Adequacy of expressed breast milk for early growth of preterm infants. Multicentre trial on feeding low birthweight infants: effects of diet on early growth. Milk protein quantity and quality in low-birthweight infants: I. Metabolic responses and effects on growth. The metabolic consequences of human milk and formula feeding in premature infants. Randomized trial of donor human milk versus preterm formula as substitutes for mothers' own milk in the feeding of extremely premature infants.
Poor weight gain observed in preterm infants who were fed expressed breast milk compared with those fed a cows' milk formular prompted a detailed study of early postnatal growth in preterm infants fed these two milks. 68 infants were divided into two categories by gestational age at birth (i) 28-32 weeks (n=28), (ii) 33-36 weeks (n=40). They were randomly allocated to a feed of expressed breast milk or a milk formula (Ostermilk 1). Rates of weight gain, linear growth, and head circumference growth were evaluated over two periods: birth-1 month, 1-2 months. The younger group who were fed breast milk showed slower overall growth rates over the first month than those fed formula. In the second month, and for the older infants over both of the 2-monthly periods, growth rates were similar in the two feeding regimens. It is concluded that expressed breast milk is inadequate for the growth of very immature preterm infants during early postnatal life. A large multicentre study on the short and long term clinical and developmental outcome of infants randomised to different diets is being undertaken. This report represents an interim analysis of the early postnatal growth performance of an unselected population of 194 preterm infants (gestation, mean (SD) 31 . 0 (2 . 9) weeks; birthweight, mean (SD) 1364 (294) g), both ill and well, examined in two (of four) parallel trials. One trial compared banked breast milk with a new preterm formula (primary trial); the other compared these diets as supplements to maternal milk (supplement trial). A major dietary effect on the number of days taken to regain birthweight and subsequent gains in weight, length, and head circumference was observed in the primary trial. Infants fed banked breast milk and weighing less than 1200 g at birth took a calculated additional three weeks to reach 2000 g compared with those fed on the preterm formula. A significant influence of diet on body proportions was seen in the relation between body weight, head circumference, and length. Similar though smaller differences in growth patterns were seen in the supplement trial. By the time they reach 2000 g, infants of birthweights 1200 to 1849 g fed on banked breast milk and infants below 1200 g fed on either banked breast milk or maternal milk supplemented (as necessary) with banked breast milk, fulfilled stringent criteria for failure to thrive (weight less than 2 SD below the mean for age). Only infants fed the preterm formula as their sole diet had maintained their birth centile by discharge from hospital. The misleading nature of comparisons between extrauterine and intrauterine steady state weight gains is emphasised. The optimal quantity and quality of protein for low-birthweight infants is undefined. In this study, 106 well, appropriate-for-gestational age, low-birthweight infants weighing 2,100 gm or less were grouped in three gestational age categories: T1 = 28 to 30 weeks; T2 = 31 to 33 weeks; T3 = 34 to 36 weeks. Each group was assigned randomly to either banked human milk (BM) or to one of four isocaloric formulas varying in quantity and quality of protein but not in mineral content or in fat content: formula 1 = 1.5 gm of protein per 100 ml, 60 parts bovine whey proteins to 40 parts bovine caseins; formula 2 = 3.0 gm of protein per 100 ml, 60:40; formula 3 = 1.5 gm of protein per 100 ml, 18:82; formula 4 = 3.0 gm of protein per 100 ml, 18:82. Caloric intake was 117 kcal/150 ml/kg/day for the formulas. Human milk was fed at 170 ml/kg/day in order to attain a caloric intake approximately equal to that of the formulas. No significant differences were found in the rate of growth in crown-rump length, in femoral length, in head circumference, or in rate of gain in weight from time of regaining birthweight to time of discharge at 2,400 gm. Blood urea nitrogen, urine osmolarity, total serum protein, serum albumin, and serum globulin varied directly with the quantity of protein in the diet: F2, F4 greater than F1, F3 greater than BM. Blood ammonia concentration varied with both quantity and quality of protein in the diet: F2, F3, F4 greater than F1, BM. Metabolic acidosis was more frequent, more severe, and more prolonged in the infants fed the casein-predominant formulas (F3,F4) than in those fed the whey protein-predominant formulas (F1, F2). Twenty premature low-birthweight infants were divided into two groups and assigned randomly to either a pooled human milk or to a cow's milk based infant formula feeding regimen. The protein intake was 2.0 g/kg/day in the human milk fed group and 4.4 g/kg/day in the formula fed group of infants. The concentrations of different metabolites were estimated at weekly intervals, and plasma amino acid analysis was performed biweekly on blood samples in the two groups of infants during the four-week study period. Formula milk fed infants had significantly lower fasting blood glucose levels and developed azotaemia, hyperaminoacidemia and metabolic acidosis in the early weeks of postnatal life. Blood lactate and plasma free fatty acid concentrations did not change significantly in the two groups during the study. No significant differences were found in the rate of weight gain between the two groups of infants, although formula fed infants regained their birthweight more slowly than human milk fed infants. High protein formula feeding causes potentially unfavorable metabolic and amino acid imbalances in preterm infants in the early postnatal life. Compared with preterm formula (PF), mother's milk (MM) is associated with lower rates of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) among premature infants. Because not all mothers of premature infants produce sufficient milk to supply their infants throughout hospitalization, we reasoned that pasteurized donor human milk (DM) would be a suitable alternative.
                Extremely premature infants (<30 weeks of gestation) whose mothers intended to breastfeed were assigned randomly to receive either pasteurized DM or PF if the supply of their own MM became insufficient during the study (birth to 90 days of age or hospital discharge). Infection-related events (LOS, NEC, meningitis, presumed sepsis, or urinary tract infection) that occurred after the attainment of a milk intake of 50 mL/kg, dietary intake, growth, skin-to-skin contact, and duration of hospital stay were compared. The primary analysis compared groups DM and PF on an intent-to-treat basis. If no differences were noted, then these groups were combined and compared with the reference group, group MM. If differences were noted, then the subsequent analyses compared each group with group MM.
                Of 243 infants, 70 (29%) received only MM; group DM included 81 infants and group PF included 92 infants. Because of poor weight gain, 17 infants (21%), all in group DM, were switched to PF. There were no differences in birth weight, gestational age, multiple births, and age at attainment of feeding of 50 mL/kg among groups. There were no differences between group DM and group PF in LOS and/or NEC, other infection-related events, hospital stay, or number of deaths. Group DM received a greater intake of milk and more nutritional supplements but had a slower rate of weight gain, compared with group PF. Compared with groups DM and PF, group MM had fewer episodes of LOS and/or NEC and total infection-related events and a shorter duration of hospital stay. Group MM also had fewer Gram-negative organisms isolated from blood cultures than did the other groups.
                In this randomized, blinded trial of feeding of extremely premature infants, we found that, as a substitute for MM, DM offered little observed short-term advantage over PF for feeding extremely premature infants. Advantages to an exclusive diet of MM were observed in terms of fewer infection-related events and shorter hospital stays.
In preterm and low birth weight infants, feeding with formula milk compared with donor breast milk results in a higher rate of short-term growth but also a higher risk of developing necrotising enterocolitis. There are only limited data on the comparison of feeding with formula milk versus nutrient-fortified donor breast milk. This limits the applicability of the findings as nutrient fortification of breast milk is now a common practice in neonatal care. Future trials may compare growth, development and adverse outcomes in infants who receive formula milk versus nutrient-fortified donor breast milk given as a supplement to maternal expressed breast milk or as a sole diet.