Table 3.
Meta-analyses of observational studies of antenatal AD use and the risk of cardiac malformations
| Reference | Studies, n | Exposure groups | Main results | Confounding and bias |
|---|---|---|---|---|
| Myles et al105 | 9 | SSRI, first trimester (n=22,412) No SSRI |
Any cardiac malformation: OR 1.15 (95% CI 0.999–1.32); paroxetine OR 1.44 (95% CI 1.12–1.86); fluoxetine 1.25 (95% CI 0.98–1.60); sertraline OR 0.93 (95% CI 0.70–1.24); Citalopram OR 1.03 (95% CI 0.80–1.32) | 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 | Any cardiovascular malformation: 13 Septal heart defects: 9 Ventral septal defects: 5 |
Any AD (n=22,537) No AD |
Any cardiovascular malformation: RR 1.36 (95% CI 108–1.71); paroxetine RR 1.43 (95% CI 1.08–1.88); fluoxetine RR 1.17 (95% CI 0.89–1.55) Septal heart defects (any): RR 1.40 (95% CI 1.10–1.77) Ventral septal defects: RR 1.54 (95% CI 0.71–1.33) | Systematic Assessment of Quality in Observational Research (SAQOR) tool used to evaluate individual study quality. |
| Riggin et al108 | 16 | Fluoxetine, first trimester (cohort studies, n=7,874; case-control studies, n= 13,346) | Any cardiac malformation: cohort studies, OR 1.6 (95% CI 1.31–1.95); case-control studies OR 0.63 (95% CI 0.39–1.03) | |
| Bar-Oz et al106 | Meta-analysis RC:4 CC:2 |
Paroxetine, first trimester (n=5,332) Nonparoxetine AD exposure No teratogen exposure | Paroxetine versus other AD or known nonteratogens: Cardiac malformation (any): OR 1.72 (95% CI 1.22–2.42) Paroxetine versus other AD: Cardiac malformation (any): OR 1.70 (95% CI 1.17–2.46) Paroxetine versus known nonteratogens: Cardiac malformation (any): OR 3.47 (95% CI 0.90–12.21) |
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 | 8 | SSRI, any exposure during pregnancy (n=906) Unexposed to SSRI |
Cardiovascular malformation: OR 1.19 (95% CI 0.53–2.68) |
Abbreviations: SSRI, selective serotonin-reuptake inhibitor; OR, odds ratio; CI, confidence interval; RR, relative risk; AD, antidepressant; RC, retrospective cohort study; CC, case control study.