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PEDIATRICS Vol. 106 No. 3 September 2000, pp. 547-553

Vitamin A Status and Postnatal Dexamethasone Treatment in Bronchopulmonary Dysplasia

Jayant P. Shenai, MD*, Beverly G. Mellen, PhDDagger , and Frank Chytil, PhD§

From the Departments of * Pediatrics, Dagger  Preventive Medicine, and § Biochemistry, Vanderbilt University, Nashville, Tennessee.


    ABSTRACT
Top
Abstract
Methods
Results
Discussion
Conclusion
References

Objective.  Vitamin A (retinol) plays an important role in epithelial regeneration during recovery from lung injury in bronchopulmonary dysplasia (BPD). Dexamethasone is used in the postnatal treatment of very low birth weight (VLBW) neonates with BPD. To test the hypothesis that the vitamin A status is critical for the beneficial pulmonary response to dexamethasone, we performed a prospective cohort study in which we characterized the changes in plasma concentrations of vitamin A and retinol-binding protein (RBP) in response to dexamethasone, and correlated these changes with the pulmonary outcome.

Methods.  VLBW neonates (birth weight <1350 g, gestational age <31 weeks, postnatal age >10 days), who had presumptive diagnosis of severe BPD and need for high ventilatory support (fraction of inspired oxygen >= .6, mean airway pressure >= 7 cm H2O), were treated with a seven-day course of dexamethasone (.5 mg/kg/d × 2 days, .25 mg/kg/d × 2 days, .1 mg/kg/d × 3 days). Plasma concentrations of vitamin A and RBP were determined sequentially at baseline, and during and after dexamethasone treatment. Pulmonary response to dexamethasone was graded daily using a composite ventilation score. The changes in plasma vitamin A and RBP concentrations were compared between infants with a positive (beneficial) pulmonary response to dexamethasone and those with a negative response.

Results.  Among 23 infants studied, 13 showed a positive pulmonary response to dexamethasone, as indicated by successful weaning from supplemental oxygen and mechanical ventilation, whereas 10 showed a negative response. A significant, yet short-term, increase in plasma concentrations of both vitamin A and RBP was observed in most infants treated with dexamethasone. The plasma vitamin A and RBP responses to dexamethasone tended to be higher in infants with a positive pulmonary response than in those with a negative response. Accounting for gender, a vitamin A response with each 10.0 µg/dL increment in plasma vitamin A concentration was associated with a 60% increase in the odds favoring a positive pulmonary response to dexamethasone.

Conclusion.  Postnatal dexamethasone treatment in VLBW neonates with BPD induces a significant, yet short-term, increase in plasma concentrations of both vitamin A and RBP. This increase probably results from endogenous mobilization of vitamin A from the liver. Our data suggest that the beneficial pulmonary response to dexamethasone in infants with BPD is influenced, at least in part, by the vitamin A status, and that gender plays a role in this response.vitamin A, dexamethasone, bronchopulmonary dysplasia.

Very low birth weight (VLBW) neonates are at increased risk for the development of bronchopulmonary dysplasia (BPD), the most prevalent form of chronic lung disease in infancy.1,2 The pathogenesis of BPD involves factors causing injury to an immature lung and factors inhibiting its healing.3 The lung injury results from such insults as hyaline membrane disease, barotrauma from mechanical ventilation, oxygen toxicity, and airway infection.4 The lung healing is influenced by nutrients, antioxidants, eicosanoids, growth factors, peptide hormones, inflammatory cells, and components of extracellular matrix.5 The role of the essential micronutrient vitamin A (retinol) in the promotion of orderly growth and differentiation of regenerating epithelial tissues makes vitamin A an important nutrient during recovery from lung injury.6,7 VLBW neonates who have BPD are often vitamin A-deficient.8,9 Vitamin A supplementation from birth in these infants can improve their vitamin A status as well as ameliorate the lung disease.10-12

Dexamethasone, a glucocorticosteroid hormone, is used increasingly in the postnatal treatment of VLBW neonates with BPD.13 Although a short-term improvement in lung function is seen in many infants, this pulmonary response to dexamethasone is variable, and the mechanism of action of dexamethasone in BPD remains unknown. Postnatal dexamethasone treatment causes a significant increase in plasma concentrations of vitamin A and its carrier retinol-binding protein (RBP) in newborn infants.14 Concomitant with these changes in the plasma vitamin A status, it is possible that the uptake and utilization of vitamin A in the lung are enhanced, and may participate in the beneficial pulmonary response to dexamethasone.

We hypothesized that the vitamin A status is critical for the beneficial pulmonary response to postnatal dexamethasone treatment in VLBW neonates with BPD. To test this hypothesis, we performed a prospective cohort study with 2 specific objectives: 1) to characterize the temporal sequence of changes in plasma concentrations of vitamin A and RBP in response to postnatal dexamethasone treatment, and 2) to correlate these changes in plasma vitamin A status with the pulmonary outcome in VLBW neonates with BPD.

    METHODS
Top
Abstract
Methods
Results
Discussion
Conclusion
References

Study Participants

VLBW neonates admitted to the neonatal intensive care unit (NICU) at Vanderbilt University Medical Center and eligible to receive postnatal dexamethasone treatment for BPD were enrolled in this study. The inclusion criteria were: birth weight <1350 g, gestational age at birth <31 weeks, appropriate growth for gestational age, postnatal age >10 days, and presumptive diagnosis of severe BPD. The latter was based on the evidence of respiratory distress,15 characteristic chest radiographic abnormalities,16 and need for mechanical ventilation with a high fraction of inspired oxygen (FIO2) >= .6 and a high mean airway pressure ([MAP] >= 7 cm H2O). These criteria were intended to identify infants at high risk for morbidity and mortality associated with BPD. The exclusion criteria were: airway infection and/or sepsis, systemic hypertension, and hyperglycemia. The diagnosis of airway infection and/or sepsis was based on abnormalities of leukocyte counts with or without thrombocytopenia, Gram staining of airway secretions, positive microbiologic cultures of airway secretions, blood, and/or cerebrospinal fluid, and clinical decision to start antimicrobial therapy. Systemic hypertension was defined as 3 or more sequential readings of systolic blood pressure >100 mm Hg during the 24-hour period just before enrollment. Hyperglycemia was defined as 3 or more sequential readings of blood glucose concentration >150 mg/dL during the same preenrollment period. These criteria were intended to exclude infants at high risk for complications of dexamethasone treatment. Infants with major congenital anomalies as well as those who received any form of glucocorticosteroid therapy before enrollment in the study also were excluded. Informed consent was obtained from the parents of each infant. The study was approved by the Committee for the Protection of Human Subjects-Health Sciences of the Institutional Review Board of Vanderbilt University.

Dexamethasone Treatment

A dexamethasone preparation (Decadron, Merck, West Point, PA) containing .4 mg/mL dexamethasone-sodium-phosphate was used. The dosage of dexamethasone included .5 mg/kg/d on days 1 and 2 of treatment, .25 mg/kg/d on days 3 and 4, and .1 mg/kg/d on days 5, 6, and 7. Each daily dose of dexamethasone was administered by bolus intravenous infusion in 2 equally divided doses at 12-hour intervals. This dosage regimen was patterned after the study by Durand et al,17 in which both short-term and long-term pulmonary benefits and minimal side effects were shown in response to dexamethasone treatment.

Study Period

The 24-hour period just before initiation of dexamethasone treatment was considered as study day 0. The data collected on study day 0 were used as baseline measurements. The first day of dexamethasone treatment was considered as study day 1. The study period included study days 1 through 7 (period of dexamethasone treatment) and study days 8 through 28 (postdexamethasone period). Each infant was studied from the day of enrollment to study day 28 or until discharge from the NICU, whichever occurred earlier.

Vitamin A Intake

The vitamin A intake from intravenous and enteral sources was calculated daily in each infant. The intravenous vitamin A was from parenteral nutrition solution estimated to contain 920 IU/dL of vitamin A.18 The enteral vitamin A was from human milk or preterm infant formula. The vitamin A concentration of human milk was estimated to be 300 IU/dL, and that of preterm infant formula was estimated to be 970 IU/dL.18 In addition, before the initiation of dexamethasone treatment, each infant received supplemental vitamin A in the form of retinyl palmitate (Aquasol A, Astra, Westboro, MA) by either intramuscular injection or orogastric administration beginning shortly after birth. The dosage of supplemental vitamin A by intramuscular route was 2000 IU/kg/dose administered every other day, and that by orogastric route was 4000 IU/kg/dose administered daily. This supplemental vitamin A was withheld during the week of dexamethasone treatment and also during the following week. This precautionary withholding of supplemental vitamin A was intended to avoid potential vitamin A toxicity associated with an increase in plasma vitamin A concentration in response to dexamethasone treatment.14 The cumulative vitamin A intake by all routes (intravenous, enteral, and intramuscular) in a given 1-week period was calculated to determine the average daily intake of vitamin A during that week and expressed per unit body weight (IU/kg/d).

Plasma Vitamin A Status

Approximately .7 mL of blood was drawn into a heparinized tube from each infant by venous puncture on study day 0 (baseline), study days 3, 5, and 8 (during the week of dexamethasone treatment), and study day 15 (1 week after completion of dexamethasone treatment). Plasma was separated from each blood sample by centrifugation, and either was analyzed immediately or stored at -20°C until analysis. Plasma vitamin A concentration (µg/dL) was determined by spectrofluorometry.19 Plasma RBP concentration (mg/dL) was determined by quantitative radial immunodiffusion (The Binding Site, Inc, San Diego, CA). The change in plasma vitamin A concentration (Delta -vitamin A) in response to dexamethasone treatment was calculated in each infant as the difference between the baseline value and the highest value obtained during study days 3, 5, and 8. The change in plasma RBP concentration (Delta -RBP) in response to dexamethasone treatment was calculated likewise.

Pulmonary Status

The NICU staff was responsible for all decisions related to ventilatory management of infants. In general, the FIO2 was adjusted either to maintain the partial pressure of arterial oxygen (PaO2) between 60 and 80 mm Hg when arterial blood gas samples were available, or to maintain the oxygen saturations, as measured by pulse oximetry (Ohmeda, Louisville, CO), between 92% and 96%. The ventilatory variables were adjusted to maintain the partial pressure of arterial carbon dioxide between 40 and 55 mm Hg as measured by arterial or capillary blood gas sampling. The pulmonary status of each infant was determined on study day 0 (baseline), study days 1 through 8, and study day 15. The following variables were examined: FIO2, ventilator rate (VR), MAP, and oxygenation index (OI [OI = FIO2 × MAP div  PaO2 × 100]). Multiple readings of each of these variables obtained in a 24-hour period were examined, and the mean value was calculated for each variable. The calculation of OI involved the measurement of PaO2. In most determinations, the PaO2 values obtained by arterial blood gas sampling were used for the calculation of OI. In rare instances, when arterial blood gas samples were not available, a PaO2 value of 60 mm Hg was assumed from the oxygen saturation measurements maintained between 92% and 96%, as reported by Hay et al.20 For infants not receiving either mechanical ventilation or continuous positive airway pressure, the MAP was assigned an arbitrary value of 1.0 cm H2O, instead of 0, so that the OI could distinguish between infants requiring high versus low FIO2, even when they received no added distending airway pressure.

Pulmonary Response

The pulmonary response to dexamethasone treatment was graded in each infant on study days 1 through 8 using the lowest daily FIO2, VR, MAP, and OI to calculate a composite ventilation score as outlined in Table 1. Based on the best ventilation score over the 8 days, each infant was assigned to 1 of 2 pulmonary response groups. The response was classified as positive (beneficial) if the maximum score was 5 through 8, and as negative (not beneficial) if the maximum score was 0 through 4. The values for FIO2, VR, and MAP used for grading this pulmonary response were selected a priori and based on the sequential changes in ventilatory variables as reported by Durand et al17 in VLBW neonates treated with a similar dexamethasone regimen. The values for OI used for grading the pulmonary response were derived from the corresponding values for FIO2 and MAP, and assuming a PaO2 value of 60 mm Hg.

                              
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TABLE 1
Components of Composite Ventilation Score

Statistical Methods

The study participants with a positive and those with a negative pulmonary response to dexamethasone treatment were evaluated for baseline differences in variables, including birth weight, gestational and postnatal age, gender, race, ventilatory requirements, and plasma concentrations of vitamin A and RBP. Among these variables, unpaired t tests or Wilcoxon rank sum tests were used for comparing continuous data as appropriate. chi 2 analysis or Fisher's Exact test were used for comparing nominal data as appropriate. A square root transformation was used for analysis when distributions were skewed. The relationship between the plasma vitamin A response to dexamethasone treatment (Delta -vitamin A) and the pulmonary response (positive vs negative) was evaluated using an unpaired t test and logistic regression analysis. In the regression analysis, the factors known to influence the pulmonary response were evaluated one at a time as potential confounders of the relationship between the vitamin A and pulmonary responses. These factors included birth weight, gestational age, gender, race, and baseline ventilatory requirements. The relationship between the plasma RBP response to dexamethasone treatment (Delta -RBP) and the pulmonary response (positive vs negative) was evaluated likewise. For all statistical tests, 2-tailed P values <= .05 were considered statistically significant. The statistical analysis was performed with Stata software (Stata Corporation, College Station, TX) and with S-PLUS software (Data Analysis Products Division, MathSoft, Inc, Seattle, WA).

    RESULTS
Top
Abstract
Methods
Results
Discussion
Conclusion
References

Study Population

Of 114 VLBW (birth weight <1350 g) infants admitted consecutively to the NICU during a 9-month enrollment period, 40 were excluded for the following reasons: major congenital anomalies (18 infants), nonviability from extreme prematurity (14), and fulminant clinical course (8). Among the remaining 74 infants, 29 were eligible to receive postnatal dexamethasone treatment for BPD. Six of these infants were excluded, because of parental refusal for participation in the study. The remaining 23 infants were enrolled and completed the study protocol.

Pulmonary Response

Thirteen infants showed a positive pulmonary response to dexamethasone treatment, as indicated by successful weaning from supplemental oxygen and mechanical ventilation. Their median ventilation score was 8 (range: 5-8). Conversely, 10 infants showed a negative pulmonary response to dexamethasone treatment. Their median ventilation score was 4 (range: 0-4). The baseline characteristics of these 2 groups of infants are compared in Table 2. There were no statistically significant differences between the groups among the variables examined, including the postnatal age and ventilatory requirements at enrollment. The subsequent ventilatory requirements were significantly lower in infants with a positive response to dexamethasone than in those with a negative response (Fig 1).

                              
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TABLE 2
Pulmonary Outcome of Study Subjects


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  		Fig. 1.   Ventilatory requirements in relation to postnatal dexamethasone treatment. Hatched bar represents the period of dexamethasone treatment; solid circles, data from infants with a positive pulmonary response; and open circles, data from infants with a negative pulmonary response. Data are shown as mean ± SEM. Baseline ventilatory requirements were similar between groups; subsequent ventilatory requirements were significantly lower in infants with a positive response to dexamethasone. Asterisks denote significant differences (P < .005) for time-specific comparisons. bpm indicates breaths per minute.

Vitamin A Intake

The average daily intake of vitamin A during the week of dexamethasone treatment ranged from 311 to 1314 IU/kg/d in all infants. Although the total vitamin A intake during the week of dexamethasone treatment did not vary between infants with a positive pulmonary response to dexamethasone and those with a negative response, the route of its administration was different between the groups (Table 3). Infants with a positive pulmonary response to dexamethasone, when compared with those with a negative response, received a significantly lower percentage of total vitamin A intake by the intravenous route (57% vs 87%, respectively, P = .05), and a correspondingly higher percentage by the enteral route (43% vs 13%, respectively, P = .05).

                              
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TABLE 3
Vitamin A Status of Study Subjects

Plasma Vitamin A Status

The plasma concentrations of vitamin A and RBP of infants with a positive pulmonary response to dexamethasone treatment and of those with a negative response are summarized in Table 3. There were no statistically significant differences between the groups with regard to baseline plasma concentrations of vitamin A and RBP. There was a significant increase from baseline values in plasma concentrations of both vitamin A and RBP during the week of dexamethasone treatment (P < .001), and a return to baseline values by study day 15 (Fig 2). The peak plasma concentrations of vitamin A and RBP were observed on study day 5 in 10 of the 23 infants and on study day 8 in the remainder. The timing of the peak values did not vary depending on the pulmonary response to dexamethasone. The mean Delta -vitamin A, reflective of the plasma vitamin A response to dexamethasone treatment, tended to be higher in infants with a positive pulmonary response to dexamethasone than in those with a negative response (P = .08; Table 3). Because there is a known gender effect on the pulmonary outcome in newborn infants,21 we evaluated the relationship between the pulmonary response and the plasma vitamin A response to dexamethasone treatment after accounting for gender. In the present cohort, a vitamin A response with each 10.0 µg/dL increment in plasma vitamin A concentration was associated with a 60% increase in the odds favoring a positive pulmonary response to dexamethasone (P = .05), accounting for gender in the analysis. The mean Delta -RBP, reflective of the plasma RBP response to dexamethasone treatment, also tended to be higher in infants with a positive pulmonary response to dexamethasone than in those with a negative response (P = .09; Table 3).


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  		Fig. 2.   Plasma vitamin A and RBP concentrations in relation to postnatal dexamethasone treatment. Hatched bar represents the period of dexamethasone treatment; solid circles, data from infants with a positive pulmonary response; and open circles, data from infants with a negative pulmonary response. Data are shown as mean ± SEM. Plasma concentrations of vitamin A and RBP were similar at baseline between groups, increased significantly (P < .001) during dexamethasone treatment, and returned to baseline values by study day 15. Asterisks denote significant differences (P < .001) from baseline values.

Postdexamethasone Course

Among the 13 infants with a positive pulmonary response to dexamethasone treatment, 11 were weaned successfully from the ventilator during the 28-day study period. Two infants required repeat tracheal intubation for mechanical ventilation, 1 for recurrent apnea and 1 for airway infection. Twelve of the 13 infants were discharged alive from the NICU, 6 required supplemental oxygen. One infant died on study day 12 (postnatal day 22) from Enterobacter cloacae sepsis and grade IV periventricular-intraventricular hemorrhage. Among the 10 infants with a negative pulmonary response to dexamethasone treatment, only 5 were weaned successfully from the ventilator during the 28-day study period. Four infants received additional courses of dexamethasone. All 10 infants were discharged alive from the NICU, and 9 required supplemental oxygen.

    DISCUSSION
Top
Abstract
Methods
Results
Discussion
Conclusion
References

In this study, postnatal dexamethasone treatment in VLBW neonates with BPD induced a significant, yet short-term, increase in plasma concentrations of both vitamin A and RBP. This finding is consistent with a previous observation by Georgieff et al.14 Our study, in addition, defines the temporal sequence of changes in plasma vitamin A and RBP concentrations in relation to dexamethasone treatment, and correlates these changes with the pulmonary outcome. The plasma vitamin A and RBP responses to dexamethasone treatment in our study tended to be higher in infants who responded favorably to dexamethasone, relative to those with a minimal pulmonary response. The association between the pulmonary response and the plasma vitamin A response to dexamethasone was statistically significant after accounting for gender in the analysis. Specifically, both the pulmonary and the plasma vitamin A responses to dexamethasone were more favorable in females than in males. The respiratory morbidity in VLBW neonates is influenced by gender, with a more favorable outcome in females than in males.21 Likewise, the vitamin A status of infants is influenced by gender, with a lesser prevalence of vitamin A deficiency among females than in males.22 These observations suggest that the beneficial pulmonary response to postnatal dexamethasone treatment in VLBW neonates with BPD is influenced, at least in part, by the vitamin A status, and that gender plays a role in this response.

The strengths of our study are the prospective design, careful selection of study participants, consistent use of postnatal dexamethasone treatment, and sequential analysis of vitamin A status and pulmonary outcome. Our criteria for administration of dexamethasone were much more stringent than those reported in literature.13 Fewer infants than expected responded favorably to dexamethasone in our study, which might be a reflection of the severity of their lung disease. The limitation of our study is the small sample size. The relationship between vitamin A status and lung function in response to dexamethasone treatment might have been strengthened by inclusion of additional study participants, as in a multicenter trial.

The plasma concentration of vitamin A is influenced by the influx of vitamin A and its efflux to and from the blood. The influx of vitamin A can be from an exogenous source, including intravenous, enteral, and intramuscular vitamin A, or from an endogenous release of vitamin A from its tissue storage sites. The efflux of vitamin A is modified by the uptake, storage, and utilization of vitamin A in the tissues. In our study, no infant received supplemental vitamin A during the week of dexamethasone treatment and also during the following week. Supplemental vitamin A, therefore, could not account for the increase in plasma vitamin A concentration seen in response to dexamethasone treatment. Also, the intake of vitamin A from both intravenous and enteral sources remained unchanged throughout the study period in all infants, which suggests that the observed increase in plasma vitamin A concentration in response to dexamethasone treatment was independent of the total intake of vitamin A. The difference in the plasma vitamin A responses between infants with a positive pulmonary response to dexamethasone treatment and those with a negative response might be attributed to the difference in the mode of provision of vitamin A. The infants with a positive pulmonary response to dexamethasone, relative to those with a negative response, were more stable clinically, tolerated enteral feeds better, and thus received a higher percentage of the total vitamin A intake via the enteral route and a correspondingly lower percentage via the intravenous route. The intravenous administration of vitamin A is inefficient, because of substantial photodegradative and adsorptive losses of the vitamin.23 As 90% of the total body reserve of vitamin A is stored in the liver in humans,24 it is most likely that the endogenous release of vitamin A from the liver in response to dexamethasone treatment resulted in the increase in plasma vitamin A concentration. Peripheral tissues, other than the liver, play a significant role in the storage and metabolism of vitamin A.25 In the perinatal period, the developing lung stores vitamin A, and may be dependent on these stores during growth and differentiation.26 Maternal antenatal dexamethasone treatment in the perinatal rat induces depletion of the fetal lung stores of vitamin A.27 These observations suggest that the endogenous release of vitamin A from the lung in response to dexamethasone treatment also might have contributed to the increase in plasma vitamin A concentration. The uptake, storage, and utilization of vitamin A in the lungs, which can modify the efflux of vitamin A from the blood and influence the plasma vitamin A concentration, have not been studied systematically in human neonates. Such studies may elucidate the potential causal relationship between the plasma vitamin A status and the pulmonary response to dexamethasone treatment.

The plasma concentration of RBP in response to dexamethasone treatment in our study followed a parallel course with that of plasma vitamin A. RBP, the specific carrier protein for vitamin A, is largely synthesized in the liver and secreted into the blood as the retinol:RBP complex.28 The parallel changes in plasma concentrations of vitamin A and RBP in our study support the contention that endogenous mobilization of vitamin A from the liver might have occurred in response to dexamethasone treatment.

Dexamethasone is used increasingly in the postnatal treatment of VLBW neonates with BPD.13 Several mechanisms of action have been proposed to explain the association between postnatal dexamethasone treatment and short-term improvement in lung function observed in some treated infants. These proposed mechanisms include suppression of cytokine-mediated inflammation in the lung,29 clearance of pulmonary edema,30 stabilization of alveolar epithelial cell membrane,31 increase in surfactant synthesis,32,33 breakdown of granulocyte aggregates with improvement in pulmonary microcirculation,34,35 enhancement of beta -adrenergic activity and resultant relaxation of bronchial smooth muscle,36 stimulation of antioxidant production,33 and inhibition of prostaglandin and leukotriene synthesis.37,38 Despite intensive research, however, the mechanism of action of dexamethasone in infants with BPD remains elusive and warrants additional investigation.

We chose to examine the vitamin A status in relation to postnatal dexamethasone treatment in VLBW neonates with BPD, because of the role of vitamin A in epithelial regeneration during recovery from lung injury,3 and the role of dexamethasone in lung development.13 Pulmonary septation, an important developmental sequence responsible for enhancement of gas exchange surface of the developing lung, is inhibited in infants with BPD.39,40 Similar inhibition of pulmonary septation occurs in association with dexamethasone treatment in experimental animals.41,42 In contrast, retinoic acid, an active metabolite of vitamin A, can prevent the dexamethasone-induced inhibition of pulmonary septation.43 These observations, together with our data, lead us to believe that the action of dexamethasone in the injured immature lung undergoing repair, characteristic of BPD, might be influenced, at least in part, by vitamin A. Additional studies are needed to determine the optimal indications, dosage, and duration of postnatal dexamethasone treatment as well as the optimal nutritional management of vitamin A in VLBW neonates with BPD.

    CONCLUSION
Top
Abstract
Methods
Results
Discussion
Conclusion
References

In summary, we examined the changes in plasma vitamin A and RBP concentrations in response to postnatal dexamethasone treatment, and correlated these changes with the pulmonary outcome in a cohort of VLBW neonates with BPD. Postnatal dexamethasone treatment induced a significant, yet short-term, increase in plasma concentrations of both vitamin A and RBP. This increase was independent of the total intake of vitamin A and probably resulted from endogenous mobilization of vitamin A from the liver. Our data suggest that the beneficial pulmonary response to dexamethasone in infants with BPD is influenced, at least in part, by the vitamin A status, and that gender plays a role in this response. Additional studies are needed to determine the optimal usage of dexamethasone and vitamin A nutrition in these infants.

    ACKNOWLEDGMENTS

This research was supported in part by a grant from General Foods (TOFC).

We thank Mark Hunt for technical assistance in the laboratory, Jeanie Smith for helping with nutritional calculations, Amy Law and Steven Steele for assistance with data collection, and Terry Johnson for providing the illustrations.

    FOOTNOTES

Received for publication Jun 29, 1999; accepted Dec 23, 1999.

Reprint requests to (J.P.S.) A-0126 MCN, Vanderbilt Medical Center, Nashville, TN 37232-2370. E-mail: jayant.shenai{at}mcmail.vanderbilt.edu

    ABBREVIATIONS

VLBW, very low birth weight; BPD, bronchopulmonary dysplasia; RBP, retinol-binding protein; NICU, neonatal intensive care unit; FIO2, fraction of inspired oxygen; MAP, mean airway pressure; Delta -vitamin A, change in plasma vitamin A concentration; Delta -RBP, change in plasma RBP concentration; PaO2, partial pressure of arterial oxygen; VR, ventilator rate; OI, oxygenation index.

    REFERENCES
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Abstract
Methods
Results
Discussion
Conclusion
References
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Pediatrics (ISSN 0031 4005). Copyright ©2000 by the American Academy of Pediatrics
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