Date of Award

January 2026

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Frances Y. Cheng

Abstract

Infants with neonatal opioid withdrawal syndrome (NOWS) face significant nutritional challenges due to increased metabolic demands from hypertonia, tremors, and irritability combined with feeding difficulties including weak and uncoordinated suckling. These infants experience greater early weight loss compared to non-opioid-exposed newborns. Feeding practices remain highly variable across the United States, with only 33% of institutions using calorically enhanced feeds and no standardized guidelines to guide clinical practice. We conducted a double-blind, randomized controlled pilot study (NCT04419857, Connecticut, USA) to assess feasibility of early high calorie feeding in infants with NOWS managed using the ESC approach. Eligible infants born at ≥36 weeks’ gestation with prenatal exposure to methadone or buprenorphine were randomized within 48 hours of birth to receive either high calorie formula (24 kcal/oz) or standard calorie formula (20 kcal/oz). Primary outcomes included enrollment, retention, and adherence to assigned feeding protocols. Secondary outcomes included maximal percent weight loss, length of hospital stay, breastfeeding rates, and stool frequency. From December 2020 through August 2023, 39 of 65 eligible families (60%) consented and 35 infants were randomized, with 25 completing hospitalization on study formula and 10 completing all 14 days. Maternal and infant characteristics were comparable between groups, including opioid agonist type, gestational age, and birth weight. 84% of feeds were adherent with study protocol during hospitalization. The high calorie group demonstrated a non-significant difference in maximal percent weight loss compared to standard calorie (-9.1% versus -5.4%, p=0.12), with similar length of stay (p=0.88). Notably, no infants in either group received pharmacologic treatment. Infants in the high calorie group were significantly more likely to receive breastmilk at discharge (52.6% versus 18.8%, p=0.04) despite similar breastfeeding intent at birth. Median stool frequency showed no difference between groups (4 stools/day, p=0.59). This pilot study demonstrates that early high calorie feeding for infants with NOWS is achievable, with reasonable consent rates and high adherence during hospitalization, and does not negatively impact breastfeeding or stooling patterns.

Comments

This thesis is restricted to Yale network users only. It will be made publicly available on 07/14/2027

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