Table 2.
Sub‐analyses of major malformations and cardiac malformations
| Major malformations (all/aggregate) | Cardiac malformations (all/aggregate) | |||||
|---|---|---|---|---|---|---|
| Number of studies | Effect size Pooled OR (95% CI) | Between‐sample heterogeneity I 2 (P value) | Number of studies |
Effect size
Pooled
OR (95% CI) |
Between‐sample heterogeneity I 2 (P value) | |
| Comparison group | ||||||
| Unexposed to paroxetine (unadjusted or adjusted ORs combined) | 15 | 1.23 (1.10, 1.38) | 1.8% (0.431) | 18 | 1.28 (1.11, 1.47) | 0.0% (0.653) |
| Unexposed to paroxetine (adjusted ORs only) | 10 | 1.26 (1.11, 1.43) | 0.0% (0.615) | 13 | 1.35 (1.23, 1.62) | 8.5% (0.361) |
| Unexposed to SSRIs (unadjusted or adjusted ORs combined) | 14 | 1.19 (1.06, 1.34) | 0.0% (0.722) | 17 | 1.27 (1.10, 1.47) | 0.0% (0.596) |
| Unexposed to SSRIs (adjusted ORs only) | 9 | 1.21 (1.06, 1.38) | 0.0% (0.936) | 11 | 1.36 (1.09, 1.56) | 21.2% (0.241) |
| Unexposed to any antidepressants (unadjusted or adjusted ORs combined) | 10 | 1.19 (1.05, 1.35) | 0.0% (0.578) | 13 | 1.23 (1.06, 1.43) | 1.0% (0.436) |
| Unexposed to any antidepressants (adjusted ORs only) | 6 | 1.21 (1.03, 1.43) | 17.5% (0.300) | 8 | 1.27 (1.03, 1.56) | 27.1% (0.212) |
| Exposed to antidepressants other than paroxetine | 2 | 1.66 (1.09, 2.53) | 30.9% (0.229) | 2 | 1.44 (0.81, 2.54) | 0.0% (0.925) |
| Diagnosed with depression and/or anxiety (exposed or unexposed to an antidepressant other than paroxetine) | 3 | 1.28 (0.74, 2.22) | 81.4% (0.005) | 4 | 1.33 (0.87, 1.71) | 38.4% (0.181) |
| Diagnosed with depression and/or anxiety but not exposed to any antidepressant | 1 | ‐ | ‐ | 2 | 1.20 (0.69, 2.08) | 73.1% (0.051) |
| Addition of other data | ||||||
| Addition of data from abstracts and unpublished studies | 18 | 1.26 (1.11, 1.42) | 16.2% (0.260) | 21 | 1.27 (1.10, 1.46) | 0.0% (0.585) |
| Study design | ||||||
| Case–control | 3 | 1.42 (1.05, 1.91) | 0.0% (0.879) | 4 | 1.51 (1.01, 2.17) | 0.0% (0.972) |
| Cohort | 13 | 1.21 (1.06, 1.38) | 15.2% (0.295) | 15 | 1.23 (1.01, 1.45) | 0.0% (0.449) |
| Where study took place | ||||||
| North America | 8 | 1.28 (1.04, 1.58) | 21.1% (0.262) | 9 | 1.23 (1.01, 1.5) | 8.0% (0.369) |
| Europe | 6 | 1.19 (1.01, 1.41) | 0.0% (0.946) | 7 | 1.40 (1.06, 1.84) | 0.0% (0.808) |
| Australia | 1 | ‐ | ‐ | 1 | ‐ | ‐ |
| More than one continent | 1 | ‐ | ‐ | 2 | 1.6 (0.69, 3.79) | 16.2% (0.275) |
| Time to malformation ascertainment | ||||||
| Less than 1 year of age | 4 | 1.69 (1.22, 2.3) | 0.0% (0.532) | 4 | 1.04 (0.84, 1.29) | 0.0% (0.438) |
| Up to 1 year or beyond | 5 | 1.27 (1,01, 1.61) | 10.5% (0.346) | 6 | 1.10 (0.66, 1.86) | 50.7% (0.07) |
| Not specified | 7 | 1.41 (0.99, 1.31) | 0.0% (0.800) | 9 | 1.51 (1.22, 1.87) | 0.0% (0.895) |
| Data source | ||||||
| Administrative/claims database | 4 | 1.39 (0.78, 2.49) | 61.1% (0.077) | 4 | 1.00 (0.79, 1.25) | 0.0% (0.491) |
| Prescription database and/or linked to birth registry | 6 | 1.21 (0.96, 1.30) | 0.0% (0.804) | 7 | 1.46 (1.13, 1.89) | 0.0% (0.884) |
| Clinic/surveillance and/or link to registries | 3 | 1.49 (1.05, 2.12) | 0.0% (0.901) | 4 | 1.48 (1.02, 2.17) | 0.0% (0.846) |
| Teratogen information services | 3 | 1.50 (0.99, 2.26) | 37.9% (0.200) | 4 | 1.62 (1.21, 2.32) | 0.0% (0.646) |
| Inclusions and exclusions | ||||||
| Studies excluded chromosomal and/or genetic defects | 5 | 1.28 (1.05, 1.55) | 21.5% (0.277) | 6 | 1.25 (0.93,1.68) | 43.8% (0.113) |
| Studies excluded or adjusted for the use of teratogenic drugs | 6 | 1.23 (1.01, 1.52) | 20.0% (0.283) | 8 | 1.18 (0.94,1.48) | 14.0% (0.320) |
| Covariates adjustments | ||||||
| Adjusted for maternal chronic diseases | 7 | 1.25 (1.01, 1.54) | 32.9% (0.189) | 10 | 1.16 (0.97,1.38) | 0.0% (0.476) |
| Adjusted for depression or used a cohort of depressed pregnant women | 5 | 1.26 (0.95, 1.69) | 45.3% (0.120) | 6 | 1.25 (0.93, 1.67) | 27.5% (0.229) |
| Definition of first trimester exposure | ||||||
| At least 30 days before to end of first trimester | 8 | 1.15 (1.00, 1.33) | 0.0% (0.681) | 10 | 1.49 (1.20, 1.85) | 0.0% (0.958) |
| Not specified | 5 | 1.27 (0.98, 1.63) | 17.7% (0.302) | 5 | 1.50 (1.08, 2.09) | 0.0% (0.623) |
OR odds ratio; 95% CI 95% confidence interval.