孕20周内母体甲状腺功能与婴幼儿体格及神经精神发育剂量反应关系的前瞻性队列研究

Dose-response relationship between maternal thyroid hormones in the first twenty weeks and physical and neuropsychological development of infants: A prospective cohort study in China

目的通过前瞻性队列研究,评价孕20周内母体甲状腺功能相关激素指标水平与新生儿出生体格和婴幼儿期神经精神发育水平之间的剂量反应关系。方法在安徽省马鞍山市建立945名孕妇队列,留取队列孕妇血清标本,使用电化学发光免疫法检测孕妇血清甲状腺功能相关激素水平;收集孕妇的一般社会人口统计学资料,测量新生儿出生体格和婴幼儿神经精神的发育情况等。结果孕期母体血清促甲状腺激素(TSH)水平处于不同百分段的孕妇所分娩的活产儿出生时身长和头围差异均有统计学意义(P<0.05)。孕期母体TSH水平<P5和≥P95的新生儿出生身长和头围比母体TSH水平位于P25~P75的新生儿偏低,差异均有统计学意义(P<0.05)。新生儿出生头围与母体TSH-Z分呈倒"U"形分布模式(Y=33.940+0.003X-0.109X2,F=4.685,P=0.009)。孕期母体TSH水平处于不同百分段的孕妇所分娩后代在出生后18~30个月时的精神发展指数(MDI)差异有统计学意义(P<0.05),孕期母体TSH水平≥P90的婴儿MDI评价水平比母体TSH水平P25~P75的婴儿低6.39分(95%CI:2.29~10.49;P=0.002)。婴幼儿18~30个月时MDI与母体TSH-Z分亦呈倒"U"形分布模式(Y=103.249-1.524X-0.939X2,F=6.616,P=0.001)。结论孕妇血清TSH水平与新生儿出生时身长、头围,以及婴幼儿18~30个月时MDI关系密切;孕期母体TSH-Z分与新生儿头围和婴幼儿18~30个月时MDI均呈现倒"U"形的分布模式。

Objective To study the dose-response relationship between maternal thyroid hormone levels in the first twenty weeks of pregnancy and the infant physical and neuropsychological development. Methods In this prospective cohort study, a total of 945 women and their children were included. Maternal serum samples during first half of the pregnancy were collected and analyzed for levels of thyroid hormones by using the electro-chemiluminescence immunoassay. Maternal social demographic information was collected by using the a self-administered questionnaire. Physical measurements of newborns and neuropsychological evaluation of infants were performed by doctors of maternal and child health care. Results The differences in newborns’ birth length and head circumference were significant among the newborns of mothers with different percentiles of maternal serum (thyroid-stimulating hormone, TSH) levels (P<0.05). Newborns with maternal TSH level ≥P95 or <P5 had significantly lower birth length and birth head circumference, compared with the newborns with maternal TSH level between P25-P75 (P<0.05). Newborns’ birth head circumferences showed an inverted U-shaped association with maternal serum TSH level (Y=33.940+0.003X-0.109X2, F=4.685, P=0.009). The difference in mental development index (MDI) of the infants at 18-30 months were significant among the infants of mothers with different percentiles of maternal serum TSH level (P<0.05). Infants with maternal TSH level ≥P90 showed lower MDI (6.39, 95%CI: 2.29-10.49, P=0.002) compared with the infants with maternal TSH level between P25-P75. Infant’s MDI at 18- 30 months also showed an inverted U-shaped association with maternal serum TSH level (Y=103.249-1.524X-0.939X2, F=6.616, P=0.001). Conclusions Maternal TSH level was associated with newborn’s birth length, birth head circumference and infant’s MDI at 18-30 months. Newborn’s birth head circumference and infant’s MDI at 18-30 months showed an inverted U-shaped association with maternal serum TSH-Z score.