Table 3. Estimates of Effect of Exposure to Benzodiazepines or Benzodiazepine-like Hypnotic Drugs.
| Exposure | Relative risk (95% CI) | ||
|---|---|---|---|
| Crude analysis | Adjusted for baseline confoundersa | Adjusted for baseline and time varying confoundersb | |
| Gestational age, d | |||
| Never | 0 [Reference] | 0 [Reference] | 0 [Reference] |
| Ever | −2.5 (−3.4 to −1.6) | −2.3 (−3.4 to −1.3) | −2.1 (−3.3 to −0.9) |
| Timing | |||
| Unexposed | 0 [Reference] | 0 [Reference] | 0 [Reference] |
| Early | 0.1 (−1.1 to 1.2) | 0.4 (−0.8 to 1.6) | 0.4 (−1.0 to 1.7) |
| Mid | −2.0 (−3.6 to −0.3) | −2.3 (−4.6 to −0.1) | −1.8 (−4.5 to 1.0) |
| Late | −3.7 (−5.4 to −2.0) | −3.4 (−5.7 to −1.0) | −3.1 (−5.7 to −0.5) |
| Duration, 4-wk inteval | |||
| 0 | 0 [Reference] | 0 [Reference] | 0 [Reference] |
| 1 | −2.5 (−3.6 to −1.4) | −2.5 (−3.8 to −1.1) | −2.6 (−4.0 to −1.1) |
| 2 | −2.0 (−4.3 to 0.3) | −1.5 (−4.5 to 1.4) | −0.7 (−3.9 to 2.4) |
| ≥3 | −2.8 (−4.7 to −1.0) | −2.5 (−4.4 to −0.5) | −1.8 (−4.2 to 0.6) |
| Preterm delivery | |||
| Never | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| Ever | 1.55 (1.17 to 2.06) | 1.45 (1.08 to 1.94) | 1.41 (1.03 to 1.94) |
| Timing | |||
| Unexposed | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| Early | 0.80 (0.50 to 1.29) | 0.71 (0.43 to 1.18) | 0.64 (0.36 to 1.12) |
| Mid | 1.10 (0.62 to 1.94) | 1.18 (0.66 to 2.11) | 1.33 (0.69 to 2.55) |
| Late | 2.45 (1.55 to 3.86) | 2.31 (1.38 to 3.86) | 2.17 (1.23 to 3.83) |
| Duration, 4-wk inteval | |||
| 0 | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| 1 | 1.56 (1.09 to 2.22) | 1.50 (1.05 to 2.14) | 1.49 (1.03 to 2.16) |
| 2 | 1.91 (0.98 to 3.71) | 1.70 (0.87 to 3.36) | 1.50 (0.73 to 3.09) |
| ≥3 | 1.28 (0.65 to 2.51) | 1.13 (0.56 to 2.26) | 1.14 (0.51 to 2.57) |
| Birth weight, g | |||
| Never | 0 [Reference] | 0 [Reference] | 0 [Reference] |
| Ever | −106.2 (−147.0 to −65.4) | −78.5 (−123.0 to −34.0) | −79.3 (−126.7 to −31.9) |
| Timing | |||
| Unexposed | 0 [Reference] | 0 [Reference] | 0 [Reference] |
| Early | −25.5 (−79.8 to 28.8) | 27.1 (−26.6 to 80.8) | 25.8 (−34.2 to 85.8) |
| Mid | −109.1 (−186.1 to −32.1) | −107.8 (−198.7 to −16.9) | −82.2 (−190.8 to 26.4) |
| Late | −97.5 (−174.7 to −20.3) | −116.7 (−208.4 to −25.0) | −107.2 (−211.1 to −3.3) |
| Duration, 4-wk inteval | |||
| 0 | 0 [Reference] | 0 [Reference] | 0 [Reference] |
| 1 | −84.8 (−135.6 to −34.0) | −63.7 (−120.9 to −6.5) | −81.7 (−143.0 to −20.4) |
| 2 | −140.9 (−247.5 to −34.3) | −92.2 (−206.3 to 21.9) | −91.3 (−211.8 to 29.2) |
| ≥3 | −146.7 (−234.1 to −59.3) | −113.8 (−197.9 to −29.7) | −41.5 (−154.4 to 71.4) |
| Birth weight relative to gestational age and sex, z score | |||
| Never | 0 [Reference] | 0 [Reference] | 0 [Reference] |
| Ever | −0.08 (−0.16 to 0.00) | −0.04 (−0.12 to 0.04) | −0.04 (−0.12 to 0.04) |
| Timing | |||
| Unexposed | 0 [Reference] | 0 [Reference] | 0 [Reference] |
| Early | −0.08 (−0.20 to 0.04) | 0.02 (−0.08 to 0.12) | 0.01 (−0.09 to 0.11) |
| Mid | −0.12 (−0.28 to 0.04) | −0.10 (−0.24 to 0.04) | −0.05 (−0.21 to 0.11) |
| Late | 0.02 (−0.14 to 0.18) | −0.05 (−0.19 to 0.09) | −0.06 (−0.22 to 0.10) |
| Duration, 4-wk inteval | |||
| 0 | 0 [Reference] | 0 [Reference] | 0 [Reference] |
| 1 | −0.03 (−0.15 to 0.09) | 0.00 (−0.10 to 0.10) | −0.03 (−0.13 to 0.07) |
| 2 | −0.23 (−0.45 to −0.01) | −0.10 (−0.26 to 0.06) | −0.14 (−0.30 to 0.02) |
| ≥3 | −0.14 (−0.34 to 0.06) | −0.14 (−0.3 to 0.02) | −0.01 (−0.21 to 0.19) |
| Small for gestational age | |||
| Never | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| Ever | 1.24 (0.93 to 1.66) | 1.11 (0.83 to 1.48) | 0.96 (0.69 to 1.33) |
| Timing | |||
| Unexposed | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| Early | 1.15 (0.78 to 1.70) | 0.93 (0.63 to 1.37) | 0.87 (0.57 to 1.32) |
| Mid | 1.39 (0.83 to 2.30) | 1.35 (0.81 to 2.24) | 0.98 (0.56 to 1.73) |
| Late | 1.09 (0.63 to 1.88) | 1.23 (0.74 to 2.04) | 1.26 (0.69 to 2.33) |
| Duration, 4-wk inteval | |||
| 0 | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| 1 | 1.01 (0.68 to 1.51) | 0.92 (0.62 to 1.37) | 0.91 (0.6 to 1.38) |
| 2 | 1.17 (0.54 to 2.55) | 1.02 (0.46 to 2.27) | 1.03 (0.45 to 2.39) |
| ≥3 | 1.97 (1.22 to 3.19) | 1.05 (0.65 to 1.71) | 1.02 (0.54 to 1.91) |
| Head circumference, cm | |||
| Never | 0 [Reference] | 0 [Reference] | 0 [Reference] |
| Ever | −0.2 (−0.3 to −0.1) | −0.1 (−0.3 to 0.0) | −0.1 (−0.3 to 0.1) |
| Timing | |||
| Unexposed | 0 [Reference] | 0 [Reference] | 0 [Reference] |
| Early | −0.1 (−0.2 to 0.1) | 0.1 (−0.1 to 0.3) | 0.1 (−0.1 to 0.3) |
| Mid | −0.1 (−0.2 to 0.1) | 0.0 (−0.4 to 0.3) | 0.1 (−0.3 to 0.6) |
| Late | −0.4 (0.3 to −1.0) | −0.4 (−0.7 to −0.1) | −0.4 (−0.7 to −0.1) |
| Duration, 4-wk inteval | |||
| 0 | 0 [Reference] | 0 [Reference] | 0 [Reference] |
| 1 | −0.2 (−0.3 to 0) | −0.1 (−0.3 to 0.1) | −0.1 (−0.3 to 0.1) |
| 2 | −0.2 (−0.5 to 0.2) | 0.0 (−0.5 to 0.5) | 0.0 (−0.5 to 0.4) |
| ≥3 | −0.3 (−0.6 to −0.1) | −0.2 (−0.4 to 0.1) | 0.1 (−0.3 to 0.4) |
| Apgar Score <7 at 5 minc | |||
| Never | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| Ever | 1.09 (0.52 to 2.28) | 1.08 (0.51 to 2.29) | 1.28 (0.59 to 2.79) |
| Timing | |||
| Unexposed | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| Early | 0.76 (0.23 to 2.48) | 0.71 (0.20 to 2.58) | 0.59 (0.15 to 2.28) |
| Mid | 0.36 (0.04 to 2.91) | 0.37 (0.04 to 3.86) | 0.44 (0.03 to 5.57) |
| Late | 2.01 (0.61 to 6.66) | 2.06 (0.54 to 7.84) | 2.90 (0.68 to 12.39) |
| Respiratory distress | |||
| Never | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| Ever | 0.96 (0.36 to 2.54) | 0.94 (0.35 to 2.51) | 0.61 (0.21 to 1.73) |
| Timing | |||
| Unexposed | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| Early | 0.89 (0.25 to 3.11) | 0.90 (0.36 to 2.25) | 0.69 (0.28 to 1.73) |
| Mid | 2.13 (0.56 to 8.13) | 2.11 (0.71 to 6.28) | 1.48 (0.57 to 3.80) |
| Late | 1.02 (0.21 to 5.06) | 0.98 (0.18 to 5.41) | 1.01 (0.26 to 3.94) |
| Duration, 4-wk inteval | |||
| 0 | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| 1 | 0.37 (0.05 to 2.64) | 0.37 (0.05 to 2.62) | 0.20 (0.03 to 1.45) |
| 2 | 3.31 (0.84 to 13.08) | 3.31 (0.80 to 13.71) | 1.77 (0.42 to 7.50) |
| ≥3 | 1.11 (0.16 to 7.84) | 1.04 (0.14 to 7.65) | 1.04 (0.14 to 7.68) |
a
Baseline covariates: body mass index before conception, smoking, illicit drug use, alcohol intake, planned pregnancy, income, ongoing or completed education, adverse life events, sleeping and mental health issues, anxiety, and lifetime history of major depression.
b
Time-varying covariates: maternal symptoms of depression and anxiety during pregnancy, comedication use during pregnancy (ie, nonsteroidal anti-inflammatory drugs, opioids, paracetamol, antidepressants, antipsychotics, and antiepileptics), and fever during pregnancy.
c
For the outcome Apgar score less than 7 at 5 minutes, duration analysis is omitted as there were no events in some exposure groups.