Short summary

The purpose is to investigate the effect of bovine colostrum used as human milk fortifier for mother's milk and/or donor milk in reducing feeding intolerance in very preterm infants (gestational age 26+0 to 30+6). This dual-center, non-blinded, randomized study will be conducted at two neonatal units in China: Nanshan People's Hospital and Baoan Maternal and Child Health Care Hospital. There is a parallel trial running currently in seven Denmark (OP_462)

Rationale

Very preterm (<32 weeks gestation) and very low birth weight (VLBW, <1500 g birth weight) show immaturity of organs and have high nutrient requirements for growth and development. In the first weeks, they have difficulties tolerating enteral nutrition (EN) and are often given supplemental parenteral nutrition (PN). A fast transition to full EN is important to improve gut maturation and reduce the high risk of late-onset sepsis (LOS), related to their immature immunity in gut and blood. Conversely, too fast increase of EN predisposes to feeding intolerance and necrotizing enterocolitis (NEC). Further, human milk feeding is not sufficient to support nutrient requirements for growth of VLBW infants. Thus, it remains a difficult task to optimize EN transition, achieve adequate nutrient intake and growth, and minimize NEC and LOS in the postnatal period of VLBW infants. Mother´s own milk (MM) is considered the best source of EN for VLBW infants and pasteurized human donor milk (DM) is the second choice, if MM is absent or not sufficient. The recommended protein intake is 4-4.5 g/kg/d for VLBW infants, when the target is a postnatal growth similar to intrauterine growth rates. This amount of protein cannot be met by feeding only MM or DM. Thus, it is common practice to enrich human milk with human milk fortifiers (HMFs, based on ingredients used in infant formulas) to increase growth, bone mineralization and neurodevelopment, starting from 7-14 d after birth and 80-160 ml/kg feeding volume per day. Bovine colostrum (BC) is the first milk from cows after parturition and is rich in protein (80-150 g/L) and bioactive components. These components may improve gut maturation, NEC protection and nutrient assimilation, even across species. Studies in preterm pigs show that feeding BC alone, or DM fortified with BC, improves growth, gut maturation and NEC resistance during the first 1-2 weeks, relative to DM, or DM fortified with conventional HMFs.On this background, we hypothesize that BC, used as a fortifier for MM or DM, can reduce feeding intolerance than conventional fortifiers. 

Objectives

1. To test if fortification of human milk with BC reduces feeding intolerance compared with currently used HMF.

2. To verify the safety and tolerability of BC fortification and to monitor the rates of growth, NEC and sepsis, as investigated in a parallel trial in Denmark 

3. To explore new markers of growth, maturation, clinical interventions and health outcomes, using samples of blood, plasma or faeces collected during the trial  

Description of the cohort

Very preterm infants admitted to the Neonatal Intensive Care Units (NICU) at Nanshan People's Hospital (NAN) and Baoan Maternal and Child Health Care Hospital in Shenzhen, China. 

Data and biological material

Clinical register data and biological materials (feces, whole blood, and plasma)

Collaborating researchers and departments

Department of Neonatology, Hans Christian Andersen Children's Hospital, Odense University Hospital

• Consultant, Gitte Zachariassen
• Per Torp Sangild

Department of Comparative Pediatrics and Nutrition, University of Copenhagen

• Per Torp Sangild
• Yanqi Li

Department of Neonatology, Rigshopitalet

• Lise Aunsholt

Department of Neonatology, Nanshan People's Hospital

• Xiaodong Li
• Zhongqian He

Department of Neonatology, Baoan Maternal and Child Health Care Hospital

Ping Zhou

Lu Zhao