Homocysteine remethylation pathway in neonates with congenital heart disease and neural tube defects
Piotr Surmiak 1  
,   Małgorzata Baumert 1  
,   Zofia Walencka 1  
,   Magdalena Paprotny 1  
,   Andrzej Witek 2  
More details
Hide details
Department of Neonatology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
Department of Gynaecology and Obstetrics, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
Piotr Surmiak   

Department of Neonatology, School of Medicine in Katowice, Medical University of Silesia, Katowice, ul. Medyków 14, 40-752 Katowice, Poland
Ann. Acad. Med. Siles. 2018;72:134–140
The etiology of congenital heart defects (CHD) and neural tube defects (NTD) remain unknown, however, the relation between homocysteine and folate levels and congenital anomalies were found. With this perspective in mind, the aim of the study was to investigate serum biomarkers of the homocysteine metabolism pathway in neonates with CHD, newborns with NTD and their mothers.

Material and methods:
Twenty-nine pairs of mothers and their neonates with CHD as well as 18 pairs of mothers and neonates with NTD were enrolled in the study. The control group consisted of 54 pairs of mothers and their healthy neonates. To estimate the total homocysteine, serum folic acid and vitamin B12 levels in plasma, mothers’ venous blood samples and umbilical cord blood were taken in the all groups.

There were significantly higher tHcy levels in the newborns with CHD compared to their mothers. The total homocysteine levels in the CHD neonates were noticeably different compared to the neonates with NTD and to the controls. The vitamin B12 levels were similar in all the investigated neonates. Significantly lower umbilical folic acid levels in the NTD and CHD groups as compared to the controls were noticed.

The observed differences in concentrations of homocysteine, folic acid and cobalamin between neonates with congenital heart and neural tube defects suggest the influence of various agents disturbing the homo-cysteine metabolic pathways in those children.

Dolk H., Loane M., Garne E. The prevalence of congenital anomalies in Europe. Adv. Exp. Med. Biol. 2010; 686: 349–364, doi: 10.1007/978-90-481-9485-8_20.
Latos-Bieleńska A., Materna-Kiryluk A.; Zespół Polskiego Rejestru Wrodzonych Wad Rozwojowych. Wrodzone wady rozwojowe w Polsce w latach 2005–2006. Dane z Polskiego Rejestru Wrodzonych Wad Rozwojowych. Ośrodek Wydawnictw Naukowych, Poznań 2011.
Ulrey C.L., Liu L., Andrews L.G., Tollefsbol T.O. The impact of metab-olism on DNA methylation. Hum. Mol. Genet. 2005; 14(Spec. No. 1): R139–R147, doi: 10.1093/hmg/ddi100.
Jakubowski H. Metabolism of homocysteine thiolactone in human cell cultures: possible mechanism for pathological consequences of elevated homocysteine levels. J. Biol. Chem. 1997; 272(3): 1935–1942.
Brustolin S., Giugliani R., Felix T.M. Genetics of homocysteine metabolism and associated disorders. Braz. J. Med. Biol. Res. 2010; 43(1): 1–7.
Rosenquist T.H., Finnell R.H. Genes, folate and homocysteine in embryonic development. Proc. Nutr. Soc. 2001; 60(1): 53–61.
Papiernik E., Zeitlin J., Delmas D., Draper E.S., Gadzinowski J., Künzel W., Cuttini M., Di Lallo D., Weber T., Kollée L., Bekaert A., Bréart G. Termination of pregnancy among very preterm births and its impact on very preterm mortality: results from ten European population-based cohorts in the MOSAIC study. BJOG 2008; 115(3): 361–368, doi: 10.1111/j.1471-0528.2007.01611.x.
Baumert M., Surmiak P., Paprotny M., Fiala M., Walencka Z. Homocysteine, folate and cobalamin concentrations in mothers and their neonates born with neural tube defects and congenital heart defects. Acta Med. Portuguesa 2012; 25(Supl. 2): 152 [PO22].
Boot M.J., Steegers-Theunissen R.P., Poelmann R.E., van Iperen L., Lindemans J., Gittenberger-de Groot A.C. Folic acid and homocysteine affect neural crest and neuroepithelial cell outgrowth and differentiation in vitro. Dev. Dyn. 2003; 227(2): 301–308, doi: 10.1002/dvdy.10303.
Ratan S.K., Rattan K.N., Pandey R.M., Singhal S., Kharab S., Bala M., Singh V., Jhanwar A. Evaluation of the levels of folate, vitamin B12, homocysteine and fluoride in the parents and the affected neonates with neural tube defect and their matched controls. Pediatr. Surg. Int. 2008; 24(7): 803–808, doi: 10.1007/s00383-008-2167-z.
Verkleij-Hagoort A.C., Verlinde M., Ursem N.T., Lindemans J., Helbing W.A., Ottenkamp J., Siebel F.M., Gittenberger-de Groot A.C., de Jonge R., Bartelings M.M., Steegers E.A., Steegers-Theunissen R.P. Maternal hyperhomocysteinaemia is a risk factor for congenital heart disease. BJOG 2006; 113(12): 1412–1418, doi: 10.1111/j.1471-0528.2006.01109.x.
Boot M.J., Steegers-Theunissen R.P., Poelmann R.E., van Iperen L., Gittenberger-de Groot A.C. Cardiac outflow tract malformations in chick embryos exposed to homocysteine. Cardiovasc. Res. 2004; 64(2): 365–373, doi: 10.1016/j.cardiores.2004.07.010.
Koz S.T., Gouwy N.T., Demir N., Nedzevetsky V.S., Etem E., Baydas G. Effects of maternal hyperhomocysteinemia induced by methionine intake on oxidative stress and apoptosis in pup rat brain. Int. J. Dev. Neurosci. 2010; 28(4): 325–329, doi: 10.1016/j.ijdevneu.2010.02.006.
Lu Y., Wang H., Wang X. Relationship of hyperhomocysteinemia in pregnant rats and congenital heart defects in the newborn rats. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2011; 36(1): 68–73, doi: 10.3969/j.issn.1672-7347.2011.01.011.
Botto L.D., Mulinare J., Erickson J.D. Occurrence of congenital heart defects in relation to maternal mulitivitamin use. Am. J. Epidemiol. 2000; 151(9): 878–884.
MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 1991; 338(8760): 131–137.
Zhao J.Y., Yang X.Y., Gong X.H., Gu Z.Y., Duan W.Y., Wang J., Ye Z.Z., Shen H.B., Shi K.H., Hou J., Huang G.Y., Jin L., Qiao B., Wang H.Y. Functional variant in methionine synthase reductase intron-1 significantly increases the risk of congenital heart disease in the Han Chinese population. Circulation 2012; 125(3): 482–490, doi: 10.1161/CIRCULATIONAHA.111.050245.
Saxena A.K., Gupta J., Pandey S., Gangopadhaya A.N., Pandey L.K. Prevalence of cystathionine beta synthase gene mutation 852Ins68 as a possible risk for neural tube defects in eastern India. Genet. Mol. Res. 2011; 10(4): 2424–2429, doi: 10.4238/2011.October.7.4.
Richter B., Stegmann K., Röper B., Böddeker I., Ngo E.T., Koch M.C. Interaction of folate and homocysteine pathway genotypes evaluated in susceptibility to neural tube defects (NTD) in a German population. J. Hum. Genet. 2001; 46(3): 105–109, doi: 10.1007/s100380170096.
Solanky N., Requena Jimenez A., D'Souza S.W., Sibley C.P., Glazier J.D. Expression of folate transporters in human placenta and implications for homocysteine metabolism. Placenta 2010; 31(2): 134–143, doi: 10.1016/j.placenta.2009.11.017.