520 - A randomized pilot study for standard- vs high-calorie feeding in infants with Neonatal Opioid Withdrawal Syndrome (NOWS) managed by the Eat, Sleep, Console (ESC) Approach

Publication Number: 520.3577

Frances Cheng, Yale University School of Medicine, New Haven, CT, United States; McKenzie R. Tuttle, Yale School of Medicine, New Haven, CT, United States; Elyssa Dionne, Yale School of Medicine, New Haven, CT, United States; Veronika Shabanova, Yale School of Medicine, New Haven, CT, United States; Sarah McCollum, Yale School of Medicine, New Haven, CT, United States; Alyssa Morrison, Duke University School of Medicine, Durham, NC, United States; Sandra anyoha, Yale-New Haven Children's Hospital, 62 High Rock Rd, CT, United States; Lynda S. Swerling, Yale-New Haven Children's Hospital, New Haven, CT, United States; Kristen Fulton, Yale-New Haven Children's Hospital, New London, CT, United States; Dhatri Abeyaratne, Yale School of Medicine, 1050 State St Apt 520, CT, United States; Grace Wang, Yale School of Medicine, New Haven, CT, United States; Christine Hodelin, Yale School of Medicine, New Haven, CT, United States; Lina A. Elmansy, Yale School of Medicine, New Haven, CT, United States; Eugene Shapiro, Yale University, New Haven, CT, United States; Matthew Grossman, Yale School of Medicine, New Haven, CT, United States

Background: Few prospective studies guide nutritional management for infants with NOWS, who face risk of greater early weight loss and poor weight gain.

Objective: This double-blind randomized pilot examines the feasibility of giving high calorie feeds within 48 hours of birth to infants with NOWS managed with the ESC approach.

Design/Methods: We randomized methadone or buprenorphine-exposed infants to standard (20kcal/oz) or high calorie (24kcal/oz) feeds, balanced by gender, gestational age, and intent to breastfeed. Exclusions included birth weight < 2200 grams, < 36 weeks gestation, NICU stay >48 hours, or congenital malformations. Primary outcomes were % parents of eligible infants agreeing to participate, retention, and adherence to assigned feeding and weighing protocols. Infant characteristics of days to weight nadir, length of stay (LOS), breastmilk at discharge, and stools per day were compared between caloric groups using the Wilcoxon rank sum test. Weight change from birth to 7 days to assess maximum % weight loss was compared using quantile regression, adjusting for primary maternal opioid type and breastmilk feeding at discharge, and summarized with medians and 95% Confidence Intervals.

Results: From December 2020-August 2023, 65 parents of eligible infants were approached for enrollment, and 35 (56.5%) were randomized (Figure 1A). Groups had comparable demographic characteristics; none received pharmacologic treatment (Table 1A). Most (86.7%) adhered to assigned feeding, and twice daily weights were obtained on 82.7% of days during hospitalization. After hospitalization, weights were available for 17 (47.2%) infants on day 7, 12 (33.3%) on day 10, and 10 (27.7%) on day 14. Standard and high-calorie groups did not differ meaningfully in maximum % weight loss [-5.4% (-7.6%, -3.3%) vs -9.2% (-10.3%, -7.6%), p = 0.12]; days to weight nadir [3.5 (2.0, 5.0) vs. 4.0 (3.0, 4.0) days, p = 0.54]; or LOS [3.9 (3.0, 5.0) vs. 3.7 (3.1, 5.3), p = 0.88]. High-calorie group infants were more likely to receive breastmilk at discharge (52.7% vs 18.8%, p = 0.04). There was no difference in stools per day between groups [4.0 (3.0, 5.0) vs 4.0 (3.0, 5.0), p = 0.59] (Table 1B).

Conclusion(s): This study suggests early initiation of high calorie feeds for infants with NOWS managed by the ESC approach is feasible and does not negatively impact breastfeeding or stooling patterns. Limitations included small sample size and low protocol adherence post-hospitalization, likely worsened by the impact of the COVID-19 pandemic.

Table 1. Patient Demographics and Newborn Clinical Outcomes.
PAS RCT Table 1 2025.pdf1A. Patient Demographics; 1B. Newborn Clinical Outcomes

Figure 1. Consort Diagram and Median Weight Change from Birth.
PAS RCT Paper Figures 2025.pdf1A. Consort Diagram. 1B. Median Weight Change from Birth

Table 1. Patient Demographics and Newborn Clinical Outcomes.
PAS RCT Table 1 2025.pdf1A. Patient Demographics; 1B. Newborn Clinical Outcomes

Figure 1. Consort Diagram and Median Weight Change from Birth.
PAS RCT Paper Figures 2025.pdf1A. Consort Diagram. 1B. Median Weight Change from Birth