Lo Joan C, Rivkees Scott A, Chandra Malini, Gonzalez Joel R, Korelitz James J, Kuzniewicz Michael W
1Division of Research, Kaiser Permanente Northern California, Oakland, California.
2Division of Endocrinology, Department of Medicine, Kaiser Permanente Oakland Medical Center, Oakland, California.
Thyroid. 2015 Jun;25(6):698-705. doi: 10.1089/thy.2014.0434. Epub 2015 Apr 14.
Increasing attention has focused on the prevalence and outcomes of hyperthyroidism in pregnancy, given concerns for hepatotoxicity and embryopathy associated with antithyroid drugs (ATDs).
In an integrated health care delivery system, we examined the prevalence of thyrotoxicosis and gestational ATD use (propylthiouracil [PTU] or methimazole [MMI]) in women with delivered pregnancies from 1996 to 2010. Birth outcomes were compared among all infants and those born to mothers with diagnosed thyrotoxicosis or ATD therapy during gestation, with examination of ATD-associated hepatotoxicity and congenital malformations in the latter subgroups.
Among 453,586 mother-infant pairs (maternal age 29.7±6.0 years, 57.1% nonwhite), 3.77 per 1000 women had diagnosed thyrotoxicosis and 1.29 per 1000 had gestational ATD exposure (86.5% PTU, 5.1% MMI, 8.4% both). Maternal PTU-associated hepatotoxicity occurred with a frequency of 1.80 per 1000 pregnancies. Infants of mothers with diagnosed thyrotoxicosis (odds ratio [OR] 1.28, 95% confidence interval [CI 1.05-1.55]) or gestational ATD use (OR 1.31 [1.00-1.72]) had an increased risk of preterm birth compared to those born to mothers without thyrotoxicosis or ATD. The risk of neonatal intensive care unit (NICU) admission was also higher with maternal thyrotoxicosis (OR 1.30 [1.07-1.59]) and ATD exposure (OR 1.64 [CI 1.26-2.13]), adjusting for prematurity. Congenital malformation rates were low and similar among infants born to mothers with thyrotoxicosis or ATD exposure (30-44 per 1000 infants).
Gestational ATD exposure occurred in 1.29 per 1000 mother-infant pairs while a much larger number had maternal diagnosed thyrotoxicosis but no drug exposure during pregnancy. Infants of mothers with gestational ATD use or diagnosed thyrotoxicosis were more likely to be preterm and admitted to the NICU. The rates of congenital malformation were low for mothers diagnosed with thyrotoxicosis and did not differ by ATD use. Among women with gestational PTU therapy, the frequency of PTU-associated hepatotoxicity was 1.8 per 1000 delivered pregnancies. These findings from a large, population-based cohort provide generalizable estimates of maternal and infant risks associated with maternal thyrotoxicosis and related pharmacotherapy.
鉴于对与抗甲状腺药物（ATD）相关的肝毒性和胚胎病的担忧，甲状腺功能亢进症在妊娠中的患病率及结局受到越来越多的关注。
在一个综合医疗保健服务系统中，我们调查了1996年至2010年分娩的孕妇中甲状腺毒症的患病率以及妊娠期ATD的使用情况（丙硫氧嘧啶[PTU]或甲巯咪唑[MMI]）。比较了所有婴儿以及母亲在妊娠期被诊断为甲状腺毒症或接受ATD治疗的婴儿的出生结局，并对后一组亚群中与ATD相关的肝毒性和先天性畸形进行了检查。
在453,586对母婴（母亲年龄29.7±6.0岁，57.1%为非白人）中，每1000名女性中有3.77人被诊断为甲状腺毒症，每1000人中有1.29人在妊娠期接触过ATD（86.5%为PTU，5.1%为MMI，8.4%两者都接触过）。与母亲使用PTU相关的肝毒性在每1000次妊娠中的发生率为1.80。与未患甲状腺毒症或未接触ATD的母亲所生的婴儿相比，母亲被诊断为甲状腺毒症（比值比[OR]1.28，95%置信区间[CI 1.05 - 1.55]）或在妊娠期使用ATD（OR 1.31[1.00 - 1.72]）的婴儿早产风险增加。调整早产因素后，母亲患甲状腺毒症（OR 1.30[1.07 - 1.59]）和接触ATD（OR 1.64[CI 1.26 - 2.13]）时，新生儿重症监护病房（NICU）收治率也更高。甲状腺毒症或接触ATD的母亲所生婴儿的先天性畸形率较低且相似（每千名婴儿中有30 - 44例）。
每1000对母婴中有1.29对在妊娠期接触过ATD，而更多的母亲被诊断为甲状腺毒症但在孕期未接触药物。妊娠期使用ATD或被诊断为甲状腺毒症的母亲所生的婴儿更易早产并入住NICU。被诊断为甲状腺毒症的母亲的先天性畸形率较低，且不因是否使用ATD而异。在接受妊娠期PTU治疗的女性中，与PTU相关的肝毒性在每1000次分娩中的发生率为1.8。这些来自大型人群队列的研究结果提供了与母亲甲状腺毒症及相关药物治疗相关的母婴风险的可推广估计值。
