Antidepressant Exposure In Late Pregnancy Associated with Increased Risk of PPHN

Trine Munk-Olsen, PhD

Although antidepressant exposure during pregnancy has been associated with an increased risk of persistent pulmonary hypertension of the newborn (PPHN), there is insufficient evidence related to risks after non-selective serotonin reuptake inhibitors (SSRIs) exposure and timing of exposure in pregnancy across type of antidepressant.

Led by Trine Munk-Olsen, PhD, Department of Clinical Research, University of Southern Denmark, investigators set out to determine detailed information on trimester- and antidepressant type-specific risk, due to the potential lethality of PPHN.

They noted an association between antidepressant exposure in late pregnancy and increased risk of PPHN, while the absolute risk of PPHN was ultimately considered low.

Through a population-based cohort study, Munk-Olsen and colleagues identified 1,246,347 live-born singleton children who were born to 707,026 mothers from January 1997 - December 2016. Data show the mean age of the mothers was 30.5 years and 44.9% were primiparous.

They determined antidepressant use during pregnancy using recorded prescriptions of antidepressants dispensed in the period 1 month before pregnancy and delivery.

The association by timing of antidepressant exposure was investigated by early pregnancy (≤20 weeks’ gestation) and late pregnancy (>20 weeks gestation). Additionally, treatment was categorized into SSRI and non-SSRI antidepressants.

Data was analyzed from March - July 2021. The team estimated adjusted odds ratios (ORs) and absolute risk differences of PPHN by antidepressant exposure status.

PPHN was identified among 79 children of the total born to mothers who used antidepressants (n = 29,822). This was at a rate of 2.6 per 1000 live births, compared to 1637 children among the unexposed cohort, at a rate of 1.3 per 1000 live births.

The findings show the adjusted OR for PPHN after antidepressant exposure, at any time during pregnancy, was 1.29 (95% CI, 0.95 - 1.74). There were differences in risk by exposure early compared to late in pregnancy (≤ 20 weeks’ gestation; OR, 0.80, 95% CI, 0.51 - 1.25 versus >20 weeks gestation; OR, 2.01, 95% CI, 1.32 - 3.05).

They found the absolute risk difference for the development of PPHN after exposure to antidepressants during late pregnancy was 1.3 per 1000 infants (95% CI, 0.2 - 2.4).

Additionally, investigators noted this data suggested between 417 and 5000 women needed to be treated with antidepressants in late pregnancy to result in 1 additional PPHN case.

Lastly, they observed a more pronounced risk in late pregnancy with non-SSRI exposure (OR, 2.56, 95% CI, 1.54 - 4.25) compared to SSRI exposure (OR, 1.36; 95% CI, 0.95 - 1.95), all P = .046.

“This study’s findings provide reassuring clinical information for a substantial proportion of women who stop or taper antidepressant use shortly after they become pregnant,” investigators wrote.

The study, “Association of Persistent Pulmonary Hypertension in Infants With the Timing and Type of Antidepressants In Utero,” was published in JAMA Network Open.