AIM: To improve feeding and growth outcomes among very low birthweight (LBW; ≤1.5kg) or
very preterm (≤32 weeks gestational age) infants admitted to neonatal intensive care
units (NICU) in India, Malawi, and Tanzania through fortification of human milk.
OBJECTIVE: To evaluate (via individually randomized controlled study) the efficacy of
feeding routinely and fortified human milk using a standardized clinical protocol to very
LBW or very preterm infants in the NICU compared to not feeding routinely fortified human
milk using the standardized clinical protocol.
STUDY DESIGN This study is a multi-site, multi-country, individually randomized
prospective trial among VLBW or VPT infants admitted to the NICU in study facilities who
consume human milk and meet eligibility criteria (along with their mothers).
SCREENING AND ENROLLMENT All infants admitted to the NICU and their mothers will be
screened for study eligibility. Screening will be performed within 24 hours of birth for
inborn infants and within 48 hours of birth for outborn infants. Eligible dyads with the
intention to feed human milk [mother's own milk (MOM) or pasteurized donor human milk
(PDHM)] whose mothers provide consent will be enrolled into the study.
Once the mother-infant dyad is enrolled and prior to randomization, they will:
Receive the guideline-driven standard of care and be provided access to breast pumps to
help initiate and advance breast milk feeding. The guideline-driven standard of care
includes facility-based lactation support/feeding counseling + KMC + WASH components
designed specifically for small vulnerable newborns and was developed as part of a
different study protocol (see NCT06390943).
Adhere to a clinical guideline including targets for initiating and advancing breast milk
feeding. Initially, this clinical guideline will help infants achieve breast milk volume
intake of at least 60 mL/kg/day, the primary criterion for randomization. After
randomization, the clinical guideline will continue to support advancing human milk
feeding for all infants advance to 180 mL/kg/day.
RANDOMIZATION Once an infant consumes at least 60 mL/kg/day of breast milk, enrolled
dyads will be assessed for eligibility for randomization. Eligible dyads will be
randomized individually in a 1:1 ratio to either the intervention or comparison arm.
Randomization sequences will be previously generated by the study statistician. If an
infant does not consume at least 60 mL/kg/day of breastmilk by day 10 of chronological
age, the mother-infant dyad will be administratively withdrawn from the study.
DELIVERY OF INTERVENTION Mothers of infants randomized to the intervention arm will
express their breast milk into a standardized measurement cup (or PDHM can be used).
Clinical research staff will mix human milk fortifier (HMF) in human milk (either MOM or
PDHM, if available) per manufacturer specifications per feed for a minimum of 21 days.
Dyads in both arms will continue to receive the guideline-driven standard of care, access
to breast pumps, and follow the volume target and trajectory protocol until they meet
stopping criteria. Data will be collected every 24 hours, including a log at every feed,
regardless of study arm assignment.
If an infant in either arm does not meet protocolized minimum volume targets or
trajectories AND that infant meets weight-based safety net criteria, clinicians will
intervene per judgment aligned with national and local protocols.
The intervention will not be continued once the infant meets stopping criteria with the
goal of the infant having fully transitioned to exclusive breast milk feeding by then.
STOPPING CRITERIA After the minimum duration of 21 days post-randomization, hospitalized
infants should continue to receive volume targeted feeding with or without HMF for as
long as they receive expressed breast milk. Once infants transition to full, direct
breastfeeding in preparation for discharge or are being discharged per clinician
discretion, they will stop adhering to the volume targets and infants in the intervention
group will stop receiving fortified human milk.
DISCHARGE FROM FACILITY TO HOME After stopping criteria are met, routine clinical care
around infant feeding will be provided. Infants can be discharged home when deemed
clinically appropriate per facility protocols and clinician judgment. The
guideline-driven standard of care will encourage all mothers to exclusively breastfeed
their infants prior to discharge and to continue doing so after discharge.
POST-DISCHARGE FACILITY VISITS All dyads will be followed up at 2 weeks of age, 4 weeks
of age, and 3 months of chronological age.