Subclinical Hypothyroidism with Negative for Thyroid Peroxidase Antibodies in Pregnancy: Intellectual Development of Offspring

Background: The adverse impact of maternal negative TPOAb of gestational subclinical hypothyroidism (SCH-TPOAb(-)) on the development of the offspring has not yet been clearly identified. A lingering controversy exists over the treatment of SCH-TPOAb(-) diagnosed during pregnancy. Therefore, this study was designed to evaluate the intellectual development of children of mothers who had SCH-TPOAb(-).Methods: A number of 139 children were recruited; 112 children were born to SCH TPOAb(-) and 27 children were born to euthyroid TPOAb(-) mothers. Based on the mothers' thyrotropin (TSH) levels during pregnancy and whether or not they received levothyroxine (LT4) treatment, the children were assigned to four groups: Group A (2.5 mIU/L < TSH <= 4.0 mIU/L, n = 31) and Group B (4.0 mIU/L < TSH <= 10.0 mIU/L, n = 26), whose mothers were treated with LT4 before eight gestational weeks, and Group C (2.5 mIU/L < TSH <= 4.0 mIU/L, n = 27) and Group D (4.0 mIU/L < TSH <= 10.0 mIU/L, n = 28), whose mothers received no treatment. A total number of 27 children whose mother's serum TSH was <2.5 mIU/L and were TPOAb(-) during their pregnancy served as the control group (Group E). The intellectual development of two-year-old children was assessed and compared using the Gesell Development Diagnosis Scale.Results: The developmental quotient (DQ) in Group D was 8.67 lower than this in Group E (p < 0.001). More specifically, gross motor quotient, fine motor quotient, adaptability quotient (ABQ), language quotient (LQ), and individual social behavior quotient (ISBQ) of DQ in Group D were significantly lower than those in Group E. No significant differences were observed in DQ among Group A, Group B, Group C, and Group E (p > 0.05). Spearman's rank correlation analysis showed that DQ, FMQ, ABQ, LQ, and ISBQ were significantly negatively correlated with the TSH level (r = -0.417, -0.253, -0.273, -0.436, and -0.272; p < 0.05). In addition, multivariate logistic regression analysis revealed that mothers' education (short education), mothers' education (medium education), and TSH level (4.0 mIU/L < TSH <= 10.0 mIU/L) were both risk factors affecting the intellectual development of the offspring (p < 0.05).Conclusion: The effects of the intellectual development of the offspring with SCH-TPOAb(-) are related to the level of TSH. Standardized treatment for SCH-TPOAb(-) pregnant women before eight gestational weeks, whose TSH level was from 4.0 to 10.0 mIU/L, may significantly improve the intellectual development levels of the approximately two-year-old offspring. Although our study was a historical cohort study, the data analyzed provide the foundation for further investigation. Further prospective intervention trials with large numbers of participants are needed to confirm our conclusions. The Clinical Trial Registration number is 2021-K-84-02.