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. Author manuscript; available in PMC: 2022 Feb 10.
Published in final edited form as: Drug Saf. 2021 Oct 5;44(12):1297–1309. doi: 10.1007/s40264-021-01115-6

Table 4.

Significant unadjusted and IP-weighted hazard ratios and 95% CI for specific opioids compared with unexposed pregnancies (time-varying exposure and covariates)

Outcome Primary analyses
Secondary analyses
Events occurred 1 week after opioid exposure
Events occurred within 1 week of opioid exposure
Unadjusted HR (95% CI) IP-Weighted HR (95% CI) Unadjusted HR (95% CI) IP-Weighted HR (95% CI)

Cesarean delivery, Yes vs No
 Hydrocodone vs unexposed 2.35 (1.01–5.40) 2.15 (0.52–8.57) 2.30 (1.09–4.85) 2.69 (0.88–8.24)
 Oxycodone vs unexposed 2.12 (0.83–5.39) 4.05 (1.92–8.56) 1.93 (0.83–4.53) 2.81 (1.00–7.88)
 Codeine vs unexposed 1.62 (0.66–3.94) 1.24 (0.48–3.29) 1.94 (0.92–4.10) 1.43 (0.61–3.33)
Neuraxial anesthesia during labor vs None/local anesthesiab
 Hydrocodone vs unexposed 1.06 (0.54–2.08) 1.84 (0.72–4.70) 1.16 (0.65–2.06) 1.51 (0.81–2.84)
 Oxycodone vs unexposed 1.53 (0.83–2.82) 1.68 (1.31–2.15) 1.32 (0.74–2.34) 1.62 (1.18–2.21)
 Codeine vs unexposed 1.88 (1.21–2.93) 1.83 (1.02–3.29) 1.96 (1.31–2.93) 1.81 (1.10–2.98)
Operative vaginal delivery, Yes, vs No
 Hydrocodone vs unexposed 1.18 (0.44–3.17) 1.47 (0.52–4.23) 0.74 (0.24–2.34) 0.65 (0.21–2.01)
 Oxycodone vs unexposed 2.58 (1.25–5.34) 3.53 (2.19–5.71) 1.97 (0.97–3.99) 4.15 (2.32–7.43)
 Codeine vs unexposed 1.09 (0.46–2.62) 0.81 (0.28–2.35) 1.52 (0.78–2.96) 1.43 (0.55–3.70)
Antepartum depression, yes, vs no
 Hydrocodone vs unexposed 1.61 (0.40–6.48) 1.87 (0.50–6.97) 2.02 (0.65–6.21) 3.00 (1.02–8.82)
 Oxycodone vs unexposed 4.36 (1.74–10.96) 13.18 (6.03–28.78) 4.08 (1.76–9.42) 11.93 (5.50–25.87)
 Codeine vs unexposed 1.36 (0.34–5.46) 1.21 (0.31–4.73) 1.18 (0.29–4.77) 0.86 (0.22–3.43)
Cardiac events, Yes, vs No
 Hydrocodone vs unexposed N/A N/A 18.13 (2.46–133.55) 38.73 (4.45–336.82)
 Oxycodone vs unexposed N/A N/A N/A N/A
 Codeine vs unexposed N/A N/A N/A N/A

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, N/A the results are not available due to the limited number of outcome events

a

Only present outcomes with a significant association with opioid low or high dose exposure

b

Assuming anesthesia during labor is missing completely at random and only complete cases were analyzed. Neuraxial anesthesia during labor includes spinal or epidural anesthesia