According to the results of a population-based cohort study published early online in the British Medical Journal, use of selective serotonin reuptake inhibitors (SSRIs) during late pregnancy may increase the risk of persistent pulmonary hypertension of the newborn (PPHN); the overall risk however remains low.

The authors note that PPHN, a life-threatening condition that occurs in up to 2 per 1000 liveborn infants, is where the pulmonary vascular resistance fails to decrease after birth, and therefore the ductus arteriosus must remain open to ensure circulation.  Several risk factors have been identified, and it is thought that use of certain drugs may cause remodelling of the vasculature.    

Use of SSRIs by pregnant women is increasing, and this may be a risk factor for PPHN.  Previous research assessing this association has been conflicting, and the authors of the current cohort study sought to evaluate this further.  They used data from national health registers in Denmark, Finland, Iceland, Norway and Sweden to assess the association between SSRI use during pregnancy and PPHN, looking at the class overall and also exposure to specific SSRIs.

A total of 1,618,255 singleton births (born after 33 weeks) registered in the participating countries between 1996 and 2007 were included in the study; 11,014 (0.7%) of these had filled a prescription for an SSRI during late pregnancy (from 140 days after the start of pregnancy until birth) and 17,053 (1.1%) in early pregnancy only (from three months before the start of pregnancy until a pregnancy length of 55 days).  The main outcome was PPHN diagnosed within seven days of birth; potential confounders considered included maternal smoking, age, BMI, purchased NSAIDs, antidiabetes drugs, diseases recorded during pregnancy, among others. 

The main results reported were as follows:

• Exposure to SSRIs in late pregnancy was associated with an increased risk of persistent pulmonary hypertension in the newborn, with an absolute risk of 3 per 1000 liveborn infants compared with the background incidence of 1.2 per 1000 (adjusted odds ratio [OR] of 2.1; 95% CI 1.5 to 3.0).

• The increased risks of PPHN were similar for each of the specific SSRIs studied (sertraline, citalopram, paroxetine, and fluoxetine), with ORs ranging from 2 to 3 [the risk estimate for escitalopram was lower, but imprecise, and no infants with PPHN had been exposed to fluvoxamine].

• Exposure to the other antidepressants with an effect on serotonin activity or norepinephrine activity (e.g. clomipramine, venlafaxine, imipramine, amitriptyline, duloxetine, trazodone, nefazodone, moclobemide) was also associated with an increased risk of PPHN (OR 2.9, 95% CI 0.9 to 8.9).

• There was a slightly increased risk of PPHN for those women who filled a prescription for an SSRI before gestational week 8 (adjusted OR 1.4; 95% CI 1.0 to 2.0); the ORs associated with exposures to specific SSRIs varied from 0.3 to 1.9.  Exposure to other antidepressants with an effect on serotonin activity or norepinephrine activity during early pregnancy only was not associated with an increased risk of PPHN.

The authors note that despite the large number of included births, only 33 infants exposed to an SSRI in late pregnancy had a diagnosis of PPHN.  They go on to discuss some of the potential limitations to their study, including information on drug intake during pregnancy (exposure was related to dispensed drugs and they were not necessarily taken), and they discuss the possible mechanism by which SSRIs may affect pulmonary vasculature and this cause PPHN.  They recommend caution when treating pregnant women with SSRIs, stating that the risks of PPHN need to be weighed against those of relapse of depression and neonatal abstinence syndrome if therapy is interrupted.