Risk Factors Associated with Severe Neonatal Abstinence Syndrome Requiring Morphine

Introduction: The number of women with opioid use disorders (OUD) in pregnancy has steadily increased over the last twenty years. Management of OUD with opioid maintenance therapy (OMT) has significantly improved maternal and neonatal outcomes, however neonatal withdraw symptoms often occur. Understanding the specific factors that lead to neonatal abstinence syndrome (NAS) and the requirement of morphine is necessary to potentially mitigate this known side effect of OMT. The aim of the study was to identify which maternal and neonatal characters were most associated with severe NAS requiring morphine treatment.

Methods: This retrospective cohort study identified mothers and their neonates through the institutions’ Maternal Opioid Management Support (MOMS) program as women receiving OMT (defined as use of methadone or buprenorphine) who delivered singleton pregnancies at or greater than 36 weeks gestation from 2017 to 2020. The primary outcome was neonatal abstinence syndrome requiring morphine treatment. Maternal demographics, pregnancy behaviors (e.g. tobacco use, active drug use), and medication exposure (e.g. OMT type and dose, psychiatric medications) were collected along with maternal and fetal outcomes. Statistical analysis included Chi square tests, student t tests, and logistic regression modeling and was performed with significance levels of <0.05 using R Studio (V1.2.5042). Characteristics independently associated with morphine treatment were included in the model.

Results: Of 208 neonates exposed to OMT in utero, 181 (87%) developed NAS and 68 (33%) were admitted to the NICU. Of the neonates admitted to the NICU, 48 (26.8%) required NAS morphine treatment. Univariate analysis found age, active drug use in pregnancy, birth weight, OMT prescriber (OB versus methadone/pain clinic), OMT dose, and OMT type (p < 0.05). However, in multivariable logistic regression analysis, only birth weight (p=0.005) and active drug use in pregnancy (p=0.016) remained significantly associated with morphine treatment. There were no differences in maternal age, race, marital status, employment, parity, adequacy of prenatal care, BMI, tobacco usage, psychiatric medication usage, birth weight, neonatal gender, gestational age at delivery, mode of delivery and maternal co-morbidities in the group that developed NAS that required morphine treatment and those that did not.

Conclusion: Birth weight and active drug use in pregnancy may play a larger role in the severity of NAS than the type or dosage of OMT the neonate was exposed to in utero.

References: 1. Kaltenbach K, Holbrook AM, Coyle MG, et al. Predicting treatment for neonatal abstinence syndrome in infants born to women maintained on opioid agonist medication. Addiction. 2012;107 Suppl 1(0 1):45-52. doi:10.1111/j.1360-0443.2012.04038.
2. Mangat AK, Schmölzer GM, Kraft WK. Pharmacological and non-pharmacological treatments for the Neonatal Abstinence Syndrome (NAS). Semin Fetal Neonatal Med. 2019;24(2):133-141. doi:10.1016/j.siny.2019.01.009
3. Seligman NS, Salva N, Hayes EJ, Dysart KC, Pequignot EC, Baxter JK. Predicting length of treatment for neonatal abstinence syndrome in methadone-exposed neonates. Am J Obstet Gynecol. 2008;199(4):396.e1-396.e3967. doi:10.1016/j.ajog.2008.06.088
4. Siu A, Robinson CA. Neonatal abstinence syndrome: essentials for the practitioner. J Pediatr Pharmacol Ther. 2014;19(3):147-155. doi:10.5863/1551-6776-19.3.147