Optimal Growth of Preterm Infants With Growth Restriction

NCT ID: NCT02999945

Last Updated: 2019-03-21

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-31
• Study Completion Date: 2022-01-31

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.

Conditions

Growth Failure; Adiposity; Diabetes; Neurologic Deficits

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SGA-enhanced nutrients

Infants will receive fortified breast milk (\>50% meals/d fortified, 1,4 g protein, 85 kcal/100ml, FM85, Nestle ®) or post discharge formula (2g protein; 73-75 kcal/100ml; Aptamil PDF, Milupa® or Beba F Nestle® ) between discharge and 52nd week of gestation (three months after term)

Group Type: ACTIVE_COMPARATOR

SGA-enhanced nutrients

Intervention Type: DIETARY_SUPPLEMENT

Infants will receive fortified breast milk (\>50% meals/d fortified, 1,4 g protein, 85 kcal/100ml, FM85, Nestle ®) or post discharge formula (2g protein; 73-75 kcal/100ml; Aptamil PDF, Milupa® or Beba F Nestle® ) between discharge and 52nd week of gestation (three months after term

SGA-standard nutrients

Infants will receive unfortified breast milk (65-70kcal/100ml) or starter formula (1,2- 1,3g protein, 66 kcal/100ml Beba Pre Pro Start, Nestle® or Aptamil Pre, Milupa ®) between discharge and 52nd week of gestation (three months after term).

Group Type: OTHER

SGA-standard nutrients

Intervention Type: OTHER

Infants will receive unfortified breast milk (65-70kcal/100ml) or starter formula (1,2- 1,3g protein, 66 kcal/100ml Beba Pre Pro Start, Nestle® or Aptamil Pre, Milupa ®) between discharge and 52nd week of gestation (three months after term)

IUGR-enhanced nutrients

Infants will receive fortified breast milk (\>50% meals/d fortified, 1,4 g protein, 85 kcal/100ml, FM85, Nestle ®) or post discharge formula (2g protein; 73-75 kcal/100ml; Aptamil PDF, Milupa® or Beba F Nestle® ) between discharge and 52nd week of gestation (three months after term

Group Type: ACTIVE_COMPARATOR

IUGR-enhanced nutrients

Intervention Type: DIETARY_SUPPLEMENT

Infants will receive fortified breast milk (\>50% meals/d fortified, 1,4 g protein, 85 kcal/100ml, FM85, Nestle ®) or post discharge formula (2g protein; 73-75 kcal/100ml; Aptamil PDF, Milupa® or Beba F Nestle® ) between discharge and 52nd week of gestation (three months after term

IUGR-standard nutrients

Infants will receive unfortified breast milk (65-70kcal/100ml) or starter formula (1,2- 1,3g protein, 66 kcal/100ml Beba Pre Pro Start, Nestle® or Aptamil Pre, Milupa ®) between discharge and 52nd week of gestation (three months after term).

Group Type: OTHER

IUGR-standard nutrients

Intervention Type: OTHER

Infants will receive unfortified breast milk (65-70kcal/100ml) or starter formula (1,2- 1,3g protein, 66 kcal/100ml Beba Pre Pro Start, Nestle® or Aptamil Pre, Milupa ®) between discharge and 52nd week of gestation (three months after term)

Interventions

SGA-enhanced nutrients

Infants will receive fortified breast milk (\>50% meals/d fortified, 1,4 g protein, 85 kcal/100ml, FM85, Nestle ®) or post discharge formula (2g protein; 73-75 kcal/100ml; Aptamil PDF, Milupa® or Beba F Nestle® ) between discharge and 52nd week of gestation (three months after term

Intervention Type: DIETARY_SUPPLEMENT

IUGR-enhanced nutrients

Infants will receive fortified breast milk (\>50% meals/d fortified, 1,4 g protein, 85 kcal/100ml, FM85, Nestle ®) or post discharge formula (2g protein; 73-75 kcal/100ml; Aptamil PDF, Milupa® or Beba F Nestle® ) between discharge and 52nd week of gestation (three months after term

Intervention Type: DIETARY_SUPPLEMENT

SGA-standard nutrients

Infants will receive unfortified breast milk (65-70kcal/100ml) or starter formula (1,2- 1,3g protein, 66 kcal/100ml Beba Pre Pro Start, Nestle® or Aptamil Pre, Milupa ®) between discharge and 52nd week of gestation (three months after term)

Intervention Type: OTHER

IUGR-standard nutrients

Infants will receive unfortified breast milk (65-70kcal/100ml) or starter formula (1,2- 1,3g protein, 66 kcal/100ml Beba Pre Pro Start, Nestle® or Aptamil Pre, Milupa ®) between discharge and 52nd week of gestation (three months after term)

Intervention Type: OTHER

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

• Maximum Eligible Age: 42 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Medical University of Graz

OTHER

Sponsor Role: collaborator

Ludwig-Maximilians - University of Munich

OTHER

Sponsor Role: collaborator

University Hospital Tuebingen

OTHER

Sponsor Role: collaborator

University of Erlangen-Nürnberg Medical School

OTHER

Sponsor Role: collaborator

University of Milan

OTHER

Sponsor Role: collaborator

Poznan University of Medical Sciences

OTHER

Sponsor Role: collaborator

Lund University

OTHER

Sponsor Role: collaborator

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Nadja Haiden,MD

Assoc. Prof. Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nadja Haiden, MD

Role: PRINCIPAL_INVESTIGATOR

MUW

Other Identifiers

OPTIGROW

Identifier Type: -

Identifier Source: org_study_id