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Review
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Prenatal Exposure to Antidepressants and Persistent Pulmonary Hypertension of the Newborn: Systematic Review and Meta-Analysis

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Review

Prenatal Exposure to Antidepressants and Persistent Pulmonary Hypertension of the Newborn: Systematic Review and Meta-Analysis

Sophie Grigoriadis et al. BMJ.

Abstract

Objective: To examine the risk for persistent pulmonary hypertension of the newborn associated with antenatal exposure to antidepressants.

Design: Systematic review and meta-analysis.

Data sources: Embase, Medline, PsycINFO, and CINAHL from inception to 30 December 2012.

Eligibility: English language studies reporting persistent pulmonary hypertension of the newborn associated with exposure to antidepressants. Two independent reviewers extracted data and assessed the quality of each article.

Results: Of the 3077 abstracts reviewed, 738 papers were retrieved and seven included. All seven studies were above our quality threshold. Quantitative analysis was only possible for selective serotonin reuptake inhibitors (SSRIs). Although exposure to SSRIs in early pregnancy was not associated with persistent pulmonary hypertension of the newborn (odds ratio 1.23, 95% confidence interval 0.58 to 2.60; P=0.58), exposure in late pregnancy was (2.50, 1.32 to 4.73; P=0.005). Effects were not significant for any of the moderator variables examined, including study design, congenital malformations, and meconium aspiration. It was not possible to assess for the effect of caesarean section, body mass index, or preterm delivery. The absolute risk difference for development of persistent pulmonary hypertension of the newborn after exposure to SSRIs in late pregnancy was 2.9 to 3.5 per 1000 infants; therefore an estimated 286 to 351 women would need to be treated with an SSRI in late pregnancy to result in an average of one additional case of persistent pulmonary hypertension of the newborn.

Conclusions: The risk of persistent pulmonary hypertension of the newborn seems to be increased for infants exposed to SSRIs in late pregnancy, independent of the potential moderator variables examined. A significant relation for exposure to SSRIs in early pregnancy was not evident. Although the statistical association was significant, clinically the absolute risk of persistent pulmonary hypertension of the newborn remained low even in the context of late exposure to SSRIs.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work [other than the granting agencies as above]; in the past three years, SG has received research grant support from the Canadian Institutes of Health Research and the Ontario Ministry of Health for the conduct of this study, and has received honorariums as a consultant, member of an advisory committee, or for lectures from Servier and Lundbeck, and research grant support from the CR Younger Foundation, outside the submitted work; LER has received research grant support from the Canadian Institutes of Health Research and the Ontario Ministry of Health and Long-Term Care for the conduct of this study; and MS has received grants from the Canadian Institutes of Health Research, Ontario Mental Health Foundation, Natural Sciences and Engineering Research Council of Canada, grants and personal fees from Society for Women’s Health Research, grants from Pfizer and Eli Lilly, grants and personal fees from Lundbeck, personal fees from AstraZeneca, Bayer Canada, and Servier, all outside of the submitted work]; no other relationships or activities that could appear to have influenced the submitted work.

Figures

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Fig 1 Identification of independent studies for inclusion in meta-analysis (adapted from PRISMA 2009 flow diagram30)
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Fig 2 Exposure to selective serotonin reuptake inhibitors in early pregnancy and risk of persistent pulmonary hypertension of the newborn: meta-analysis of all studies
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Fig 3 Exposure to selective serotonin reuptake inhibitors in late pregnancy and risk of persistent pulmonary hypertension of the newborn: meta-analysis of all studies

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