Level 2: Mid-level evidence 


Persistent pulmonary hypertension of the newborn (PPHN) is a life-threatening condition in which the infant fails to transition from high pulmonary vascular resistance and low pulmonary blood flow characteristic of fetal circulation to low pulmonary vascular resistance and high pulmonary blood flow of postnatal circulation.

It occurs in 0.1%-0.2% of live births, with death in 10%-20% of cases (N Engl J Med. 2006;354:579-587). 


To date, evidence for a link between maternal use of selective serotonin reuptake inhibitors (SSRIs) for depression and risk of PPHN has been inconsistent. In December 2011, the FDA recommended that providers not alter their current practice for treating depression during pregnancy. However, a large retrospective cohort study, published one month after the FDA statement, strongly suggests that SSRI exposure does increase PPHN risk (BMJ. 2012;344:d8012.


A total of 1,618,255 infants born after 33 weeks gestational age in five Nordic countries were evaluated for maternal use of any SSRIs. Mothers were stratified by date of SSRI exposure (at >20 weeks gestational age, prior to pregnancy or before eight weeks gestational age, or no exposure). PPHN developed in 0.29% of infants with later pregnancy exposure, 0.19% of infants with early pregnancy exposure, and 0.12% of infants with no exposure.

Later exposure to any SSRI was associated with a significant increase in PPHN risk compared with no exposure (adjusted hazard ratio 2.1, 95% CI 1.5-3, NNH 416-1,666). Early exposure was associated with a trend toward increased risk. Results of subgroup analyses for individual SSRIs were similar to the overall analysis. 


While there now appears to be a significantly increased risk, the condition is rare and the absolute risk remains low. These risks must be weighed against the benefits of treating the depression and compared with alternative options for the mother.



Alan Ehrlich, MD, is a deputy editor for DynaMed, in Ipswich, Mass., and assistant clinical professor in Family Medicine, University of Massachusetts Medical School in Worcester.

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