Parsing risk for the use of selective serotonin reuptake inhibitors in pregnancy.
Parsing risk for the use of selective serotonin reuptake inhibitors in pregnancy.
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解析妊娠期使用选择性血清素再摄取抑制剂的风险。
DOI：
10.1176/appi.ajp.2008.08111703
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发表时间：
2009
期刊：
影响因子：
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通讯作者：
Yonkers,KimberlyA
中科院分区：
文献类型：
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作者：
Yonkers,KimberlyA
许多报告探讨了与母亲使用抗抑郁药，特别是选择性5-羟色胺再摄取抑制剂（SSRIs）有关的胎儿风险。这个庞大的数据库在SSRIs和胎儿畸形方面产生了不一致的结果（1），导致一位专家指出SSRIs不是“主要的致畸剂”（2）。然而，并发症可能包括其他新生儿和产妇的结果。为了说明，早产与母亲使用抗抑郁药有关，尽管这可能会缩短分娩不到1周（3）。本期杂志上的一篇文章讨论了在怀孕期间服用SSRIs的妇女中发现的妊娠期高血压和先兆子痫的风险较高。Toh等人(4)研究了一组来自斯隆流行病学中心的妇女，她们分娩的婴儿没有畸形。研究护士获得有关分娩结局、健康习惯、药物使用、身体状况和医疗并发症的信息。然而，研究人员在分娩后采访了受试者，没有查看病历。包括199名在怀孕前2个月内使用SSRIs的妇女，可能在怀孕期间。92名妇女在第一个三个月后继续服药。非暴露组包括5，532名未服用SSRIs的孕妇。该分析控制了人口统计学变量、妊娠、多胎妊娠、不孕治疗、糖尿病、孕前体重和有害物质使用。20周后高血压的发病发生在那些没有使用SSRI的人中的9%和在研究期间的某个时候使用SSRI的199名妇女中的19%。在整个怀孕期间继续使用SSRIs的女性比例为26%。可能的先兆子痫分别有2.4%和3.7%的妇女使用和不使用SSRI，但如果妇女在妊娠早期继续使用SSRI，则发生率为15（相对危险度= 4.9; 95%置信区间[CI]= 2.7-8.8）。重要的是传播新的信息，例如这些数据，因为它们可能说明母亲面临重大风险。然而，提供背景和了解报告的局限性也至关重要。妊娠期高血压是一种相对常见的异质性疾病，包括妊娠20周后新发高血压的妇女。相比之下，先兆子痫的特征是高血压（收缩压> 140 mmHg和舒张压> 90 mmHg，间隔至少4至6小时[根据两次测量]），伴有蛋白尿（24小时内> 300 mg）（5）。大约6%的女性会患上先兆子痫。在四分之一的病例中，病情将是严重的，并与血压显著升高、分娩生长受限的婴儿以及其他母体器官系统（包括肝、肾和血液系统）的潜在受累相关。不幸的是，如果没有详细的病历审查，就不可能确认Toh等人研究中受影响的妇女确实患有这种疾病。风险因素包括既存的慢性疾病，如糖尿病、血栓形成障碍、风湿病和肾病。增加风险的个人特征、临床因素和习惯是肥胖、多胎妊娠、单胎产次、双胎产次、高龄产妇、酗酒、其他药物滥用（非尼古丁）和配子供体。
Anumber of reports have explored the fetal risks related to maternal use of antidepressant agents, particularly selective serotonin reuptake inhibitors (SSRIs). This considerable database has yielded inconsistent findings with regard to SSRIs and fetal malformations (1), leading one expert to state that SSRIs are not “major teratogens”(2). However, complications may include other neonatal and maternal outcomes. To illustrate, preterm delivery has been linked with maternal use of antidepressants, although this may shorten delivery by less than 1 week (3). One article in this issue of the Journal discusses higher risks of gestational hypertension and preeclampsia found among women who took SSRIs during pregnancy. Toh et al.(4) studied a cohort of women assembled from the Slone Epidemiology Center who delivered nonmalformed infants. Study nurses obtained information on birth outcomes, health habits, medication use, physical conditions, and medical complications. However, researchers interviewed subjects after delivery and did not review medical charts. Included were 199 women who used SSRIs during the 2 months prior to pregnancy and possibly during pregnancy. Ninety-two women continued medication beyond the first trimester. The nonexposed group included 5,532 pregnant women who did not take SSRIs. The analysis controlled for demographic variables, gravidity, multifetal gestation, infertility treatment, diabetes, prepregnancy weight, and hazardous substance use. The onset of hypertension after 20 weeks occurred in 9% of those who did not use a SSRI and 19% of the 199 women who used a SSRI at some point during the study interval. The rate for women who continued SSRIs throughout pregnancy was 26%. Possible preeclampsia was experienced by 2.4% and 3.7% of women who did and did not use SSRIs, respectively, but the rate was 15% if a woman continued treatment with a SSRI beyond the first trimester (relative risk= 4.9; 95% confidence interval [CI]= 2.7–8.8).It is important to disseminate new information, such as these data, since they may illustrate an important risk for mothers. However, it is also critical to provide context and understand the limitations of the report. Gestational hypertension is a relatively common heterogeneous condition and includes women who develop new onset hypertension after the 20th week of pregnancy. In contrast, preeclampsia is characterized by hypertension (systolic blood pressure> 140 mmHg and diastolic blood pressure> 90 mmHg at least 4 to 6 hours apart [according to two measurements]) accompanied by proteinuria (> 300 mg within 24 hours)(5). About 6% of women will develop preeclampsia. In one-quarter of cases, the condition will be severe and associated with marked elevations in blood pressure, delivery of a growth restricted infant, and potential involvement of other maternal organ systems, including hepatic, renal, and hematological systems. Unfortunately, without detailed medical chart reviews, it is impossible to confirm that the affected women in the Toh et al. study truly had the disease. Risk factors include pre-existing chronic medical conditions such as diabetes, thrombophilias, rheumatologic illnesses, and renal disease. Personal characteristics, clinical factors, and habits that increase risk are obesity, multifetal gestation, primiparity, primipaternity, older maternal age, alcohol abuse, other drug abuse (non-nicotine), and gamete dona-