Clinical trial NCT02999945: Optimal Growth of Preterm Infants With Growth Restriction
Official title: Body Composition, Metabolic Programming and Long Term Outcome of Growth Restricted Preterm Infants Under Different Nutritional Management A Prospective Randomized Controlled Multicenter Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Growth Failure
Adiposity
Diabetes
Neurologic Deficits
Keywords: preterm infants
SGA infants
IUGR infants
growth
body composition
metabolomics
microbiome
adiposity markers
metabolic programming
neurodevelopmental outcome
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
Collaborators: name: Medical University of Graz
name: Ludwig-Maximilians - University of Munich
name: University Hospital Tuebingen
name: University of Erlangen-Nürnberg Medical School
name: University of Milan
name: Poznan University of Medical Sciences
name: Lund University
First posted: 2016-12-21
Enrollment: 0
Sex: ALL
Maximum age (years): 42
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In this prospective randomized controlled multi center trial the investigators stratify "Very Low Birthweight " (VLBW)-infants with growth retardation in small for gestational age (SGA) or intrauterine growth restricted (IUGR) - infants and aim to investigate the impact of a nutritional management with enhanced nutrients from discharge up to the 52nd week of postconceptional age on growth, body composition, metabolic programming, metabolomics, microbiome and long term neurodevelopmental outcome. In this study, the investigators will evaluate the difference in metabolic profiles of SGA and IUGR preterm infants. The investigators will further longitudinally assess, how different nutritional interventions affect the altered pathways in the first year of life and identify, in combination with data available from metabolic markers, microbiome and breast milk analysis, potential pathways resulting in increased disease risk later in life.

Detailed description: Prematurity is the leading cause for mortality and morbidity in newborns with very low birth weight (VLBW) infants (\< 1500g birth weight) at highest risk. Ten to thirty percent of VLBW infants are also born too small for their gestational age defined by a birth weight below the 10th percentile. In daily neonatal intensive care, consequential long term-follow up and most studies all growth restricted premature infants are treated the same, importantly this includes the nutritional management after birth. However, different groups of patients with different causal pathologies are subsumed under the definition growth restriction or born too small. One group of growth restricted patients refers to the infants born constitutionally small or small for gestational age (SGA). The other group refers to infants with an intrauterine growth restriction (IUGR) caused by a complex antenatal pathology. Consequently, the nutritional management after birth is very important to minimize the potential risk for developing obesity, diabetes and cardiovascular diseases later in life and to achieve optimal growth. So far we do not consider the different underlying pathomechanisms of growth restriction in our nutritional concepts for preterm infants and therefore cause long-term consequences. The European society of pediatric gastroenterology, hematology and nutrition (ESPGHAN) recommends to feed enhanced nutrients up to 52nd week of gestation in all growth restricted preterm infants- regardless if they are SGA or IUGR premature. Actually, reliable data guaranteeing that the recommended "enhanced nutrients strategy" providing extra nutrients up to 52 weeks for SGA and IUGR infants is safe and effective for both groups in terms of long-term growth and metabolic programming are lacking.

A total of 348 preterm infants born and discharged below the 10th percentile at term will be included in the study and stratified according to SGA or IUGR by a combination of antenatal ultrasound parameters and growth parameters (including 10% screening failures and 20% drop out. Furthermore IUGR and SGA growth restricted preterm infants will be stratified according to breastfeeding or formula feeding and randomized in one of the following groups: Standard nutrients group (breastfeeding or starter formula) or Enhanced nutrients group (fortified breast milk or post-discharge formula. Body composition measurements will be performed by air displacement plethysmography - a non-invasive method. Anthropometric measurements will be performed by measuring weight, height and head circumference. Furthermore, parameters of metabolic programming, metabolomics, the stool microbiome and neurodevelopmental outcome will be determined. Additionally, the stool microbiome will be characterized from infant stool samples and compared between the two groups. After an interventional period of three months infants will be followed up until 2 years of age.

Eligibility criteria: Inclusion Criteria:

* Preterm infants with a birth weight \<1500g and birth weight \<10th percentile.
* Weight at term \<10th percentile
* Informed consent

Exclusion Criteria:

* Genetic or metabolic diseases with the primary effect on growth
* Necrotizing enterocolitis
* Intraventricular hemorrhage (IVH) \>Grade II
* Periventricular leukomalacia (PVL) Stage III
* Genetic or metabolic disorders
* Bronchopulmonary dysplasia

Primary outcomes:
measure: Fat Free Mass
timeFrame: 3 months
Secondary outcomes:
measure: anthropometry-length
timeFrame: 24 months
measure: anthropometry-weight
timeFrame: 24 months
measure: anthropometry-HC
timeFrame: 24 months
measure: anthropometry-z-score
timeFrame: 24 months
measure: parameters of metabolic programming- IGF1
timeFrame: 12 months
measure: parameters of metabolic programming-IGF3
timeFrame: 12 months
measure: parameters of metabolic programming-IGF-BP
timeFrame: 12 months
measure: parameters of metabolic programming-Leptin
timeFrame: 12 months
measure: parameters of metabolic programming-Adiponectin
timeFrame: 12 months
measure: neurodevelopmental outcome
timeFrame: 24months
measure: metabolomics
timeFrame: 12 months
measure: stool microbiome
timeFrame: 24 months
measure: macronutrients in breastmilk-fat
timeFrame: 6 months
measure: macronutrients in breastmilk-Lactose
timeFrame: 6 months
measure: macronutrients in breastmilk-protein
timeFrame: 6 months
Other outcomes:
Locations:
Study officials:
affiliation: MUW
name: Nadja Haiden, MD
role: PRINCIPAL_INVESTIGATOR
References: