Serum bilirubin levels at 72 hours by selected characteristics in breastfed and formula-fed term infants delivered by cesarean section.

UNLABELLED: The present multicenter study analysed the relative impact of maternal and infant factors on serum bilirubin levels at 72 +/- 12 h in exclusively breastfed vs formula-fed term infants. End-tidal carbon monoxide levels corrected for ambient air (ETCOc), an index of bilirubin production, were measured in exclusively breastfed (B = 66) or formula-fed (F = 210) term infants at 2-8 h of age. Inclusion criteria included cesarean section to ensure a 3 d hospitalization, birthweight > or = 2,500 g, gestational age >37 wk and absence of any illness. The ETCOc for B infants and F infants did not differ significantly (1.3 +/- 0.7 ppm vs 1.3 +/- 0.8 ppm). The serum bilirubin level at 72 +/- 12 h was significantly higher in B infants than in F infants (8.5 +/- 3.4mg dl(-1) vs 6.7 +/- 3.4mg dl(-1) p < 0.001), as was the percentage weight loss from birthweight. Serum bilirubin levels were significantly higher in infants who were male, who did not have meconium-stained amniotic fluid, and in those whose mothers were insulin-dependent diabetics or hypertensive. There was no difference between groups in the need for phototherapy or exchange transfusion. CONCLUSION: Although higher bilirubin levels were observed in group B at 72 +/- 12 h compared with group F, this finding was not of clinical or therapeutic consequence in this study. The lack of difference in ETCOc between the groups may be a factor of the timing of ETCOc measurement in this study, or may suggest that early increased bilirubin production is not a significant contributor to jaundice observed in exclusively breastfed infants. Key words: bilirubin, breastfeeding, jaundice

Vitamin A supplementation for extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network.

BACKGROUND: Vitamin A supplementation may reduce the risk of chronic lung disease and sepsis in extremely-low-birth-weight infants. The results of our pilot study suggested that a dose of 5000 IU administered intramuscularly three times per week for four weeks was more effective than the lower doses given in past trials. METHODS: We performed a multicenter, blinded, randomized trial to assess the effectiveness and safety of this regimen as compared with sham treatment in 807 infants in need of respiratory support 24 hours after birth. The mean birth weight was 770 g in the vitamin A group and 769 g in the control group, and the respective gestational ages were 26.8 and 26.7 weeks. RESULTS: By 36 weeks' postmenstrual age, 59 of the 405 infants (15 percent) in the vitamin A group and 55 of the 402 infants (14 percent) in the control group had died. The primary outcome - death or chronic lung disease at 36 weeks' postmenstrual age - occurred in significantly fewer infants in the vitamin A group than in the control group (55 percent vs. 62 percent; relative risk, 0.89; 95 percent confidence interval, 0.80 to 0.99). Overall, 1 additional infant survived without chronic lung disease for every 14 to 15 infants who received vitamin A supplements. The proportions of infants in the vitamin A group and the control group who had signs of potential vitamin A toxicity were similar. The proportion of infants with serum retinol values below 20 microg per deciliter (0.70 micromol per liter) was lower in the vitamin A group than in the control group (25 percent vs. 54 percent, P<0.001). CONCLUSIONS: Intramuscular administration of 5000 IU of vitamin A three times per week for four weeks reduced biochemical evidence of vitamin A deficiency and slightly decreased the risk of chronic lung disease in extremely-low-birth-weight infants.

Vitamin A to prevent bronchopulmonary dysplasia in very-low-birth-weight infants: has the dose been too low? The NICHD Neonatal Research Network.

OBJECTIVE: Inconsistent effects of vitamin A supplementation on prevention of bronchopulmonary dysplasia have been reported. Meta-analysis of these reports resulted in a relative risk of 0.69-1.02 for death or bronchopulmonary dysplasia associated with vitamin A supplementation. Effective dosage regimens or serum retinol concentrations have not been determined in previous reports. The purpose of this pilot study was to define a vitamin A regimen that produces serum retinol concentrations of 25-55 micrograms/dl. STUDY DESIGN: In this three-phase study, 91 infants (mean birth weight 799-864 g) were enrolled. Vitamin A was administered three times/week for 4 weeks at an average daily dose of 986-2143 IU/day. Physical examinations were performed and serum retinol specimens were collected weekly to assess clinical signs of toxicity. RESULTS: The majority of serum retinol concentrations remained < 25 micrograms/dl until an intramuscular vitamin A dose of 5000 IU/dose three times/week was used. No clinical signs of toxicity were associated with the higher dosage and higher serum concentrations of vitamin A. CONCLUSION: A large clinical trial of vitamin A supplementation with 5000 IU/dose three times/week (25-114% more than the dose used in the three published clinical trials) is needed to assess whether vitamin A supplementation safely reduces the risk of bronchopulmonary dysplasia in very-low-birth-weight infants.

Depressed immune response to tetanus in children with vitamin A deficiency.

A randomized, double-masked, placebo-controlled clinical trial was conducted with 236 preschool children, age 3-6 y, in Indonesia to assess immune status in mild vitamin A deficiency. The immune response to tetanus immunization was used as a measure of immune competence. Clinically normal children (n = 118) and children with mild xerophthalmia (n = 118) were randomly assigned to receive oral vitamin A (60,000 micrograms retinol equivalent) or placebo treatment for a total of four study groups. Two weeks after treatment, children were immunized with diphtheria-pertussis-tetanus vaccine. The immunoglobulin G (IgG) responses to tetanus at baseline and 3 wk following immunization were measured by ELISA. After adjusting for previous tetanus immunization, clinically normal and xerophthalmic children receiving vitamin A had a significantly greater IgG response to tetanus than clinically normal and xerophthalmic children receiving placebo (P less than 0.05). These results suggest that children with mild vitamin A deficiency have a relative immune depression compared with children who have been supplemented to normal vitamin A levels.

Determinants of community-based coverage: periodic vitamin A supplementation. Aceh Study Group.

Factors related to preschool child receipt of vitamin A during the first year of a semi-annual vitamin A capsule delivery program were investigated in 229 villages in Aceh, Indonesia. Coverage was higher in villages which were more rural and less economically developed. Highest performance was achieved by village distributors who represented the local status quo in this rural area (farmers, or non-farmers with minimum education) rather than more upwardly mobile, highly educated residents. Household or child-level characteristics were not associated with coverage. This information may be useful for planning direct service programs in the community.

Influence of participation on mortality in a randomized trial of vitamin A prophylaxis.

Mortality of Sumatran children living in villages randomized to participate in a vitamin A capsule (200,000 IU) distribution program who received the capsule (n = 9776) was compared with those who did not (n = 2447) and with children living in villages randomized to serve as control subjects (n = 12,173). During the 4 mo after completion of the first distribution, mortality among preschool capsule recipients was less than 4% that of nonrecipients (p less than 0.001). Mortality among preschool nonrecipients was three times that of controls (p less than 0.05), suggesting strong selection bias. The potential biologic impact on childhood mortality attributable to vitamin A supplementation is estimated to exceed the 34% previously derived from the more conservative intent-to-treat analysis. One capsule every 6 mo may provide adequate protection for the vast majority of children. The single major limitation to maximum impact appears to be inadequate program coverage.

Impact of vitamin A supplementation on childhood mortality. A randomised controlled community trial.

450 villages in northern Sumatra were randomly assigned to either participate in a vitamin A supplementation scheme (n = 229) or serve for 1 year as a control (n = 221). 25 939 preschool children were examined at baseline and again 11 to 13 months later. Capsules containing 200 000 IU vitamin A were distributed to preschool children aged over 1 year by local volunteers 1 to 3 months after baseline enumeration and again 6 months later. Among children aged 12-71 months at baseline, mortality in control villages (75/10 231, 7.3 per 1000) was 49% greater than in those where supplements were given (53/10 919, 4.9 per 1000) (p less than 0.05). The impact of vitamin A supplementation seemed to be greater in boys than in girls. These results support earlier observations linking mild vitamin A deficiency to increased mortality and suggest that supplements given to vitamin A deficient populations may decrease mortality by as much as 34%.