A randomised, double-blind, controlled trial to evaluate the effects of a new human milk fortifier on growth and tolerance in preterm infants.

Preterm birth (birth before start of the 37th week of gestation) has long-term
adverse consequences for health and neurodevelopment and is a major determinant
of neonatal morbidity and mortality.
Every year, an estimated 15 million infants worldwide are born prematurely, and
this number is rising. Infants who are both preterm and small for gestational
age are at even higher risk of medical complications and death than infants
with one of these conditions. These babies have much higher nutrient
requirements than term infants.
The preferred nutrition for all infants including preterm infants is human
milk; however human milk alone does not sufficiently meet the nutritional needs
of preterm infants. Therefore human milk fortifiers (HMF) are usually added to
milk for preterm infants.
Recent research suggests positive effects on the growth and development by
adding lipids to the feedings for preterm infants and that is why Nutricia has
developed an HMF with lipids. The composition of the HMF with lipids, when
added to human milk, complies with the increased nutritional needs of preterm
infants with a low birth weight, as recently indicated by experts in the field,
and is in line with the European Society for Paediatric Gastroenterology
Hepatology and Nutrition (ESPGHAN) recommendations for intake of nutrients for
preterm infants with a very low birth weight.

The primary goal is to demonstrate that weight growth velocity (in g/kg/day)
from baseline to study day 21 in preterm infants (gestational age <32 weeks and
birth weight <1500 g) receiving the HMF with lipids is non-inferior to those
receiving the current commercially available HMF without lipids.

Please note that the intervention is intended to last until study day 21 or
longer. The intervention will end when the subject is not in need of HMF
anymore (according to local feeding procedures), is discharged to a level II or
level I NICU that has not been approved for participation in the study or is
discharged home, whichever comes first.

The secondary goals are to compare the effects of the HMF with lipids to the
effects of the HMF without lipids in preterm infants (gestational age <32 weeks
and birth weight <1500 g) concerning growth and gastro-intestinal tolerance.

This is a randomised, controlled, double blind, parallel-group, multi-centre,
multi-country study.

During the intervention phase, HMF is added to the mother's milk/donor milk as
per the local feeding protocols. Group 1 receives the test product (HMF with
lipids); group 2 receives the control product (HMF without lipids). The
intervention will end when the subject is not in need of HMF anymore, is
discharged to a level II or level I NICU that has not been approved for
participation in the study, or is discharged home, whichever comes first.

Burden: Most visits and assessments described in the protocol are part of the
standard treatment of this group of premature babies. There are no additional
assessments that the child has to undergo for this study, except that in some
hospitals, length is measured every 2 weeks as part of standard of care. This
will be done weekly for the study in all hospitals.
At the Isala, the follow up visit at 6 months is not standard of care and will
be done extra for the study. Also at the Isala, the follow-up visits at 12 and
24 months (including the development test) is not standard of care in children
born between 30 and 32 weeks of gestational age, and will also be done extra
for the study.

The intervention period lasts at least 21 days. Of the children who received
less than 15 days of study product due to circumstances, not all follow-up data
is included in the statistical analysis. Collecting follow-up data of subjects
that is already known not to be used in the end, should be considered
unethical. The FUP visits of 12 and 24 months therefore will not be performed
for these children.

Risk: Up to now, no previous studies have been conducted with the HMF with
lipids. The composition of the HMF with lipids complies with the guidelines
and expert recommendations on the nutritional needs of preterm children and
safety. The added lipids are already being used as components in (preterm and
term) infant formula, without adverse effects due to these lipids.
However there may be unknown side effects. The safety and tolerance of the
product will be closely monitored throughout the study.