Table 3.
Significant unadjusted and IP-weighted hazard ratios and 95% CI for exposure to low dose (MME < 90 per week) and high dose (≥90 per week) opioids compared with unexposed pregnancies (time-varying exposure and covariates)
| Outcome eventsa | Low dose (MME < 90/week) vs unexposed |
High dose (MME ≥ 90/week) vs unexposed |
||
|---|---|---|---|---|
| Unadjusted HR (95% CI) | IP-weighted HR (95% CI) | Unadjusted HR (95% CI) | IP-weighted HR (95% CI) | |
|
| ||||
| Primary analyses: events occurred 1 week after opioid exposure | ||||
| Cesarean delivery | 1.36 (0.64–2.88) | 0.90 (0.33–2.42) | 3.22 (1.78–5.83) | 3.97 (2.26–6.97) |
| Neuraxial anesthesia during labor vs None/local anesthesiab | 1.18 (0.77–1.81) | 1.48 (0.80–2.77) | 2.05 (1.34–3.15) | 2.12 (1.48–3.04) |
| Operative vaginal delivery, Yes, vs No | 1.67 (0.95–2.96) | 2.25 (1.06–4.79) | 1.67 (0.83–3.34) | 2.37 (1.32–4.27) |
| Postpartum hemorrhage, Yes, vs No | 3.42 (0.85–13.72) | 6.74 (1.22–37.15) | N/A | N/A |
| Antepartum depression, Yes, vs No | 2.06 (0.86–4.96) | 2.08 (0.85–5.10) | 1.78 (0.59–5.37) | 6.05 (1.79–20.46) |
| Secondary analyses: events occurred within 1 week of opioid exposure | ||||
| Cesarean delivery, Yes, vs No | 0.78 (0.29–2.09) | 0.56 (0.17–1.82) | 3.81 (2.19–6.63) | 4.37 (2.59–7.38) |
| Neuraxial anesthesia at labor vs None/local anesthesiab | 1.18 (0.77–1.81) | 1.47 (0.79–2.74) | 2.06 (1.34–3.15) | 2.13 (1.46–3.11) |
| Operative vaginal delivery, Yes, vs No | 1.25 (0.66–2.40) | 1.72 (0.76–3.88) | 2.08 (1.12–3.86) | 2.75 (1.60–4.72) |
| Postpartum hemorrhage, Yes, vs No | 3.42 (0.85–13.72) | 6.78 (1.18–38.97) | N/A | N/A |
| Antepartum depression, Yes, vs No | 2.07 (0.86–4.97) | 2.00 (0.89–4.49) | 2.38 (0.92–6.18) | 6.56 (2.28–18.93) |
| Cardiac events, Yes, vs No | N/A | N/A | 14.79 (2.01–108.54) | 27.06 (3.13–234.24) |
Adjusted for previous exposure history, baseline covariates (i.e., time interval and polynomial terms, maternal age, quadratic form of maternal age, race, year of birth, multiple gestation, pre-existing comorbid conditions) in the numerator models, and previous exposure history, baseline covariates, time-varying pain indications and comedication use in the denominator models
90 MME per gestational week is the estimated median of weekly cumulative MME in the exposed pregnancies
CI confidence interval, HR hazard ratio, IP inverse probability, MME milligram morphine equivalent, N/A the results are not available due to the limited number of outcome events
Only present outcomes with a significant association with opioid low or high dose exposure
Assuming anesthesia during labor is missing completely at random and only complete cases were analyzed. Neuraxial anesthesia during labor includes spinal or epidural anesthesia