Until recently, data suggesting a beneficial impact of maternal milk feeding on BPD were limited. Some investigators had concluded that maternal milk decreased incidence of BPD [7, 11–14], but others had not thought it useful [15]. Thus we can make two postulations: either high-volume maternal milk feeding daily directly impacts BPD or BPD has an obvious effect on volume maternal milk feeding .
The proportion of preterm infants receiving breastfeeding in NICUs has increased from 23.0% in 2005 to 37.2% in 2015 in China [8, 16] as our understanding of breastfeeding and strategies to promote breastfeeding continue to improve. Breastfeeding rates are rising in NICUs of China. The proportion of VLBW infants with a length of hospital stay > 28 days exclusively formula-fed in this study was 28.9%, less than one-third of the total. The proportion of mixed feeding of breast milk and formula was significantly higher than that of exclusive breastfeeding and exclusive formula feeding, due to limitations from various factors. This led to the question of whether there existed a dose-dependent effect from maternal milk on the risk of BPD and other morbidities in VLBW infants. Several meta-analyses comparing human milk or own mother’s milk and any maternal milk with exclusive formula draw different conclusions, although most have found that exclusive breast milk feeding was associated with decreased incidence of BPD. Partially receiving breast milk has also been shown to provide a protective effect compared with exclusive formula feeding, but the level of evidence is not high [7, 17]. Patel et al. [18] revealed a 9.5% reduction in the odds of BPD for each 10% increase in enteral feedings consisting of mothers’ milk received from birth to 36 weeks PMA. Another study found that for every 10 ml/kg/day increase in breastfeeding within 14 days in VLBW infants was associated with 0.26 fewer hospitalizations at 1 year and 0.21 fewer pediatric subspecialist types and 0.20 fewer specialized therapy types at 2 years [19]. Other research found that the risk of BPD was reduced when the average breast milk volume given was more than 7 ml/kg/day at 42 days after birth [20]. This dose of maternal milk was far lower than our study. The difference may be explained by different time period and different gestational ages. The gestational age of their study was less than 32 weeks and the time of feeding was 42 days after birth, while gestational age of our study was less than and equal to 34 weeks and the time was 28 days after birth. The time of feeding in our study was selected according to the definition of BPD.
Furman et al. [17] and Schanler et al. [15, 21] found that feeding with at least 50 ml/kg/day of breast milk reduced the incidence of LOS. But the effect on NEC and BPD was not consistent, due to a limited sample size. Our study collected the detailed clinical and feeding information of VLBW infants from 19 NICUs in Jiangsu province in 2018, giving a sufficiently large sample. We found that at least 50 ml/kg of maternal milk daily given up to the end of the fourth week of life decreased the rates of BPD as well as NEC, LOS, and EUGR in VLBW infants.
Oxidative stress is one common pathway shared by BPD, NEC, sepsis, and EUGR and causes lipid, protein, and DNA damage. Preterm infants have poor antioxidant defenses in response to oxidative challenge, because the physiologic increase in antioxidant ability occurs at the end of term birth [22–26]. Therefore, preterm infants are more susceptible to reactive oxygen species (ROS)-induced damage. Inadequate nutrition increases oxidative stress [26]. Human breast milk has many bioactive components that prevent oxidative stress [27–29]. The composition of human breast milk can vary with the infant’s requirements according to its age and other characteristics [30, 31]. High-dose maternal milk feeding may provide nutritional and bioactive components that mitigate oxidative stress, inflammation, and nutritional inadequacies [32, 33]. Furthermore, these protective components of maternal milk are highly concentrated as the volume of maternal milk increases.
A limitation of our study is that there were baseline differences in the subjects who received different volumes of maternal milk daily for the first 4 weeks of life. Our statistical analyses adjusted for these differences; however, it is possible that not all the differences between these groups could be controlled for statistically. Additionally, maternal milk included own mother’s milk and donor milk. There were breast milk banks in only two of the NICUs in our multicenter study. The volumes of donor milk were low and were combined with maternal milk. The methods of storage and disinfection of donor milk may also have affected its nutritional composition [34, 35]. Further research will enable us to conclude if the sample size of donor milk was sufficient.