Neonatal Abstinence Syndrome in the MATernaL and Infant clinical NetworK

Neonatal abstinence syndrome (NAS) is a group of conditions occurring when newborns experience withdrawal symptoms from exposure to certain substances during pregnancy, predominately opioids (defined recently as neonatal opioid withdrawal syndrome [NOWS]).1 From 2010 to 2021, NAS diagnoses increased from 4.0 to 6.2 per 1000 birth hospitalizations in the United States.2Accurate identification of NAS/NOWS is essential for public health surveillance, resource allocation, and ensuring infants receive appropriate care. However, the clinical diagnosis of and the surveillance methods for NAS/NOWS vary considerably, leading to inconsistent prevalence estimates.3 Recently, standardized clinical and public health case definitions have been released but not evaluated in a large, multisite study.4,5 Understanding how different definitions affect estimates is critical for interpreting surveillance data and guiding clinical practice; therefore, we used data from the MATernaL and Infant clinical NetworK (MAT-LINK)6 to calculate NAS/NOWS prevalence estimates using current case definitions to understand differences in estimates and explore overlap.We analyzed data from 7 clinical sites providing care for women with opioid use disorder (OUD) during pregnancy and participating in the MAT-LINK surveillance system, a network of 10 sites providing electronic health record (EHR) information for multiple cohorts of pregnant woman–infant linked dyads based on exposures of interest. Individuals were included in the OUD cohort if they had a known pregnancy outcome occurring between January 1, 2014, and August 31, 2021, and an OUD diagnosis during that pregnancy, described elsewhere.6 Sampling weights were used to account for unequal selection probabilities between pregnancies that did not receive medication for OUD (MOUD), including buprenorphine and methadone.6 We calculated the weighted prevalence of NAS/NOWS among live-born infants (N = 5022) using 4 case definitions: (1) Council of State and Territorial Epidemiologists (CSTE) 2023 NAS tier 1 standardized surveillance confirmed case definition4; (2) EHR indication of a chief complaint of NAS/NOWS (infant’s chief complaint or diagnosis from progress notes or problem list); (3) NOWS clinical case definition5; and (4) International Classification of Diseases, 9 and 10th Revision, Clinical Modification (ICD-9/10-CM) codes (779.5, P96.1) (Supplemental Material 1). For this analysis, NAS and NOWS are used interchangeably to examine all available case definitions. We examined overlap among infants with information on components of all case definitions.This activity was determined to be nonresearch and exempt from review by the Centers for Disease Control and Prevention (CDC) Institutional Review Board (IRB) and was conducted consistent with applicable federal law and policy (eg, 45 CFR part 46.102.l.2; 21 CFR part 56; 42 USC §241.d; 5 USC §552a; 44 USC §3501; et seq). MAT-LINK sites underwent local IRB review and received approval or exemption.NAS/NOWS prevalence among infants born to women with OUD in MAT-LINK ranged from 47.2% (ICD-9/10-CM codes) to 85.9% (CSTE case definition) (Table 1). Among infants meeting the CSTE case definition, 77.3% had a documented chief complaint of NAS/NOWS, and 59.9% had a corresponding ICD-9/10-CM code. ICD codes were documented among 69.7% of those with a chief complaint and 60.7% of those meeting the NOWS clinical case definition (Table 2). Among infants meeting the NOWS clinical case definition, overlap with the CSTE case definition was 84.9%. Among infants meeting at least 1 case definition, 76.1% were identified by 2 or more case definitions.Prevalence of NAS/NOWS varied, with moderate to substantial overlap noted. ICD-9/10-CM code estimates were lowest, consistent with previous research3; the CSTE case definition identified the most infants; and the NOWS and EHR chief complaint case definitions fell in between. Higher estimates for the CSTE definition might reflect NAS diagnoses capturing a broader set of exposures, including opioids, benzodiazepines, and barbiturates, whereas NOWS only captures opioids.A study strength was the multicenter approach. However, limitations include the focus on clinical sites specializing in treating substance use disorder during pregnancy, and results may be more applicable to sites with specialized perinatal addiction care. High rates of MOUD among pregnant women at these sites may result in higher NAS/NOWS prevalence than in other populations.2,7These findings indicate that infants may be overlooked if relying solely on ICD codes for identification. ICD codes are frequently used for surveillance but might underestimate this condition’s true prevalence. Improving clinical documentation of NAS/NOWS, including diagnoses/chief complaint, withdrawal signs, and evidence of substance exposure might improve identification of infants, which can facilitate referral to support services. Future studies may consider examining reasons for variability in infant identification and classification using these case definitions.The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC. This project was supported in part by an appointment to the Research Participation Program at the CDC administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the CDC.