Anemia and Vitamin B-12 and Folate Status in Women of Reproductive Age in Southern India: Estimating Population-Based Risk of Neural Tube Defects

Julia L Finkelstein, Amy Fothergill, Christina B Johnson, Heather M Guetterman, Beena Bose, Shameem Jabbar, Mindy Zhang, Christine M Pfeiffer, Yan Ping Qi, Charles E Rose, Jennifer L Williams, Wesley Bonam, Krista S Crider, Julia L Finkelstein, Amy Fothergill, Christina B Johnson, Heather M Guetterman, Beena Bose, Shameem Jabbar, Mindy Zhang, Christine M Pfeiffer, Yan Ping Qi, Charles E Rose, Jennifer L Williams, Wesley Bonam, Krista S Crider

Abstract

Background: Women of reproductive age (WRA) are a high-risk population for anemia and micronutrient deficiencies. However, there are few representative population-level data from India, which could help inform evidence-based recommendations and policy.

Objective: To conduct a population-based biomarker survey of anemia and vitamin B-12 and folate status in WRA as part of a periconceptional surveillance program in southern India.

Methods: Participants were WRA (15-40 y) who were not pregnant or lactating. Whole blood (n = 979) was analyzed for hemoglobin via a Coulter counter (Coulter HMX). Plasma, serum, and RBCs were processed and stored at -80°C or less until batch analysis. Vitamin B-12 concentrations were measured via chemiluminescence; RBC and serum folate concentrations were evaluated via microbiological assay. Anemia and severe anemia were defined as hemoglobin <12.0 g/dL and <8.0 g/dL, respectively. Vitamin B-12 deficiency and insufficiency were defined as total vitamin B-12 <148 pmol/L and <221 pmol/L, respectively. Folate deficiency and insufficiency were defined as RBC folate <305 nmol/L and <748 nmol/L. A previously developed Bayesian model was used to predict neural tube defect (NTD) prevalence per 10,000 births.

Results: A total of 41.5% of WRA had anemia and 3.0% had severe anemia. A total of 48.3% of WRA had vitamin B-12 deficiency and 74.3% had vitamin B-12 insufficiency. The prevalence of RBC folate deficiency was 7.6%, and 79.3% of WRA had RBC folate <748 nmol/L, the threshold for optimal NTD prevention. Predicted NTD prevalence per 10,000 births based on RBC folate concentrations was 20.6 (95% uncertainty interval: 16.5-25.5).

Conclusions: The substantial burden of anemia, vitamin B-12 deficiency, and RBC folate insufficiency in WRA in this setting suggests an opportunity for anemia and birth defects prevention. Findings will directly inform the development of a randomized trial for anemia and birth defects prevention in southern India.This study was registered at clinicaltrials.gov as NCT04048330.

Keywords: India; NTDs; anemia; folate; periconceptional; surveillance; vitamin B-12.

© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.

Figures

FIGURE 1
FIGURE 1
Participant flow chart. AMC, Arogyavaram Medical Center; appt, appointment; NTD, neural tube defect; WRA, women of reproductive age.

References

    1. World Health Organization (WHO) . The global prevalence of anaemia in 2011. WHO report. Geneva (Switzerland): World Health Organization; 2015.
    1. World Health Organization (WHO) . Nutritional anaemias tools for effective prevention and control. Geneva (Switzerland): World Health Organization; 2017.
    1. World Health Organization (WHO) . Global anaemia reduction efforts among women of reproductive age: impact, achievement of targets and the way forward for optimizing efforts. Geneva (Switzerland): World Health Organization; 2020.
    1. Rahman MM, Abe SK, Rahman MS, Kanda M, Narita S, Bilano V, Ota E, Gilmour S, Shibuya K. Maternal anemia and risk of adverse birth and health outcomes in low- and middle-income countries: systematic review and meta-analysis. Am J Clin Nutr. 2016;103(2):495–504.
    1. Geelhoed D, Agadzi F, Visser L, Ablordeppey E, Asare K, O'Rourke P, Van Leeuwen JS, Van Roosmalen J. Maternal and fetal outcome after severe anemia in pregnancy in rural Ghana. Acta Obstet Gynecol Scand. 2006;85(1):49–55.
    1. Rahman A, Khan N, Rahman M. Maternal anaemia and risk of adverse obstetric and neonatal outcomes in South Asian countries: a systematic review and meta-analysis. Public Health in Practice. 2020;1:100021.
    1. Anand T, Rahi M, Sharma P, Ingle GK. Issues in prevention of iron deficiency anemia in India. Nutrition. 2014;30(7-8):764–70.
    1. Lone FW, Qureshi RN, Emanuel F. Maternal anaemia and its impact on perinatal outcome. Trop Med Int Health. 2004;9(4):486–90.
    1. Brabin BJ, Hakimi M, Pelletier D. An analysis of anemia and pregnancy-related maternal mortality. J Nutr. 2001;131(2):604S–15S.; discussion 14S–15S.
    1. Daru J, Zamora J, Fernández-Félix BM, Vogel J, Oladapo OT, Morisaki N, Tunçalp Ö, Torloni MR, Mittal S, Jayaratne Ket al. . Risk of maternal mortality in women with severe anaemia during pregnancy and post partum: a multilevel analysis. Lancet Global Health. 2018;6(5):e548–54.
    1. Molloy AM, Kirke PN, Brody LC, Scott JM, Mills JL. Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, infant, and child development. Food Nutr Bull. 2008;29(2 Suppl1):S101–11.; discussion S12–15.
    1. Green R, Datta Mitra A. Megaloblastic anemias: nutritional and other causes. Med Clin North Am. 2017;101(2):297–317.
    1. Finkelstein JL, Layden AJ, Stover PJ. Vitamin B-12 and perinatal health. Adv Nutr. 2015;6(5):552–63.
    1. Molloy AM. Should vitamin B12 status be considered in assessing risk of neural tube defects?. Ann NY Acad Sci. 2018;1414(1):109–25.
    1. De-Regil LM, Pena-Rosas JP, Fernandez-Gaxiola AC, Rayco-Solon P. Effects and safety of periconceptional oral folate supplementation for preventing birth defects. Cochrane Database Syst Rev. 2015;(12):CD007950.
    1. Murray CJL, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C, Ezzati M, Shibuya K, Salomon JA, Abdalla Set al. . Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet North Am Ed. 2012;380(9859):2197–223.
    1. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SYet al. . Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet North Am Ed. 2012;380(9859):2095–128.
    1. Zaganjor I, Sekkarie A, Tsang BL, Williams J, Razzaghi H, Mulinare J, Sniezek JE, Cannon MJ, Rosenthal J. Describing the prevalence of neural tube defects worldwide: a systematic literature review. PLoS One. 2016;11(4):e0151586.
    1. Blencowe H, Kancherla V, Moorthie S, Darlison MW, Modell B. Estimates of global and regional prevalence of neural tube defects for 2015: a systematic analysis. Ann NY Acad Sci. 2018;1414(1):31–46.
    1. Liu J, Li Z, Ye R, Liu J, Ren A. Periconceptional folic acid supplementation and sex difference in prevention of neural tube defects and their subtypes in China: results from a large prospective cohort study. Nutr J. 2018;17(1):115.
    1. Lo A, Polsek D, Sidhu S. Estimating the burden of neural tube defects in low- and middle-income countries. J Global Health. 2014;4(1):010402.
    1. Atta CA, Fiest KM, Frolkis AD, Jette N, Pringsheim T, St Germaine-Smith C, Rajapakse T, Kaplan GG, Metcalfe A. Global birth prevalence of spina bifida by folic acid fortification status: a systematic review and meta-analysis. Am J Public Health. 2016;106(1):e24–34.
    1. Allagh KP, Shamanna BR, Murthy GV, Ness AR, Doyle P, Neogi SB, Pant HB; Wellcome Trust–PHFI Folic Acid Project Team . Birth prevalence of neural tube defects and orofacial clefts in India: a systematic review and meta-analysis. PLoS One. 2015;10(3):e0118961.
    1. Bhide P, Sagoo GS, Moorthie S, Burton H, Kar A. Systematic review of birth prevalence of neural tube defects in India. Birth Defects Res A Clin Mol Teratol. 2013;97(7):437–43.
    1. Hibbard ED, Smithells RW. Folic acid metabolism and human embryopathy. Lancet North Am Ed. 1965;285(7398):1254.
    1. Smithells RW, Sheppard S, Schorah CJ. Vitamin deficiencies and neural tube defects. Arch Dis Child. 1976;51(12):944–50.
    1. MRC Vitamin Study Research Group . Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet North Am Ed. 1991;338(8760):131–7.
    1. Czeizel AE, Dudas I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med. 1992;327(26):1832–5.
    1. Berry RJ, Li Z, Erickson JD, Li S, Moore CA, Wang H, Mulinare J, Zhao P, Wong LY, Gindler Jet al. . Prevention of neural-tube defects with folic acid in China. China-U.S. Collaborative Project for Neural Tube Defect Prevention. N Engl J Med. 1999;341(20):1485–90.
    1. Institute of Medicine . Dietary Reference Intakes guiding principles for nutrition labeling and fortification. Washington (DC): National Academies Press;2003.
    1. Crider KS, Bailey LB, Berry RJ. Folic acid food fortification-its history, effect, concerns, and future directions. Nutrients. 2011;3(3):370–84.
    1. Wang H, De Steur H, Chen G, Zhang X, Pei L, Gellynck X, Zheng X. Effectiveness of folic acid fortified flour for prevention of neural tube defects in a high risk region. Nutrients. 2016;8(3):152.
    1. Williams J, Mai CT, Mulinare J, Isenburg J, Flood TJ, Ethen M, Frohnert B, Kirby RS. Updated estimates of neural tube defects prevented by mandatory folic acid fortification—United States, 1995–2011. MMWR Morb Mortal Wkly Rep. 2015;64(1).
    1. Centeno Tablante E, Pachon H, Guetterman HM, Finkelstein JL. Fortification of wheat and maize flour with folic acid for population health outcomes. Cochrane Database Syst Rev. 2019;7:CD012150.
    1. World Health Organization . Guideline: optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects. Geneva (Switzerland): World Health Organization; 2015.
    1. Cordero AM, Crider KS, Rogers LM, Cannon MJ, Berry RJ. Optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects: World Health Organization guidelines. MMWR Morb Mortal Wkly Rep. 2015;64(15):421–3.
    1. Crider KS, Devine O, Hao L, Dowling NF, Li S, Molloy AM, Li Z, Zhu J, Berry RJ. Population red blood cell folate concentrations for prevention of neural tube defects: Bayesian model. BMJ. 2014;349:g4554.
    1. Chen MY, Rose CE, Qi YP, Williams JL, Yeung LF, Berry RJ, Hao L, Cannon MJ, Crider KS. Defining the plasma folate concentration associated with the red blood cell folate concentration threshold for optimal neural tube defects prevention: a population-based, randomized trial of folic acid supplementation. Am J Clin Nutr. 2019;109(5):1452–61.
    1. Tinker SC, Hamner HC, Qi YP, Crider KS. U.S. women of childbearing age who are at possible increased risk of a neural tube defect-affected pregnancy due to suboptimal red blood cell folate concentrations, National Health and Nutrition Examination Survey 2007 to 2012. Birth Defects Res A Clin Mol Teratol. 2015;103(6):517–26.
    1. Rogne T, Tielemans MJ, Chong MF, Yajnik CS, Krishnaveni GV, Poston L, Jaddoe VW, Steegers EA, Joshi S, Chong YSet al. . Associations of maternal vitamin B12 concentration in pregnancy with the risks of preterm birth and low birth weight: a systematic review and meta-analysis of individual participant data. Am J Epidemiol. 2017;185(3):212–23.
    1. Allen LH, Miller JW, de Groot L, Rosenberg IH, Smith AD, Refsum H, Raiten DJ. Biomarkers of Nutrition for Development (BOND): vitamin B-12 review. J Nutr. 2018;148(Suppl 4):1995S–2027S.
    1. World Health Organization . Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993–2005. Geneva (Switzerland): World Health Organization; 2008.
    1. Gonmei Z, Toteja GS. Micronutrient status of Indian population. Indian J Med Res. 2018;148(5):511–21.
    1. Green R, Allen LH, Bjorke-Monsen AL, Brito A, Gueant JL, Miller JW, Molloy AM, Nexo E, Stabler S, Toh BHet al. . Vitamin B12 deficiency. Nat Rev Dis Primers. 2017;3(1):17040.
    1. Allen L, Rosenberg IH, Oakley GP, Omenn GS. Considering the case for vitamin B12 fortification of flour. Food Nutr Bull. 2010;31(1_suppl1):S36–46.
    1. Rogers LM, Cordero AM, Pfeiffer CM, Hausman DB, Tsang BL, De-Regil LM, Rosenthal J, Razzaghi H, Wong EC, Weakland APet al. . Global folate status in women of reproductive age: a systematic review with emphasis on methodological issues. Ann NY Acad Sci. 2018;1431(1):35–57.
    1. Finkelstein JL, Fothergill A, Johnson CB, Guetterman HM, Bose B, Jabbar S, Zhang M, Pfeiffer C, Qi YP, Rose CEet al. . Periconceptional surveillance for prevention of anaemia and birth defects in southern India: protocol for a biomarker survey in women of reproductive age. BMJ Open. 2020;10(10):e038305.
    1. Ruth CJ, Huey SL, Krisher JT, Fothergill A, Gannon BM, Jones CE, Centeno-Tablante E, Hackl LS, Colt S, Finkelstein JLet al. . An electronic data capture framework (ConnEDCt) for global and public health research: design and implementation. J Med Internet Res. 2020;22(8):e18580.
    1. World Health Organization . Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Geneva (Switzerland): World Health Organization; 2011.
    1. Yetley EA, Pfeiffer CM, Phinney KW, Bailey RL, Blackmore S, Bock JL, Brody LC, Carmel R, Curtin LR, Durazo-Arvizu RAet al. . Biomarkers of vitamin B-12 status in NHANES: a roundtable summary. Am J Clin Nutr. 2011;94(1):313S–21S.
    1. Bailey LB, Stover PJ, McNulty H, Fenech MF, Gregory JF 3rd, Mills JL, Pfeiffer CM, Fazili Z, Zhang M, Ueland PMet al. . Biomarkers of Nutrition for Development—folate review. J Nutr. 2015;145(7):1636S–80S.
    1. World Health Organization . Obesity: preventing and managing the global epidemic. Report of a WHO consultation. WHO Technical Report. Geneva (Switzerland): World Health Organization; 2000.
    1. WHO Expert Consultation . Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet North Am Ed. 2004;363(9403):157–63.
    1. US Department of Health and Human Services . Managing overweight and obesity in adults: systematic evidence review from the Obesity Expert Panel, 2013. Washington (DC): US Department of Health and Human Services; NIH; National Heart, Lung and Blood Institute; 2013.
    1. World Health Organization [Internet]. Global Health Observatory data repository. [Cited 2021 Feb 24]. Available from: .
    1. International Institute for Population Sciences (IIPS) . National Family Health Survey (NFHS-4) 2015–2016. Mumbai (India): International Institute for Population Sciences; 2017.
    1. Singh S, Geddam JJB, Reddy GB, Pallepogula DR, Pant HB, Neogi SB, John N, Kolli SR, Doyle P, Kinra Set al. . Folate, vitamin B12, ferritin and haemoglobin levels among women of childbearing age from a rural district in South India. BMC Nutr. 2017;3(1):50.
    1. Chowdhury R, Taneja S, Dhabhai N, Mazumder S, Upadhyay RP, Sharma S, Tupaki-Sreepurna A, Dewan R, Mittal P, Chellani Het al. . Burden of preconception morbidity in women of reproductive age from an urban setting in North India. PLoS One. 2020;15(6):e0234768.
    1. Lilare RR, Sahoo DP. Prevalence of anaemia and its epidemiological correlates among women of reproductive age group in an urban slum of Mumbai. Int J Community Med Public Health. 2017;4(8):2841.
    1. Sathya P, Gandhimathi R, Viruthasurani K, Rodriguez PM, Rajeswari PM, Subhathra N, Merlin MS. A study to assess the prevalence of anemia among women in a selected urban area in Coimbatore district. J Sci Innovative Res. 2017;6:11–5.
    1. International Institute for Population Sciences . National Family Health Survey (NFHS-5) 2019–2020; state fact sheet Andhra Pradesh. Mumbai (India): International Institute for Population Sciences; 2020.
    1. International Institute for Population Sciences . National Family Health Survey (NFHS-5) 2019–2020; district fact sheet Chittoor. Mumbai (India): International Institute for Population Sciences; 2020.
    1. Menon KC, Skeaff SA, Thomson CD, Gray AR, Ferguson EL, Zodpey S, Saraf A, Das PK, Toteja GS, Pandav CS. Concurrent micronutrient deficiencies are prevalent in nonpregnant rural and tribal women from central India. Nutrition. 2011;27(4):496–502.
    1. Chakraborty S, Chopra M, Mani K, Giri AK, Banerjee P, Sahni NS, Siddhu A, Tandon N, Bharadwaj D. Prevalence of vitamin B12 deficiency in healthy Indian school-going adolescents from rural and urban localities and its relationship with various anthropometric indices: a cross-sectional study. J Hum Nutr Diet. 2018;31(4):513–22.
    1. Naik S, Mahalle N, Bhide V. Identification of vitamin B12 deficiency in vegetarian Indians. Br J Nutr. 2018;119(6):629–35.
    1. McLean E, Benoist B, Allen L. Review of the magnitude of folate and vitamin B12 deficiencies worldwide. Food Nutr Bull. 2008;29(2 Suppl 1):S38–51.
    1. Brito A, Mujica-Coopman MF, Lopez de Romana D, Cori H, Allen LH. Folate and vitamin B12 status in Latin America and the Caribbean: an update. Food Nutr Bull. 2015;36(2 Suppl):S109–18.
    1. Allen LH. Folate and vitamin B12 status in the Americas. Nutr Rev. 2004;62(6):29–33.
    1. Bailey RL, Carmel R, Green R, Pfeiffer CM, Cogswell ME, Osterloh JD, Sempos CT, Yetley EA. Monitoring of vitamin B-12 nutritional status in the United States by using plasma methylmalonic acid and serum vitamin B-12. Am J Clin Nutr. 2011;94(2):552–61.
    1. International Centre for Diarrhoeal Diseases Research Bangladesh (ICDDR B); Global Alliance for Improved Nutrition (GAIN); Institude of Public Health and Nutrition (IoPHa) . National Micronutrient Status Survey 2011–2012. Final report. Dhaka (Bangladesh): International Centre for Diarrhoeal Diseases Research; 2013.
    1. Anaya-Loyola MA, Brito A, Villalpando S, Allen LH. Prevalence of low serum vitamin B12 in Mexican children and women: results from the first National Nutrition Survey (1999) as a basis for interventions and progress. Int J Vitam Nutr Res. 2020;90(3–4):325–32.
    1. Rosenthal J, Largaespada N, Bailey LB, Cannon M, Alverson CJ, Ortiz D, Kauwell GP, Sniezek J, Figueroa R, Daly Ret al. . Folate deficiency is prevalent in women of childbearing age in Belize and is negatively affected by coexisting vitamin B-12 deficiency: Belize National Micronutrient Survey 2011. J Nutr. 2017;147(6):1183–93.
    1. Rosenthal J, Lopez-Pazos E, Dowling NF, Pfeiffer CM, Mulinare J, Vellozzi C, Zhang M, Lavoie DJ, Molina R, Ramirez Net al. . Folate and vitamin B12 deficiency among non-pregnant women of childbearing-age in Guatemala 2009–2010: prevalence and identification of vulnerable populations. Matern Child Health J. 2015;19(10):2272–85.
    1. Soofi S, Khan GN, Sadiq K, Ariff S, Habib A, Kureishy S, Hussain I, Umer M, Suhag Z, Rizvi Aet al. . Prevalence and possible factors associated with anaemia, and vitamin B 12 and folate deficiencies in women of reproductive age in Pakistan: analysis of national-level secondary survey data. BMJ Open. 2017;7(12):e018007.
    1. MacFarlane AJ, Greene-Finestone LS, Shi Y. Vitamin B-12 and homocysteine status in a folate-replete population: results from the Canadian Health Measures Survey. Am J Clin Nutr. 2011;94(4):1079–87.
    1. Finkelstein JL, Leal CG, Chu W, Krisher JT, Haas JD, Mehta S, Freire W. Anemia and iron, vitamin B12, and folate deficiencies in women of reproductive age in Ecuador: results from the Ecuadorian National Health and Nutrition Survey. Curr Dev Nutr. 2019;3(Suppl 1):782.
    1. Jordan Ministry of Health; Global Alliance for Improved Nutrition; Centers for Disease Control and Prevention; United Nations Children's Fund–Jordan . National Micronutrient Survey, Jordan 2010. Amman (Jordan): Jordan Ministry of Health; 2011.
    1. Abeyá E, Durán P, Mangialavori G, Biglieri A, Kogan L. Encuesta Nacional De Nutricion Y Salud; Documento de Resultados. Ministerio De Salud Presidencia de la Nacion. Buenos Aires, Argentina; 2007.
    1. Herran OF, Ward JB, Villamor E. Vitamin B12 serostatus in Colombian children and adult women: results from a nationally representative survey. Public Health Nutr. 2015;18(5):836–43.
    1. Ministerio De Salud, Instituto Costarricense de investigacion y ensenanza en nutricion y salud, Caja costarricenses de seguro social, instituto nacional de estadistica y censos, drogas ics. Encuesta Nacional de Nutrition 2008–2009. Fasciculo Micronutrientes. 2. San Jose (Costa Rica); 2012.
    1. Ruston D, Hoare J, Henderson L, Gregory J, Bates C, Prentice A, Birch M, Swan G, Farron M. The National Diet and Nutrition Survey: adults aged 19 to 64 years. Nutritional status (anthropometry and blood analytes), blood pressure and physical activity. London: Her Majesty's Stationery Office; 2004.
    1. Thamm M, Mensink GB, Thierfelder W. [Folic acid intake of women in childbearing age] Gesundheitswesen. 1999;61(Spec No):S207–12.
    1. Christian AM, Krishnaveni GV, Kehoe SH, Veena SR, Khanum R, Marley-Zagar E, Edwards P, Margetts BM, Fall CH. Contribution of food sources to the vitamin B12 status of South Indian children from a birth cohort recruited in the city of Mysore. Public Health Nutr. 2015;18(4):596–609.
    1. Samuel TM, Duggan C, Thomas T, Bosch R, Rajendran R, Virtanen SM, Srinivasan K, Kurpad AV. Vitamin B12 intake and status in early pregnancy among urban South Indian women. Ann Nutr Metab. 2013;62(2):113–22.
    1. Allen LH. Causes of vitamin B12 and folate deficiency. Food Nutr Bull. 2008;29(2 Suppl 1):S20–34.; discussion S5–7.
    1. Indian Institute for Population Sciences . National Family Health Survey (NFHS-4) 2015–16: India. Mumbai (India): Indian Institute for Population Sciences; 2017.
    1. Bellows AL, Kachwaha S, Ghosh S, Kappos K, Escobar-Alegria J, Menon P, Nguyen PH. Nutrient adequacy is low among both self-declared lacto-vegetarian and non-vegetarian pregnant women in Uttar Pradesh. Nutrients. 2020;12(7):2126.
    1. Colapinto CK, O'Connor D, Tremblay MS. Folate status of the population in the Canadian Health Measures Survey. Can Med Assoc J. 2011;183(2):E100–6.
    1. Crider KS, Qi YP, Devine O, Tinker SC, Berry RJ. Modeling the impact of folic acid fortification and supplementation on red blood cell folate concentrations and predicted neural tube defect risk in the United States: have we reached optimal prevention?. Am J Clin Nutr. 2018;107(6):1027–34.
    1. Rosenthal J, Reeve ME, Ramirez N, Crider KS, Sniezek J, Vellozzi C, Devine O, Lopez-Pazos E. Red blood cell folate insufficiency among nonpregnant women of childbearing age in Guatemala 2009 to 2010: prevalence and predicted neural tube defects risk. Birth Defects Res A Clin Mol Teratol. 2016;106(7):587–95.
    1. Mai CT, Isenburg JL, Canfield MA, Meyer RE, Correa A, Alverson CJ, Lupo PJ, Riehle-Colarusso T, Cho SJ, Aggarwal Det al. . National population-based estimates for major birth defects, 2010–2014. Birth Defects Res. 2019;111(18):1420–35.
    1. National Center for Health Statistics [Internet]. NHANES Response Rates and Population Totals. [Cited 2021 Feb 24]. Available from: .

Source: PubMed

3
Subskrybuj