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Maternal supplementation with vitamin A or β-carotene and cardiovascular risk factors among pre-adolescent children in rural Nepal

  • C. P. Stewart (a1), P. Christian (a2), J. Katz (a2), K. J. Schulze (a2), L. S. F. Wu (a2), S. C. LeClerq (a2) (a3), T. R. Shakya (a3), S. K. Khatry (a3) and K. P. West (a2)...


Vitamin A plays an important role in fetal renal and cardiovascular development, yet there has been little research on its effects on cardiovascular risk factors later in childhood. To examine this question, we followed the children of women who had been participants in a cluster-randomized, double blind, placebo-controlled trial of weekly supplementation with 7000 μg retinol equivalents of preformed vitamin A or 42 mg of β-carotene from 1994 to 1997 in rural Nepal. Women received their assigned supplements before, during and after pregnancy. Over a study period of 3 years, 17,531 infants were born to women enrolled in the trial. In 2006–2008, we revisited and assessed 13,118 children aged 9–13 years to examine the impact of maternal supplementation on early biomarkers of chronic disease. Blood pressure was measured in the entire sample of children. In a subsample of 1390 children, venous blood was collected for plasma glucose, Hb1Ac and lipids and a morning urine specimen was collected to measure the ratio of microalbumin/creatinine. Detailed anthropometry was also conducted in the subsample. The mean ± s.d. systolic and diastolic blood pressure was 97.2 ± 8.2 and 64.6 ± 8.5 mm Hg, respectively, and about 5.0% had high-blood pressure (⩾120/80 mm Hg). The prevalence of microalbuminuria (⩾30 mg/g creatinine) was also low at 4.8%. There were no differences in blood pressure or the risk of microalbuminuria between supplement groups. There were also no group differences in fasting glucose, glycated hemoglobin, triglycerides or cholesterol. Maternal supplementation with vitamin A or β-carotene had no overall impact on cardiovascular risk factors in this population at pre-adolescent age in rural Nepal.


Corresponding author

*Address for correspondence: Dr K. P. West, Department of International Health, Center for Human Nutrition, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205, USA. (Email


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1.WHO. Preventing Chronic Disease: A Vital Investment. A WHO Global Report, 2005. World Health Organization, Geneva, Switzerland.
2.Huxley, RR, Shiell, AW, Law, CM. The role of size at birth and postnatal catch-up growth in determining systolic blood pressure: a systematic review of the literature. J Hypertens. 2000; 18, 815831.
3.Whincup, PH, Kaye, SJ, Owen, CG, et al. Birth weight and risk of type 2 diabetes: a systematic review. JAMA. 2008; 300, 28862897.
4.Roseboom, TJ, van der Meulen, JH, Ravelli, AC, et al. Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview. Mol Cell Endocrinol. 2001; 185, 9398.
5.McMillen, IC, Robinson, JS. Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev. 2005; 85, 571633.
6.Christian, P, Stewart, CP. Maternal Micronutrient Deficiency, Fetal Development, and the Risk of Chronic Disease. J Nutr. 2010; 140, 437445.
7.WHO. Global Prevalence of vitamin A Deficiency in Populations at Risk 1995–2005, 2009. World Health Organization, Geneva, Switzerland.
8.Black, RE, Allen, LH, Bhutta, ZA, et al. Maternal and child undernutrition: global and regional exposures and health consequences. Lancet. 2008; 371, 243260.
9.West, KP Jr, Katz, J, Khatry, SK, et al. Double blind, cluster randomised trial of low dose supplementation with vitamin A or beta carotene on mortality related to pregnancy in Nepal. The NNIPS-2 Study Group. BMJ. 1999; 318, 570575.
10.Katz, J, Khatry, SK, West, KP, et al. Night blindness is prevalent during pregnancy and lactation in rural Nepal. J Nutr. 1995; 125, 21222127.
11.Christian, P, West, KP Jr, Khatry, SK, et al. Night blindness during pregnancy and subsequent mortality among women in Nepal: effects of vitamin A and beta-carotene supplementation. Am J Epidemiol. 2000; 152, 542547.
12.Christian, P, West, KP Jr, Khatry, SK, et al. Maternal night blindness increases risk of mortality in the first 6 months of life among infants in Nepal. J Nutr. 2001; 131, 15101512.
13.Katz, J, West, KP Jr, Khatry, SK, et al. Maternal low-dose vitamin A or beta-carotene supplementation has no effect on fetal loss and early infant mortality: a randomized cluster trial in Nepal. Am J Clin Nutr. 2000; 71, 15701576.
14.Dreyfuss, ML, West, KP Jr, Katz, J, et al. Effects of maternal vitamin A or B-carotene supplementation on intrauterine/neonatal and early infant growth in Nepal (abstract). In Report of the XVIII International Vitamin A Consultative Group Meeting, Cairo, Egypt, 1997. ISLI Research Foundation, Washington, DC.
15.Pan, J, Baker, KM. Retinoic acid and the heart. Vitam Horm. 2007; 75, 257283.
16.Burrow, CR. Retinoids and renal development. Exp Nephrol. 2000; 8, 219225.
17.Wilson, JG, Roth, CB, Warkany, J. An analysis of the syndrome of malformations induced by maternal vitamin A deficiency. Effects of restoration of vitamin A at various times during gestation. Am J Anat. 1953; 92, 189217.
18.Wilson, JG, Warkany, J. Cardiac and aortic arch anomalies in the offspring of vitamin A deficient rats correlated with similar human anomalies. Pediatrics. 1950; 5, 708725.
19.Lelievre-Pegorier, M, Vilar, J, Ferrier, ML, et al. Mild vitamin A deficiency leads to inborn nephron deficit in the rat. Kidney Int. 1998; 54, 14551462.
20.Bhat, PV, Manolescu, DC. Role of vitamin A in determining nephron mass and possible relationship to hypertension. J Nutr. 2008; 138, 14071410.
21.Ministry of Health Nepal, Population International, New ERA, Macro International. Nepal Demographic and Health Survey 2006, 2007. New ERA: Kathmandu, Nepal.
22.Friedewald, WT, Levy, RI, Fredrickson, DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972; 18, 499502.
23.National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004; 114, 555576.
24.Chobanian, AV, Bakris, GL, Black, HR, et al. Seventh Report of the National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003; 42, 12061252.
25.Zeger, SL, Liang, KY. Longitudinal data analysis for discrete and continuous outcomes. Biometrics. 1986; 42, 121130.
26.Jones, CA, Francis, ME, Eberhardt, MS, et al. Microalbuminuria in the US population: third National Health and Nutrition Examination Survey. Am J Kidney Dis. 2002; 39, 445459.
27.Zeger, SL, Liang, KY, Albert, PS. Models for longitudinal data: a generalized estimating equation approach. Biometrics. 1988; 44, 10491060.
28.Hawkesworth, S, Prentice, AM, Fulford, AJ, Moore, SE. Maternal protein-energy supplementation does not affect adolescent blood pressure in The Gambia. Int J Epidemiol. 2009; 38, 119127.
29.Zile, MH. Function of vitamin A in vertebrate embryonic development. J Nutr. 2001; 131, 705708.
30.Zile, MH. Vitamin a requirement for early cardiovascular morphogenesis specification in the vertebrate embryo: insights from the avian embryo. Exp Biol Med. 2004; 229, 598606.
31.Gilbert, T. Vitamin A and kidney development. Nephrol Dial Transplant. 2002; 17(Suppl 9), 7880.
32.Merlet-Bénichou, C. Influence of fetal environment on kidney development. Int J Dev Biol. 1999; 43, 453456.
33.Hiller, JE, Crowther, CA, Moore, VA, Willson, K, Robinson, JS. Calcium supplementation in pregnancy and its impact on blood pressure in children and women: follow up of a randomised controlled trial. Aust N Z J Obstet Gynaecol. 2007; 47, 115121.
34.Hatton, DC, Harrison-Hohner, J, Coste, S, Reller, M, McCarron, D. Gestational calcium supplementation and blood pressure in the offspring. Am J Hypertens. 2003; 16, 801805.
35.Belizan, JM, Villar, J, Bergel, E, et al. Long-term effect of calcium supplementation during pregnancy on the blood pressure of offspring: follow up of a randomised controlled trial. BMJ. 1997; 315, 281285.
36.Hawkesworth, S. Conference on “Multidisciplinary approaches to nutritional problems”. Postgraduate symposium. Exploiting dietary supplementation trials to assess the impact of the prenatal environment on CVD risk. Proc Nutr Soc. 2009; 68, 7888.
37.Vaidya, A, Saville, N, Shrestha, BP, et al. Effects of antenatal multiple micronutrient supplementation on children’s weight and size at 2 years of age in Nepal: follow-up of a double-blind randomised controlled trial. Lancet. 2008; 371, 492499.
38.Hawkesworth, S, Ekstrom, EC, Persson, LA, et al. Blood pressure and kidney function at 4.5 years of age in the offspring of the MINIMat trial: effect of maternal food and multiple micronutrient supplementation. Abstract presented at the Developmental Origins of Health and Disease Meeting, 2009, Santiago, Chile. J DOHaD. 2009; 1, S320.
39.Stewart, CP, Christian, P, Schulze, KJ, et al. Antenatal micronutrient supplementation reduces metabolic syndrome in 6- to 8-year-old children in rural Nepal. J Nutr. 2009; 139, 15751581.
40.Stewart, CP, Christian, P, LeClerq, SC, West, KP Jr, Khatry, SK. Antenatal supplementation with folic acid+iron+zinc improves linear growth and reduces peripheral adiposity in school-age children in rural Nepal. Am J Clin Nutr. 2009; 90, 132140.
41.Gluckman, PD, Hanson, MA, Beedle, AS. Early life events and their consequences for later disease: a life history and evolutionary perspective. Am J Hum Biol. 2007; 19, 119. Onis, M, Onyango, AW, Borghi, E, et al. Development of a WHO growth reference for school-aged children and adolescents. Bull World Health Organ. 2007; 85, 660667.
43.Jafar, TH, Islam, M, Poulter, N, et al. Children in South Asia have higher body mass-adjusted blood pressure levels than white children in the United States: a comparative study. Circulation. 2005; 111, 12911297.
44.Syme, C, Abrahamowicz, M, Leonard, GT, et al. Sex differences in blood pressure and its relationship to body composition and metabolism in adolescence. Arch Pediatr Adolesc Med. 2009; 163, 818825.
45.Ostchega, Y, Carroll, M, Prineas, RJ, et al. Trends of elevated blood pressure among children and adolescents: data from the National Health and Nutrition Examination Survey 1988–2006. Am J Hypertens. 2009; 22, 5967.


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Maternal supplementation with vitamin A or β-carotene and cardiovascular risk factors among pre-adolescent children in rural Nepal

  • C. P. Stewart (a1), P. Christian (a2), J. Katz (a2), K. J. Schulze (a2), L. S. F. Wu (a2), S. C. LeClerq (a2) (a3), T. R. Shakya (a3), S. K. Khatry (a3) and K. P. West (a2)...


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