Short summary

Objective:
To determine if bovine colostrum, compared with preterm formula, used as the supplemental nutrition when mother's own milk is not available or insufficient in amounts during the first 14 days of life, results in a shorter time to full enteral feeding in very preterm infants.

Design:
A multicenter, two-arm, un-blinded, randomized, controlled trial.

Setting:
Neonatal departments in the following hospitals:

Shenzhen People's Hospital, Shenzhen, China

Shenzhen Luohu Maternal and Child Health Hospital, Shenzhen, China

Shenzhen Nanshan Maternal and Child Health Hospital, Shenzhen, China

Shenzhen Guangming People's Hospital, Shenzhen, China

Longgang District Central Hospital of Shenzhen, Shenzhen, China

The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China 

Foshan Maternal

and Child Health Hospital, Foshan, China

China Medical University Children Hospital, Taichung, Taiwan

The First Affiliated Hospital of Jinan Medical University, Guangzhou, China 

Population:

Very preterm infants born between gestational ages of 26+0 and 31+6 weeks admitted to the participating hospitals within 24 hours of birth and without any infant formula feeding.

Methods:
Infants are randomly assigned into two groups: control group receiving available mother's own milk supplemented with preterm formula and intervention group receiving available mother's own milk supplemented with bovine colostrum from initiation of enteral feeding until maximum postnatal day 14.

Main outcome: 
Time to reach full enteral feeding (150 mL/kg/d), sustained for 72 hours.

Rationale

Feeding intolerance is a common problem in very preterm born infants due to their immature digestive system. This intolerance extends the time to full enteral feeding and thereby also prolongs the time on parenteral nutrition (PN). Prolonged time to full enteral feeding may predispose these infants to higher risk of growth retardation, infections and organ dysfunctions (e.g. liver, brain). Mother's own milk (MM) is considered the optimal nutrition for very preterm born infants and is superior to infant formula (including preterm formula, PF) in stimulating gut maturation, feeding tolerance, resistance against necrotizing enterocolitis (NEC) and late onset sepsis (LOS), and improves long-term neurodevelopmental outcomes. However, MM is often absent, or not available in sufficient amounts, during the first days or weeks after preterm delivery. Human donor milk (DM) is probably a better supplement to MM than PF, but DM is not available for all hospitals. To supplement insufficient MM during the early neonatal period in hospital settings with no access to donor milk, we suggest that bovine colostrum (BC) may be used instead of PF for very preterm infants during early life. BC, the first milk from cows after birth, is a rich source of protein and bioactive components, including lactoferrin, lysozyme, lactoperoxidase, immunoglobulins, and various growth factors, such as, IGF-I and -II, EGFs, and TGF-Beta. BC has repeatedly been shown to improve gut maturation and NEC/LOS resistance in a well-established piglet model of preterm infants. We suggest a randomized, controlled trial to investigate the effects of BC vs. PF, supplemented to MM during the first 2 weeks, on the time to full enteral feeding in very preterm infants.

Description of the cohort

Very preterm infants born between gestational ages of 26+0 and 31+6 weeks admitted to the participating hospitals until discharge home or postconceptional age of 37 weeks, whichever comes first.

Data and biological material

Demographic characteristics, nutritional intake (type and volume of parenteral and enteral nutrition), growth data (body weight, length, and head circumference), and major diagnoses will be extracted from patient charts or recorded in case report forms. Routine blood tests results on postnatal day 7 and 14 will be extracted from patient charts. Spot blood from heel prick will be taken on day 7 and 14 for amino acid analysis. Stool samples will be collected on day 7 and 14 and at 1 and 2 months for gut microbiota analysis. 

Collaborating researchers and departments

Comparative Pediatrics and Nutrition, University of Copenhagen

• Professor Per Torp Sangild, PhD, DMSc, DVSc
• Assistant Professor Yanqi Li, PhD
• PhD-student Xudong Yan, MD

H.C. Andersen Children's Hospital, Odense University Hospital

• Associate Professor Gitte Zachariasen, MD, PhD
• Postdoc Nana Hyldig, MHSc, PhD

Department of Pediatrics, Shenzhen People's Hospital, Shenzhen, China

• Professor Benqing Wu, MD, PhD

Department of Pediatrics, China Medical University Children Hospital, Taichung, Taiwan

• Professor Hung-Chih Lin, MD, PhD

Department of Pediatrics, Luohu Maternal and Child Health Hospital, Shenzhen, China

• Yuefeng Li, MD

Department of Neonatology, Nanshan Maternal and Child Healthcare Hospital, Shenzhen, China

• Luanying Tian, MD

Department of Pediatrics, Guangming People's Hospital, Shenzhen, China

• Zhenzhi Ye, MD

Department of Pediatrics, Longgang District Central Hospital, Shenzhen, China

• Huixian Qiu, MD

Department of Neonatology, Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

• Hu Hao, MD 

Department of Neonatology, Foshan Maternal and Child Health Hospital, Foshan, China

• Yiheng Dai, MD

Department of Pediatrics, First Affiliated Hospital of Jinan Medical University, Guangzhou, China 

• Professor Guosheng Liu, MD