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 different vitamin A intakes on very-low-birth-weight infants. 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. Vitamin A supplementation improves retinal function in infants at risk of retinopathy of prematurity. Early vs delayed vitamin A supplementation in very-low-birth-weight infants. Intramuscular versus enteral vitamin A supplementation in very low birth weight neonates. Effect of vitamin A supplementation on morbidity of 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. A trial of vitamin A therapy to facilitate ductal closure in premature infants. Improved vitamin A supplementation regimen for breastfed very low birth weight infants Absorption of high-dose enteral vitamin A in low-birth-weight neonates. 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. Persistently low blood retinol levels during and after parenteral feeding of very low birth weight infants: examination of losses into intravenous administration sets and a method of prevention by addition to a lipid emulsion. Vitamin A Supplementation for Extremely Low Birth Weight Infants: Outcome at 18 to 22 Months A comparison of three vitamin A dosing regimens in extremely-low-birth-weight infants. Characterization of the vitamin A transport in preterm infants after repeated high-dose vitamin A injections Vitamin A supplementation in extremely low-birth-weight infants: subgroup analysis in small-for-gestational-age infants.
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 Formula-fed infants with birth weights < or = 1500 g ( n = 61 ) were stratified by 250-g birth-weight ranges and r and omly assigned to receive one of three preterm infant formulas ( vitamin A contents of 820 IU , 1640 IU , or 2900 IU/MJ ; 1 RE = 3.3 IU vitamin A activity ) when subjects tolerated 0.314 MJ.kg-1.d-1 . Experimental formula feedings were continued until infants weighed approximately 2 kg or until hospital discharge . Vitamin A status as indicated by serum retinol and retinol-binding protein ( RBP ) concentrations significantly decreased during experimental formula feeding at the lowest vitamin A intake . All subjects fed the formula providing the lowest vitamin A intake had hyporetinolemia ( < 0.70 mumol/L , or < 20 micrograms/dL ) , which occurred less frequently ( P < 0.05 ) with the intermediate ( 6 of 20 ) and the high ( 6 of 21 ) vitamin A intakes . Other outcome measures , including increases in weight , length , and head circumference , and ventilatory support and oxygen therapy , were not different among groups . After the end of the experimental formula-feeding period , all infants were fed st and ard infant formulas with a vitamin A content of 715 IU/MJ . In a subset of 19 of these infants , subsequent vitamin A status was monitored at ages 6 - 12 mo and was found to be comparable with that of older children and adults , regardless of the vitamin A content of the formula fed during hospitalization . ( ABSTRACT TRUNCATED AT 250 WORDS 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 OBJECTIVE Preterm infants show reduced retinal sensitivity at term corrected age compared with newborn term infants . We tested the hypothesis that retinal sensitivity in preterm infants is improved by early , high-dose vitamin A. STUDY DESIGN We report a double-blind , r and omized controlled trial of infants < 32 weeks ' gestation and /or < 1501 g birth weight . Supplemented infants received additional intramuscular vitamin A 10 000 IU 3 times weekly from day 2 for a minimum of 2 weeks or until establishment of oral feeding . Hepatic stores were assessed by relative dose response ( RDR ) . The primary outcome measure was cone-corrected dark-adapted retinal rod sensitivity measured by electroretinogram at 36 weeks ' postmenstrual age ( PMA ) . RESULTS Eighty-nine infants ( 42 supplemented and 47 controls ) were recruited .  Plasma retinol was higher in supplemented infants at 7 and 28 days ( median , 1.0 vs 0.5 μmol/L and 0.7 vs 0.6 μmol/L ; P < .001 and .03 , respectively ) . Neither plasma retinol nor RDR differed between groups at 36 weeks ' PMA . Retinal sensitivity was greater in supplemented infants ( -0.81 vs -0.61 log cd • s • m(-2 ) ; P < .03 ) and was not related to RDR . CONCLUSIONS Early high-dose intramuscular vitamin A supplementation for infants at risk of retinopathy of prematurity  improves retinal function at 36 weeks ' PMA 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 BACKGROUND Low-birth-weight ( LBW ) infants ( < 2,500 g ) are at increased risk of respiratory infection in the first few months of life and have low liver stores of vitamin A. As retinol is essential for respiratory epithelial cell differentiation , deficiency could result in pathological changes in the respiratory epithelium , with respiratory problems . OBJECTIVE A r and omised , double-blind , placebo-controlled trial to investigate the effect of vitamin A supplementation on the incidence and severity of respiratory infections in LBW infants during their first year of life . METHOD One hundred and thirty LBW infants ( gestational age < 36 weeks and birth weight 950 - 1,700 g ) were enrolled in the study . The infants were r and omly allocated to a vitamin A or placebo group . Infants in the vitamin A group received 25,000 IU of vitamin A ( retinyl palmitate , Arovit drops , Roche , Basle , Switzerl and ) on study days 1 , 4 and 8 . Study day 1 was between 36 and 60 hours after delivery . Infants in the placebo group received a placebo ( formulated by Roche ) with a similar appearance and packed in the same dropper bottles as the vitamin A drops . RESULTS Vitamin A supplementation markedly improved serum retinol levels . After the last vitamin A dose , the vitamin A group had higher mean serum retinol concentrations than the placebo group ( 45.77 + /- 17.07 micrograms/dl v. 12.88 + /- 6.48 micrograms/dl , P = 0.0001 ) . There was no evidence of improvement in neonatal or post-neonatal respiratory problems associated with vitamin A supplementation . Vitamin A and placebo groups did not differ in the occurrence or duration of respiratory distress or the need for head-box oxygen . There were also no significant differences in the cumulative probability of developing lower or upper respiratory tract infection through the first year of life . There was a slight suggestion of an increase in the risk of hospitalisation with pneumonia associated with vitamin A supplementation . The cumulative probability of being hospitalised with pneumonia by 6 months of age was 24.6 % ( 7 hospitalisations ) in the vitamin A group compared with 7.4 % ( 2 hospitalisations ) in the placebo group ( log rank test P = 0.04 ) . After adjusting for risk factors this difference was no longer significant . CONCLUSION Vitamin A supplementation in LBW neonates may not reduce incidence or severity of respiratory infections . These results do not negate the importance of improving vitamin A status in children as an important public health measure to reduce morbidity and mortality from other childhood infections 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 OBJECTIVE To determine whether postnatal vitamin A therapy increased ductal closure rate in premature infants . STUDY DESIGN This was a prospect i ve , double-blind , placebo-controlled trial . Subjects ( n=40 ) were recruited on day of life 1 . Inclusion criteria were premature neonates weighing 500 to 1500 g with an indwelling umbilical line .  Vitamin A was administered intramuscularly on days 1 , 3 , and 7 . Blood vitamin A and retinol binding protein levels were obtained on days 1 and 3 . Echocardiography was performed on days 1 , 3 , 7 , and 14 . Failure of ductal closure was defined as the presence of a moderate to large patent ductus arteriosus on day 14 , indomethacin therapy , or surgical ligation . RESULTS Comparison between the treatment and placebo groups revealed no differences in gestational age , weight , or oxygenation index . Vitamin A and retinol binding protein levels did not differ between the groups at entry but increased significantly after vitamin A treatment . Failure of ductal closure occurred in 22 of 40 babies without any difference between the groups ( 12/22 vs 10/18 , P = NS ) . Four infants required surgical ligation , all in the treatment group ( P=.04 ) . Clinical outcome did not vary between groups . CONCLUSION Postnatal vitamin A therapy did not improve ductal closure rates in premature infants Objective : Preterm infants usually have low retinol status  at birth and at discharge from hospital . We have evaluated a new protocol design ed to improve plasma retinol in very low birth weight infants ( VLBW , birth weight < 1500 g ) A r and omised , double-blind placebo-controlled trial was design ed to determine whether high-dose ( 25,000 IU ) enteral vitamin A , to correct deficiency , would be absorbed and well tolerated in low-birth-weight ( LBW ) neonates . Thirty-five LBW infants ( 950 - 1700 g ; gestational age 27 - 36 weeks ) were allocated to receive either placebo or vitamin A ( 25,000 IU ) via nasogastric tube on the first day of the study ( between 36 and 60 hours after delivery ) . The dose was repeated on study days 4 and 8 . Serum retinol concentrations were determined pre- and post-supplementation . Toxic effects of vitamin A were monitored by noting vomiting , drowsiness and irritability , and palpating for a bulging fontanelle . The mean serum retinol concentration was significantly higher following supplementation in the vitamin A-treated group than in the placebo group ( 45.77 + /- 17.07 micrograms/dl v. 12.88 + /- 6.48 micrograms/dl ; P = 0.0001 ) . Toxic effects were not detected in any of the infants . In conclusion , high-dose enteral vitamin A is well absorbed in LBW neonates and three doses of 25,000 IU given over a period of 8 days are not associated with any detectable toxic effects 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 Very low birth weight infants have little storage of hepatic retinol and are , therefore , highly dependent upon an exogenous supply . The recent association between low serum retinol level and bronchopulmonary dysplasia and the persistently low serum levels of retinol during total parenteral nutrition prompted a prospect i ve study to evaluate serial changes in serum retinol levels during 1 month of total parenteral nutrition ( retinol dose 455 micrograms/d ) and again during 1 month of total enteral feeding ( retinol dose 200 to 300 micrograms/d ) in the same infants . Infants were divided into two groups . Group 1 consisted of infants weighing less than 1,000 g ( n = 24 ) and group 2 consisted of infants weighing 1,000 to 1,500 g ( n = 17 ) . Although initial mean levels of retinol were similar in both groups ( 14.8 + /- 0.9 and 13.5 + /- 0.7 micrograms/dL ) , there was wide variation between infants . In group 1 infants , there was a significant ( P less than .01 ) decline in retinol level by the second week of life ( to 9.2 + /- 1 micrograms/dL ) , which persisted during total parenteral nutrition , but increased to 13.4 + /- 2 after 1 week of enteral feeding . This level was maintained throughout enteral feeding . In group 2 infants , there was no significant change in serum retinol level throughout the study . During total parenteral nutrition , several infants had retinol levels below 10 micrograms/dL , a level associated with signs of retinol deficiency in older children . Because losses of retinol are known to occur in smaller volume total parenteral nutrition solutions , it was speculated that losses of retinol in our patients were due to retinol losses in the total parenteral nutrition delivery system . ( ABSTRACT TRUNCATED AT 250 WORDS Background . A National Institute of Child Health and Human Development Neonatal Research Network r and omized trial showed that vitamin A supplementation reduced bronchopulmonary dysplasia ( O2 at 36 weeks ' postmenstrual age ) or death in extremely low birth weight ( ELBW ) neonates ( relative risk [ RR ] : 0.89 ) . As with postnatal steroids or other interventions , it is important to ensure that there are no longer-term adverse effects that outweigh neonatal benefits . Primary Objective . To determine if vitamin A supplementation in ELBW infants during the first month after birth affects survival without neurodevelopmental impairment at a corrected age of 18 to 22 months . Design / Methods . Infants enrolled in the National Institute of Child Health and Human Development vitamin A trial were evaluated at 18 to 22 months by carefully st and ardized assessment s : Bayley Mental Index ( MDI ) and Psychomotor Index ( PDI ) , visual and hearing screens , and physical examination for cerebral palsy ( CP ) . The medical history was also obtained . Neurodevelopmental impairment ( NDI ) was predefined as ≥1 of MDI < 70 , PDI < 70 , CP , blind in both eyes , or hearing aids in both ears . Results . Of 807 enrolled infants , 133 died before and 16 died after discharge . Five hundred seventy-nine ( 88 % ) of the 658 remaining infants were followed up . The primary outcome of NDI or death could be determined for 687 of 807 r and omized infants ( 85 % ) . Baseline characteristics and predischarge and postdischarge mortality were comparable in both study groups . NDI or death by 18 to 22 months occurred in 190 of 345 ( 55 % ) infants in the vitamin A group and in 204 of 342 ( 60 % ) of the control group ( RR : 0.94 ; 95 % confidence interval : 0.80 - 1.07 ) . RRs for low MDI , low PDI , and CP were also < 1.0 . We found no evidence that neonatal vitamin A supplementation reduces hospitalizations or pulmonary problems after discharge . Conclusion . Vitamin A supplementation for ELBW infants  reduces bronchopulmonary dysplasia without increasing mortality or neurodevelopmental impairment at 18 to 22 months . However , this study was not powered to evaluate small magnitudes of change in long-term outcomes OBJECTIVE Vitamin A supplementation reduces bronchopulmonary dysplasia (BPD)/death in extremely low birth weight neonates . It was hypothesized that compared with the st and ard regimen of 5000 IU 3 times per week for 4 weeks , ( 1 ) a higher dose ( 10,000 IU 3 x per week ) would increase serum retinol and retinol binding protein ( RBP ) and lower relative dose responses ( RDR ) , and ( 2 ) once-per-week dosing ( 15,000 IU once per week ) would lead to equivalent levels , RBP , and RDR . STUDY DESIGN Extremely low birth weight neonates ( n = 120 ) receiving O(2)/mechanical ventilation at 24 hours were r and omly assigned to ( 1 ) st and ard , ( 2 ) higher dose , or ( 3 ) once-per-week regimens . Measures of vitamin A deficiency were serum retinol < 20 microg/dL , RBP < 2.5 mg/dL , and /or RDR > 10 % on day 28 . BPD was defined as O(2)/mechanical ventilation at 36 weeks ' postmenstrual age . RESULTS Groups were similar at enrollment ( median gestational age , 25 weeks ; birth weight , 689 g ) . Possible toxicity was seen in < 5 % . The higher dose regimen did not increase retinol or RBP , decrease RDR , or improve outcomes . Infants in the once-per-week regimen had lower retinol levels and higher RDR without an effect on outcomes . CONCLUSIONS Compared with the st and ard regimen , once-per-week dosing worsened , and higher doses did not reduce , vitamin A deficiency . Therefore , the st and ard regimen is recommended Background / Objectives : Preterm infants have low vitamin A stores at birth , and parenteral administration of high-dose vitamin A reduces pulmonary morbidity . The aim was to characterize vitamin A transport and status . Subjects/ Methods : Prospect i ve study of 69 preterm infants ( median birth weight 995 g , gestational age 28 weeks ) , in which 51 received 5000 IU vitamin A three times per week intramuscular ( i.m . ) for 4 weeks and 18 infants without i.m . vitamin A served as controls .  Serum retinol , retinyl palmitate , total retinol-binding protein 4 ( RBP4 ) , retinol-unbound RBP4 ( apo-RBP4 ) and transthyretin concentrations were determined at days 3 ( D3 ) and 28 ( D28 ) of life . Results : D3 retinol concentrations were low for the entire group ( 382 ( 285/531 ) nmol/l ; median/interquartile range ) and unrelated to gestational age . D28 retinol was unchanged in controls ( 382 ( 280/471 ) nmol/l ) , but increased in the vitamin A group ( 596 ( 480/825 ) nmol/l ; P<0.001 ) . A similar pattern was observed for RBP4 . The calculated retinol-to-RBP4 ratio rose in vitamin A infants ( D3 : 0.81 ( 0.57/0.94 ) , D28 : 0.98 ( 0.77/1.26 ) ; P<0.01 ) but not in controls . In the vitamin A group , the retinol-to-RBP4 ratio was > 1 in 15 % of all infants on D3 and in 45 % of infants on D28 , but was ⩽1 in all , but one , controls on D28 . Conclusions : In preterm infants receiving a 4-week course of high-dose i.m . vitamin A  , serum retinol concentrations increased by 55 % , with molar concentrations of retinol exceeding those of RBP4 in 45 % of the infants suggesting transport mechanisms other than RBP4 OBJECTIVE Preterm infants with intrauterine growth restriction are at increased risk of respiratory distress syndrome and bronchopulmonary dysplasia ( BPD ) . A r and omized clinical trial by the Eunice Kennedy Shriver National Institute of Child Health and Human Development ( NICHD ) Neonatal Research Network demonstrated that vitamin A supplementation in extremely low-birth-weight ( ELBW ) preterm infants requiring early respiratory support decreased the risk of developing BPD . STUDY DESIGN A subgroup analysis of small-for-gestational-age ( SGA ) infants from the original NICHD trial was performed to test the hypothesis that in infants requiring early respiratory support , vitamin A supplementation decreases the relative risk of BPD or death in premature SGA infants to a greater extent than in gestational age-equivalent vitamin A-treated appropriate-for-gestational-age ( AGA ) infants . RESULTS Although vitamin A supplementation significantly increased serum retinol concentrations in AGA ELBW infants ( median [ 5th percentile , 95th percentile ] : 16.3 [ -7.0 , 68.8 ] versus 2.4 [ -13.9 , 55.1 ] ; p < 0.001 ) , no increases were noted in SGA ELBW infants . CONCLUSIONS Given the limited power of this analysis due to a low number of SGA infants , these data did not provide evidence to support the hypothesis that vitamin A supplementation in preterm SGA infants requiring early respiratory support decreases the relative risk of BPD or death as compared with preterm AGA infants
BACKGROUND Vitamin A is necessary for normal lung growth and the integrity of respiratory tract epithelial cells .
Preterm infants have low vitamin A status at birth and this has been associated with an increased risk of developing chronic lung disease .
OBJECTIVES To evaluate supplementation with vitamin A on the incidence of death or neonatal chronic lung disease and long-term neurodevelopmental disability in very low birth weight ( VLBW ) infants compared with a control ( placebo or no supplementation ) , and to consider the effect of the supplementation route , dose , and timing .