European Journal of Nutrition

, Volume 47, Issue 7, pp 357–365

Maternal intake of fat, riboflavin and nicotinamide and the risk of having offspring with congenital heart defects

  • Huberdina P. M. Smedts
  • Maryam Rakhshandehroo
  • Anna C. Verkleij-Hagoort
  • Jeanne H. M. de Vries
  • Jaap Ottenkamp
  • Eric A. P. Steegers
  • Régine P. M. Steegers-Theunissen
ORIGINAL CONTRIBUTION

Abstract

Background

With the exception of studies on folic acid, little evidence is available concerning other nutrients in the pathogenesis of congenital heart defects (CHDs). Fatty acids play a central role in embryonic development, and the B-vitamins riboflavin and nicotinamide are co-enzymes in lipid metabolism.

Aim of the study

To investigate associations between the maternal dietary intake of fats, riboflavin and nicotinamide, and CHD risk in the offspring.

Methods

A case-control family study was conducted in 276 mothers of a child with a CHD comprising of 190 outflow tract defects (OTD) and 86 non-outflow tract defects (non-OTD) and 324 control mothers of a non-malformed child. Mothers filled out general and food frequency questionnaires at 16 months after the index-pregnancy, as a proxy of the habitual food intake in the preconception period. Nutrient intakes (medians) were compared between cases and controls by Mann–Whitney U test. Odds ratios (OR) for the association between CHDs and nutrient intakes were estimated in a logistic regression model.

Results

Case mothers, in particular mothers of a child with OTD, had higher dietary intakes of saturated fat, 30.9 vs. 29.8 g/d; < 0.05. Dietary intakes of riboflavin and nicotinamide were lower in mothers of a child with an OTD than in controls (1.32 vs. 1.41 mg/d; < 0.05 and 14.6 vs. 15.1 mg/d; < 0.05, respectively). Energy, unsaturated fat, cholesterol and folate intakes were comparable between the groups. Low dietary intakes of both riboflavin (<1.20 mg/d) and nicotinamide (<13.5 mg/d) increased more than two-fold the risk of a child with an OTD, especially in mothers who did not use vitamin supplements in the periconceptional period (OR 2.4, 95%CI 1.4–4.0). Increasing intakes of nicotinamide (OR 0.8, 95%CI 0.7–1.001, per unit standard deviation increase) decreased CHD risk independent of dietary folate intake.

Conclusions

A maternal diet high in saturated fats and low in riboflavin and nicotinamide seems to contribute to CHD risk, in particular OTDs.

Keywords

congenital heart anomaly saturated fat B-vitamins risk factors prevention 

References

  1. 1.
    Boot MJ, Steegers-Theunissen RP, Poelmann RE, Van Iperen L, Lindemans J, Gittenberger-de Groot AC (2003) Folic acid and homocysteine affect neural crest and neuroepithelial cell outgrowth and differentiation in vitro. Dev Dyn 227:301–308CrossRefGoogle Scholar
  2. 2.
    Botto LD, Correa A (2003) Decreasing the burden of congenital heart anomalies: an epidemiologic evaluation of risk factors and survival. Prog Pediatr Cardiol 18:111–121CrossRefGoogle Scholar
  3. 3.
    Botto LD, Mulinare J, Erickson JD (2003) Do multivitamin or folic acid supplements reduce the risk for congenital heart defects? Evidence and gaps. Am J Med Genet A 121:95–101CrossRefGoogle Scholar
  4. 4.
    Brauer PR, Rosenquist TH (2002) Effect of elevated homocysteine on cardiac neural crest migration in vitro. Dev Dyn 224:222–230CrossRefGoogle Scholar
  5. 5.
    Cikot RJ, Steegers-Theunissen RP, Thomas CM, de Boo TM, Merkus HM, Steegers EA (2001) Longitudinal vitamin and homocysteine levels in normal pregnancy. Br J Nutr 85:49–58CrossRefGoogle Scholar
  6. 6.
    De Walle HEK, De Jong-van den Berg LTW (2007) Growing gap in folic acid intake with respect to level of education in the Netherlands. Community Genet 10:93–96Google Scholar
  7. 7.
    Devine CM, Bove CF, Olson CM (2000) Continuity and change in women’s weight orientations and lifestyle practices through pregnancy and the postpartum period: the influence of life course trajectories and transitional events. Soc Sci Med 50:567–582CrossRefGoogle Scholar
  8. 8.
    Feunekes GI, Van Staveren WA, De Vries JH, Burema J, Hautvast JG (1993) Relative and biomarker-based validity of a food-frequency questionnaire estimating intake of fats and cholesterol. Am J Clin Nutr 58:489–496Google Scholar
  9. 9.
    Gittenberger-de Groot AC, Bartelings MM, Deruiter MC, Poelmann RE (2005) Basics of cardiac development for the understanding of congenital heart malformations. Pediatr Res 57:169–176CrossRefGoogle Scholar
  10. 10.
    Goldberg GR, Black AE, Jebb SA, Cole TJ, Murgatroyd PR, Coward WA, Prentice AM (1991) Critical evaluation of energy intake data using fundamental principles of energy physiology: 1. Derivation of cut-off limits to identify under-recording. Eur J Clin Nutr 45:569–581Google Scholar
  11. 11.
    Groenen PM, van Rooij IA, Peer PG, Ocke MC, Zielhuis GA, Steegers-Theunissen RP (2004) Low maternal dietary intakes of iron, magnesium, and niacin are associated with spina bifida in the offspring. J Nutr 134:1516–1522Google Scholar
  12. 12.
    Health Council of the Netherlands (2000) Nutritional Norms: calcium, vitamin D, thiamin, riboflavin, niacin, pantothenic acid, biotin. Health Council of the Netherlands, The Hague, The Netherlands; Publication Nr 2000/12Google Scholar
  13. 13.
    Hobbs CA, Malik S, Zhao W, James SJ, Melnyk S, Cleves MA (2006) Maternal homocysteine and congenital heart defects. JACC 47:683–685Google Scholar
  14. 14.
    Hoffman JI, Kaplan S (2002) The incidence of congenital heart disease. JACC 39:1890–1900Google Scholar
  15. 15.
    Innis SM (2007) Fatty acids and early human development. Early Hum Dev 83:761–766CrossRefGoogle Scholar
  16. 16.
    Khan IY, Dekou V, Douglas G, Jensen R, Hanson MA, Poston L, Taylor PD (2005) A high-fat diet during rat pregnancy or suckling induces cardiovascular dysfunction in adult offspring. Am J Physiol Regul Integr Comp Physiol 288:R127–R133Google Scholar
  17. 17.
    Kirby ML, Waldo KL (1995) Neural crest and cardiovascular patterning. Circ Res 77:211–215Google Scholar
  18. 18.
    Kirkland JB, Rawling JM (2001) Niacin. In: Rucker RB, Suttie JW, McCormick DB, Machlin LJ (eds) Handbook of vitamins. 3rd edn. Marcel Dekker, Inc, New York, pp 213–254Google Scholar
  19. 19.
    Krapels IP, van Rooij IA, Ocke MC, van Cleef BA, Kuijpers-Jagtman AM, Steegers-Theunissen RP (2004) Maternal dietary B vitamin intake, other than folate, and the association with orofacial cleft in the offspring. Eur J Nutr 43:7–14CrossRefGoogle Scholar
  20. 20.
    Lao O, van Duijn K, Kersbergen P, de Knijff P, Kayser M (2006) Proportioning whole-genome single-nucleotide-polymorphism diversity for the identification of geographic population structure and genetic ancestry. Am J Hum Genet 78:680–690CrossRefGoogle Scholar
  21. 21.
    Netherlands Nutrition Centre (1993) Dutch national food consumption survey 1992. In: Dutch. (Zo eet Nederland 1992). Netherlands Nutrition Centre, The Hague, The Netherlands Google Scholar
  22. 22.
    Netherlands Nutrition Centre (1998) Dutch national food consumption survey 1998. In: Dutch. (Zo eet Nederland 1998). Netherlands Nutrition Centre. The Hague, The NetherlandsGoogle Scholar
  23. 23.
    Netherlands Nutrition Centre (2001) NEVO: Dutch food composition database 2001. Netherlands Nutrition Centre, The Hague, The NetherlandsGoogle Scholar
  24. 24.
    Nielsen GL, Norgard B, Puho E, Rothman KJ, Sorensen HT, Czeizel AE (2005) Risk of specific congenital abnormalities in offspring of women with diabetes. Diabet Med 22:693–696CrossRefGoogle Scholar
  25. 25.
    Powers HJ (2003) Riboflavin (vitamin B-2) and health. Am J Clin Nutr 77:1352–1360Google Scholar
  26. 26.
    Ray JG, O’Brien TE, Chan WS (2001) Preconception care and the risk of congenital anomalies in the offspring of women with diabetes mellitus: a meta-analysis. QJM 94:435–444CrossRefGoogle Scholar
  27. 27.
    Rivlin RS, Pinto JT (2001) Riboflavin (vitamin B2). In: Rucker RB, Suttie JW, McCormick DB, Machlin LJ (eds) Handbook of vitamins, 3rd edn. Marcel Dekker, Inc, New York, 255–273Google Scholar
  28. 28.
    Rosenquist TH, Bennet GD, Brauer PR, Stewart ML, Chaudoin TR, Finnell RH (2007) Microarray analysis of homocysteine-responsive genes in cardiac neural crest cells in vitro. Dev Dyn 236:1044–1054CrossRefGoogle Scholar
  29. 29.
    Shaw GM, Carmichael SL, Laurent C, Rasmussen SA (2006) Maternal nutrient intakes and risk of orofacial clefts. Epidemiology 17:285–291Google Scholar
  30. 30.
    Shaw GM, O’Malley CD, Wasserman CR, Tolarova MM, Lammer EJ (1995) Maternal periconceptional use of multivitamins and reduced risk for conotruncal heart defects and limb deficiencies among offspring. Am J Med Genet 59:536–545CrossRefGoogle Scholar
  31. 31.
    Statistics Netherlands Classification of educational level. Internet: http://www.cbs.nl/en-GB/menu/methoden/methoden-per-thema/default.htm. Voorburg/Heerlen, the Netherlands. Accessed on Augustus 27, 2007
  32. 32.
    Verkleij-Hagoort AC, Verlinde M, Ursem NT, Lindemans J, Helbing WA, Ottenkamp J, Siebel FM, Gittenberger-de Groot AC, de Jonge R, Bartelings MM, Steegers EA, Steegers-Theunissen RP (2006) Maternal hyperhomocysteinaemia is a risk factor for congenital heart disease. BJOG 113:1412–1418CrossRefGoogle Scholar
  33. 33.
    Verkleij-Hagoort AC, de Vries JH, Stegers MP, Lindemans J, Ursem NT, Steegers-Theunissen RP (2007) Validation of the assessment of folate and vitamin B12 intake in women of reproductive age: the method of triads. Eur J Clin Nutr 61:610–615Google Scholar
  34. 34.
    Verkleij-Hagoort AC, de Vries JH, Ursem NT, de Jonge R, Hop WC, Steegers-Theunissen RP (2006) Dietary intake of B-vitamins in mothers born a child with a congenital heart defect. Eur J Nutr 45:478–486CrossRefGoogle Scholar
  35. 35.
    Vujkovic M, Ocke MC, van der Spek PJ, Yazdanpanah N, Steegers EAP, Steegers-Theunissen RPM (2007) Maternal western dietary patterns and the risk of developing a cleft lip with or without a cleft palate. Obstet Gynecol 110:378–384Google Scholar
  36. 36.
    Waller DK, Shaw GM, Rasmussen SA, Hobbs CA, Canfield MA, Siega-Riz AM, Gallaway MS, Correa A, National Birth Defects Prevention Study (2007) Prepregnancy obesity as a risk factor for structural birth defects. Arch Pediatr Adolesc Med 161:745–750CrossRefGoogle Scholar
  37. 37.
    Waterland RA, Michels KB (2007) Epigenetic epidemiology of the developmental origins hypothesis. Annu Rev Nutr 27:363–388CrossRefGoogle Scholar
  38. 38.
    Watkins ML, Rasmussen SA, Honein MA, Botto LD, Moore CA (2003) Maternal obesity and risk for birth defects. Paediatrics 111:1152–1158Google Scholar
  39. 39.
    Willett W (1998) Nature of variation in diet. In: Willet W (ed) Nutritional epidemiology. Oxford University Press, New York, pp. 33–50Google Scholar
  40. 40.
    Willett WC, Howe GR, Kushi LH (1997) Adjustment for total energy intake in epidemiologic studies. Am J Clin Nutr 65:1220S–1231SGoogle Scholar

Copyright information

© Spinger 2008

Authors and Affiliations

  • Huberdina P. M. Smedts
    • 1
  • Maryam Rakhshandehroo
    • 1
    • 2
  • Anna C. Verkleij-Hagoort
    • 1
  • Jeanne H. M. de Vries
    • 2
  • Jaap Ottenkamp
    • 3
  • Eric A. P. Steegers
    • 1
  • Régine P. M. Steegers-Theunissen
    • 1
    • 4
    • 5
    • 6
  1. 1.Obstetrics and Gynaecology, Division of Obstetrics and Prenatal MedicineErasmus MC, University Medical CentreRotterdamThe Netherlands
  2. 2.Human NutritionWageningen UniversityWageningenThe Netherlands
  3. 3.Paediatric Cardiology, CAHAL-centre for congenital anomalies of the heart, Amsterdam/LeidenLeiden University Medical CentreLeidenThe Netherlands
  4. 4.EpidemiologyErasmus MC, University Medical CentreRotterdamThe Netherlands
  5. 5.Clinical GeneticsErasmus MC, University Medical CentreRotterdamThe Netherlands
  6. 6.Paediatrics/Division of Pediatric CardiologyErasmus MC–Sophia Children’s Hospital, University Medical CentreRotterdamThe Netherlands

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