Selective serotonin reuptake inhibitors and venlafaxine in early pregnancy and risk of birth defects: population based cohort study and sibling design.
Selective serotonin reuptake inhibitors and venlafaxine in early pregnancy and risk of birth defects: population based cohort study and sibling design.
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DOI：
10.1136/bmj.h1798
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发表时间：
2015-04-17
期刊：
影响因子：
--
通讯作者：
Nørgaard M
中科院分区：
文献类型：
--
作者：
Furu K;Kieler H;Haglund B;Engeland A;Selmer R;Stephansson O;Valdimarsdottir UA;Zoega H;Artama M;Gissler M;Malm H;Nørgaard M
目的评估妊娠早期使用特异性选择性5-羟色胺再摄取抑制剂（SSRIs）或文拉法辛是否与出生缺陷风险增加相关，重点是心血管出生缺陷，即使考虑生活方式或其他家族混杂因素。设计多国人群队列研究，包括同胞对照设计。设置北欧人口（丹麦，芬兰，冰岛，挪威和瑞典）确定从全国健康登记在1996年至2010年的不同时期。人口完整的研究队列包括生育230万活产单胎的女性。同胞队列包括2288例单胎活产。同胞对照分析包括暴露于SSRIs或文拉法辛和出生缺陷不一致的同胞对。主要结果测量出生缺陷的患病率，包括心脏缺陷的亚型。出生缺陷的优势比：logistic和条件logistic回归分析。结果在36772例妊娠早期暴露于SSRI的婴儿中，出生缺陷发生率为3.7%（n=1357），而在2266875例未暴露的婴儿中，出生缺陷发生率为3.1%（n=1357），协变量校正比值比为1.13（95%可信区间1.06 ~ 1.20）。在同胞对照分析中，调整后的比值比降至1.06（0.91至1.24）。在协变量校正分析中，使用任何SSRI或文拉法辛的任何心源性出生缺陷的比值比为1.15（95%置信区间1.05至1.26），在同胞对照分析中为0.92（0.72至1.17）。对于房间隔缺损和室间隔缺损，协变量校正的比值比为1.17（1.05至1.31）。暴露于任何SSRI或文拉法辛增加右心室流出道梗阻缺陷的患病率，协变量校正比值比为1.48（1.15至1.89）。在同胞对照分析中，任何SSRIs或文拉法辛暴露与右心室流出道梗阻缺陷的校正比值比降至0.56（0.21至1.49）。结论：在这项大型北欧研究中，未发现宫内暴露于SSRIs或文拉法辛的婴儿总体心脏出生缺陷患病率显著增加。尽管暴露婴儿的间隔缺损和右心室流出道缺损的患病率较高，但在兄弟姐妹对照分析中缺乏相关性，这表明这些药物具有致畸作用。
Objective To assess whether use of specific selective serotonin reuptake inhibitors (SSRIs) or venlafaxine in early pregnancy is associated with an increased risk of birth defects, with emphasis on cardiovascular birth defects even when accounting for lifestyle or other familial confounding. Design Multicountry population based cohort study, including sibling controlled design. Setting Nordic population (Denmark, Finland, Iceland, Norway, and Sweden) identified from nationwide health registers at different periods in 1996-2010. Population The full study cohort included women giving birth to 2.3 million live singletons. The sibling cohort included 2288 singleton live births. The sibling controlled analyses included sibling pairs who were discordant for exposure to SSRIs or venlafaxine and birth defects. Main outcome measure Prevalence of birth defects, including subtypes of cardiac defects. Odds ratio of birth defects from logistic and conditional logistic regression. Results Among 36 772 infants exposed to any SSRI in early pregnancy, 3.7% (n=1357) had a birth defect compared with 3.1% of 2 266 875 unexposed infants, yielding a covariate adjusted odds ratio of 1.13 (95% confidence interval 1.06 to 1.20). In the sibling controlled analysis the adjusted odds ratio decreased to 1.06 (0.91 to 1.24). The odds ratios for any cardiac birth defect with use of any SSRI or venlafaxine were 1.15 (95% confidence interval 1.05 to 1.26) in the covariate adjusted analysis and 0.92 (0.72 to 1.17) in the sibling controlled analysis. For atrial and ventricular septal defects the covariate adjusted odds ratio was 1.17 (1.05 to 1.31). Exposure to any SSRI or venlafaxine increased the prevalence of right ventricular outflow tract obstruction defects, with a covariate adjusted odds ratio of 1.48 (1.15 to 1.89). In the sibling controlled analysis the adjusted odds ratio decreased to 0.56 (0.21 to 1.49) for any exposure to SSRIs or venlafaxine and right ventricular outflow tract obstruction defects. Conclusions In this large Nordic study no substantial increase was found in prevalence of overall cardiac birth defects among infants exposed to SSRIs or venlafaxine in utero. Although the prevalence of septal defects and right ventricular outflow tract defects was higher in exposed infants, the lack of an association in the sibling controlled analyses points against a teratogenic effect of these drugs.
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DOI：
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发表时间：
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影响因子：
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作者：
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发表时间：
2010-02-01
影响因子：
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作者：
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通讯作者：
de Jong-van den Berg, Lolkje T. W.
影响因子：
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作者：
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