Antipsychotic Use in Pregnancy and the Risk for Congenital Malformations.
Antipsychotic Use in Pregnancy and the Risk for Congenital Malformations.
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DOI：
10.1001/jamapsychiatry.2016.1520
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发表时间：
2016-09-01
期刊：
影响因子：
25.8
通讯作者：
Bateman BT
中科院分区：
文献类型：
--
作者：
Huybrechts KF;Hernández-Díaz S;Patorno E;Desai RJ;Mogun H;Dejene SZ;Cohen JM;Panchaud A;Cohen L;Bateman BT
在过去的十年中，妊娠期间使用抗精神病药（AP）的频率大约翻了一番。然而，关于它们对发育中的胎儿的安全性知之甚少，并且已经提出了与先天性畸形的潜在关联的担忧。检查与妊娠早期暴露于AP相关的先天性畸形和心脏畸形的风险。这一全国范围内的1 360 101名孕妇参加了医疗补助与活产婴儿构成的怀孕队列嵌套在医疗补助分析提取数据库，其中包括从2000年1月1日至2010年12月31日的数据。参与者从末次月经前3个月到分娩后至少1个月参加医疗补助。使用广义线性模型估计相对风险（RR），并对倾向评分进行精细分层，以控制潜在的精神疾病和其他潜在的混杂因素。数据在2015年进行了分析。在头三个月使用AP，这是器官形成的病因相关时期。在分娩后的前90天内发现的主要先天性畸形和心脏畸形。在1341715例符合入选标准（女性平均[SD]年龄，24.02 [5.77]岁）的妊娠中，9258例（0.69%）在妊娠早期至少填写了1份非典型AP处方，733例（0.05%）在妊娠早期至少填写了1份典型AP处方。总体而言，每1000例未暴露于AP的新生儿中有32.7例（95% CI，32.4-33.0）被诊断为先天性畸形，而每1000例暴露于非典型AP的新生儿中有44.5例（95% CI，40.5-48.9），每1000例暴露于典型AP的新生儿中有38.2例（95% CI，26.6-54.7）。未校正的分析表明，非典型AP的总体畸形风险增加（RR，1.36; 95% CI，1.24-1.50），但典型AP的风险没有增加（RR，1.17; 95% CI，0.81-1.68）。经混杂因素校正后，非典型AP的RR降至1.05（95%CI，0.96-1.16），典型AP的RR降至0.90（95%CI，0.62-1.31）。心脏畸形的结果相似。对于检查的单个药物，发现利培酮的总体畸形（RR，1.26; 95%CI，1.02-1.56）和心脏畸形（RR，1.26; 95%CI，0.88-1.81）风险略有增加，与测量的混杂因素无关。这项大型研究的证据表明，在怀孕早期使用AP通常不会有意义地增加先天性畸形的风险，特别是心脏畸形。使用利培酮时观察到的畸形风险小幅增加需要进一步研究。
The frequency of antipsychotic (AP) use during pregnancy has approximately doubled during the last decade. However, little is known about their safety for the developing fetus, and concerns have been raised about a potential association with congenital malformations. To examine the risk for congenital malformations overall and cardiac malformations associated with first-trimester exposure to APs. This nationwide sample of 1 360 101 pregnant women enrolled in Medicaid with a live-born infant constituted the pregnancy cohort nested in the Medicaid Analytic Extract database, which included data from January 1, 2000, to December 31, 2010. Participants were enrolled in Medicaid from 3 months before their last menstrual period through at least 1 month after delivery. Relative risks (RRs) were estimated using generalized linear models with fine stratification on the propensity score to control for the underlying psychiatric disorders and other potential confounders. Data were analyzed during 2015. Use of APs during the first trimester, the etiologically relevant period for organogenesis. Major congenital malformations overall and cardiac malformations identified during the first 90 days after delivery. Of the 1 341 715 pregnancies that met inclusion criteria (mean [SD] age of women, 24.02 [5.77] years), 9258 (0.69%) filled at least 1 prescription for an atypical AP and 733 (0.05%) filled at least 1 prescription for a typical AP during the first trimester. Overall, 32.7 (95% CI, 32.4–33.0) per 1000 births not exposed to APs were diagnosed with congenital malformations compared with 44.5 (95% CI, 40.5–48.9) per 1000 births exposed to atypical and 38.2 (95% CI, 26.6–54.7) per 1000 births exposed to typical APs. Unadjusted analyses suggested an increased risk for malformations overall for atypical APs (RR, 1.36; 95% CI, 1.24–1.50) but not for typical APs (RR, 1.17; 95% CI, 0.81–1.68). After confounding adjustment, the RR was reduced to 1.05 (95% CI, 0.96–1.16) for atypical APs and 0.90 (95% CI, 0.62–1.31) for typical APs. The findings for cardiac malformations were similar. For the individual agents examined, a small increased risk in overall malformations (RR, 1.26; 95% CI, 1.02–1.56) and cardiac malformations (RR, 1.26; 95% CI, 0.88–1.81) was found for risperidone that was independent of measured confounders. Evidence from this large study suggests that use of APs early in pregnancy generally does not meaningfully increase the risk for congenital malformations overall or cardiac malformations in particular. The small increase in the risk for malformations observed with risperidone requires additional study.