SSRIs and PPHN revisited.(DRUGS, PREGNANCY, & LACTATION)

The risks associated with selective serotonin reuptake inhibitor use in pregnancy have been addressed in previous columns because of the accumulating data suggesting that depression during pregnancy is common and that many pregnant women use SSRIs. A recent study indicated that as many as 8% of pregnant women are treated with SSRIs, so clearly delineating the spectrum of associated risks is of critical clinical importance.

Although an increasing amount of data suggests that the teratogenic risks associated with fetal exposure to SSRIs are small and the potential for problems with neonatal adaptation symptoms are common (about 30%) but typically self-limited, several recent studies have evaluated the risk for persistent pulmonary hypertension of the newborn (PPHN) associated with late trimester exposure to SSRIs.

I have reviewed several studies suggesting a spectrum of risk, dating back to the case-control study using data from a birth defects database, which ascribed about a sixfold increase in risk for PPHN to late trimester exposure to SSRIs (N. Engl. J. Med. 2006;354:579-87). This was followed by a case-control study published last year from the Swedish Medical Birth Register, which found approximately a twofold increased risk of PPHN associated with SSRI exposure late in pregnancy (Pharmacoepidemiol. Drug Saf. 2008; 17:801-6).

Recently, another study using an administrative database from four health plans in an ongoing HMO research network study of birth outcomes provided yet another estimate. The investigators retrospectively identified 1,104 full-term infants whose mothers were dispensed an antidepressant in the third trimester and 1,104 full-term infants whose mothers did not receive an antidepressant in the third trimester (Pharmacoepidemiol. Drug Saf. 2009 January 15 fdoi:10.1002/ pds.1710]).

Possible cases of PPHN were identified using different diagnosis and procedure codes and confirmed with reviews of hospital records. There was no difference in risk for PPHN between exposed and unexposed children: The prevalence of PPHN was 2.14 per 1,000 among infants exposed to an SSRl during the third trimester and 2.72 per 1,000 among the infants not exposed to SSRIs. Only a small number of cases of possible PPHN were confirmed--two among SSRI-exposed infants and three among those not exposed--and some cases may have been missed, hence one of the limitations of the study.

The conflicting data are not terribly surprising because these studies are not prospective and they use various databases; each has its own respective limitations. It is noteworthy, ...