Cleft Lip and Palate in Newborns Diagnosed With Neonatal Abstinence Syndrome

Abstract

Objective Cleft lip and/or cleft palate (CLP) is the most common major congenital malformation of the head and neck. Previous studies suggested an association between fetal opioid exposure and CLP. This study seeks to evaluate the associations between CLP and neonatal abstinence syndrome (NAS) in the United States. Study Design Population-based inpatient registry analysis. Setting Academic medical center. Subjects and Methods Kids’ Inpatient Database (2016) was used to identify weighted in-hospital births with diagnoses of CLP or NAS. Demographic information was obtained. Results Among 3.8 million weighted in-hospital births, prevalence rates of CLP in the NAS and non-NAS populations were 3.13 and 1.35 per 1000, respectively. The odds ratios for patients with NAS developing CLP, isolated cleft palate, isolated cleft lip, and cleft lip and palate when compared with the reference population were 2.33 (95% CI, 1.87-2.91; P < .001), 4.97 (95% CI, 3.84-6.43; P < .001), 1.01 ( P = .98), and 0.80 ( P = .46). Independent predictors of CLP within the NAS population included median household income for patients’ zip code, race, hospital region, payment method, and maternal use of tobacco or other drugs of addiction. The binary logistic regression model accounting for possible confounding variables produced an odds ratio of 1.74 (95% CI, 1.36-2.23; P < .001) for the association between NAS and CLP. Conclusion Our study found an association between NAS and CLP, specifically isolated cleft palate, suggesting that prenatal exposure to opioids may be an environmental risk factor in the development of CLP.

Cleft Lip and/or Palate in Infants Prenatally Exposed to Opioids

“…In the NOWS groups, the prevalence of CL/P per 1000 in this study at 6.80 was virtually identical to that of Mullins et al (2019) at 6.79. Both of these prevalence numbers were much higher than that reported by Danis et al (2020) at 3.13, most likely due to the national nature of their study and large population.…”

“…Now that there are similar findings from 3 large scale studies of the association between prenatal OE and CL/P, consideration of a theoretical view is warranted. Both Mullens et al (2019) and Danis et al (2020) emphasized the need for better understanding of the environmental risk factors for CL/P in the NOWS population. However, the likelihood of isolating risk factors individually is challenging, given the complexity of the population (Kocherlakota, 2014; Bailey et al, 2017).…”

“…Most recently 2 very large retrospective cohort studies were conducted by Mullens et al (2019) and Danis et al (2020) to better understand the association between NOWS and CL/P. Mullens et al (2019) analyzed 11 599 live hospital births in West Virginia University’s tertiary care center between 2013 and 2017.…”

“…We hypothesized that across CL/P categories, infants with NOWS would have prevalence rates and odds ratios higher than those not exposed to opioids (Mullens et al, 2019; Danis et al, 2020). We had no predictions about infants prenatally opioid exposed but without NOWS.…”

Does Prematurity Play a Role in Newborn Microtia-Anotia?

“…This is a technique, which has been used in in another paper looking at associations within the KID database. 35 Due to the variability in household incomes within a single zip code, which encompasses multiple communities, this may be an imprecise measure of socioeconomic status. There may also be a selection bias against extremely premature infants, who are at greater risk of mortality in early life.…”