A randomized controlled trial protocol comparing the feeds of fresh versus frozen mother\u2019s own milk for preterm infants in the NICU

Huiqing Sun ,Yun Cao,Jiao Lü ,Fengqin Yu,Xiaolan Zhang,Li‐Ping Shi ,Xinnian Pan,Li Li,Ling Liu,Jiajie Zhang,Song Han ,Qi Zhou,Xiuyong Cheng,Xiaoying Li,Laishuan Wang,Jiahua Pan,Rui Cheng,Long Li,Rensheng Wang,Chuanzhong Yang,Changhong Yan,Yang Liu ,Mingxia Li ,Zhankui Li,Shiwen Xia,Fanxing Xu ,Min Wu ,Foteini Kakulas,Xiang Y Ye,Jiang-Qin Liu ,Jie Yang ,Xin Ding,Mou Wei,Sharon Unger,Shoo K Lee

doi:10.1186/s13063-019-3981-4

Abstract

BackgroundNecrotizing enterocolitis (NEC) is the leading cause of death among preterm infants born at < 30 weeks’ gestation. The incidence of NEC is reduced when infants are fed human milk. However, in many neonatal intensive care units (NICUs), it is standard practice to freeze and/or pasteurize human milk, which deactivates bioactive components that may offer additional protective benefits. Indeed, our pilot study showed that one feed of fresh mother’s own milk per day was safe, feasible, and can reduce morbidity in preterm infants. To further evaluate the benefits of fresh human milk in the NICU, a randomized controlled trial is needed.MethodsOur prospective multicenter, double-blinded, randomized, controlled trial will include infants born at < 30 weeks’ gestation and admitted to one of 29 tertiary NICUs in China. Infants in the intervention (fresh human milk) group (n = 1549) will receive at least two feeds of fresh human milk (i.e., within 4 h of expression) per day from the time of enrollment until 32 weeks’ corrected age or discharge to home. Infants in the control group (n = 1549) will receive previously frozen human milk following the current standard protocols. Following informed consent, enrolled infants will be randomly allocated to the control or fresh human milk groups. The primary outcome is the composite outcome mortality or NEC ≥ stage 2 at 32 weeks’ corrected age, and the secondary outcomes are mortality, NEC ≥ stage 2, NEC needing surgery, late-onset sepsis, retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), weight gain, change in weight, increase in length, increase in head circumference, time to full enteral feeds, and finally, the number and type of critical incident reports, including feeding errors.DiscussionOur double-blinded, randomized, controlled trial aims to examine whether fresh human milk can improve infant outcomes. The results of this study will impact both Chinese and international medical practice and feeding policy for preterm infants. In addition, data from our study will inform changes in health policy in NICUs across China, such that mothers are encouraged to enter the NICU and express fresh milk for their infants.Trial registrationChinese Clinical Trial Registry; #ChiCTR1900020577; registered January 1, 2019; http://www.chictr.org.cn/showprojen.aspx?proj=34276

Highlights

Necrotizing enterocolitis (NEC) is the leading cause of death among preterm infants born at < 30 weeks’ gestation
We recently conducted a pilot study entitled “Testing the feasibility and safety of feeding preterm infants fresh mother’s own milk in the neonatal intensive care unit (NICU): a pilot study,” where we evaluated the feasibility and safety of providing preterm infants with at least one daily feed of fresh mother’s own milk, within 4 h of expression, until they reached 32 weeks’ corrected age [19]
The results showed that one feed of fresh human milk per day was both safe and feasible in the NICU, and it reduced morbidity among infants of < 30 weeks’ gestation

Summary

Methods

Double-blinded, randomized, controlled trial will include infants born at < 30 weeks’ gestation and admitted to one of 29 tertiary NICUs in China. Infants in the intervention (fresh human milk) group (n = 1549) will receive at least two feeds of fresh human milk (i.e., within 4 h of expression) per day from the time of enrollment until 32 weeks’ corrected age or discharge to home. Infants in the control group (n = 1549) will receive previously frozen human milk following the current standard protocols. Following informed consent, enrolled infants will be randomly allocated to the control or fresh human milk groups. The primary outcome is the composite outcome mortality or NEC ≥ stage 2 at 32 weeks’ corrected age, and the secondary outcomes are mortality, NEC ≥ stage 2, NEC needing surgery, late-onset sepsis, retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), weight gain, change in weight, increase in length, increase in head circumference, time to full enteral feeds, and the number and type of critical incident reports, including feeding errors

Discussion

Background

Methods/Design

Findings