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J Perinatol. 2018 Jan;38(1):75-79. doi: 10.1038/jp.2017.157. Epub 2017 Oct 19.

Antenatal methadone vs buprenorphine exposure and length of hospital stay in infants admitted to the intensive care unit with neonatal abstinence syndrome.

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Division of Neonatology, Department of Pediatrics, Baylor University Medical Center and Pediatrix Medical Group, Dallas, TX, USA.
Division of Neonatology, Department of Pediatrics, Feinberg School of Medicine, Northwestern University, and the Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
Office of the Chief Quality Officer, Baylor Scott & White Health, Dallas, TX, USA.
Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Department of Economics, Clemson University, Clemson, SC, USA.
Department of Pediatrics, Duke University, Durham, NC, USA.
Pediatrix Medical Group, Greenville Memorial Hospital, Greenville, SC, USA.
Center for Research, Education, and Quality, Mednax, Inc, Sunrise, FL, USA.



Antenatal exposure to methadone or buprenorphine often causes neonatal abstinence syndrome (NAS) in newborns. However, comparative effects on affected infants' hospital courses are inconclusive. We sought to estimate the relationship of antenatal exposure with methadone or buprenorphine and infants' length of stay among hospitalized infants with NAS.


This was a retrospective cohort study of hospitalized infants with NAS with either maternal exposure. Eligible infants were singleton infants born ⩾36 weeks' gestation and diagnosed with NAS<7 days of age between 2011 and 2014 in the Pediatrix Clinical Data Warehouse. Infant with congenital anomalies and those of multiple gestation were excluded.


Of 3364 eligible infants, 2202 (65%) were exposed to methadone and 1162 (34%) to buprenorphine. Infants exposed to buprenorphine had a lower rate of pharmacologic treatment for NAS (88 vs 91%, P<0.001). Median length of hospital stay was shorter among infants exposed to buprenorphine (21 days (inter-quartile range; 13-31) vs methadone (24 days (15-38), P<0.0001)). On multivariable Cox proportional hazard analyses, buprenorphine was associated with a shorter length of stay (hazard ratio (HR)=1.47 (95% confidence interval (CI): 1.32-1.62, P<0.001) after controlling for maternal age, parity, race or ethnicity, prenatal care, smoking status, use of antidepressants, use of benzodiazepines, and infant gestational age, small for gestational age status, cesarean delivery, sex, out born status, type of pharmacotherapy, breast milk use, year and center. We observed similar results in model using infants matched 1:1 with propensity scores for antenatal medication exposure (HR 1.39 for buprenorphine, CI 1.32-1.62, P<0.001).


Among infants born ⩾36 weeks' gestation with NAS, antenatal buprenorphine exposure was associated with a decreased length of stay relative to antenatal methadone exposure.


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