A randomized clinical study in NAS infants managed via the Eat, Sleep, Console (ESC) approach comparing early weight loss on a standard-caloric density versus high-caloric density feeding regimen.

The aims of the study is to systematically evaluate the benefit of high-caloric diet regimens given to NAS infants in the first three weeks of life. Breastfeeding is the preferred feeding method for NAS infants as it has shown to reduce NAS severity and infant weight loss, though women who are not adherent to drug treatment programs or have the potential to use illicit drugs are not able to breastfeed due to the risks posed to the infant. Several studies have demonstrated the potential for caloric enhancement of formula and breast milk to support weight gain in NAS infants. Through a randomized control trial analyzing infant weight gain on standard-calorie vs. high-calorie diet regimens, we aim to quantify weight patterns in NAS infants and show that increasing caloric intake can improve weight gain.

Infant Inclusion Criteria:

• Infants with NAS born to mothers age 18-45 with methadone exposure before or during pregnancy who do not intend to place their infants for adoption
• Infants > 2200 g Infants at least 36 weeks gestational age
• Delivered at: Yale New Haven Hospital
• Mothers/infants able to return to outpatient pediatric provider for 2 month and 4 month weights visits

Infant Exclusion Criteria:

• Infants with major congenital malformations
• Infants enrolled to NICU >24 hours for medical conditions other than NAS treatment before 3 days of life

Mother's Inclusion criteria -

• Pregnant women (age 18-45) who have started methadone treatment at obstetrics or other YNHH appointments
• Confirm methadone treatment is received from a licensed treatment program
• Confirm that mothers are planning to deliver their infant(s) at Yale New Haven Hospital
• Confirm that mothers do not intend to place the infant(s) for adoption
• Confirm mother's willingness to participate in the study (including attending the 2-month and 4-month follow up weigh-ins with pediatrician)
• Consent forms will be signed and faxed to study staff

1 month

Study limitations include a small sample size and limited post-discharge retention. In the high-calorie arm, breastmilk was not fortified to 24 kcal/oz however, low intake (average 2 feeds/day) likely biased results toward the null. Additionally, infants with > 12% weight loss were excluded per protocol for safety. While this may impact weight loss findings, it prioritized patient safety and maintained consistency with the study design.