Randomized pilot study comparing standard vs high-calorie feeding in infants with Neonatal Opioid Withdrawal Syndrome

Objective: We assessed feasibility of high-calorie feeds in infants with NOWS at risk for excessive weight loss managed using Eat, Sleep, Console. Study design: In this double-blind pilot study (NCT04419857, Connecticut, USA), we randomized methadone- or buprenorphine-prenatally-exposed infants <48 h old to standard- or high-calorie feeds. Primary outcomes were enrollment, adherence, and retention; exploratory outcomes included breastfeeding and stooling frequency. Results: From December 2020 to August 2023, 35/65 infants (53.8%) were randomized. During hospitalization, 84% of feeds adhered to the randomized feeding approach. In-hospital retention was 71.4%; 14-day post-discharge retention was 28.6%. Groups did not differ significantly in demographic characteristics, maximum percent weight loss (p = 0.12), length of stay (p = 0.88), or stool frequency (p = 0.59). High-calorie-fed infants more frequently received breastmilk at discharge (p = 0.04). Conclusion: Enrollment, adherence, and in-hospital retention were comparable to other feasibility trials; post-discharge follow-up was poor. Early high-calorie feeding did not appear to be negatively associated with breastfeeding or stooling.