Intestinal Function in Neonates With Complex Congenital Heart Disease

The overall goal of this proposal is to address a widespread health problem in the pediatric
cardiac infant population - poor postnatal growth - through a collaborative effort between
pediatric cardiology, cardiothoracic surgery, neonatology, microbiology, and immunology. The
foundational hypothesis of this proposal is that term neonates (≥ 37 weeks gestation) with
complex congenital heart disease (CHD) are vulnerable to disturbances in intestinal mucosal
function, permeability, microflora, and local immune function, which ultimately result in
feeding intolerance and poor somatic growth. By identifying biologic targets for
perioperative intestinal protection, this project has the potential to shift and improve the
paradigm of perioperative care for neonates with complex CHD. This pilot study will generate
the data necessary to pursue K23 and R01 funding to further investigate postnatal intestinal
maturation and function in neonates with complex CHD and cyanosis, specifically as it
pertains to local immune function and inflammatory response.

The objectives of this proposal are to perform a single-center (MUSC), prospective,
randomized pilot trial to investigate postnatal intestinal function in cardiac infants
through the following Specific Aims:

Specific Aim 1: To compare the decrease in intestinal permeability as determined by urine
lactulose: mannitol ratios of the trophic breastmilk fed group (intervention) vs. NPO
(nothing by mouth) group (current care) amongst neonates with complex CHD over 3 different
time points (postnatal day 3-4, post-operative day 7-8, and post-operative day 13-14).

H1: Infants who receive trophic breastmilk feeds in the pre-operative period will
demonstrate a more rapid decrease in intestinal permeability (improved postnatal intestinal
maturation) over the first 2 weeks of life compared to those infants who were strictly NPO
in the pre-operative period.

Specific Aim 2: To compare the duration (in days) until goal enteral feeds are successfully
achieved in the trophic breastmilk fed group vs. NPO group.

H1: Infants who receive trophic breastmilk feeds in the pre-operative period will
successfully achieve goal enteral feeds in a shorter duration of time compared to those
infants who were strictly NPO in the pre-operative period.

Specific Aim 3: To qualitatively compare the intestinal microflora pattern over the first
postpartum month as determined by stool microbiota of the trophic breastmilk fed group vs.
NPO group.

H1: The microbiota patterns of those infants who receive trophic breastmilk feeds in the
pre-operative period will differ from those infants who were strictly NPO in the
pre-operative period.

Inclusion Criteria:

- Study subjects will be male and female neonates admitted to MUSC PCICU or NICU prior
to 72 hours of life who are gestational age ≥ 37 weeks.

- inpatient status at MUSC for a minimum of 48 hours prior to planned surgery and have
a postnatal diagnosis of complex congenital heart disease - defined as a structural
heart defect requiring cardiac surgery (reparative or palliative) prior to hospital
discharge.

Exclusion Criteria:

- Infants with hemodynamic instability in the pre-operative period requiring mechanical
circulatory support or

- who have the presence of lactate > 3 after the first 24 hours of admission

- admission from home

- major congenital extracardiac abnormalities (i.e. renal, brain, GI)

- cardiac surgery will not be performed at MUSC, and

- mother does not plan to pump breastmilk during the infant's first week of life.