Comparison of enteral and intramuscular vitamin A supplementation in preterm infants

doi:10.1016/0378-3782(92)90143-5

Early Human Development

Volume 30, Issue 2, September 1992, Pages 163-170

https://doi.org/10.1016/0378-3782(92)90143-5 Get rights and content

Abstract

Vitamin A deficiency associated with preterm delivery is not readily reversible using the recommended supplement of 1500 IU per day. It has been reported that 2000 IU of intramuscular vitamin A administered on alternate days for 28 days will correct the deficiency. The objective of this study was to compare this regime with the practice in our nursery of giving 5000 IU of vitamin A per day with the early introduction of feeds. The vitamin A status of ten preterm infants (mean gestation 30.5 weeks) who received intramuscular vitamin supplementation was compared with that of nine infants (mean gestation 30.7 weeks) given enteral vitamin A. Vitamin A status was evaluated on the 32nd day of life using plasma retinol and retinol-binding protein (RBP) concentrations and a modified relative dose response (RDR) test. Plasma retinol and RBP concentrations were similar in the two groups shortly after birth revealing vitamin A deficiency. By the 32nd day of life, plasma retinol and RBP concentrations had risen significantly in both groups and in 70% the modified RDR was normal. Differences between the groups were not observed irrespective of the method of vitamin A administration. None of the infants developed clinical or biochemical vitamin A toxicity. In most preterm infants who tolerate feeds, vitamin A deficiency can be corrected safely by supplementing the feeds with 5000 IU of vitamin A per day.

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Cited by (40)

Systematic review and meta-analysis of the relative dose-response tests to assess vitamin a status
2021, Advances in Nutrition
Vitamin A (VA) is an essential nutrient often lacking in the diets of people in developing countries. Accurate biomarkers of VA status are vital to inform public health policy and monitor interventions. The relative dose-response (RDR) and modified-RDR (MRDR) tests are semi-quantitative screening tests for VA deficiency that have been used in Demographic and Health Surveys and VA intervention studies. A systematic review and meta-analysis of sensitivity and specificity were conducted to summarize the physiological evidence to support the RDR tests as methods to assess VA status and investigate the impact of different pathological and physiological states on the tests. A total of 190 studies were screened for inclusion, with 21 studies comparing the RDR tests with the gold-standard biomarker, liver VA concentration (68% and 80% sensitivity and 85% and 69% specificity for the RDR and MRDR, respectively). Nearly all studies with VA interventions in VA-deficient populations demonstrated a response of the tests to VA intake that would be expected to improve VA status. The impacts of chronic liver disease, protein malnutrition, age, pregnancy and lactation, infection and inflammation, and various other conditions were examined in 51 studies. The RDR and MRDR tests were reported to have been used in 39 observational studies, and the MRDR has been used in at least 6 national micronutrient surveys. The RDR and MRDR are sensitive tests for determining population VA status and assessing VA interventions. Although they are robust to most physiological and pathological states, caution may be warranted when using the tests in neonates, individuals with chronic liver disease, and those with protein or iron malnutrition. Research on further improvements to the tests to increase accessibility, such as sampling breast milk instead of blood or using intramuscular doses in subjects with malabsorption, will allow wider adoption. This review was registered with PROSPERO as CRD42019124180.
Nutrition Assessment, Exposures, and Interventions for Very-Low-Birth-Weight Preterm Infants: An Evidence Analysis Center Scoping Review
2019, Journal of the Academy of Nutrition and Dietetics
Citation Excerpt :
Nineteen of the articles had sample sizes of at least 101,116,117,121,124,127-129,133,134,138,144-148,151,152,155,156 and nine of these articles had sample sizes of more than 300.117,124,128,145-147,152,155,156 Because of the limited quantity of micronutrient interventions identified in our initial search, the workgroup elected to include all study designs, and 37 articles were included.154,158-193 The majority of included articles were clinical trials, but three cohort studies were also included.166,179,186
Vitamin A for preterm infants; where are we now?
2013, Seminars in Fetal and Neonatal Medicine
Citation Excerpt :
Established guidelines (based on very few historical data) recommend 700–1500 IU vitamin A/kg/day42 but more recently doses of 2000–3000 IU/kg/day have been suggested for those infants with significant lung disease.25,43,44 In term infants (except those with malabsorption), vitamin A is well absorbed enterally and in a small study of VLBW infants 5000 IU/day vitamin A administered orally in conjunction with early feeds achieved similar plasma levels of retinol and RDR to alternate-day i.m. injections of 2000 IU.45 In ELBW infants, however, 5000 IU/kg/day of vitamin A administered orally from birth did not increase plasma levels of vitamin A or improve outcome, compared with placebo.3
In the 35 years since low plasma vitamin A levels were first described in premature infants, much effort has gone into attempting to describe the functional consequences of vitamin A deficiency in this population. Supplementation of extremely low birth weight infants with intramuscular (i.m.) vitamin A has a significant but modest beneficial effect upon the development of chronic lung disease (NNT 13), most likely due to reduced production of pro-inflammatory cytokines. Early high dose i.m. vitamin A also improves retinal development and there are limited clinical and laboratory data suggesting a role for vitamin A in prevention of retinopathy of prematurity. Despite evidence of benefit, there is reluctance to give routine i.m. vitamin A in the neonatal intensive care unit, but current intravenous supplementation is almost certainly inadequate. Further work is required to identify the optimal dose and most appropriate route of administration of vitamin A for preterm infants.
Is it justifiable to administrate vitamin A, E and D for 6 months in the premature infants?
2007, Archives de Pediatrie
Les données sur le statut vitaminique A et E du prématuré sont peu nombreuses dans la littérature, dans les premiers mois de vie. La présente étude avait pour but d'évaluer le statut vitaminique A, E et D et la protéine porteuse du rétinol (retinol binding protein, RBP) chez des prématurés à la naissance et à 1, 2 et 6 mois de vie chez des prématurés nourris soit au lait de leur mère, soit avec une formule pour prématurés.
Cette étude prospective et longitudinale a concerné 17 prématurés (32–34 semaines de gestation) recevant, dès la naissance, 3000 UI/j de vitamine A, 5 mg/j de vitamine E et 1000 UI/j de vitamine D.
À la naissance, les concentrations plasmatiques des vitamines A, E, D et de la RBP étaient basses et respectivement à 0,66 (0,41–0,96) μmol/l, 8,1 (4,2–16,9) μmol/l, 25 (20–40) nmol/l et 0,45 (0,22–0,71) μmol/l. Ces concentrations augmentaient en fonction du temps, mais la concentration plasmatique en vitamine A n'atteignait pas, même à 6 mois, des valeurs plasmatiques considérées comme normales chez l'enfant et l'adulte. À 6 mois, les valeurs plasmatiques de 25 hydroxyvitamine D (25 OHD) étaient de 92 (71–116) nmol/l, considérées comme normales et non toxiques.
L'apport de vitamine A doit être augmenté à 5000 UI/j au moins pendant le premier mois. Pour la vitamine D et E, l'apport utilisé dans cette étude est nécessaire et suffisant pour normaliser les taux plasmatiques bas à la naissance.
Information on the vitamin A and E nutritional status in preterm infants is scarce.
In the present prospective and longitudinal study, we measured the plasma concentrations of vitamins A, E, D and of retinol binding protein (RBP) in preterm infants (32–34 weeks of gestation) at birth, and verified whether oral supplementation with these 3 vitamins for 1, 3 and 6 months affected their plasma concentrations. The 17 consecutively recruited premature infants received daily 3000 IU of vitamin A, 5 mg of vitamin E and 1000 IU of vitamin D.
At birth, premature infants exhibited a low plasma concentrations of vitamin A (0.66 [0.41–0.96]) μmol/l, vitamin E (8.1 [4.2-16.9] μmol/l), RBP (0.45 [0.22–0.71] μmol/l) and 25 hydroxyvitamine D (25 OHD) (20 [20–40] nmol/l). Plasma vitamin A, E , D and RBP concentrations increased with time, but vitamin A at 1, 3 and 6 months did not attain values considered normal in term infants or adolescents. At 6 months, the plasma 25 OHD was at 92 (71–116) nmol/l, a concentration considered normal and non-toxic.
We recommend to increase oral administration of vitamin A to 5000 IU/day, at least for the first month of life and, thereafter to administer 3000 IU for 5 months. As for vitamin E and vitamin D, the doses used in this study are sufficient but should be administered for 6 months.
Assessment of vitamin A nutritional status in newborn preterm infants
2007, Nutrition
Citation Excerpt :
Therefore, they are considered by several investigators as the best categorical indicators of vitamin A status. Although not perfect, the RDR test offers more information than serum retinol alone and is more sensitive to liver reserve changes [24,34,35]. The principle of the RDR test is based on the fact that, in the presence of hepatic vitamin A deficiency, RBP will accumulate in the liver.
This study assessed the vitamin A nutritional status of preterm infants determined by the vitamin A relative dose-response test (RDR) compared with serum levels of vitamin A, retinol-binding protein (RBP), transthyretin (TTR), and retinol relations with carrier proteins.
Serum levels of retinol, RBP, and TTR and retinol/RBP, retinol/TTR, and RBP/TTR molar ratios were determined in 120 infants at 7 d and in 92 at 28 d. For the determination of the performance of the tests, the RDR was considered the reference method. The sensitivity and specificity for all possible cutoff values were determined by constructing receiver operator characteristic curves. The areas under the curves were used to estimate the overall accuracy of the tests. The best cutoff values to be used for the calculation of sensitivity and specificity were determined with 95% confidence intervals.
RDR indicated vitamin A deficiency in 60% of the infants at 7 d and in 51.1% at 28 d. In the receiver operator characteristic curves, the best area under the curve was 0.710 obtained for serum retinol at 28 d of postnatal age and considered moderately accurate. The least inadequate cutoff level was set at 25 mg/dL, but no value was considered adequate due to low sensitivity and/or low specificity.
Compared with RDR, the determination of serum levels of retinol, RBP, and TTR and their molar ratios are not adequate to assess nutritional vitamin A status in preterm infants.
A comparison of three vitamin a dosing regimens in extremely-low-birth-weight infants
2003, Journal of Pediatrics
Citation Excerpt :
Previous regimens ranged from 2000 IU/kg IM per dose on alternate days7 to 5000 IU IM per dose 3 times per week for 4 weeks.4,6 Although higher doses have been used orally, with as much as 5000 IU given per day for 28 days in ELBW neonates,14 this dose is only equivalent to approximately 2000 IU given by intramuscular injection on alternate days.15 Vitamin A supplementation in large doses has been generally safe in neonates, with as much as 50,000 IU given as a single dose orally to term neonates.16,17
Objective Vitamin A supplementation reduces bronchopulmonary dysplasia (BPD)/death in extremely low birth weight neonates. It was hypothesized that compared with the standard regimen of 5000 IU 3 times per week for 4 weeks, (1) a higher dose (10,000 IU 3 × 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 O₂/mechanical ventilation at 24 hours were randomly assigned to (1) standard, (2) higher dose, or (3) once-per-week regimens. Measures of vitamin A deficiency were serum retinol <20 μg/dL, RBP <2.5 mg/dL, and/or RDR >10% on day 28. BPD was defined as O₂/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 standard regimen, once-per-week dosing worsened, and higher doses did not reduce, vitamin A deficiency. Therefore, the standard regimen is recommended. (J Pediatr 2003;142:656-61)

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^∗: Present address: Neonatal Department, Bene Baraq Hospital, 'Ma'aynei Hayeshua', 17 Sharet Street, Bene Baraq, Israel.

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Comparison of enteral and intramuscular vitamin A supplementation in preterm infants

Abstract

Early Hum. Dev.

J. Pediatr.

J. Pediatr.

J. Nutr.

J. Pediatr.

J. Pediatr.

J. Pediatr.

Am. J. Clin. Nutr.

Am. J. Clin. Nutr.