children, hippocampal volumes were negatively correlated with maternal third-trimester TSH levels and positively correlated with third-trimester fT4. HYPO cases scored significantly below controls on one objective and several subjective memory indices, and these were correlated with hippocampal volumes. Conclusion: Early TH insufficiency from maternal hypothyroidism affects offspring hippocampal development and memory.