#Grand Rounds

Does SSRI Exposure in Utero Increase Risk for Persistent Pulmonary Hypertension in Newborns?

BACKGROUND AND PURPOSE:

Selective serotonin reuptake inhibitors (SSRIs) include
- Fluoxetine | Paroxetine | Sertraline | Citalopram | Escitalopram | Fluvoxamine
Serotonin norepinephrine reuptake inhibitors (SNRIs) include
- Venlafaxine
Associations have been identified between SSRIs and adverse fetal outcomes including persistent pulmonary hypertension of the newborn (PPHN)
PPHN relatively rare with 2–6 cases per 1000 live births
Regulatory agencies’ guidance
- FDA: Cannot draw conclusions regarding SSRI and PPHN
- UK Regulatory Body: SSRIs associated with increased risk for PPHN >20 weeks | No clear conclusion for SNRIs
Masarwa et al. (AJOG, 2018) assessed whether exposure to SSRIs and SNRIs increased risk of PPHN

Systematic review and meta-analysis
- Retrospective cohort studies | Case-control studies
- Studies included risks for PPHN
Exposures: SSRI or SNRI in pregnancy
The primary outcome: Risk for PPHN

11 studies |156,978 women and offspring
452 cases of PPHN
- Incidence rate: 2.9 cases per 1000 live births
The risk for persistent pulmonary hypertension of the newborn was significantly increased after exposure to SSRI/SNRI
- Exposure in any trimester: Odds ratio (OR) 1.82 (95% CI, 1.31–2.54)
- Exposure only >20 weeks: OR 2.08 (95% CI, 1.44–3.01)
Of the SSRIs, sertraline was ranked most likely to have the lowest risk for persistent pulmonary hypertension of the newborn (P = .83)

Exposure to SSRI/SNRI during gestation increased the risk of persistent pulmonary hypertension in newborns
Sertraline associated with the lowest risk (percentage of drug that crosses placenta is lower than others)

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