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Postnatal intestinal function in cardiac infants. 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 hypothesis is that term neonates with complex congenital heart disease (CHD) who receive trophic breastmilk feeds in the pre-operative period will show improved gut function than neonates who were strictly NPO (nothing by mouth) in the pre-operative period.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1: NPO pre-operative | Other | 1) Current care - NPO (nothing by mouth) postnatal intestinal function of neonates with complex CHD who receive enteral trophic breastmilk (10cc/kg/day) feeds (intervention) vs NPO (nothing by mouth) in the pre-operative period. |
|
| Arm 2: Fresh Breast Milk pre-operative | Active Comparator | 2) Intervention - Trophic mother's own fresh (non-frozen) breastmilk gavage feeds via nasogastric tube every 3 hours at 10 cc/kg/day |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Arm 1: NPO by mouth pre-operative | Other | Current treatment for infants born with cardiac defects awaiting surgery is to keep them NPO pre-operatively. Arm 1 will make no changes to this current policy. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in urine lactulose/mannitol ratio over time | Specific Aim 1: compare decrease in intestinal permeability 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). | post-natal day 3-4 (baseline), post-op days 7 and 14 |
| Measure | Description | Time Frame |
|---|---|---|
| Enteral Feeds | 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. | Duration (in days) until goal enteral feeds are achieved, an expected average of 3 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sinai C Zyblewski, MD | Medical University of South Carolina | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19619784 | Background | Anderson JB, Beekman RH 3rd, Border WL, Kalkwarf HJ, Khoury PR, Uzark K, Eghtesady P, Marino BS. Lower weight-for-age z score adversely affects hospital length of stay after the bidirectional Glenn procedure in 100 infants with a single ventricle. J Thorac Cardiovasc Surg. 2009 Aug;138(2):397-404.e1. doi: 10.1016/j.jtcvs.2009.02.033. Epub 2009 May 23. | |
| 16500550 |
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| ID | Term |
|---|---|
| D006330 | Heart Defects, Congenital |
| D005183 | Failure to Thrive |
| ID | Term |
|---|---|
| D018376 | Cardiovascular Abnormalities |
| D002318 | Cardiovascular Diseases |
| D006331 | Heart Diseases |
| D000013 | Congenital Abnormalities |
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| Arm 2: Fresh Breast Milk pre-operative | Other | Infants randomized to Arm 2 of the study will receive their mother's own breast milk pre-operatively. |
|
| Intestinal Microflora Pattern | 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. | 30 days 1st post-partum month |
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| 25962930 | Derived | Zyblewski SC, Nietert PJ, Graham EM, Taylor SN, Atz AM, Wagner CL. Randomized Clinical Trial of Preoperative Feeding to Evaluate Intestinal Barrier Function in Neonates Requiring Cardiac Surgery. J Pediatr. 2015 Jul;167(1):47-51.e1. doi: 10.1016/j.jpeds.2015.04.035. Epub 2015 May 8. |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |