Buprenorphine vs. morphine: impact on neonatal opioid withdrawal syndrome (NOWS) outcomes in a single center retrospective study.

OBJECTIVES: To compare clinical outcomes for infants with neonatal opioid withdrawal syndrome (NOWS) treated with buprenorphine or morphine. STUDY DESIGN: Retrospective study of infants born ≥35 weeks' gestation and admitted to the NICU for NOWS treatment between 2011 and 2022. Length of treatment, length of stay in the hospital, and the need for secondary medications were compared between buprenorphine and morphine treated neonates. Multiple regression analysis was performed, adjusting for baseline differences and confounders. RESULTS: 417 neonates were treated with morphine and 232 with buprenorphine. The buprenorphine group had shorter treatment days [-10.8 days; 95% CI: -8.08 to -13.53] and shorter hospital stay [-11.8 days; 95% CI: -8.83 to -14.78]. The buprenorphine group was no more likely to receive phenobarbital or clonidine (26% vs. 29%). CONCLUSION: In this large single-center study, buprenorphine was associated with shorter lengths of treatment and hospital stay in the treatment of NOWS compared to morphine.

DNA methylation patterns in umbilical cord blood from infants of methadone maintained opioid dependent mothers.

Methadone maintenance treatment for opioid dependent mothers is standard of care. Infants of methadone maintained opioid dependent (MMOD) mothers have better outcomes compared to infants of opioid dependent mothers without treatment. However, when compared to non-exposed infants, infants of MMOD mothers are associated with worse outcomes. We conducted a pilot study to examine genome wide differential DNA methylation using cord blood samples from sixteen term and near-term infants of MMOD and opioid naïve mothers, excluding Infants with chorioamnionitis. A total of 152 differentially methylated loci were identified at a difference > + 2, < - 2 and p-value < 0.05. There were 90 hypermethylated loci (59 annotated genes) and 62 hypomethylated loci (38 annotated genes) observed. The hypermethylated and hypomethylated DNA changes involved multiple genes, pathways and networks that may explain some of the changes seen in infants of MMOD mothers. Top hypermethylated and hypomethylated genes involved areas of cell growth, neurodevelopment, vision and xenobiotic metabolism functions. Our data may explain the role of key pathways and genes relevant to neonatal outcomes seen from methadone exposure in pregnancy. Functional studies on the identified pathways and genes could lead to improved understanding of the mechanisms and identify areas for intervention.

Sex-Related Differences in the Severity of Neonatal Opioid Withdrawal Syndrome: A Single-Center, Retrospective Cohort Study.

OBJECTIVE: Factors associated with the development and expression of Neonatal Opioid Withdrawal Syndrome (NOWS) are poorly understood. There are conflicting data on the role of infant sex in NOWS. Some studies have suggested that infant sex predicts NOWS severity and adverse outcomes, with male infants being more vulnerable. This study aimed to analyze if infant sex is associated with the severity of NOWS among those who require pharmacologic treatment. STUDY DESIGN: This is a retrospective cohort study of term and late-preterm infants (≥35 weeks gestation) exposed to in utero opioids, born between September 2006 and August 2022, and required pharmacologic treatment for NOWS. Maternal and infant demographics were collected. Indicators of the severity of NOWS (duration of medical treatment (DOT), duration of hospitalization, maximum dose of opioid treatment, and use of secondary medications) were compared between male and female infants. Standard statistical tests and regression analysis were used to establish the differences in outcomes after accounting for confounders and baseline differences. RESULTS: Out of the 1,074 infants included in the study, 47.9% were female, and 52.1% were male. There was no significant difference in demographic and baseline clinical characteristics between groups except for anthropometry (birth weight, head circumference, and length) and Apgar score at 5 minutes. The median DOT (25 days [14, 39] vs. 23 days [13, 39], p = 0.57), length of hospital stay (31.5 days [20, 44] vs. 28 days [20, 44], p = 0.35), treatment with phenobarbital (24.7 vs. 26.3%, p = 0.56), and clonidine (3.9 vs. 3.8%, p = 0.9) were similar in both groups. The differences remained nonsignificant after adjusting for birth anthropometric measurements, gestational age, 5-minute Apgar score, small for gestational age status, and maternal exposure to benzodiazepines. CONCLUSION: In this cohort of neonates, sex-related differences were not identified to influence the severity of NOWS among those who required pharmacological treatment. KEY POINTS: · Vulnerability to NOWS is multifactorial.. · The role of infant sex in the severity of NOWS is not concrete.. · We noted that sex did not impact NOWS severity in those treated..