Table 3.
Crude and adjusted (IP-weighted) odds ratios of adverse neonatal and pregnancy outcomes associated with prenatal exposure to buprenorphine or methadone early (alone) or late (alone) in pregnancy compared with untreated pregnancies.
| Exposure to OAT in early pregnancy only | Exposure to OAT in late pregnancy only | |||
|---|---|---|---|---|
| Crude OR (95% CI) | Weighted OR (95% CI) | Crude OR (95% CI) | Weighted OR (95% CI) | |
| Neonatal outcomes | ||||
| Preterm birth (<37 weeks) | ||||
| Buprenorphine | 0.53 (0.16, 1.73) | 0.30 (0.08, 1.11) | 0.50 (0.13, 1.88) | 0.58 (0.14, 2.38) |
| Methadone | 0.80 (0.37, 1.76) | 0.56 (0.16, 1.97) | 2.53 (1.15, 5.60) | 4.53 (1.39, 14.76) |
| Untreated | Ref. | Ref. | Ref. | Ref. |
| Low birthweight (<2500 g) | ||||
| Buprenorphine | 0.78 (0.18, 3.30) | 1.18 (0.21, 6.60) | 0.40 (0.08, 2.17) | 0.34 (0.05, 2.30) |
| Methadone | 1.95 (0.78, 4.87) | 0.95 (0.21, 4.32) | 1.09 (0.44, 2.72) | 3.14 (0.78, 12.69) |
| Untreated | Ref. | Ref. | Ref. | Ref. |
| Neonatal Intensive Care Unit Admission (NICUa) | ||||
| Buprenorphine | 0.69 (0.25, 1.88) | 0.71 (0.19, 2.59) | 2.66 (0.96, 7.33) | 2.51 (0.67, 9.42) |
| Methadone | 1.64 (0.77, 3.52) | 1.41 (0.59, 3.35) | 3.59 (1.66, 7.75) | 3.58 (1.51, 8.45) |
| Untreated | Ref. | Ref. | Ref. | Ref. |
| Neonatal abstinence syndrome (NAS) | ||||
| Buprenorphine | 1.07 (0.41, 2.80) | 1.46 (0.43, 4.91) | 7.76 (2.95, 20.45) | 7.04 (2.03, 24.43) |
| Methadone | 0.71 (0.26, 1.91) | 0.62 (0.19, 1.97) | 14.85 (5.28, 41.72) | 18.39 (5.74, 58.98) |
| Untreated | Ref. | Ref. | Ref. | Ref. |
| Respiratory symptoms | ||||
| Buprenorphine | 0.95 (0.30, 2.97) | 1.23 (0.31, 4.85) | 1.60 (0.50, 5.13) | 1.45 (0.35, 6.08) |
| Methadone | 1.61 (0.53, 4.88) | 1.58 (0.48, 5.16) | 1.48 (0.49, 4.52) | 1.72 (0.53, 5.58) |
| Unexposed | Ref. | Ref. | Ref. | Ref. |
| Feeding difficulties | ||||
| Buprenorphine | 1.02 (0.40, 2.56) | 0.90 (0.36, 2.24) | 1.18 (0.45, 3.08) | 1.69 (0.61, 4.75) |
| Methadone | 0.33 (0.12, 0.92) | 0.12 (0.04, 0.38) | 1.49 (0.55, 4.02) | 4.68 (1.63, 13.45) |
| Unexposed | Ref. | Ref. | Ref. | Ref. |
| Small for gestational age | ||||
| Buprenorphine | 0.88 (0.44, 1.76) | 0.91 (0.42, 2.64) | 2.80 (1.39, 5.66) | 3.45 (1.47, 8.05) |
| Methadone | 4.49 (1.59, 12.66) | 4.45 (1.38, 14.33) | 0.59 (0.22, 1.62) | 0.80 (0.26, 2.46) |
| Unexposed | Ref. | Ref. | Ref. | Ref. |
| Maternal and obstetrical complications | ||||
| Length of maternal hospital stay (>7 days)c | ||||
| Buprenorphine | 0.68 (0.24, 1.88) | 1.04 (0.28, 3.82) | 4.95 (1.77, 13.84) | 3.71 (0.98, 13.99) |
| Methadone | 1.78 (0.80, 3.96) | 2.76 (1.11, 6.88) | 6.51 (2.93, 14.44) | 5.26 (2.12, 13.06) |
| Unexposed | Ref. | Ref. | Ref. | Ref. |
| Caesarean delivery | ||||
| Buprenorphine | 0.36 (0.13, 1.01) | 0.51 (0.16, 1.59) | 2.98 (1.06, 8.35) | 2.10 (0.65, 6.78) |
| Methadone | 1.10 (0.52, 2.32) | 1.38 (0.53, 3.60) | 0.56 (0.27, 1.19) | 0.58 (0.23, 1.47) |
| Unexposed | Ref. | Ref. | Ref. | Ref. |
Abbreviations: IP = inverse probability; OR = odds ratios; CI = confidence intervals.
Counts and percentages of events were not reported due to small counts (<11) for most of the outcomes of interest.
Stabilized inverse-probability treatment weights (IPTWs) weights of early and late exposure were computed with the numerator model adjusting for baseline covariates (i.e., maternal age, race, year of birth, multiple gestation, pre-existing comorbid conditions, and healthcare resource utilization at baseline), and the denominator model adjusting for additional time-varying comedication use, substances use, and markers of OUD severity. Previous exposure history was included in the models for late exposure. Infant sex was included for adverse neonatal outcomes. A product of stabilized IPTWs for early and late exposure was used in outcome models.
Missing values were ≤0.5% and only complete cases were analyzed.