Vitamin A Status of Neonates with Bronchopulmonary Dysplasia Randomised controlled trial of oral vitamin A supplementation in preterm infants to prevent chronic lung disease Effect of vitamin A supplementation of intravenous lipids on early vitamin A intake and status of premature infants. Clinical trial of vitamin A supplementation in infants susceptible to bronchopulmonary dysplasia. Early vs delayed vitamin A supplementation in very-low-birth-weight infants. Intramuscular versus enteral vitamin A supplementation in very low birth weight neonates. Vitamin A to prevent bronchopulmonary dysplasia in very-low-birth-weight infants: has the dose been too low? The NICHD Neonatal Research Network. Trial of vitamin A supplementation in very low birth weight infants at risk for bronchopulmonary dysplasia. Plasma retinol-binding protein response to vitamin A administration in infants susceptible to bronchopulmonary dysplasia. Impact of neonatal vitamin A supplementation on infant morbidity and mortality. Vitamin A supplementation for extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network.
ABSTRACT : We prospect ively assessed and compared the vitamin A status of two groups of preterm neonates ( < 1500 g birth weight , < 32 wk gestation ) , one who developed clinical and radiographic evidence of bronchopulmonary dysplasia ( BPD ) ( n = 10 ) , and the other ( control ) who developed no significant lung disease ( n = 8) . The infants with BPD in this study required prolonged mechanical ventilation and supplemental O2 therapy , and had a higher incidence of cardiorespiratory complications when compared to controls . Their mean plasma vitamin A concentrations were significantly lower than those of controls at four sampling times in the 1st postnatal month . In contrast to the controls , infants with BPD showed a substantial decline in their plasma vitamin A concentrations from the initial values , and a high percentage of individual values of plasma vitamin A concentration in these infants were < 10 μg/dl during the 8-wk postnatal period of observation . Delayed establishment of gastrointestinal feeding and a lower vitamin A intake in these infants relative to controls may have accounted for this decline . Our data show that preterm neonates who develop BPD  have suboptimal plasma vitamin A concentrations for extended periods of time postnatally . We speculate that the necrotizing bronchiolitis and squamous metaplasia of conducting airways associated with vitamin A deficiency could influence the orderly repair of lung injury in susceptible neonates who are mechanically ventilated and could contribute to the pathophysiology of BPD in these infants . Further studies are needed to determine whether more efficient management of these neonates with regard to their vitamin A nutrition and early achievement of vitamin A sufficiency could result in a decrease in the incidence and severity of BPD BACKGROUND Intramuscular supplementation with vitamin A in large doses may reduce the incidence of chronic lung disease . AIM To investigate whether oral supplementation with vitamin A would reduce the incidence of chronic lung disease in a group of extremely low birthweight infants . METHODS Infants with birth weight < 1000 g were r and omised at birth to receive oral vitamin A supplementation ( 5000 IU/day ) or placebo for 28 days . The primary outcome was oxygen dependency at 28 days of age or death . RESULTS A total of 154 infants were r and omised ; 77 received vitamin A ( median birth weight ( interquartile range ) 806 ( 710–890 ) g ) , and 77 received placebo ( median birth weight ( interquartile range ) 782 ( 662–880 ) g ) . Plasma vitamin A concentrations in the supplemented group were significantly higher at 24 hours of age but did not differ significantly at birth , 12 hours of age , 7 days , or 28 days of life . There were no significant differences in the proportion of infants who survived , required oxygen at 28 days , required oxygen at 36 weeks postmenstrual age , survived without chronic lung disease at 36 weeks , survived without significant retinopathy , or who survived without significant intraventricular haemorrhage . CONCLUSIONS Oral supplementation with 5000 IU vitamin A in extremely low birthweight infants does not significantly alter the incidence of chronic lung disease . However , this dose may have been inadequate to achieve optimal serum retinol concentrations Preterm infants were r and omly assigned to receive routine vitamin A supplementation ( Regular A ) or additional vitamin A in intravenous lipids ( High A ) . Because infants with bronchopulmonary dysplasia ( BPD ) have poorer vitamin A status than infants who do not develop BPD , High A and Regular A infants were divided by BPD ( no or yes ) before determining the effects of treatment on intake and plasma concentration of retinol in the first month . Compared with infants without BPD , those with BPD received less retinol ( RE.kg-1.d-1 ) if assigned to Regular A and more if assigned to High A ( BPD by vitamin A interaction , P < 0.002 ) . High A-BPD infants compared with Regular A-BPD infants had significantly higher plasma retinol concentrations in the first month . Retinyl palmitate appears to be an effective adjunct to routine vitamin A administration . Infants most likely to benefit from receiving vitamin A in intravenous lipids are those advanced more slowly to full enteral feeding We conducted a r and omized , double-blind , controlled trial to determine whether vitamin A supplementation from early postnatal life could reduce the morbidity associated with bronchopulmonary dysplasia in very low birth weight ( VLBW ) neonates . Forty VLBW neonates ( 700 to 1300 g birth weight , 26 to 30 weeks gestational age ) , who were oxygen dependent and required mechanical ventilation for at least 72 hours after birth , were given by the intramuscular route either supplemental vitamin A ( retinyl palmitate 2000 IU ) or 0.9 % saline solution on postnatal day 4 and every other day thereafter for a total of 14 injections over 28 days . The study groups were comparable in gestational maturity , clinical characteristics , initial lung disease , and vitamin A status at entry into the trial . Vitamin A administration result ed in significantly higher mean plasma concentrations of vitamin A and retinol-binding protein in treated infants compared with controls . Bronchopulmonary dysplasia was diagnosed in nine of 20 infants given vitamin A supplement and in 17 of 20 control infants ( P less than 0.008 ) . Four of 19 infants in the vitamin A group and 11 of 20 in the control group required mechanical ventilation on study day 28 ( P less than 0.029 ) . The need for supplemental oxygen , mechanical ventilation , and intensive care was reduced in infants given vitamin A supplement compared with controls . Airway infection and retinopathy of prematurity were less frequent in the vitamin A group . We conclude that vitamin A supplementation at the dosage used in this trial in VLBW neonates not only improves their vitamin A status but also appears to promote regenerative healing from lung injury , as evidence d by a decrease in the morbidity associated with bronchopulmonary dysplasia The purpose of this trial was to test the hypothesis that vitamin A adequacy may decrease the incidence of  bronchopulmonary dysplasia ( BPD ) in very-low-birth-weight infants .  Serum vitamin A levels were measured and the effects of two regimens of vitamin A supplementation on the incidence of BPD were compared . There were 24 infants in each of two groups with a mean birth weight less than 1000 g , a mean gestational age of 27 weeks , and similar sexual and racial mixes . In group I ,  vitamin A levels  were measured after 1 week of parenteral nutrition and , if low , the infant was given a 2000-IU supplement intramuscularly three times a week , beginning on the 10th to 14th day of life . In group II , the same supplementation was begun on the second to fourth day of life . In both groups , when enteral feedings reached 60 kcal/kg per day , 2500 IU/d vitamin A was given orally . The incidence of oxygen support at 28 days was similar in both groups , although in group II there was a trend toward less vigorous ventilatory support . chi 2 analysis showed that a significantly smaller proportion of infants in group II had BPD at 36 weeks ' gestational age than in group I. Length of neonatal intensive care unit stay was significantly reduced from 81 to 60 days . We conclude that vitamin A supplementation should be administered early to small , premature infants who are at risk for BPD and that monitoring of plasma levels is essential We conducted a r and omized trial in very low birth weight neonates ( n = 51 ) to determine whether vitamin A supplementation by enteral administration would increase plasma vitamin A concentrations to the same degree as by intramuscular administration .  Mean plasma vitamin A concentrations were significantly higher in the intramuscular-administration group than in the enteral-administration group by postnatal day 7 ; this effect persisted throughout the remainder of the trial . At the dosage used in this trial , vitamin A supplementation by the enteral route is not as effective as that by the intramuscular route in very low birth weight neonates OBJECTIVE Inconsistent effects of vitamin A supplementation on prevention of  bronchopulmonary dysplasia  have been reported . Meta- analysis of these reports result ed 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 We performed a r and omized , double-blind , controlled trial to determine whether vitamin A supplementation in a group of very low birth weight infants would reduce the incidence of bronchopulmonary dysplasia .  Forty-nine infants ( birth weight 700 to 1100 gm ) requiring mechanical ventilation and supplemental oxygen at 96 hours age were r and omly assigned to receive either 2000 IU retinyl palmitate ( n = 27 ) or saline placebo ( n = 22 ) intramuscularly every other day for up to 14 doses . There were no differences between treatment groups in the incidences of bronchopulmonary dysplasia at 31 days of postnatal age ( vitamin A group 48 % , placebo group 55 % ; p = 0.776 ) , supplemental oxygen requirement at 34 weeks of postconceptional age , or other complications of prematurity . The vitamin A group had higher mean plasma vitamin A concentrations than the placebo group , but mean plasma vitamin A concentrations were greater than 20 micrograms/dl ( suggesting sufficiency ) in both groups after the first study week . By study day 28 , only one fourth of the infants in either group had plasma vitamin A concentrations less than 20 micrograms/dl . In contrast to an earlier report , we found no change in the incidence of BPD with vitamin A supplementation . Our findings may reflect a low baseline incidence of vitamin A deficiency in the study population and recent changes in the respiratory care of very low birth weight infants . The latter may have lessened the potential impact of vitamin A deficiency on lung disease We hypothesized that changes in plasma retinol-binding protein ( RBP ) concentration in response to vitamin A administration might be useful for evaluating vitamin A status of very low birth weight infants susceptible to bronchopulmonary dysplasia . We prospect ively studied 24 consecutively admitted neonates ( birth weight less than 1350 gm , gestational age less than 31 weeks , ventilator dependent for greater than 24 hours after birth ) , who were eligible to receive 2000 IU supplemental vitamin A by intramuscular injection on postnatal day 1 and on alternate days thereafter for 28 days . In addition to serial assessment of vitamin A status , we measured plasma RBP just before and 1 , 3 , and 6 hours after an intramuscular injection of vitamin A ( 2000 IU/kg retinyl palmitate ) on days 1 and 28 . The percent increase in plasma RBP ( delta-RBP ) was high ( mean + /- SD : 61 + /- 37 % ) and plasma vitamin A and RBP values were low on day 1 , indicative of vitamin A deficiency . Supplemental vitamin A improved vitamin A status of all infants as shown by low delta-RBP ( mean + /- SD : 8 + /- 9 % ) and normal plasma vitamin A and RBP values on day 28 . Bronchopulmonary dysplasia was diagnosed in 12 of 24 infants . Infants with bronchopulmonary dysplasia had a higher mean ( + /- SD ) delta-RBP on day 28 than those without bronchopulmonary dysplasia ( 13 + /- 10 % vs 3 + /- 3 % , p less than 0.01 ) , indicative of persistence of low vitamin A status in infants with lung disease despite supplementation . We conclude that the plasma RBP response to vitamin A is a useful indicator of vitamin A status in very low birth weight infants . Although vitamin A supplementation at the dosage used in this study normalizes conventional plasma indexes of vitamin A in very low birth weight infants , the plasma RBP response to vitamin A may continue to reflect persistence of low vitamin A status in the more immature infants with significant lung disease . We suggest that the plasma RBP response to vitamin A may be a useful functional test in such infants OBJECTIVE To determine whether vitamin A supplementation at birth could reduce  infant morbidity and mortality .  STUDY DESIGN We conducted a placebo-controlled trial among 2067 Indonesian neonates who received either 52 micromol ( 50,000 IU ) orally administered vitamin A or placebo on the first day of life . Infants were followed up at 1 year to determine the impact of this intervention on infant mortality . A subgroup ( n = 470 ) was also examined at 4 and 6 months of age to examine the impact on morbidity . RESULTS Vital status was confirmed in 89 % of infants in both groups at 1 year . There were 19 deaths in the control group and 7 in the vitamin A group ( relative risk = 0.36 ; 95 % confidence interval = 0.16 , 0.87 ) . The impact was stronger among boys , infants of normal compared with low birth weight , and those of greater ponderal index . Among infants examined at 4 months of age , the 1-week period prevalence of common morbidities was similar for vitamin A and control infants . However , during this same 4-month period , 73 % and 51 % more control infants were brought for medical treatment for cough ( p = 0.008 ) and fever ( p = 0.063 ) , respectively . CONCLUSIONS Neonatal vitamin A supplementation may reduce the infant mortality rate and the prevalence of severe respiratory infection among young infants 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 , r and omized 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
BACKGROUND Vitamin A is necessary for normal lung growth and the ongoing integrity of respiratory tract epithelial cells .
Preterm infants have low vitamin A status at birth and this has been associated with increased risk of developing chronic lung disease .
Several studies have been undertaken to assess whether vitamin A supplementation beyond that routinely given in multivitamin preparations can reduce the incidence of this outcome .
OBJECTIVES To assess the benefit of supplementation with vitamin A in very low birthweight infants .