Effect of fluid administration on the development of symptomatic patent ductus arteriosus and congestive heart failure in premature infants. A randomized, controlled trial of very early prophylactic ligation of the ductus arteriosus in babies who weighed 1000 g or less at birth. Early enteral feeding does not affect the incidence of necrotizing enterocolitis. Oral probiotics prevent necrotizing enterocolitis in very low birth weight preterm infants: a multicenter, randomized, controlled trial. Prophylactic treatment of asymptomatic patent ductus arteriosus in premature infants with respiratory distress syndrome.
We studied 170 premature infants with birth weights between 751 and 2000 g in a randomized sequential trial comparing "high" and "low" volumes of fluid intake. Beginning on the third day of life, the low-volume group received only enough water to meet average estimated requirements, and the high-volume group received an excess of at least 20 ml per kilogram of body weight per day (mean excess, 47 ml per kilogram per day). Sequential analysis showed that the risk of patent ductus arteriosus with congestive heart failure was greater in infants receiving the high-volume regimen. Thirty-five of 85 infants in the high-volume group acquired murmurs consistent with patent ductus arteriosus, and 11 of these 35 had congestive heart failure. Only nine of 85 infants in the low-volume group had murmurs consistent with patent ductus arteriosus, and two of these nine had congestive heart failure. More cases of necrotizing enterocolitis also occurred in the high-volume group. We conclude that limitation of fluid intake to amounts estimated to meet requirements for excretion, insensible loss, and growth can reduce the risks of patent ductus arteriosus and congestive heart failure in premature infants. We speculated that prophylactic ligation of the ductus arteriosus would reduce mortality and morbidity in very-low-birth-weight infants. To test this hypothesis, we randomly assigned 84 babies who weighed 1000 g or less at birth and required supplemental oxygen either to receive standard treatment (n = 44) or to undergo prophylactic surgical ligation of the ductus arteriosus on the day of birth (n = 40). The ductus was ligated in babies in the control group only if the shunt was hemodynamically important. All the babies were followed for one year. The incidence of necrotizing enterocolitis was reduced in the group that underwent prophylactic ligation (3 of 40 [8 percent]) as compared with the control group (13 of 44 [30 percent]; P = 0.002). The frequency of death, bronchopulmonary dysplasia, retinopathy of prematurity, and intraventricular hemorrhage was similar in both groups. Because early enteral feeding may have increased the incidence of necrotizing enterocolitis, we analyzed separately the babies who were fed early. Among the infants who were fed within 14 days of birth, those who underwent prophylactic ligation had a lower incidence of necrotizing enterocolitis (1 of 11 [9 percent]) than those who did not (13 of 24 [54 percent]; P = 0.001). Within the control group, the infants who were fed within 14 days of birth and whose ductus was ligated for medical reasons within 5 days of birth had a lower incidence of necrotizing enterocolitis (2 of 10 [20 percent]) than those whose ductus was ligated later or not at all (11 of 14 [79 percent]; P = 0.004). We conclude that early surgical closure of the ductus arteriosus reduces the risk of necrotizing enterocolitis in infants of very low birth weight who require supplemental oxygen. To begin to determine the optimal time for initiating enteral feedings, 34 sick, very low birth weight infants were prospectively selected from all neonates of less than 1,500 g (N = 116) and randomly divided into two groups. Infants were fed either on day 1 (early) or 7 (late) of life, according to a feeding protocol which included parenteral nutrition and a scheduled progression from sterile water to 2.5% dextrose, half-strength, and finally full-strength formula over seven days. The incidence of necrotizing enterocolitis and subsequent hospital course were compared. Initiating enteral feedings on day 1 did not significantly increase the incidence of necrotizing enterocolitis, produce a clustering of cases, or induce an earlier onset of necrotizing enterocolitis. The overall incidence of necrotizing enterocolitis in sick, very low birth weight neonates was 29% (5/17) and 35% (6/17) in the early and late groups, respectively, compared with 4.2% (2/47) in minimally sick, very low birth weight neonates. No significant differences between groups were seen in obstetrical complications, birth weight, gestational age, Apgar scores, presence of patent ductus arteriosus or intraventricular hemorrhage, use of umbilical catheterization, and respiratory or oxygen requirements. Infants fed enterally from day 1 did show a significantly higher energy and protein intake during the second week of life. These data show that providing dilute, early enteral calories does not adversely affect the incidence of necrotizing enterocolitis. The goal was to investigate the efficacy of orally administered probiotics in preventing necrotizing enterocolitis for very low birth weight preterm infants.
                A prospective, blinded, randomized, multicenter controlled trial was conducted at 7 NICUs in Taiwan, to evaluate the beneficial effects of probiotics in necrotizing enterocolitis among very low birth weight infants (birth weight: <1500 g). Very low birth weight infants who survived to start enteral feeding were eligible and were assigned randomly to 2 groups after parental informed consent was obtained. Infants in the study group were given Bifidobacterium bifidum and Lactobacillus acidophilus, added to breast milk or mixed feeding (breast milk and formula), twice daily for 6 weeks. Infants in the control group were fed with breast milk or mixed feeding. The clinicians caring for the infants were blinded to the group assignment. The primary outcome measurement was death or necrotizing enterocolitis (Bell's stage >or=2).
                Four hundred thirty-four infants were enrolled, 217 in the study group and 217 in the control group. The incidence of death or necrotizing enterocolitis (stage >or=2) was significantly lower in the study group (4 of 217 infants vs 20 of 217 infants). The incidence of necrotizing enterocolitis (stage >or=2) was lower in the study group, compared with the control group (4 of 217 infants vs 14 of 217 infants). No adverse effect, such as sepsis, flatulence, or diarrhea, was noted.
                Probiotics, in the form of Bifidobacterium and Lactobacillus, fed enterally to very low birth weight preterm infants for 6 weeks reduced the incidence of death or necrotizing enterocolitis. Early treatment of premature infants with indomethacin has been proposed as a means of reducing the morbidity associated with respiratory distress syndrome complicated by symptomatic patent ductus arteriosus. We identified 26 infants less than 48 hours old with severe respiratory distress syndrome who had an asymptomatic patent ductus arteriosus. These infants were treated with either indomethacin or placebo. There was a significant difference in the frequency of ductal closure after receiving indomethacin treatment. No significant difference was observed in the time required for mechanical ventilation, time receiving supplemental oxygen, or time in the hospital, and there were no significant differences in the incidence of bronchopulmonary dysplasia, intraventricular hemorrhage, retinopathy of prematurity, or death between the two groups.
Based on this analysis, the most prudent prescription for water intake to premature infants would seem to be careful restriction of water intake so that physiological needs are met without allowing significant dehydration. This practice could be expected to decrease the risks of patent ductus arteriosus and necrotizing enterocolitis without significantly increasing the risk of adverse consequences.