576 - Health Outcomes through 2 Years of Age for Infants in the Eating, Sleeping, Consoling for Neonatal Opioid Withdrawal (ESC-NOW) study

Publication Number: 576.5226

Lori A.. Devlin, University of Louisville School of Medicine, Louisville, KY, United States; Zhuopei Hu, UAMS, Little Rock, AR, United States; Stephanie L. Merhar, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Song Ounpraseuth, UAMS, Little Rock, AR, United States; Brian Smith, Duke University, Durham, NC, United States; Rachel G. Greenberg, Duke Clinical Research Institute, Durham, NC, United States; Abhik Das, RTI International, North Potomac, MD, United States; Jessica Snowden, Univ of Tennessee Health Science Center, Memphis, TN, United States; Leslie Young, Larner College of Medicine at the University of Vermont, Burlington, VT, United States; NICHD Neonatal Research Network, National Institute of Child Health and Human Development, Bethesda, MD, United States; ECHO IDeA States Pediatric Clinical Trials Network, n/a, North Bethesda, MD, United States

Background: Infants with neonatal opioid withdrawal syndrome (NOWS) are at risk of poor feeding, suboptimal growth, hospital readmissions, and non-accidental trauma during early childhood. The relationship between these risks and care approaches for NOWS has not been well defined. We hypothesized that management with the ESC care approach would be associated with improved health outcomes through 2 years of age.

Objective: To determine if use of ESC is associated with improved health outcomes through 2 years when compared to usual care in a subpopulation of consented infants from the ESC-NOW trial.

Design/Methods: In this prospective cohort we compared differences in feeding, growth, nonscheduled medical care, non-accidental trauma, and death through 2 years of age for infants with NOWS born at ≥ 36weeks gestation and cared for with ESC vs usual care during the newborn hospitalization. Growth outcomes included data from infants 22-30 months of age.
Mixed-effects Poisson regression with robust error variance to report relative risk for binary outcomes and Firth's bias-reduced logistic regression for binary outcomes with rare events, to report odds ratios were used. Linear mixed-effects models with random intercepts for sites were used for continuous variables.

Results: Of the 1,305 infants enrolled in ESC-NOW, 674 (52%) were consented for follow-up (368 (55%) in usual care and 306 (45%) in ESC). Baseline characteristics were similar between groups except for ethnicity and rurality (Table 1).
A higher proportion of infants in the ESC group received maternal breastmilk at 6 months (6.2% vs 14%, absolute difference 7.7%; 95%CI:3.1,12.3;p < 0.001) when compared to usual care. No difference in exclusive breastfeeding at 6 months was noted between groups, although numbers were small. Anthropometric z-scores at the 2 year visit were similar between groups, however, the change in the head circumference z-score between birth and the 2 year visit was substantially greater (1.08 vs 0.66; absolute difference 0.42;95%CI:0.08, 0.77) in the ESC group when compared to usual care (Table 2). No substantial differences were noted between groups in the mean number of emergency room/urgent care visits or hospital readmissions through 2 years of age. All 7 reports of nonaccidental trauma were in the usual care group. Deaths were equally distributed between groups (3 in usual care vs 4 in ESC).

Conclusion(s): Use of the ESC care approach for the assessment and management of infants with NOWS was associated with improved health outcomes as evidenced by increased receipt of maternal breastmilk and enhanced head growth through 2 years of age.

Table 1: Maternal and Infant Characteristics for the ESC-NOW Follow-up Cohort
* MOUD - Medication for Opioid Use Disorder, RUCA - Rural-Urban Commuting Area Codes
a Race and ethnicity were obtained from the electronic medical record. Difference in ethnicity between the 2 groups was significant at p = 0.02 with Fisher’s Exact test.
b Difference between 2 groups was significant with Chi-square test

Table 2: Infant Wellness Parameters through 2 Years of Age for the ESC-NOW Follow-up Cohort
The sample size for feeding and healthcare utilization outcomes varied based on caregiver report of the outcome on follow-up questionnaires and the sample size for growth outcomes varied based on measurement of growth at the 2 year visit (weight recorded in the electronic medical record between 22 and 30 months of age was allowed if weight was not successfully obtained at the 2 year visit)
* Adjusted for race/ethnicity, adequate prenatal care, MOUD use, RUCA, marital status, gestational age, polysubstance exposure, discharge home with parents, and any change in custody
** BMI - Body Mass Index, ER - Emergency Room
a z-scores were calculated using the World Health Organization’s growth standards for infants aged 0 to 2 years at birth
b z-scores were calculated using the CDC growth standards at the 2 years follow-up visit
ꝉ Reported as Relative Risk (RR) based on mixed effect Poisson regression model with robust error variance
ꝉ ꝉ The number of events is less than 5%. Firth’s Bias-Reduced logistic regression was implemented and reported as Odds ratio
*** p value <0.05
**** p value <0.001