RCT of High- vs. Standard-Calorie Formula for Methadone-Exposed Infants
Condition: Neonatal Abstinence Syndrome
MeSH terms: Neonatal Abstinence Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      Neonatal abstinence syndrome (NAS) symptoms contribute to poor infant weight gain. Early
      caloric enhancement for infants exposed to methadone is inexpensive, readily available, easy
      to implement and could improve early outcomes for these high-risk infants. We will conduct a
      preliminary randomized clinical trial of high-calorie vs. standard-calorie formula for
      methadone exposed infants to evaluate the adequacy of recruitment, protocol feasibility and
      estimates of whether high-calorie formula results in more normal patterns of weight loss and
      gain, less severe NAS symptoms and shorter hospital stays.
    

Detailed description: 
      Background: Infants exposed to methadone during pregnancy experience high rates of neonatal
      abstinence syndrome (NAS). Common NAS symptoms (tremulousness, increased muscle tone,
      sweating, excessive crying, vomiting and diarrhea) increase infants' metabolic needs. Another
      frequent NAS symptom, weak and uncoordinated suckling, impairs infants' ability to take in
      adequate calories. These combined problems compromise infant weight gain. The current
      standard of care for opiate-exposed infants requires evidence of poor weight gain or
      excessive weight loss before initiating high-calorie formula. We hypothesize that inadequate
      caloric intake among methadone exposed infants may result in excessive weight loss, slow
      weight regain and exacerbation of NAS. These factors lead to the newborn's requirement for
      higher morphine doses and longer duration of hospitalization. Therefore, methadone exposed
      infants may benefit from early caloric enhancement. A nutritional intervention for
      opiate-exposed infants has not been previously evaluated. This application will provide data
      on adequacy of recruitment, protocol feasibility, performance of selected measures, and
      preliminary estimates of efficacy for a comprehensive R01 submission.

      Specific Aims:

        1. For methadone exposed infants, compare infants randomized to high (24 kcal/oz) versus
           standard (20 kcal/oz) formula for the following outcomes:

             -  Weight loss and gain patterns. The primary dependent measure will be days until the
                infant returns to birth weight. Secondary measures will be maximum percent weight
                loss and days to weight nadir.

             -  NAS severity measured by: a) total length of hospital stay for NAS; b) duration of
                NAS treatment; c) mean Finnegan scores on days 2-10; d) maximum concentration of
                morphine used to treat NAS.

        2. Describe the suck quality at 4-6 days of age among methadone exposed infants. Evaluate
           the association between the infant suck quality and infant weight loss and gain patterns
           and measures of NAS severity.

      Design: Women on methadone will be recruited during pregnancy and will attend a single brief
      visit late in pregnancy. After delivery, infants will be randomized in a double blind trial
      of either high-calorie or standard-calorie formula which will be started at 72 hours after
      birth and be continued through 21 days of age. Infants will be weighed daily and will have
      outpatient study visits at 1 and 3 months. For this pilot study, up to 70 mothers will be
      enrolled over 18 months. This pilot study is needed to establish the feasibility of the study
      methods and to better estimate differences that can be observed between the groups. For the
      primary outcome variable, days until the infant returns to birth weight, discrete survival
      methods will be used.

      Potential Impact: Early caloric enhancement for methadone-exposed infants is inexpensive,
      readily available, easy to implement and could improve outcomes of these high-risk infants.
      High-calorie formula could result in a more normal pattern of weight loss and gain, less
      severe NAS symptoms and shorter hospital stays.
    

Intervention name(s): High Calorie Infant formula; Standard Calorie Infant Formula
Intervention type(s): Other; Other
Intervention description(s): Infants were randomized to be fed high calorie formula from 72 hours of life until age 21 days.; Infants were randomized to be fed standard calorie formula from 72 hours of life until age 21 days.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: prenatal opioid exposure; infant; weight gain; infant formula