Gestational exposure to antidepressants and risk of seizure in offspring: A systematic review and meta-analysis

Leung, Miriam T Y; Wong, Kirstie H T W; Ho, Phoebe W.H.; Ip, Patrick; Wei, Li; Wong, Ian C K; Man, Kenneth K C

doi:10.1016/j.neubiorev.2021.09.040

Cited by 4 publications

(1 citation statement)

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“…Because general population comparisons do not adjust adequately for confounding, they should not be used as a sole basis for making clinical decisions, see discussion) Study (year) Outcomes N AD type Psychiatric control Sibling control Main findings Kautzky (2022) [ 106 ] PNAS 17 SSRI, SNRI Y N Statistically significant associations with preterm birth (OR = 2.36, 95% CI 1.35–4.15), admission to neonatal intensive care (OR = 2.64, 95% CI 1.58–4.40), respiratory problems (OR = 2.85, 95% CI 1.26–6.43), lower gestational age (MD = −0.36, 95% CI −0.81 to 0.08), and lower 5-minute Apgar score (MD = −0.32, 95% CI −0.54 to −0.11) in untreated maternal depression comparisons Vlenterie (2022) [ 107 ] GA, BW, SGA, Apgar score 215 Any N N In general population comparisons, preterm birth associated with prenatal depression (OR = 1.6, 95% CI 1.2–2.1), untreated prenatal depression (OR = 2.2, 95% CI 1.7–3.0), and prenatal antidepressant use for any indication (OR = 1.4, 95% CI 1.1–1.8) Low (<5) 5-minute Apgar score associated with prenatal depression (OR = 1.5, 95% CI 1.3–1.7), and prenatal antidepressant use for any indication (OR = 1.6, 95% CI 1.1–2.5) but not untreated prenatal depression Preterm birth associated with prenatal SSRI use for depression (OR = 1.6, 95% CI 1.0–2.5) and prenatal SSRI use for any indication (OR = 1.9, 95% CI 1.2–2.8) Low 5-minute Apgar score associated with prenatal SSRI use for any indication (OR = 1.7, 95% CI 1.1–2.8) AD use during pregnancy not associated with low BW or SGA De Vries (2021) [ 108 ] Congenital heart defects a 20 Any N N In general population comparisons, statistically significant association between prenatal AD exposure and congenital heart defects (OR = 1.28, 95% CI 1.17–1.41) Statistically significant associations for SSRIs (OR = 1.25, 95% CI 1.15–1.37), SNRIs (OR = 1.69, 95% CI 1.37–2.10), paroxetine (OR = 1.57, 95% CI 1.20–1.97), fluoxetine (OR = 1.36, 95% CI 1.08–1.72), sertraline (OR = 1.29, 95% CI 1.14–1.45), and bupropion (OR = 1.23, 95% CI 1.01–1.49). TCAs, citalopram, escitalopram, and venlafaxine not associated with an increased risk Leung (2021) [ 109 ] …”

Section: What Types Of Study Are To Be Preferred?mentioning

confidence: 99%

Should Antidepressants be Avoided in Pregnancy?

Besag

Vasey²

2022

Drug Saf

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Many (> 40%) women discontinue antidepressants during pregnancy because of concerns about effects on the foetus, based on information from inadequately-controlled studies. The sibling-control study design provides the best control for confounding factors, notably maternal depression. The purpose of this review was to investigate the evidence from sibling-control analyses for adverse outcomes in offspring associated with antidepressant exposure during pregnancy. Fourteen sibling-control studies were identified through searches of PubMed and Embase. Outcomes included preterm birth, small for gestational age, neonatal size, birth defects, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), behavioural problems, neurodevelopmental deficits, and scholastic attainment. For the majority of these outcomes, no statistically significant associations were found when comparing exposed and unexposed siblings. Single studies reported associations with preterm birth, reduced gestational age, ADHD, anxiety at 36 months, and lower mathematics test scores, which persisted in the sibling-control analyses. However, differences were small and possibly not clinically significant. Moreover, effects of residual confounding could not be excluded. These findings provide evidence that many of the previously reported associations between prenatal antidepressant exposure and adverse outcomes in offspring are no longer statistically significant when exposed offspring are compared with unexposed siblings. The few statistically significant differences in sibling-control analyses were generally small with doubtful clinical significance. Decisions on antidepressant treatment during pregnancy should be made individually, based on evidence from properly controlled studies, not on misleading information based on studies that have not controlled adequately for confounding factors.

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