Clinical trial NCT00865150: Amino Acid and Acylcarnitine Profiles in Premature Neonates
Official title: How Illness and Nutritional Support Influence Amino Acid and Acylcarnitine Profiles in Premature Neonates
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Prematurity
Neonatal Screening
Parenteral Nutrition
Keywords: Prematurity
Neonatal screening
Parenteral nutrition
Amino acids
Acylcarnitine
Lead sponsor: Pediatrix
Sponsor class: OTHER
First posted: 2009-03-19
Enrollment: 1003
Sex: ALL
Minimum age (years): 23
Maximum age (years): 31
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Hospital

Brief summary: Primary Hypotheses of the study include:

* Metabolic profiles are influenced by gestational age, chronological age, type and degree of nutritional support and illness
* Metabolic profiles differ between neonates who receive commercial formula and neonates who receive primarily human breast milk
* Neonates who develop parenteral associated cholestasis have metabolic markers that identify at risk patients (high serum urea nitrogen, citrulline, histidine, methionine, and succinyl carnitine and low thyroxine, serine and glutamate)
* Neonates that have hypothyroidism have abnormal metabolic profiles (low tyrosine levels)

Detailed description: Malnutrition is a common problem in the neonatal intensive care unit. Recent studies indicate that prematurely born neonates commonly develop a severe nutritional deficit during the first weeks after birth, referred to as extrauterine growth restriction. Despite an increase in growth during the second month of hospitalization, many neonates are ultimately discharged home having grown inadequately. The early nutritional deficit affects weight gain as well as growth in length and head circumference. Aggressive administration of parenteral amino acids to improve protein accretion rates in very preterm neonates has been supported in the literature. Although tolerance of high dose amino acids has been described, researchers acknowledge that sensitive tests to monitor amino acid toxicity are not readily available in the clinical setting.

The goals of this study are:

* To better define normal amino acid and acylcarnitine values and how they change in premature neonates
* To measure the effect nutritional support has (human breastmilk vs. formula) on amino acid and acylcarnitines profiles
* To measure the effect of illness (parenteral nutrition associated cholestasis) on amino acid and acylcarnitine profiles
* To better define abnormal metabolic profiles (low tyrosine levels) in neonates that have hypothyroidism.

Eligibility criteria: Inclusion Criteria

* Documentation of informed consent
* Inborn
* Less than or equal to twenty four (24) hours of age
* Gestational age between twenty three (23) weeks and 0/7 days and thirty one (31) weeks and 0/7 days as per the best estimate by the neonatologist
* If subject is transferred to another hospital, the ability to obtain follow-up data on outcomes
* No known major anomalies (inborn error of metabolism, chromosomal abnormalities, cyanotic congenital heart disease, gastroschisis, omphalocele, diaphragmatic hernia or other major gastrointestinal anomalies, major neurological injury or anomaly, and multiple congenital anomalies)

Exclusion Criteria

* Outborn (transferred for intensive care from another hospital)
* Greater than twenty four (24) hours of age
* Gestational age \< 23 weeks or \> 31 weeks
* Any known major congenital anomalies

Primary outcomes:
measure: Metabolic Profile - Serum amino acid, acylcarnitine and thyroxine levels. Day of birth, (first 24 hours), Day 7, (parenteral nutrition effect), Day 28, (enteral nutrition effect), Day 42, or discharge (established enteral feeding and growth)
timeFrame: 42 Days of Life
Secondary outcomes:
measure: Occurrence of any of the following: death, cholestatic liver disease, positive blood or CSF culture, NEC, IVH, or respiratory support at 36 weeks PMA.
timeFrame: 42 Days of Life
Other outcomes:
Locations:
city: South Bend
country: United States
facility: Memorial Hospital South Bend
state: Indiana
city: Florence
country: United States
facility: McLeod Regional Medical Center
state: South Carolina
Study officials:
affiliation: Pediatrix Medical Group, Inc.
name: Reese Clark, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Clark RH, Chace DH, Spitzer AR. Impact of l-carnitine supplementation on metabolic profiles in premature infants. J Perinatol. 2017 May;37(5):566-571. doi: 10.1038/jp.2016.253. Epub 2017 Jan 12.
citation: Jacob J, Kamitsuka M, Clark RH, Kelleher AS, Spitzer AR. Etiologies of NICU deaths. Pediatrics. 2015 Jan;135(1):e59-65. doi: 10.1542/peds.2014-2967. Epub 2014 Dec 8. Erratum In: Pediatrics. 2015 Apr;135(4):775-7. doi: 10.1542/peds.2014-4207.