NCT03822104

Bovine Colostrum as a Human Milk Fortifier for Preterm Infants

Bovine Colostrum to Fortify Human Milk for Preterm Infants: A Randomized, Controlled Trial

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 139 (actual)
• Sponsor: Per Torp Sangild · Academic / Other
• Sex: All
• Age: 5 Days – 3 Weeks
• Healthy volunteers: Not accepted

Summary

Very preterm infants (\<32 weeks gestation) show the 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 very preterm 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 very preterm infants. Mother´s own milk (MM) is considered the best source of EN for very preterm 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 very low birth 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, the investigators hypothesize that BC, used as a fortifier for MM or DM, can reduce feeding intolerance than conventional fortifiers.

Detailed description

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 Trial design This study is a dual-center, non-blinded, two-armed, randomized, controlled trial. Participants Parents to eligible very preterm infants admitted to the Neonatal Intensive Care Units (NICU) at Nanshan People's Hospital (NAN) and Baoan Maternal and Children's Hospital in Shenzhen, China will be asked for participation. Sample size 68 infants per group, 136 in total Data type Clinical data A parallel trial on BC used as human milk fortifier is conducting in Denmark (NCT03537365)

Conditions

• Feeding Intolerance
• Necrotizing Enterocolitis
• Postnatal Growth
• Late-Onset Neonatal Sepsis

Interventions

Type	Name	Description
DIETARY_SUPPLEMENT	Bovine Colostrum	Infants randomized to the intervention group will receive a maximum of 2.8 g bovine colostrum (BC, Biofiber, Gesten, Denmark), as the HMF added to 100 ml of MM and/or DM, when EN has reached a dose of 80-100 ml/kg/d. The infants start with 1 g (0.5 g protein) BC per 100 ml human milk on the first day, increased to 2 g (1.0 g protein) on day 3, and finally 2.8 g (1.4 g protein) on day 5 if the infants only receive DM. The intervention lasts until the infants reach postmenstrual age (PMA) 35+6 weeks or in no-need of fortification due to sufficient growth, whichever comes first.
DIETARY_SUPPLEMENT	FM85	Infants randomized to the control group will receive a maximum of 4 g PreNAN FM85 (Nestlé, Vevey, Switzerland) as HMF, added to 100 ml MM and/or DM, when EN has reached a dose of 80-100 ml/kg/d. The infants starts with 1 g (0.35 g protein) FM85 per 100 ml human milk on the first day, which will be increased to 3 g (1.05 g protein) on day 3 and finally 4 g (1.4 g protein) on day 5, if the infants only receive DM. The infants will receive FM85 as the HMF as long as additional protein in the milk is needed until discharge.

Timeline

• Start date: 2019-05-01
• Primary completion: 2021-06-13
• Completion: 2021-07-08
• First posted: 2019-01-30
• Last updated: 2022-01-28

Locations

2 sites across 1 country: China