An interventional study of High-calorie formula in Neonatal Abstinence Syndrome, sponsored by Yale University. Completed at 1 site in United States. Per ClinicalTrials.gov, last updated 2026-06-30.
Sponsored by Yale University · Not applicable, Interventional, and Supportive care
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:
Infant Exclusion Criteria:
Mother's Inclusion criteria -
Infant randomly assigned to high-calorie formula for 14 days
Dietary Supplement: High-calorie formula
Infant randomly assigned to standard-calorie formula for 14 days
Infant randomly assigned to high-calorie formula for 14 days
Maximal Percent Weight Loss Compared to Birth Weight
this will be measured by twice daily weights while in the hospital and once daily weights at home for two weeks after birth compared with birth weight
Time frame: 2 weeks
Median Days to Weight Nadir
Measured by determining the days of life that the maximal percent weight loss was obtained for each patient, assessed within the first two weeks after birth
Time frame: 2 weeks
Number of Participants That Return to Birthweight
Number of participants that regained birthweight, assessed within the first month after birth
Time frame: 1 month
Percent Weight Change Per Day
Measured by comparing the weight from the weight obtained the day prior, assessed daily for the first 7 days after birth
Time frame: first 7 days after birth
Length of Hospital Stay
Measured by comparing admission time to discharge time, assessed at hospital discharge
Time frame: up to 6.5 days
| Milestone | Standard Calorie Formula | High-calorie Formula |
|---|---|---|
| Started | 16 | 19 |
| Completed | 16 | 19 |
| Not completed | 0 | 0 |
this will be measured by twice daily weights while in the hospital and once daily weights at home for two weeks after birth compared with birth weight
| percent weight loss | Standard Calorie Formula | High-calorie Formula |
|---|---|---|
| Maximal Percent Weight Loss Compared to Birth Weight | -5.4 (-7.7 to -4.0) | -9.1 (-10.4 to -8.2) |
Measured by determining the days of life that the maximal percent weight loss was obtained for each patient, assessed within the first two weeks after birth
| days | Standard Calorie Formula | High-calorie Formula |
|---|---|---|
| Median Days to Weight Nadir | 3.5 (2.0 to 5.0) | 4.0 (3.0 to 4.0) |
Number of participants that regained birthweight, assessed within the first month after birth
| Participants | Standard Calorie Formula | High-calorie Formula |
|---|---|---|
| Yes | 8 | 9 |
| No | 3 | 7 |
| Unknown | 5 | 3 |
Measured by comparing the weight from the weight obtained the day prior, assessed daily for the first 7 days after birth
| percentage weight change | Standard Calorie Formula | High-calorie Formula |
|---|---|---|
| Day 1 | -1.43 ± 1.95 | -2.76 ± 2.16 |
| Day 2 | -4.85 ± 1.99 | -6.50 ± 3.5 |
| Day 3 | -4.99 ± 3.2 | -8.52 ± 1.92 |
| Day 4 | -5.7 ± 3.0 | -8.70 ± 2.50 |
| Day 5 | -5.67 ± 3.65 | -8.17 ± 3.02 |
| Day 6 | -5.29 ± 5.01 | -7.00 ± 2.85 |
| Day 7 | -2.34 ± 9.48 | -5.94 ± 3.27 |
Measured by comparing admission time to discharge time, assessed at hospital discharge
| days | Standard Calorie Formula | High-calorie Formula |
|---|---|---|
| Length of Hospital Stay | 4.4 ± 2.5 | 4.1 ± 1.4 |
Collected over 1 month. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Standard Calorie Formula | 0/16 (0%) | 0/16 (0%) | 1/16 (6.3%) |
| High-calorie Formula | 0/19 (0%) | 0/19 (0%) | 3/19 (15.8%) |
| Event | Standard Calorie Formula | High-calorie Formula |
|---|---|---|
| Weight lossMetabolism and nutrition disorders | 1/16 | 3/19 |
| Age, Continuous(weeks) | Standard Calorie Formula | High-calorie Formula | Total |
|---|---|---|---|
| Mean | 39.4 ± 1.2 | 38.9 ± 1.6 | 39.1 ± 1.4 |
| Sex: Female, Male(Participants) | Standard Calorie Formula | High-calorie Formula | Total |
|---|---|---|---|
| Female | 6 | 11 | 17 |
| Male | 10 | 8 | 18 |
| Race (NIH/OMB)(Participants) | Standard Calorie Formula | High-calorie Formula | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 1 | 1 |
| White | 16 | 17 | 33 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 1 | 1 |
| Ethnicity (NIH/OMB)(Participants) | Standard Calorie Formula | High-calorie Formula | Total |
|---|---|---|---|
| Hispanic or Latino | 1 | 1 | 2 |
| Not Hispanic or Latino | 15 | 16 | 31 |
| Unknown or Not Reported | 0 | 2 | 2 |
| Birth weight(kilograms) | Standard Calorie Formula | High-calorie Formula | Total |
|---|---|---|---|
| Mean | 3.0 ± 0.4 | 2.9 ± 0.5 | 3.0 ± 0.5 |
| Head Circumference(centimeters) | Standard Calorie Formula | High-calorie Formula | Total |
|---|---|---|---|
| Mean | 33.2 ± 1.6 | 32.9 ± 2.3 | 33.0 ± 2.0 |
| Gestational Age(weeks) | Standard Calorie Formula | High-calorie Formula | Total |
|---|---|---|---|
| Mean | 39.4 ± 1.2 | 38.9 ± 1.6 | 39.1 ± 1.4 |
| Delivery, Vaginal(Participants) | Standard Calorie Formula | High-calorie Formula | Total |
|---|---|---|---|
| Count of participants | 11 | 11 | 22 |
8 further baseline measures are reported on the registry.
Documents are hosted by the registry — open the source record to download them.
Plan to share: No
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Yale University