Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: population based cohort study from the five Nordic countries

Abstract

Objective To assess whether maternal use of selective serotonin reuptake inhibitors (SSRIs) increases the risk of persistent pulmonary hypertension in the newborn, and whether such an effect might differ between specific SSRIs.Design Population based cohort study using data from the national health registers.Setting Denmark, Finland, Iceland, Norway, and Sweden, 1996-2007. Participants More than 1.6 million infants born after gestational week 33.Main outcome measures Risks of persistent pulmonary hypertension of the newborn associated with early and late exposure to SSRIs during pregnancy and adjusted for important maternal and pregnancy characteristics. Comparisons were made between infants exposed and not exposed to SSRIs.Results Around 30 000 women had used SSRIs during pregnancy and 11 014 had been dispensed an SSRI later than gestational week 20. Exposure to SSRIs in late pregnancy was associated with an increased risk of persistent pulmonary hypertension in the newborn: 33 of 11 014 exposed infants (absolute risk 3 per 1000 liveborn infants compared with the background incidence of 1.2 per 1000); adjusted odds ratio 2.1 (95% confidence interval 1.5 to 3.0). The increased risks of persistent pulmonary hypertension in the newborn for each of the specific SSRIs (sertraline, citalopram, paroxetine, and fluoxetine) were of similar magnitude. Filling a prescription with SSRIs before gestational week 8 yielded slightly increased risks: adjusted odds ratio 1.4 (95% confidence interval 1.0 to 2.0). ConclusionsThe risk of persistent pulmonary hypertension of the newborn is low, but use of SSRIs in late pregnancy increases that risk more than twofold. The increased risk seems to be a class effect. IntroductionPersistent pulmonary hypertension of the newborn is a life threatening condition that occurs in up to 2 per 1000 liveborn infants and most often in those born full term or post term. [1][2][3] In this condition the pulmonary vascular resistance fails to decrease after birth and the ductus arteriosus must remain open to ensure circulation. Persistent pulmonary hypertension of the newborn and persistent fetal circulation are often used synonymously. 4 The pathophysiology is not clearly mapped out, but persistent pulmonary hypertension of the newborn might result from constricted pulmonary vasculature or because the vasculature is hypoplastic or remodelled.3 The constricted form is most commonly caused by meconium aspiration, the hypoplastic form can be seen in connection with diaphragmatic hernia, and presumably certain drugs can cause a remodelling of the vasculature.Depression during pregnancy is common, and estimated rates vary from 7% to 25%. 5 6 Use of selective serotonin reuptake inhibitors (SSRIs) is increasing among pregnant women, and use in late pregnancy may be a risk factor for persistent pulmonary hypertension of the newborn.7 During the past 15 years six studies have specifically assessed this association, with inconsistent findings from no association to a sixfold increased risk. [7][8][...

Transcranial magnetic stimulation for treatment of major depression during pregnancy: a review

“…14 Although some meta-analyses have provided risk estimates that have not been confirmed at the same magnitude in some other studies, we do know that SSRI use may be related, for example, to pulmonary hypertension; although the risk of persistent pulmonary hypertension of the newborn is low, use of SSRIs in late pregnancy increases that risk more than twofold. 15 One meta-analysis found that paroxetine and fluoxetine are associated with a small, but significantly increased risk of major malformations and paroxetine in particular is associated with cardiac malformation. 14 While a systematic review did not show increased risk of heart defects or minor malformations, it did detect an increased risk of major malformations and miscarriage following the use of SSRIs during pregnancy.…”

Fetal Effects of Selective Serotonin Reuptake Inhibitor Treatment During Pregnancy: Immediate and Longer Term Child Outcomes

“…Infants exposed to SSRIs in the final trimester should be considered at risk of adaptation symptoms and should be monitored accordingly. The critical condition of persistent pulmonary hypertension is reported across a number of large cohorts to be increased across SSRIs, with Kieler et al 55 suggesting that there is a class effect. Later exposure is reported to carry the increased risk.…”

“…SSRIs Six studies investigated the prevalence of persistent pulmonary hypertension following prenatal exposure to SSRIs [52][53][54][55][56][57] and four demonstrated an association [53][54][55][56] ( 55 demonstrated that the risk of persistent pulmonary hypertension was similar across all SSRIs studied (sertraline, citalopram, paroxetine, and fluoxetine) and concluded that this indicated a treatment class effect. No other identified studies investigated the prevalence of persistent pulmonary hypertension following exposure to specific SSRI treatment types.…”

Nonsteroidal Antiinflammatory Drugs in Late Pregnancy and Persistent Pulmonary Hypertension of the Newborn

“…[10][11][12][13]37,38 One recent study of the association between selective serotonin reuptake inhibitors and PPHN risk from 5 Nordic countries observed no association between NSAID use and PPHN. 39 The main limitation of the current study is the reliance on maternal recall for information about exposure status. Several factors suggest, however, that recall bias is an unlikely explanation for our study results.…”