ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Thyroid Endocrinology
Effect of Maternal Isolated Hypothyroxinemia in the First Trimester on Offspring Neurodevelopment: A Prospective Cohort Study
Provisionally accepted
- Peking University International Hospital, Beijing, China
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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 (2nd 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.
Keywords: Attention Deficit Hyperactivity Disorder, Autism Spectrum Disorder, Hypothyroxinemia, Intelligence, offspring, Pregnancy
Received: 29 Oct 2025; Accepted: 29 Jan 2026.
Copyright: © 2026 Du, Xu, Yuan and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jing Du
Xiaomei Zhang
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