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Opioid use disorder and neonatal abstinence syndrome (NAS) increased in Massachusetts from 1999 to 2013 (1,2). In response, in 2016, the state passed a law requiring birth hospitals to report the number of newborns who were exposed to controlled substances to the Massachusetts Department of Public Health (MDPH)* by mandating monthly reporting of International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic codes related to maternal dependence on opioids (F11.20) or benzodiazepines (F13.20) and to newborns affected by maternal use of drugs of addiction (P04.49) or experiencing withdrawal symptoms from maternal drugs of addiction (P96.1) separately.† MDPH uses these same codes for monthly, real-time crude estimates of NAS and uses P96.1 alone for official NAS state reporting.§ MDPH requested CDC's assistance in evaluating the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of either maternal or newborn codes to identify substance-exposed newborns, and of newborn exposure codes (both exposure [P04.49] or withdrawal [P96.1]) and the newborn code for withdrawal alone (P96.1) to identify infants with NAS cases related to three exposure scenarios: 1) opioids, 2) opioids or benzodiazepines, and 3) any controlled substance. Confirmed diagnoses of substance exposure and NAS abstracted from linked clinical records for 1,123 infants born in 2017 and their birth mothers were considered the diagnostic standard and were compared against hospital-reported ICD-10-CM codes. For identifying substance-exposed newborns across the three exposure scenarios, the newborn exposure codes had higher sensitivity (range = 31%-61%) than did maternal drug dependence codes (range = 16%-41%), but both sets of codes had high PPV (≥74%). For identifying NAS, for all exposure scenarios, the sensitivity for either newborn code (P04.49 or P96.1) was ≥92% and the PPV was ≥64%; for P96.1 alone the sensitivity was ≥79% and the PPV was ≥92% for all scenarios. Whereas ICD-10-CM codes are effective for NAS surveillance in Massachusetts, they should be applied cautiously for substance-exposed newborn surveillance. Surveillance for substance-exposed newborns using ICD-10-CM codes might be improved by increasing the use of validated substance-use screening tools and standardized facility protocols and improving communication between patients and maternal health and infant health care providers. [ABSTRACT FROM AUTHOR]