Skip to main content Accessibility help

Maternal and neonatal micronutrient levels in newborns with CHD

  • Dilek Dilli (a1), Nazan Neslihan Doğan (a1), Utku Arman Örün (a2), Murat Koç (a3), Ayşegül Zenciroğlu (a1), Selmin Karademir (a2) and Hasan Akduman (a1)...



It is suggested that folic acid and/or multivitamins, taken periconceptionally, have a role in the prevention of many congenital anomalies. The aim of this study was to determine the serum micronutrient levels in mother–infant pairs with CHD compared with those with healthy newborns and their mothers.


Serum levels of folic acid, homocysteine, zinc, vitamin A, vitamin D, and vitamin B12 were measured from 108 newborns with CHD (study group) and 103 healthy newborns (control group). The mothers’ micronutrient levels were also measured simultaneously.


When compared with healthy newborns, for both maternal and neonatal data, homocysteine and zinc levels were higher and vitamin D levels were lower in the study group. In multivariate analysis, only maternal high zinc levels were associated with CHD in the newborns (p=0.02, OR: 0.9, 95% CI 0.8–0.9). The results did not change when analysed for truncal anomalies including truncus arteriosus, tetralogy of Fallot, and d-transposition of great arteries. There were positive correlations between maternal and neonatal levels of micronutrients, except vitamin B12.


We thought that high homocysteine and zinc levels and low vitamin D levels in mother–infant pairs might have a role in the aetiopathogenesis of CHD. Large-scale, prospective studies are needed to clarify the role of micronutrients in CHDs.


Corresponding author

Correspondence to: D. Dilli, Dr Sami Ulus Kadın Sağlığı, ÇocukSağlığı ve Hastalıkları, SUAM, Yenidoğan Kliniği, Sağlık Bilimleri Üniversitesi, Babürcaddesi, Ankara, Turkey. Tel: +00 90 312 906 3619; Fax: 400 90 312 305 6016; E-mail:


Hide All
1. Botto, LD, Mulinare, J, Erickson, JD. Occurrence of congenital heart defects in relation to maternal multivitamin use. Am J Epidemiol 2000; 151: 878884.
2. Botto, LD, Olney, RS, Erickson, JD. Vitamin supplements and the risk for congenital anomalies other than neural tube defects. Am J Med Genet C Semin Med Genet 2004; 125: 1221.
3. Bower, C, Miller, M, Payne, J, et al. Folate intake and the primary prevention of non-neural birth defects. Aust N Z J Public Health 2006; 30: 258261.
4. Czeizel, AE, Vereczkey, A, Szabó, I. Folic acid in pregnant women associated with reduced prevalence of severe congenital heart defects in their children: a national population-based case-control study. Eur J Obstet Gynecol Reprod Biol 2015; 193: 3439.
5. Shaw, GM, O’Malley, CD, Wasserman, CR, Tolarova, MM, Lammer, EJ. Maternal periconceptional use of multivitamins and reduced risk for conotruncal heart defects and limb deficiencies among offspring. Am J Med Genet 1995; 59: 536545.
6. Canfield, MA, Collins, JS, Botto, LD, et al. Changes in the birth prevalence of selected birth defects after grain fortification with folic acid in the United States: findings from a multi-state population based study. Birth Defects Res A Clin Mol Teratol 2005; 73: 679689.
7. Castilla, E, Orioli, I, Lopez-Camelo, J, et al. Preliminary Data on changes in neural tube defect prevalence rates after folic acid fortification in South America. Am J Med Genet A 2003; 123A: 123128.
8. Smithells, RW, Seller, MJ, Harris, R, et al. Further experience of vitamin supplementation for prevention of neural tube defect recurrences. Lancet 1983; 1: 10271031.
9. Werler, MW, Shapiro, S, Mitchell, AA. Periconceptional folic acid exposure and risk of occurrent neural tube defects. JAMA 1993; 269: 12571261.
10. Botto, LD, Khoury, MJ, Mulinare, J, et al. Periconceptional multivitamin use and the occurrence of conotruncal heart defects. Pediatrics 1996; 98: 911917.
11. Aguilera, O, Fernandez, AF, Munoz, A, et al. Epigenetics and environment: a complex relationship. J Appl Phys 2010; 109: 243251.
12. Czeizel, AE. Reduction of urinary tract and cardiovascular defects by periconceptional multivitamin supplementation. Am J Med Genet 1996; 62: 179183.
13. Huhta, JJ, Linask, KK. Environmental origins of congenital heart disease: the heart-placenta connection. Semin Fetal Neonatal Med 2013; 18: 245250.
14. Duffy, JY, Overmann, GJ, Keen, CL, et al. Cardiac abnormalities induced by zinc deficiency are associated with alterations in the expression of genes regulated by the zinc-finger transcription factor GATA-4. Birth Defects Res B Dev Reprod Toxicol 2004; 71: 102109.
15. Lopez, V, Keen, CL, Lanoue, L. Prenatal zinc deficiency: influence on heart morphology and distribution of key heart proteins in a rat model. Biol Trace Elem Res 2008; 122: 238255.
16. Lonescu-Ittu, R, Marelli, AJ, Mackie, AS, et al. Prevalence of severe congenital heart disease after folic acid fortification of grain products: time trend analysis in Quebec, Canada. BMJ 2009; 338: b1673.
17. Çelik, , Aygün, C, Gülten, S, et al. Assessment of different folic acid supplementation doses for low-birth weight infants. Turk Pediatri Ars 2016; 51: 210216.
18. Mills, JL, McPartlin, JM, Kirke, PN, et al. Homocysteine metabolism in pregnancies complicated by neural-tube defects. Lancet 1995; 345: 149151.
19. Steegers-Theunissen, RP, Boers, GH, Blom, HJ, et al. Neural tube defects and elevated homocysteine levels in amniotic fluid. Am J Obstet Gynecol 1995; 172: 14361441.
20. Molloy, AM, Kirke, PN, Brody, LC, et al. Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, infant, and child development. Food Nutr Bull 2008; 29 (2 Suppl): S101S111; discussion S112–S115.
21. Kapusta, L, Haagmans, ML, Steegers, EA, et al. Congenital heart defects and maternal derangement of homocysteine metabolism. J Pediatr 1999; 135: 773774.
22. Hurley, LS, Swenerton, H. Congenital malformations resulting from zinc deficiency in rats. Proc Soc Exp Biol Med 1966; 123: 692696.
23. Warkany, J, Petering, HG. Congenital malformations of the brain produced by short zinc deficiencies in rats. Am J Ment Defic 1973; 77: 645653.
24. Sever, LE, Emanuel, I. Is there a connection between maternal zinc deficiency and congenital malformations of the central nervous system? Teratology 1973; 7: 117.
25. Moghimi, M, Ashrafzadeh, S, Rassi, S, et al. Maternal zinc deficiency and congenital anomalies in newborns. Pediatr Int 2017; 59: 443446.
26. Zeyrek, D, Soran, M, Cakmak, A, et al. Serum copper and zinc levels in mothers and cord blood of their newborn infants with neural tube defects: a case-control study. Indian Pediatr 2009; 46: 675680.
27. Turker, G, Ergen, K, Karakoç, Y, et al. Concentrations of toxic metals and trace elements in the meconium of newborns from an industrial city. Biol Neonate 2006; 89: 244250.
28. Kundak, AA, Pektas, A, Zenciroglu, A, et al. Do toxic metals and trace elements have a role in the pathogenesis of conotruncal heart malformations? Cardiol Young 2017; 27: 312317.
29. Holick, MF. Vitamin D deficiency. Review. N Engl J Med 2007; 357: 266281.
30. Daglar, K, Tokmak, A, Kirbas, A, et al. Maternal serum vitamin D levels in pregnancies complicated by neural tube defects. J Matern Fetal Neonatal Med 2016; 29: 298302.
31. Nasri, K, Ben Fradj, MK, Feki, M, et al. Maternal 25-hydroxyvitamin D level and the occurrence of neural tube defects in Tunisia. Int J Gynaecol Obstet 2016; 134: 131134.


Maternal and neonatal micronutrient levels in newborns with CHD

  • Dilek Dilli (a1), Nazan Neslihan Doğan (a1), Utku Arman Örün (a2), Murat Koç (a3), Ayşegül Zenciroğlu (a1), Selmin Karademir (a2) and Hasan Akduman (a1)...


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed