Comparative characteristics of extremely low birth weight children receiving and not receiving folic acid

Abstract

One of the essential micronutrients for the development of a newborn child is vitamin B9, which includes folates (folic acid compounds). Folic acid is a synthetic substance that is often used as a medicinal vitamin supplement and for food fortification. Both insufficient and excessive intake of folic acid can have negative consequences for the developing organism.

Aim. Assess the availability of folates in premature infants at the hospital.

Material and methods. The study included 62 children born at 26–31 weeks of gestation and were in the National Medical Research Center for Obstetrics, Gyn8ecology and Perinatology named after Academician

V.I. Kulakov of Ministry of Healthcare of the Russian Federation from May 2017 to December 2018. Group A (n=31) received folic acid 100 mcg/day for body weight <1500 g and 250 mcg/day for body weight >1500 g orally from day 14 of life, group B (n=31) – did not receive. The folate level in serum and erythrocytes was assessed in the first 7 days, 1.5 and 3 months, the number of erythrocytes and hemoglobin level – in 2, 6, 8 and 12 weeks, the concentration of ferritin, transferrin, iron – in 1.5 months. All patients received prevention/treatment of early anemia of prematurity: epoetin alfa 200 IU/kg 3 times a week s/c from day 7, iron 4–6 mg/kg/day from day 14, vitamin E 10% 5–10 mg/day orally.

Results. The average folate level in serum and erythrocytes in the groups of children at the age of the first 7 days of life, 1.5 and 3 months was high in relation to the reference values. At the age of 1.5 and 3 months, the concentration of folates in serum and erythrocytes in group A was higher than in group B, however, this difference was not statistically significant. None of the children had levels below the reference values. Folic acid supplementation did not have a statistically significant effect on the level of transferrin, ferritin, hemoglobin, the number of erythrocytes and the need for blood transfusions in children.

Conclusion. Against the background of the use of modern feeding schemes, very preterm infants do not have folate deficiency, and they do not require routine folic acid supplementation.

Keywords:folic acid; folates; anemia of prematurity; prematurity

Funding. The study had no sponsor support.

Conflict of interest. The authors declare no conflict of interest.

For citation: Lazareva V.V., Narogan M.V., Vedikhina I.A., Ivanets T.Yu., Zubkov V.V., Ryumina I.V., Degtyarev D.N. Comparative characteristics of extremely low birth weight children receiving and not receiving folic acid. Neonatologiya: novosti, mneniya, obuchenie [Neonatology: News, Opinions, Training]. 2022; 10 (4): 8–16. DOI: https://doi.org/10.33029/2308-2402-2022-10-4-8-16

(in Russian)

REFERENCES

1. Narogan M.V., Ryumina I.I., Kukhartseva M.V., et al. Practical experience in the application of clinical recommendations «Enteral feeding of premature babies». Akusherstvo i ginekologiya [Obstetrics and Gynecology]. 2018; (9): 106–14. (in Russian)

2. Jonker H., Capelle N., Lanes A., et al. Maternal folic acid supplementation and infant birthweight in low- and middle-income countries: a systematic review. Matern Child Nutr. 2020; 16 (1): e12895.

3. Welch A.D. Folic acid: discovery and the exciting first decade. Perspect Biol. Med. 1983; 27 (1): 64–75.

4. Ryumina I.I., Narogan M.V., Grosheva E.V., Degtyareva A.V. Difficult issues of enteral feeding of premature babies. Doctor.Ru. 2014; 91 (3): 12–7. (in Russian)

5. Scaglione F., Panzavolta G. Folate, folic acid and 5-methyltetrahydrofolate are not the same thing. Xenobiotica. 2014; 44 (5): 480–8.

6. Choi J.H., Yates Z., Veysey M., et al. Contemporary issues surrounding folic acid fortification initiatives. Prev Nutr Food Sci. 2014; 19 (4): 247–60.

7. Greenberg J.A., Bell S.J., Guan Y., Yu Y.H. Folic acid supplementation and pregnancy: more than just neural tube defect prevention. Rev Obstet Gynecol. 2011; 4 (2): 52–9.

8. Revakova T., Revak O., Vasilenkova A., et al. Amount of folic acid in different types of nutrition used in the neonatal period. Bratisl Lek Listy. 2015; 116 (6): 349–53.

9. Ancheva I.A. Functional nutrition during pregnancy. Voprosy pitaniia [Problems of Nutrition]. 2016; 85 (4): 22–8. (in Russian)

10. Houghton L.A., Yang J., O’Connor D.L. Unmetabolized folic acid and total folate concentrations in breast milk are unaffected by low-dose folate supplements. Am J Clin Nutr. 2009; 89 (1): 216–20.

11. Pustotina O.A. The load of non-lethal mutations is a problem of the 21st century. StatusPraesens. Ginekologiya. Akusherstvo. Besplodniy brak [StatusPraesens. Gynecology. Obstetrics. Barren Marriage]. 2014; (6): 91–8. (in Russian)

12. Cristofalo E.A., Schanler R.J., Blanco C.L., et al. Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants. J Pediatr. 2013; 163 (6): 1592–5.

13. McStay C.L., Prescott S.L., Bower C., Palmer D.J. Maternal folic acid supplementation during pregnancy and childhood allergic disease outcomes: a question of timing? Nutrients. 2017; 9 (2): E123.

14. Pustotina O.A. Achievements and risks of folate use outside and during pregnancy. Meditsinskiy sovet [Medical Council]. 2015; (9): 92–9. (in Russian)

15. Sanjay S. (ed.). Nutrition for the Preterm Neonate, а Clinical Perspective. New York: Springer, 2013: 450 p.

16. Baybarina E.N., Degtyarev D.N. (eds). Selected clinical guidelines for neonatology. Moscow: GEOTAR-Media, 2016: 240 p. (in Russian)

17. Agostoni C., Buonocore G., Carnielli V.P., et al. Enteral nutrient supply for preterm infants: commentary from the Europe Society of Pediatric Gastroenterology, Hepatology and Nutrition Commitee on Nutrition. J Pediatr Gastroenterol Nutr. 2010; 50: 85–91.

18. Proceedings of the Global Neonatal Consensus Symposium: Feeding the Preterm Infant, October 13–15, 2010, Chicago, Illinois. Guest ed. R. Uauy. J Pediatr. 2013l; 162 (3): S1–116.

19. Rogers L.M., Cordero A.M., Pfeiffer C.M., et al. Global folate status in women of reproductive age: a systematic review with emphasis on methodological issues. Ann N Y Acad Sci. 2018; 1431 (1): 35–57.

20. Neu J. Gastroenterology and Nutrition: Neonatology Questions and Controversies. 2nd ed. Philadelphia: Saunders, 2012: 430 p.

21. Stettler N., Iotova V. Early growth patterns and long-term obesity risk. Curr Opin Clin Nutr Metab Care. 2010; 13: 294–9.

22. Ly L., Chan D., Aarabi M., et al. Intergenerational impact of paternal lifetime exposures to both folic acid deficiency and supplementation on reproductive outcomes and imprinted genemethylation. Mol Hum Reprod. 2017; 23 (7): 461–77.

23. Oncel M.Y., Calisici E., Ozdemir R., Yurttutan S., Erdeve O., Karahan S., et al. Is folic acid supplementation really necessary in preterm infants ≤ 32 weeks of gestation? J Pediatr Gastroenterol Nutr. 2014; 58 (2): 188–92.

24. Jyothi S., Misra I., Morris G., et al. Red cell folate and plasma homocysteine in preterm infants. Neonatology. 2007; 92: 264–8.

25. Çelik F.Ç., Aygün C., Gülten S., Bedir A., Çetinoğlu E., Küçüködük S., et al. supplementation doses for low-birth-weight infants. Turk Pediatri Ars. 2016; 51 (4): 210–6. DOI: https://doi.org/10.5152/TurkPediatriArs.2016.4235

26. Tamura T., Yoshimura Y., Arakawa T. Human milk folate and folate status in lactating mothers and their infants. Am J Clin Nutr. 1980; 33: 193–7.

27. Fuller N.J., Bates C.J., Cole T.J., Lucas A. Plasma folate levels in preterm infants, with and without a 1 mg daily folate supplement. Eur J Pediatr. 1992; 151: 48–50.

28. Zikavska T., Brucknerova I. Extremely high concentration of folates in premature newborns. Bratisl Lek Listy. 2014; 115 (2): 103–6.

29. Narogan M.V., Lazareva V.V., Ryumina I.I., Vedikhina I.A. Importance of folate for child health and development. Akusherstvo i ginekologiya [Obstetrics and Gynecology]. 2019; (8): 46–53. (in Russian)

30. Bailey L.B., Hausman D.B. Folate status in women of reproductive age as basis of neural tube defect risk assessment. Ann N Y Acad Sci. 2018; 1414 (1): 82–95. DOI: https://doi.org/10.1111/nyas.13511

31. Pfeiffer C.M., Sternberg M.R., Hamner H.C., Crider K.S., Lacher D.A., Rogers L.M., et al. Applying inappropriate cutoffs leads to misinterpretation of folate status in the US population. Am J Clin Nutr. 2016; 104 (6): 1607–15.

32. Glader B. Anemias of inadequate production. 2006–2017. In: R.M. Kliegman (ed.). Nelson Textbook of Pediatrics. Philadelphia: Elsevier, 2007.

33. Soldin S.J., Wong E.C., Brugnara C., Soldin O.P. (eds). Pediatric Reference Intervals. 7th ed. Washington: AACC Press, 2011: 304 p.

34. Mihatsch W.A., Braegger C., Bronsky J. et al. ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition. Clin Nutr. 2018; 37 (6 pt B): 2303–429.

35.Haiden N., Klebermass K., Cardona F., et al. A randomized, controlled trial of the effects of adding vitamin B12 and folate to erythropoietin for the treatment of anemia of prematurity. Pediatrics. 2006; 118 (1): 180–8.

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)

CHIEF EDITOR
CHIEF EDITOR
Degtyarev Dmitriy Nikolaevich
Doctor of Medical Sciences, Professor, Deputy Director for Scientific Research of the V.I. Kulakov Obstetrics, Gynecology and Perinatology National Medical Research Center of Ministry of Healthсаre of the Russian Federation, Head of the Chair of Neonatology at the Clinical Institute of Children's Health named after N.F. Filatov, I.M. Sechenov First Moscow State Medical University, Chairman of the Ethics Committee of the Russian Society of Neonatologists, Moscow, Russian Federation

ORCID iD 0000-0001-8975-2425

Journals of «GEOTAR-Media»