妊娠合并甲状腺功能亢进症患者抗甲状腺药物治疗后对其新生儿先天畸形的影响

目的探讨妊娠合并甲状腺功能亢进症（甲亢）患者抗甲状腺药物（ATDs）治疗对其新生儿先天畸形的影响。方法采用回顾性分析方法对1983年1月1日-2003年12月31日在北京协和医院分娩的100例妊娠合并甲亢患者及其101例新生儿的临床资料进行研究。根据妊娠合并甲亢患者的甲状腺功能（甲功）状态及服用ATDs的情况对其新生儿先天畸形发生率、影响因素进行分析。结果（1）妊娠合并甲亢患者分娩的101例新生儿中,合并先天畸形7例,新生儿先天畸形发生率为6．9％,显著高于同期出生的新生儿先天畸形发生率的0．9％（212／22765）。其相对危险性为同期出生新生儿的7．9倍（P〈0．01）。（2）101例新生儿中,其母孕早期合并甲功亢进52例,新生儿先天畸形5例,先天畸形发生率为9．6％（5／52）;其母孕早期甲功正常49例,新生儿先天畸形2例,先天畸形发生率为4．1％（2／49）,两者新生儿先天畸形发生率比较,差异无统计学意义（P〉0．05）。（3）其母孕早期服用甲巯咪唑的12例新生儿中,合并新生儿先天畸形5例,先天畸形发生率为41．7％;其母孕早期服用丙基硫氧嘧啶的28例新生儿中,合并新生儿先天畸形1例,先天畸形发生率为3．6％;其母孕早期未服用ATDs的61例新生儿中,合并新生儿先天畸形1例,先天畸形发生率为1．6％。3者之间新生儿先天畸形发生率比较,差异有统计学意义（P〈0．01）。其中服用甲巯咪唑患者的新生儿先天畸形发生率显著高于服用丙基硫氧嘧啶者（P〈0．01）和未用药者（P〈0．01）。妊娠合并甲亢孕早期服用甲巯咪唑患者新生儿发生先天畸形的危险性,为服用丙基硫氧嘧啶患者的19．3倍;为未服用ATDs患者的42．9倍。对数线性模型分析显示,妊娠合并甲亢患者孕早期服用不同种类的ATDs,对新生儿先天畸形的形成存在显著的差异（P=0．0003）。结论妊娠合并甲亢患者其新生儿发生先天畸形的危险性增加。妊娠合并甲亢患者孕早期服用甲巯咪唑可能是导致新生儿先天畸形的主要因素之一。因此,妊娠合并甲亢患者应避免选用甲巯咪唑,以减少发生新生儿先天畸形的危险性。

Effects of maternal hyperthyroidism and antithyroid drug therapy on congenital malformation of newborn infants

Objective To evaluate the relationship between the incidence of congenital malformations of newborns and maternal hyperthyroidism with antithyroid drug (ATD) therapy during pregnancy.Methods The clinical data of 100 cases of pregnant women with hyperthyroidism and their 101 offsprings born in Peking Union Medical College Hospital during 1983-2003 were analyzed retrospectively. According to the maternal thyroid function, and antithyroid drugs taken during the first trimester of pregnancy, subjects were divided into different groups. The incidence of congenital malformations of newborns and risk factors, especially the effects of maternal hyperthyroidism with antithyroid drug therapy were analysed.Results The prevalence of congenital malformation in infants born to mothers who had hyperthyroidism during pregnancy (6.9%, 7/101) was significantly higher than that of all the infants born in the same hospital during the same period (0.9%, 212/22 765, P <0.01). The difference of the incidence of malformed infants born to mothers with hyperthyroidism (9.6%, 5/52) or euthyroidism (4.1%, 2/49) during the first trimester was not significant ( P >0.05). The incidence of malformed infants whose mothers received methimazole (MMI; 41.7%, 5/12)was significantly higher than that of mothers treated with propylthiouracil (PTU)(3.6%,1/28) and without ATDs(1.6%,1/61) , respectively ( P <0.01). The Loglinear model analyses showed that mothers receiving MMI during the first trimester of pregnancy was independent risk factor for the increased incidence of malformation of their infants (L.R. square= 15.668, P =0.0003). Conclusions The risk of congenital malformation in infants whose mothers take MMI during the first trimester may be increased. Therefore, we suggest that MMI should not be used as a choice of drug in treatment of pregnant women with hyperthyroidism.