Abstract
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.