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Selective serotonin reuptake inhibitors and preeclampsia: A quality assessment and meta-analysis
Journal article   Open access

Selective serotonin reuptake inhibitors and preeclampsia: A quality assessment and meta-analysis

Serena B Gumusoglu, Brandon M. Schickling, Julie A. Vignato, Donna A. Santillan and Mark K. Santillan
Pregnancy hypertension, Vol.30, pp.36-43
12/2022
DOI: 10.1016/j.preghy.2022.08.001
PMCID: PMC9712168
PMID: 35963154
url
https://www.ncbi.nlm.nih.gov/pmc/articles/9712168View
Open Access

Abstract

•Reviewed studies linking SSRIs to preeclampsia(PE)/gestational hypertension (GH).•SSRIs may modulate pathoetiology of hypertensive disorders of pregnancy.•Pooled SSRI-associated PE/GH risk ratio was 1.43 (95% CI: 1.15–1.78).•Studies demonstrate bias and poorly control for cofactors (dose, comorbidities).•Future studies should utilize model organisms or SSRIs in healthy participants. Serotonin modulates vascular, immune, and neurophysiology and is dysregulated in preeclampsia. Despite biological plausibility that selective serotonin reuptake inhibitors (SSRIs) prevent preeclampsia pathophysiology, observational studies have indicated increased risk and providers may be hesitant. The objective of this meta-analysis and quality assessment was to evaluate the evidence linking SSRI use in pregnancy to preeclampsia/gestational hypertension. PubMed was searched through June 5, 2020 manually and using combinations of terms: “preeclampsia”, “serotonin”, and “SSRI”. This review followed MOOSE guidelines. Inclusion criteria were: 1) Observational cohort or population study, 2) exposure defined as SSRI use during pregnancy, 3) cases defined as preeclampsia or gestational hypertension, and 4) human participants. Studies were selected that addressed the hypothesis that gestational SSRI use modulates preeclampsia and/or gestational hypertension risk. Review Manager Web was used to synthesize study findings. Articles were read and scored (Newcastle-Ottawa Quality Assessment Scale) for quality by two independent reviewers. Publication bias was assessed using a funnel plot and the Egger test. Of 179 screened studies, nine were included. The pooled risk ratio (random effects model) was 1.43 (95 % CI: 1.15–1.78, P < 0.001; range 0.96–4.86). Two studies were rated as moderate quality (both with total score of 6); others were high quality. Heterogeneity was high (I2 = 88 %) and funnel asymmetry was significant (p < 0.00001). Despite evidence for increased preeclampsia risk with SSRIs, shared risk factors and other variables are poorly controlled. Depression treatment should not be withheld due to perceived gestational hypertension risk. Mechanistic evidence for serotonin modulation in preeclampsia demonstrates a need for future research.
Gestational hypertension Meta-analysis Mood disorders Preeclampsia Serotonin SSRI

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