妊娠早期母亲亚临床甲状腺功能减退症对其后代脑发育影响的前瞻性研究

目的 研究妊娠早期母亲亚临床甲状腺功能减退症(甲减)对其20～30月龄后代智力和运动发育的影响.方法对来自沈阳市10家医院的妊娠8周左右的妇女1 761名,测定血清TSH、FT4、甲状腺过氧化物酶抗体(TPOAb)及尿碘水平.以TSH≥2.5 mIU/L为切点筛查到亚临床甲减孕妇38例,采用妊娠特异性甲状腺功能参考范围将其进一步分为两个亚组:A组(2.5 mIU/L≤TSH＜3.93 mIU/L),18例;B组(TSH≥3.93 mIU/L),20例.同时选择同一队列中30名甲状腺功能正常、TPOAb阴性的妊娠妇女作为对照组.对研究对象的后代在20～30月龄时进行智力和运动发育指数测评.结果妊娠早期母亲亚临床甲减组及A、B亚组后代平均智力评分分别比对照组低6.55、3.39和9.40分(P=0.001、P=0.125及P＜0.001),平均运动评分分别比对照组低6.31、4.35和8.07分(P=0.003、P=0.070及P=0.001).智力评分和运动评分与母亲血清TSH水平呈明显负相关(r=-0.425,P＜0.001;r=-0.394,P=0.001).多组间比较显示不同水平TSH影响后代智力和运动评分(F=9.277,P＜0.001;F=5.909,P=0.004).有序logistic回归分析显示母亲血清TSH≥3.93 mIU/L导致后代智力和运动评分降低的风险分别是对照组的8.66、6.27倍(OR=8.66,95%CI 2.72～27.57;OR=6.27,95%CI 2.03～19.34).结论采用妊娠特异性的诊断标准诊断的妊娠早期母亲亚临床甲减是其20～30月龄后代智力和运动发育评分减低的独立危险因素.

Impact of maternal subclinical hypothyroidism during the first trimester on brain development of the offspring: a prospective study

Objective To assess the effects of maternal subclinical hypothyroidism (SCH) during the first trimester on neuropsychological development of the offspring by 20-30 months. Methods In this study, 1 761 pregnant women from 10 hospitals with about 8 weeks of gestation were enrolled. Urinary iodine excretion and serum thyrotropin ( TSH ), free thyroxine ( FT4 ), and thyroid peroxidase antibody ( TPOAb ) levels were determined in all subjects. Pregnant women with SCH (TSH≥2.5 mIU/L) were divided into two subgroups using trimester-specific thyroid function reference: group A (2.5 mIU/L≤TSH＜3.93 mIU/L, 18 cases), and group B (TSH ≥3.93 mIU/L, 20 eases). Thirty euthyroid and TPOAb-negative women from the same cohort were selected as controls. Intellectual and motor development score evaluations were performed in the children by 20-30 months of age. Results Children of women with SCH and subgroups A and B had lower mean intelligence scores 6.55,3.39, and 9.40 points compared with those of the control group (P=0. 001, P=0. 125, and P＜0. 001 ); the respective mean motor scores were 6.31,4.35, and 8.07 points being lower than that of the control ( P=0. 003,P=0. 070, and P=0. 001 ). Intelligence scores and motor scores were negatively correlated with TSH levels (r=-0.425, P＜0. 001 and r=-0. 394, P=0. 001 ). Multiple group comparisons revealed that differences of TSH affected intelligence and motor scores (F=9. 277, P＜0. 001 and F=5. 909, P=0. 004). Ordinal logistic regression analysis showed that possibilities for the reduction of filial mental development index ( MDI ) and psychomotor development index ( PDI ) scores in SCH with maternal TSH levels≥3.93 mIU/L were 8.66 and 6.27 times that of controls ( OR = 8.66,95% CI 2.72-27.57, OR =6.27,95% CI 2.03-19.34 ). Conclusion Maternal elevated TSH levels diagnosed by trimester-specific reference during early gestation are independently associated with lowered filial neurodevelopment scores by 20-30 months.