Table 1.
Analysis | No. of Studies | Within Group | Effect of Moderator | ||||||
---|---|---|---|---|---|---|---|---|---|
Heterogeneity | |||||||||
Odds Ratio or Mean Difference (95% CI)a | P value | Q(df) Within | P Value | I 2 (Percentage of Variance Explained) | Q(df) Between | P Value | I 2 (Percentage of Variance Explained) | ||
Spontaneous abortion | |||||||||
All studies | 5 | 1.86 (1.43 to 2.42) | <0.001 | 16.834 | 0.002 | 76.0 | |||
Study Quality | 0.021 | 0.89 | 0.0 | ||||||
Above quality threshold | 4 | 1.85 (1.3 to, 2.49) | <0.001 | 16.333 | 0.001 | 82.0 | |||
Below quality threshold | 1 | 1.93 (1.10 to 3.40) | 0.02 | ||||||
Timing of BZD exposure | 16.192 | <0.001 | 87.6 | ||||||
Any time in pregnancy | 3 | 2.30 (1.79 to 2.96) | <0.001 | 0.632 | 0.73 | 0.0 | |||
First trimester | 1 | 1.40 (1.26 to 1.57) | <0.001 | ||||||
Up to 22 weeks gestation | 1 | 1.91 (1.54 to 2.37) | <0.001 | ||||||
Any adjusted data | 3.171 | 0.07 | 68.5 | ||||||
Adjusted findings | 2 | 1.61 (1.19 to 2.18) | 0.002 | 6.241 | 0.01 | 84.0 | |||
Unadjusted findings | 3 | 2.30 (1.79 to 2.96) | <0.001 | 0.632 | 0.73 | 0.0 | |||
Exposure to other psychotropics | 14.961 | <0.001 | 93.3 | ||||||
No, exclusion criteria | 1 | 1.40 (1.26 to 1.57) | <0.001 | ||||||
Not specified/assessed | 4 | 2.07 (1.76 to 2.44) | <0.001 | 1.863 | 0.60 | 0.0 | |||
Controlled for psychiatric diagnoses | 16.192 | <0.001 | 87.6 | ||||||
Yes, adjusted | 1 | 1.91 (1.54 to 2.37) | <0.001 | ||||||
Exclusion criteria | 1 | 1.40 (1.26 to 1.57) | <0.001 | ||||||
Not specified/assessed | 3 | 2.30 (1.79 to 2.96) | <0.001 | 0.632 | 0.73 | 0.0 | |||
Country | 3.632 | 0.16 | 44.9 | ||||||
North America | 2 | 2.40 (1.82 to 3.17) | <0.001 | 0.171 | 0.68 | 0.0 | |||
Europe | 2 | 1.61 (1.19 to 2.18) | 0.002 | 6.241 | 0.01 | 84.0 | |||
Other | 1 | 1.93 (1.10 to 3.40) | 0.02 | ||||||
Preterm birth | |||||||||
All studies | 6 | 1.96 (1.25 to 3.08) | 0.004 | 28.945 | <0.001 | 83.0 | |||
Study quality | |||||||||
Above quality threshold | 6 | 1.96 (1.25 to 3.08) | 0.004 | 28.945 | <0.001 | 83.0 | |||
Below quality threshold | 0 | ||||||||
Timing of BZD exposure | 0.451 | 0.50 | 0.0 | ||||||
Any time in pregnancy | 5 | 2.05 (1.05 to 3.99) | 0.04 | 25.964 | <0.001 | 85.0 | |||
Second and/or third trimester | 1 | 1.62 (1.37 to 1.91) | <0.001 | ||||||
Any adjusted data | |||||||||
Adjusted findings | 6 | 1.96 (1.25 to 3.08) | 0.004 | 28.945 | <0.001 | 83.0 | |||
Unadjusted findings | 0 | ||||||||
Exposure to other psychotropics | 1.811 | 0.18 | 44.9 | ||||||
Yes, adjusted | 3 | 1.41 (0.95 to 2.10) | 0.09 | 1.312 | 0.52 | 0.0 | |||
Not specified/assessed | 3 | 2.51 (1.20 to 5.27) | 0.01 | 26.312 | <0.001 | 92.0 | |||
Controlled for psychiatric diagnoses | 1.811 | 0.18 | 44.9 | ||||||
Yes, adjusted | 3 | 1.41 (0.95 to 2.10) | 0.09 | 1.312 | 0.52 | 0.0 | |||
Not specified/assessed | 3 | 2.51 (1.20 to 5.27) | 0.01 | 26.312 | <0.001 | 92.0 | |||
Country | 1.021 | 0.31 | 1.5 | ||||||
North America | 3 | 2.71 (0.96 to 7.65) | 0.06 | 13.452 | 0.001 | 85.0 | |||
Europe | 3 | 1.58 (1.36 to 1.83) | <0.001 | 1.142 | 0.57 | 0.0 | |||
Other | 0 | ||||||||
Birth weight | |||||||||
All studies | 5 | −151.35 (−329.73 to 27.03) | 0.10 | 31.904 | <0.001 | 87.0 | |||
Study quality | 2.841 | 0.09 | 64.7 | ||||||
Above quality threshold | 4 | −204.65 (−444.70 to 35.39) | 0.09 | 23.024 | <0.001 | 87.0 | |||
Below quality threshold | 1 | 15.40 (−73.93 to 104.73) | 0.74 | ||||||
Timing of BZD exposure | |||||||||
Any time in pregnancy | 5 | −151.35 (−329.73 to 27.03) | 0.10 | 31.904 | <0.001 | 87.0 | |||
First trimester | 0 | ||||||||
Second and/or third trimester | 0 | ||||||||
Any adjusted data | 0.031 | 0.86 | 0.0 | ||||||
Adjusted findings | 1 | −137.77 (−226.52 to −49.02) | 0.002 | ||||||
Unadjusted findings | 4 | −163.89 (−437.83 to 110.04) | 0.24 | 30.103 | <0.001 | 90.0 | |||
Exposure to other psychotropics | 0.001 | 0.98 | 0.0 | ||||||
No, exclusion criteria | 3 | −143.47 (−478.13 to 191.20) | 0.40 | 28.382 | <0.001 | 93.0 | |||
Not specified/assessed | 2 | −147.14 (−231.77 to −62.51) | <0.001 | 0.471 | 0.49 | 0.0 | |||
Controlled for psychiatric diagnoses | 0.001 | 0.98 | 0.0 | ||||||
Yes (exclusion criteria) | 2 | −147.14 (−231.77 to −62.51) | <0.001 | 0.471 | 0.49 | 0.0 | |||
No (not specified/assessed) | 3 | −143.47 (−478.13 to 191.20) | 0.40 | 28.382 | <0.001 | 93.0 | |||
Country | 6.952 | 0.03 | 71.2 | ||||||
North America | 2 | −233.02 (−873.62 to 407.58) | 0.48 | 22.291 | <0.001 | 96.0 | |||
Europe | 2 | −147.14 (−231.77 to −62.51) | <0.001 | 0.471 | 0.49 | 0.0 | |||
Other | 1 | 15.40 (−73.93 to 104.73) | 0.74 | ||||||
Low birth weight | |||||||||
All studies | 6 | 2.34 (1.41 to 3.88) | 0.001 | 32.404 | <0.001 | 85.0 | |||
Study quality | |||||||||
Above quality threshold | 6 | 2.34 (1.41 to 3.88) | 0.001 | 32.404 | <0.001 | 85.0 | |||
Below quality threshold | 0 | ||||||||
Timing of BZD exposure | 3.621 | 0.06 | 72.4 | ||||||
Any time in pregnancy | 5 | 2.70 (1.42 to 5.15) | 0.003 | 22.414 | <0.001 | 82.0 | |||
Second and/or third trimester | 1 | 1.40 (1.14 to 1.72) | 0.001 | ||||||
Any adjusted data | |||||||||
Adjusted findings | 6 | 2.34 (1.41 to 3.88) | 0.001 | 32.404 | <0.001 | 85.0 | |||
Unadjusted findings | 0 | ||||||||
Exposure to other psychotropics | 0.171 | 0.68 | 0.0 | ||||||
Yes, adjusted | 3 | 2.06 (1.10 to 3.89) | 0.02 | 4.162 | 0.13 | 52.0 | |||
Not specified/assessed | 3 | 2.57 (1.11 to 5.95) | 0.03 | 28.182 | <0.001 | 93.0 | |||
Controlled for psychiatric diagnoses | 0.171 | 0.68 | 0.0 | ||||||
Yes | 3 | 2.06 (1.10 to 3.89) | 0.02 | 4.162 | 0.13 | 52.0 | |||
No | 3 | 2.57 (1.11 to 5.95) | 0.03 | 28.182 | <0.001 | 93.0 | |||
Country | 9.891 | 0.002 | 89.9 | ||||||
North America | 3 | 4.48 (2.28 to 8.82) | <0.001 | 4.082 | 0.13 | 51.0 | |||
Europe | 3 | 1.46 (1.23 to 1.74) | <0.001 | 1.302 | 0.52 | 0.0 | |||
Other | 0 | ||||||||
Gestational age | |||||||||
All studies | 5 | −0.49 (−1.18 to 0.19) | 0.16 | 44.354 | <0.001 | 91.0 | |||
Study quality | 0.741 | 0.39 | 0.0 | ||||||
Above quality threshold | 4 | −0.62 (−1.76 to 0.52) | 0.29 | 41.803 | <0.001 | 93.0 | |||
Below quality threshold | 1 | −0.10 (−0.40 to 0.20) | 0.51 | ||||||
Timing of BZD exposure | |||||||||
Any time in pregnancy | 5 | −0.49 (−1.18 to 0.19) | 0.16 | 44.354 | <0.001 | ||||
First trimester | 0 | ||||||||
Second and/or third trimester | 0 | ||||||||
Any adjusted data | 1.521 | 0.22 | 34.2 | ||||||
Adjusted findings | 2 | −1.47 (−3.82 to 0.88) | 0.22 | 34.021 | <0.001 | 97.0 | |||
Unadjusted findings | 3 | 0.02 (−0.30 to 0.35) | 0.90 | 2.322 | 0.31 | 14.0 | |||
Exposure to other psychotropics | 0.331 | 0.57 | 0.0 | ||||||
Yes, exclusion criteria | 2 | −0.28 (−0.52 to −0.05) | 0.02 | 0.371 | 0.54 | 0.0 | |||
Not specified/assessed | 3 | −0.75 (−2.32 to 0.83) | 0.35 | 43.952 | <0.001 | 95.0 | |||
Controlled for psychiatric diagnoses | 0.331 | 0.57 | 0.0 | ||||||
Yes, exclusion criteria | 2 | −0.28 (−0.52 to −0.05) | 0.02 | 0.371 | 0.54 | 0.0 | |||
Not specified/assessed | 3 | −0.75 (−2.32 to 0.83) | 0.35 | 43.952 | <0.001 | 95.0 | |||
Country | 1.192 | 0.55 | 0.0 | ||||||
North America | 2 | −1.10 (−4.23 to 2.04) | 0.49 | 35.731 | <0.001 | 97.0 | |||
Europe | 2 | −0.28 (−0.52 to −0.05) | 0.02 | 0.371 | 0.54 | 0.0 | |||
Other | 1 | −0.10 (−0.40 to 0.20) | 0.51 |
Note. GA = gestational age; SGA = small for gestational age.
a Pooled effect size estimated using random-effects model.
b Other countries include Australia, Israel, Singapore, and Taiwan.