Table 2.
Meta-analyses of observational studies of antenatal AD use and the risk of congenital malformations
| Reference | Studies, n | Exposure groups | Main results | Confounding and bias |
|---|---|---|---|---|
| Myles et al105 | Major malformations: 16 Minor malformations: 4 |
SSRI, first trimester (n=23,919) No SSRI |
Any malformation: all SSRIs, OR 1.10 (95% CI 1.03–1.16); paroxetine, OR 1.29 (95% CI 1.11–1.49); fluoxetine, OR 1.14 (95% CI 1.01–1.30); sertraline, OR 1.01 (95% CI 0.88–1.17); citalopram, OR 1.04 (95% CI 0.92–1.17) | Separate analyses conducted for studies that considered early versus continuous SSRI exposure; controlled for tobacco, alcohol, or illicit drug use; controlled for maternal age; controlled for maternal parity; and exclusion of chromosomal or genetic abnormalities. |
| Grigoriadis et al107 | 12 | Any AD (n=17,915) No AD |
Any malformation: RR 0.93 (95% CI 0.85–1.02) Major malformations: RR 1.07 (95% CI 0.99–1.17) |
Systematic Assessment of Quality in Observational Research (SAQOR) tool used to evaluate individual study quality. |
| Riggin et al108 | 21 | Fluoxetine, first trimester (cohort studies, n=11,225; case-control studies, n=9,800) | Any malformation: cohort studies, OR 1.12 (95% CI 0.98–1.28); case-control studies, OR 3.72 (95% CI 0.74–18.79) | |
| Bar-Oz et al106 | 6 | Paroxetine, first trimester (n=2,621) No paroxetine AD exposure No teratogen exposure |
Paroxetine versus other AD or known nonteratogens: Any malformation: OR 1.31 (95% CI 1.03–1.67) Paroxetine versus other AD: Any malformation: OR 1.30 (95% CI 0.92–1.80) Paroxetine versus known nonteratogens: Any malformation: OR 1.54 (95% CI 0.99–2.41) |
Diagnostic tests in pregnancy: Significantly greater use in AD users versus nonusers; no significant difference between paroxetine and other AD, using population-based registry data. Diagnostic tests in infancy: Significantly higher rates of echocardiograms with in utero SSRI exposure versus no AD exposure, using population-based registry data. Indication: Significantly higher proportion of use for anxiety disorders with paroxetine versus other SSRIs. |
| Rahimi et al109 | 9 | SSRI, any exposure during pregnancy (n=1,102) Unexposed to SSRI |
Any major malformation: OR 1.39 (95% CI 0.91–2.15) | |
| Addis et al110 | 4 | Fluoxetine, first trimester (n=367) | Any major malformation: weighted average 2.6% (95% CI 1%–4.2%) |
Abbreviations: SSRI, selective serotonin-reuptake inhibitor; OR, odds ratio; CI, confidence interval; RR, relative risk; AD, antidepressant.