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Nitrous oxide in labor and neonatal hyperbilirubinemia: a retrospective propensity score-matched study (2012-2023)
P Vovk Racman1, T Stopar Pintaric1, I Verdenik2
1Department of Anaesthesiology and Surgical Intensive Therapy, University Medical Centre Ljubljana, Ljubljana, Slovenia; Medical Faculty, University of Ljubljana, Vrazov trg 2, Ljubljana, Slovenia.
Background:
We aimed to evaluate the association between intrapartum nitrous oxide analgesia and neonatal hyperbilirubinemia compared with other analgesic methods, and to assess additional short-term neonatal outcomes.
Methods:
This retrospective epopulation-based, retrospective propensity score-matched cohort study used data from the Slovenian National Perinatal Database. Singleton pregnancies at ≥35 weeks' gestation from 2012 to 2023 were included. Cases with intrapartum nitrous oxide analgesia, remifentanil, pethidine, or neuraxial analgesia were matched 1:1:1:1 based on maternal age, parity, body-mass-index, socioeconomic status, smoking, gestational age, and labor duration. The primary outcome was neonatal hyperbilirubinemia. Secondary outcomes included neonatal intensive care unit (NICU) admission, Apgar scores <7 at 1 and 5 min, neonatal hypoglycemia, and a composite of respiratory morbidity. Outcomes were compared using chi-square tests with Bonferroni-corrected pairwise comparisons.
Results:
The study included 32,744 births (8,186 per group). Neonatal hyperbilirubinemia rate was 13.5% with nitrous oxide exposure, 14.9% with remifentanil, 15.8% with pethidine, and 14.2% with neuraxial analgesia (P = 0.0003). Hyperbilirubinemia rate was significantly higher after pethidine exposure compared with nitrous oxide (P = 0.0002) however NICU admission was more common after nitrous oxide exposure (n = 244; P < 0.001). Pethidine exposure was associated with more frequent Apgar <7 at 1 min (n = 245; P < 0.001), and remifentanil was associated with more frequent neonatal hypoglycemia (n = 222; P < 0.001). There were no significant differences in Apgar <7 at 5 min or respiratory morbidity between exposures.
Conclusions:
Intrapartum nitrous oxide analgesia was not associated with increased neonatal hyperbilirubinemia compared with other labor analgesic modalities. However, the NICU admission rate after nitrous oxide exposure was significantly higher.
