母体产前甲状腺过氧化物酶抗体阳性可能与学龄前儿童的认知发育存在性别特异性关联

Sex-specific associations between maternal thyroid peroxidase antibodies and cognitive development in preschool children: A prospective cohort study

母亲甲状腺过氧化物酶抗体与学龄前儿童认知发育之间的性别特异性关联：一项前瞻性队列研究

Author: Yuzhu Teng, Jixing Zhou, Linlin Zhu, Mengting Yang, Xue Ru, Juan Tong, Yan Han, Shuangqin Yan, Fangbiao Tao, Kun Huang

Source: Thyroid

DOI: 10.1089/thy.2023.0612

Abstract:

Background: An association between maternal thyroid dysfunction throughout pregnancy and subsequent risk of neurodevelopmental abnormalities in offspring has been demonstrated. However, the potential effects of maternal thyroid autoimmunity on neurodevelopment in the absence of maternal hypothyroidism remain unclear. Therefore, in this study, we explored the association between maternal thyroid peroxidase antibody (TPOAb) positivity and cognitive development in preschool children.

Methods: A total of 1849 mother-child pairs were recruited from the Ma'anshan Birth Cohort Study. During the follow-up period, an electrochemiluminescence immunoassay was used to retrospectively measure serum TPOAb levels in pregnant women. The cognitive development of preschool children was evaluated by using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition. A growth mixture model was used to fit the trajectory of TPOAb. Multiple linear regression and logistic regression models were used to explore the associations between the developmental trajectory of TPOAb-positivity at different gestational periods and the cognitive development of preschool children by sex.

Results: A total of 1849 mother-child pairs (mean [SD] age: 26.7 [3.6] years) were enrolled in the final study. Maternal TPOAb positivity in the first trimester was associated with a risk of below-average processing speed index in girls (OR: 2.07; 95% CI: 1.06~4.01) and below-average full-scale intelligence quotient (FSIQ) in boys (OR: 2.36; 95% CI: 1.10~5.05). Maternal TPOAb positivity in the third trimester was associated with below-average working memory (WMI) (OR: 2.51; 95% CI: 1.02~6.20) in girls. In girls, the WMI (β= -3.17, 95% CI: -5.82~ -0.52), fluid reasoning index (FRI) (β= -4.49, 95% CI: -7.18~ -1.80), and FSIQ score (β= -2.43, 95% CI: -4.77~ -0.08) decreased, whereas in mothers, the level of lgTPOAb increased during pregnancy.

Conclusions: Positive maternal thyroid peroxidase antibody levels during pregnancy may be associated with poorer cognitive development in preschool children. These findings require independent confirmation in other populations.

Keywords: TPOAb exposure, Pregnancy, Cognition, Sex-specific effect, Dynamic changes

摘要：

背景：母体在妊娠期的甲状腺功能障碍与后代神经发育异常风险之间存在关联。然而，在母体无甲状腺功能减退的情况下，母体甲状腺自身免疫对神经发育的潜在影响仍不清楚。因此，在本研究中，我们探讨了母体甲状腺过氧化物酶抗体（TPOAb）阳性与学龄前儿童认知发育之间的关系。

方法：马鞍山出生队列共招募了1849对母子。在随访期间，采用电化学发光免疫分析法回溯性测定孕妇血清 TPOAb 水平。学龄前儿童的认知发育采用韦氏幼儿智力量表第四版中文版进行评估。采用增长混合模型来拟合 TPOAb 的变化轨迹。采用多元线性回归和逻辑回归模型探讨了不同孕期TPOAb阳性的发展轨迹与不同性别学龄前儿童认知发育之间的关联。

结果：共有 1849 对母子（平均 [SD] 年龄：26.7 [3.6] 岁）纳入了最终研究。孕早期母体 TPOAb 阳性与女童低于平均水平的加工速度指数（OR：2.07；95% CI：1.06~4.01）和男童低于平均水平的总智商（FSIQ）（OR：2.36；95% CI：1.10~5.05）有关。母体 TPOAb 阳性与女童低于平均水平的工作记忆（WMI）有关（OR：2.51；95% CI：1.02~6.20）。女童的工作记忆指数（WMI）（β= -3.17，95% CI：-5.82~ -0.52）、流体推理指数（FRI）（β= -4.49，95% CI：-7.18~ -1.80）和总智商分数（β= -2.43，95% CI：-4.77~ -0.08）随着母体妊娠期的 lgTPOAb 水平上升，而逐渐下降。

结论：孕期母体甲状腺过氧化物酶抗体阳性可能与较差的学龄前儿童认知发育有关。这些发现需要在其他人群中得到独立证实。