Characterizing Associations between Neonatal Abstinence Syndrome and Orofacial Clefting

Orofacial clefting is the most common developmental craniofacial malformation, with a prevalence of about 1 in 700(1,2). Etiologies are thought to be multifactorial(1,2). West Virginia is at the epicenter of the current opioid crisis in the United States(3). Our center has witnessed a large number of newborn infants recovering from neonatal abstinence syndrome (NAS) secondary to in-utero narcotics exposure. Within this group, orofacial clefting has been noted. We sought to characterize the prevalence and associations of orofacial clefting in infants with NAS.

This retrospective study analyzed live births at our institution from 2013-2017 to determine the prevalence of orofacial clefting in our general inborn population compared to infants born with concomitant NAS.

There were 11,599 live births in the study period, 1179 of which had documented NAS. 25 patients were born with orofacial clefting, 8 of whom were recovering from NAS. Odds ratios for NAS patients having developed orofacial clefting, isolated cleft palate, isolated cleft lip, and combined cleft lip and palate compared to the general inborn population were found to be 4.18 (p=.001), 5.92 (p=.001), 3.79 (p=.05), and 2.94 (p=.35), respectively. In comparing the orofacial clefting populations in the NAS and general inborn populations, no significant differences existed in terms of gender, race/ethnicity, birth weight, gestational age at birth, length at birth, head circumference at birth, APGAR scores, and/or newborn screen findings. Additionally, there were no significant differences between the two groups related to prenatal care, folate supplementation during the first trimester, gestational alcohol, cigarette, or marijuana exposures. The only discernable difference between the two populations were exposures to drugs of addiction. In the NAS population, where orofacial clefting was observed, all 8 newborns had documented exposure to opiates during the first trimester – 7 patients were exposed to buprenorphine and 1 patient was exposed to methadone. In the general inborn population with clefting, only 1 patient had exposure to drugs of addiction, which were Percocet and amphetamines.

Prevalence of orofacial clefting in infants with NAS in our population was significantly higher than the general population of live births. Isolated cleft palate and isolated cleft lip, specifically, were significantly more prevalent in NAS patients compared to the general population in this cohort. Interestingly, all 8 patients with orofacial clefting in the NAS inborn population were associated with physician-prescribed opiates, buprenorphine and methadone. Future efforts will involve development of a statewide registry to capture all live births in the state detailing true incidence of NAS, opiate exposure, clefting, and associations between them.

References:

1. Ramanathan A, Deepak T, Krishna S, Ravindra S, Lakhani H. Cleft Lip and Cleft Palate: A Comprehensive Understanding of Etiology, Pathogenesis and an Oral Physician’s Role in Comprehensive Care. Science 2016;5(4-1):14-19
2. Dixon MJ, Marazita ML, Beaty TH, Murray JC. Cleft lip and palate: understanding genetic and environmental influences. Nature Reviews Genetics 2011;12(3):167-78
3. Hedegaard H, Warner M, Miniño AM. Drug overdose deaths in the United States, 1999-2015: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics, 2017.