Effect of maternal isolated hypothyroxinemia in the first trimester on offspring neurodevelopment: a prospective cohort study

Objective This study aimed to examine the effect of maternal isolated hypothyroxinemia (IH) during early pregnancy on the neuropsychological development of the offspring. Methods This single-center prospective cohort study included 100 mother–child pairs, with 50 pairs in the IH group and an equal number in the euthyroid group. Levels of free thyroxine, thyroid-stimulating hormone, and thyroid peroxidase antibody in maternal serum were measured during the first trimester. Offspring neurodevelopment was evaluated using the Chinese Developmental Scale for Children Aged 0–6 Years (2 nd Edition), Conners Parent Symptom Questionnaire, and Social Responsiveness Scale (SRS). Results After adjusting for confounding factors, multiple linear regression analysis indicated that maternal IH in the first trimester was significantly associated with a decreased developmental quotient in the offspring (adjusted β = −3.28, 95% CI: −5.09 to −1.47, P < 0.001). The highest association was observed in the language domain (adjusted β = −5.72, 95% CI: −8.00 to −3.43, P < 0.001). Moreover, first-trimester IH exposure was linked to increased scores on the offspring’s impulsive–hyperactive behavior (adjusted β = 0.38, 95% CI: 0.16–0.60, P = 0.001) and hyperactivity index (adjusted β = 0.23, 95% CI: 0.06–0.41, P = 0.011). In addition, the offspring’s social awareness (adjusted β = 1.21, 95% CI: 0.10–2.31, P = 0.035) and social communication (adjusted β = 3.01, 95% CI: 0.50–5.53, P = 0.021) subscale scores as well as the total SRS score (adjusted β = 6.51, 95% CI: 0.33–12.69, P = 0.042) were elevated. Conclusion Maternal IH in the first trimester is associated with lower intellectual developmental scores and higher scores on screening scales for symptoms related to attention-deficit/hyperactivity disorder and autism spectrum disorder in the offspring.