Abstract
Objective: To determine whether regulating vitamin C (ascorbic acid: AA) intake to achieve higher or lower plasma concentrations was associated with improved clinical outcome.
Design: A double blind, randomised controlled trial.
Setting: Neonatal intensive care unit at Christchurch Women's Hospital.
Patients: Infants with birth weight <1500 g or gestation <32 weeks, admitted to the unit within 48 hours of birth.
Intervention: Infants were randomised to one of three protocols with regard to AA supplementation for the first 28 days of life: group LL received low supplementation throughout; group LH received low until day 10 and then high: group HH received high throughout.
Main outcome measures: Primary outcome measures were oxygen requirement at 28 days and 36 weeks postmenstrual age, total days supplemental oxygen, and retinopathy of prematurity. AA concentrations were measured at study entry (day 2), and days 10, 21, and 28.
Results: A total of 119 infants were enrolled over 24 months (mean gestation 28.4 weeks; birth weight 1161 g). Six infants died, and these had significantly higher AA concentrations before randomisation than surviving infants (116 µmol/l (95% confidence interval 90 to 142) v 51 µmol/l (45 to 58), p<0.0001). There were no significant differences in primary outcomes between the groups. However, the proportion of surviving infants with an oxygen requirement at 36 weeks postmenstrual age in group HH (19%) was half that in group LL (41%) (p = 0.06).
Conclusions: In a randomised controlled trial, no significant benefits or harmful effects were associated with treatment allocation to higher or lower AA supplementation throughout the first 28 days of life.
Full Text
The Full Text of this article is available as a PDF (87.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arad I. D., Eyal F. G. High plasma ascorbic acid levels in premature neonates with intraventricular hemorrhage. Am J Dis Child. 1983 Oct;137(10):949–951. doi: 10.1001/archpedi.1983.02140360013004. [DOI] [PubMed] [Google Scholar]
- Bass W. T., Malati N., Castle M. C., White L. E. Evidence for the safety of ascorbic acid administration to the premature infant. Am J Perinatol. 1998 Feb;15(2):133–140. doi: 10.1055/s-2007-993913. [DOI] [PubMed] [Google Scholar]
- Behrens W. A., Madère R. A highly sensitive high-performance liquid chromatography method for the estimation of ascorbic and dehydroascorbic acid in tissues, biological fluids, and foods. Anal Biochem. 1987 Aug 15;165(1):102–107. doi: 10.1016/0003-2697(87)90206-5. [DOI] [PubMed] [Google Scholar]
- Berger T. M., Frei B. Pro- or antioxidant activity of vitamin C in preterm infants? Arch Dis Child Fetal Neonatal Ed. 1995 May;72(3):F211–F212. doi: 10.1136/fn.72.3.f211-b. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berger T. M., Frei B., Rifai N., Avery M. E., Suh J., Yoder B. A., Coalson J. J. Early high dose antioxidant vitamins do not prevent bronchopulmonary dysplasia in premature baboons exposed to prolonged hyperoxia: a pilot study. Pediatr Res. 1998 Jun;43(6):719–726. doi: 10.1203/00006450-199806000-00002. [DOI] [PubMed] [Google Scholar]
- Berger T. M., Polidori M. C., Dabbagh A., Evans P. J., Halliwell B., Morrow J. D., Roberts L. J., 2nd, Frei B. Antioxidant activity of vitamin C in iron-overloaded human plasma. J Biol Chem. 1997 Jun 20;272(25):15656–15660. doi: 10.1074/jbc.272.25.15656. [DOI] [PubMed] [Google Scholar]
- Buss H., Chan T. P., Sluis K. B., Domigan N. M., Winterbourn C. C. Protein carbonyl measurement by a sensitive ELISA method. Free Radic Biol Med. 1997;23(3):361–366. doi: 10.1016/s0891-5849(97)00104-4. [DOI] [PubMed] [Google Scholar]
- Buss I. H., McGill F., Darlow B. A., Winterbourn C. C. Vitamin C is reduced in human milk after storage. Acta Paediatr. 2001 Jul;90(7):813–815. [PubMed] [Google Scholar]
- Böhles H. Antioxidative vitamins in prematurely and maturely born infants. Int J Vitam Nutr Res. 1997;67(5):321–328. [PubMed] [Google Scholar]
- Carr A., Frei B. Does vitamin C act as a pro-oxidant under physiological conditions? FASEB J. 1999 Jun;13(9):1007–1024. doi: 10.1096/fasebj.13.9.1007. [DOI] [PubMed] [Google Scholar]
- Ciccoli Lucia, Rossi Viviana, Leoncini Silvia, Signorini Cinzia, Paffetti Patrizia, Bracci Rodolfo, Buonocore Giuseppe, Comporti Mario. Iron release in erythrocytes and plasma non protein-bound iron in hypoxic and non hypoxic newborns. Free Radic Res. 2003 Jan;37(1):51–58. doi: 10.1080/1071576021000032122. [DOI] [PubMed] [Google Scholar]
- Darlow B. A., Clemett R. S. Retinopathy of prematurity: screening and optimal use of the ophthalmologist's time. Aust N Z J Ophthalmol. 1990 Feb;18(1):41–46. doi: 10.1111/j.1442-9071.1990.tb00583.x. [DOI] [PubMed] [Google Scholar]
- Dvir M., Kohelet D., Arbel E., Goldberg M. Umbilical ascorbic acid levels in fetal distress. J Nutr Sci Vitaminol (Tokyo) 1992 Oct;38(5):511–515. doi: 10.3177/jnsv.38.511. [DOI] [PubMed] [Google Scholar]
- Evans P. J., Evans R., Kovar I. Z., Holton A. F., Halliwell B. Bleomycin-detectable iron in the plasma of premature and full-term neonates. FEBS Lett. 1992 Jun 1;303(2-3):210–212. doi: 10.1016/0014-5793(92)80521-h. [DOI] [PubMed] [Google Scholar]
- Frei B., England L., Ames B. N. Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6377–6381. doi: 10.1073/pnas.86.16.6377. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greene H. L., Hambidge K. M., Schanler R., Tsang R. C. Guidelines for the use of vitamins, trace elements, calcium, magnesium, and phosphorus in infants and children receiving total parenteral nutrition: report of the Subcommittee on Pediatric Parenteral Nutrient Requirements from the Committee on Clinical Practice Issues of the American Society for Clinical Nutrition. Am J Clin Nutr. 1988 Nov;48(5):1324–1342. doi: 10.1093/ajcn/48.5.1324. [DOI] [PubMed] [Google Scholar]
- Halliwell B. Vitamin C: antioxidant or pro-oxidant in vivo? Free Radic Res. 1996 Nov;25(5):439–454. doi: 10.3109/10715769609149066. [DOI] [PubMed] [Google Scholar]
- Inder T. E., Carr A. C., Winterbourn C. C., Austin N. C., Darlow B. A. Vitamin A and E status in very low birth weight infants: development of an improved parenteral delivery system. J Pediatr. 1995 Jan;126(1):128–131. doi: 10.1016/s0022-3476(95)70515-5. [DOI] [PubMed] [Google Scholar]
- Kime R., Gibson A., Yong W., Hider R., Powers H. Chromatographic method for the determination of non-transferrin-bound iron suitable for use on the plasma and bronchoalveolar lavage fluid of preterm babies. Clin Sci (Lond) 1996 Nov;91(5):633–638. doi: 10.1042/cs0910633. [DOI] [PubMed] [Google Scholar]
- Levy R., Herzberg G. R., Andrews W. L., Sutradhar B., Friel J. K. Thiamine, riboflavin, folate, and vitamin B12 status of low birth weight infants receiving parenteral and enteral nutrition. JPEN J Parenter Enteral Nutr. 1992 May-Jun;16(3):241–247. doi: 10.1177/0148607192016003241. [DOI] [PubMed] [Google Scholar]
- Lindeman J. H., van Zoeren-Grobben D., Schrijver J., Speek A. J., Poorthuis B. J., Berger H. M. The total free radical trapping ability of cord blood plasma in preterm and term babies. Pediatr Res. 1989 Jul;26(1):20–24. doi: 10.1203/00006450-198907000-00008. [DOI] [PubMed] [Google Scholar]
- Moore M. C., Greene H. L., Phillips B., Franck L., Shulman R. J., Murrell J. E., Ament M. E. Evaluation of a pediatric multiple vitamin preparation for total parenteral nutrition in infants and children. I. Blood levels of water-soluble vitamins. Pediatrics. 1986 Apr;77(4):530–538. [PubMed] [Google Scholar]
- Moran J. R., Vaughan R., Stroop S., Coy S., Johnston H., Greene H. L. Concentrations and total daily output of micronutrients in breast milk of mothers delivering preterm: a longitudinal study. J Pediatr Gastroenterol Nutr. 1983 Nov;2(4):629–634. doi: 10.1097/00005176-198311000-00010. [DOI] [PubMed] [Google Scholar]
- Podmore I. D., Griffiths H. R., Herbert K. E., Mistry N., Mistry P., Lunec J. Vitamin C exhibits pro-oxidant properties. Nature. 1998 Apr 9;392(6676):559–559. doi: 10.1038/33308. [DOI] [PubMed] [Google Scholar]
- Powers H. J., Loban A., Silvers K., Gibson A. T. Vitamin C at concentrations observed in premature babies inhibits the ferroxidase activity of caeruloplasmin. Free Radic Res. 1995 Jan;22(1):57–65. doi: 10.3109/10715769509147528. [DOI] [PubMed] [Google Scholar]
- Proteggente A. R., England T. G., Rice-Evans C. A., Halliwell B. Iron supplementation and oxidative damage to DNA in healthy individuals with high plasma ascorbate. Biochem Biophys Res Commun. 2001 Oct 19;288(1):245–251. doi: 10.1006/bbrc.2001.5749. [DOI] [PubMed] [Google Scholar]
- Silvers K. M., Gibson A. T., Powers H. J. High plasma vitamin C concentrations at birth associated with low antioxidant status and poor outcome in premature infants. Arch Dis Child Fetal Neonatal Ed. 1994 Jul;71(1):F40–F44. doi: 10.1136/fn.71.1.f40. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Streeter M. L., Rosso P. Transport mechanisms for ascorbic acid in the human placenta. Am J Clin Nutr. 1981 Sep;34(9):1706–1711. doi: 10.1093/ajcn/34.9.1706. [DOI] [PubMed] [Google Scholar]
- Styrud J., Thunberg L., Nybacka O., Eriksson U. J. Correlations between maternal metabolism and deranged development in the offspring of normal and diabetic rats. Pediatr Res. 1995 Mar;37(3):343–353. doi: 10.1203/00006450-199503000-00015. [DOI] [PubMed] [Google Scholar]