SSRIs and Persistent Pulmonary Hypertension of the Newborn (PPHN)

There’s a new study in the January 2014 issue of the BMJ:  Grigoriadis et al, Prenatal exposure to antidepressants and persistent pulmonary hypertension of the newborn: systematic review and meta-analysisThanks to Nanu Grewal for the link.

PPHN is a relatively rare condition.  The authors report that the estimated prevalence is about 1.9 per 1000 live births.  The disease is essentially a failure of the newborn’s circulatory system to switch from oxygen supply via the placental blood, to oxygen supply via the baby’s own lungs.  The condition is usually diagnosed at birth or shortly thereafter.  Symptoms include:  rapid and difficult breathing, fast heart rate, and blue skin color.  PPHN is a serious condition.  A 2010 article by Robin Steinhorn, MD, states:

“Even with appropriate therapy, the mortality for PPHN remains between 5-10%.  In addition, approximately 25% of infants with moderate or severe PPHN will exhibit significant neurodevelopmental impairment at 12-24 months.”

Delaney et al (2012) describe PPHN as “…a syndrome without either optimally effective preventative or treatment strategies,” and states that it “…remains a major cause of morbidity and mortality in neonatal centers across the globe.”

The BMJ article is a meta-analysis, combining the data from seven previous studies that examined the link between maternal use of SSRI’s and PPHN.  Here are their results:


SSRI Use Odds Ratio Confidence Interval 95% Statistical Significance
Early pregnancy 1.23 0.58-2.60 NS
Any time in pregnancy 1.55 0.79-3.04 NS
Most or all of pregnancy 3.33 1.58-7.02 S (0.002)
Late pregnancy 2.50 1.32-4.73 S (0.005)


Essentially what this means is that a woman who used SSRI’s for “most or all” of her pregnancy had a 3.33 times greater risk of delivering a child with PPHN than a woman who had not used SSRI’s.  The risk for late pregnancy use was 2.50 times greater.

Given a baseline prevalence estimate of 1.9 per 1000 births, and an odds ratio of 2.5, the expected incidence of PPHN in late-pregnancy SSRI cases would be about 4.75 (2.5 x 1.9).  This represents an excess of 2.85 cases per 1000 as compared to the general prevalence.


In the article’s abstract, the authors concluded:

“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.”

In the text of the article a more detailed analysis was offered:

“Depression during pregnancy must not be left untreated, as the potential for untoward effects is not negligible and can extend into the postpartum period. Selection of treatment is based on several factors, and antidepressant drugs may be necessary, especially in severe depressive episodes…Although the odds for persistent pulmonary hypertension of the newborn seem to be greater with the use of SSRIs later in pregnancy, despite the limitations of the original studies, the risk is still low. Results from this meta-analysis still concur with earlier statements…that fewer than about 1 infant in 100 will develop persistent pulmonary hypertension of the newborn after antenatal exposure to SSRIs. Although this condition is serious and death rates between 5% and 10% have been reported, when it is associated with other conditions (such as some congenital malformations, meconium aspiration, sepsis, and idiopathic disease), it can be managed favourably…The death rate in infants with persistent pulmonary hypertension of the newborn who have been exposed to SSRIs, however, remains unknown (although one study did report 9.1% of the infants died who were exposed to SSRIs compared with 9.5% of those who were not exposed…”

The deference to the “need” for antidepressant drugs is noteworthy.  This kind of disclaimer has become almost routine in research of this kind.

In my view the essential point of the article is that it demonstrates one more serious adverse effect of these drugs.