Development and Validation of a Model to Predict Neonatal Abstinence Syndrome

J Pediatr. 2021 Feb:229:154-160.e6. doi: 10.1016/j.jpeds.2020.10.030. Epub 2020 Oct 17.


Objectives: To develop and validate clinical risk prediction tools for neonatal abstinence syndrome (NAS).

Study design: We developed prediction models for NAS based on a set of 30 demographic and antenatal exposure covariates collected during pregnancy. Data (outpatient prescription, vital, and administrative records), were obtained from enrollees in the Tennessee Medicaid Program from 2009 to 2014. Models were created using logistic regression and backward selection based on improvement in the Akaike information criterion, and internally validated using bootstrap cross-validation.

Results: A total of 218 020 maternal and infant dyads met inclusion criteria, of whom 3208 infants were diagnosed with NAS. The general population model included age, hepatitis C virus infection, days of opioid used by type, number of cigarettes used daily, and the following medications used in the last 30 day of pregnancy: bupropion, antinausea medicines, benzodiazepines, antipsychotics, and gabapentin. Infant characteristics included birthweight, small for gestational age, and infant sex. A high-risk model used a smaller number of predictive variables. Both models discriminated well with an area under the curve of 0.89 and were well-calibrated for low-risk infants.

Conclusions: We developed 2 predictive models for NAS based on demographics and antenatal exposure during the last 30 days of pregnancy that were able to risk stratify infants at risk of developing the syndrome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Analgesics / administration & dosage
  • Analgesics / adverse effects
  • Antiemetics / administration & dosage
  • Antiemetics / adverse effects
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / adverse effects
  • Benzodiazepines / administration & dosage
  • Benzodiazepines / adverse effects
  • Bupropion / administration & dosage
  • Bupropion / adverse effects
  • Female
  • Gabapentin / administration & dosage
  • Gabapentin / adverse effects
  • Hepatitis C / epidemiology
  • Humans
  • Infant, Low Birth Weight
  • Infant, Newborn
  • Infant, Small for Gestational Age
  • Male
  • Maternal Age
  • Maternal Exposure / adverse effects
  • Maternal-Fetal Exchange
  • Neonatal Abstinence Syndrome / diagnosis*
  • Opiate Substitution Treatment
  • Opioid-Related Disorders / drug therapy
  • Pregnancy
  • Retrospective Studies
  • Risk Assessment / methods*
  • Sex Distribution
  • Smoking / epidemiology
  • Smoking Cessation Agents / administration & dosage
  • Smoking Cessation Agents / adverse effects
  • Young Adult


  • Analgesics
  • Antiemetics
  • Antipsychotic Agents
  • Smoking Cessation Agents
  • Bupropion
  • Benzodiazepines
  • Gabapentin