Early Life Exposure to Mycotoxins and Child Linear Growth in Nepal: Methods and Design of a Prospective Birth Cohort Study

Andrews-Trevino JY^1, , Webb P¹, Baral K², Davis D³, Shrestha R¹, Pokharel A³, Acharya S³, Lamichhane A³, Shively G⁴, Paudel K⁵, Xue KS⁶, Wang JS⁶ and Ghosh S¹

¹Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University, 150 Harrison Ave, Boston, Massachusetts, USA

²Patan Academy of Health Sciences, Patan Hospital, Satdobato Rd, 44700, Lalitpur, Nepal

³Helen Keller International-Nepal, Green Block, Ward No 10, Chakupat, Patandhoka Road, Lalitpur 44700, Nepal

⁴Department of Agricultural Economics, Purdue University, 610 Purdue Mall, West Lafayette, IN 47907 USA

⁵Kanti Hospital, Maharajgunj, Kathmandu - 3, Nepal

⁶Department of Environmental Health Science, College of Public Health, University of Georgia, 150 Green Street, Athens, GA, USA

Cite this paper

Andrews-Trevino JY, Webb P, Baral K, Davis D, Shrestha R, Pokharel A, Acharya S, Lamichhane A, Shively G, Paudel K, Xue KS, Wang JS and Ghosh S. Early Life Exposure to Mycotoxins and Child Linear Growth in Nepal: Methods and Design of a Prospective Birth Cohort Study. Journal of Food Security. 2020; 8(1):1-10. doi: 10.12691/JFS-8-1-1

Abstract

A growing body of mainly cross-sectional evidence suggests an association between mycotoxins, particularly aflatoxin exposure, and poor linear growth in children. We describe the design and methods of a rigorous longitudinal birth cohort study aimed to deepen our understanding of this hypothesized relationship and to validate dried blood spots as a less invasive, low-cost collection method for venous blood samples. The AflaCohort study was conducted in Banke district of Nepal from 2015 to 2019. A total of 1,675 pregnant women ages 16-49 were recruited from 17 Village Development Committees of the district. The research team collected maternal and child anthropometry data at birth and every 3 months from birth through the first year of life. Children were revisited at 18-22 months and 24-26 months of age. Questionnaires administered at the household level assessed risk factors for aflatoxin exposure and poor linear growth. One maternal venous blood sample was collected during gestation and child blood samples were collected at 3, 6, 12 and 18-22 months of age to assess concentrations of aflatoxin B₁ (AFB₁)-lysine adduct. One breast milk sample was collected from mothers when the child was 3 months of age to assess levels of aflatoxin M₁. Serum ochratoxin A and urinary levels of fumonisin B₁ and deoxynivalenol were measured at 18-22 months of age. Environmental enteric dysfunction was assessed using a lactulose:mannitol (L:M) test at 18-22 months of age. The study collected dried blood spots from a subset (n≈1200) of mothers and children to compare AFB₁ concentrations with those found in matching venous blood samples. Biomarker assessments were conducted using a high-performance liquid chromatograph method. Findings from the study will help identify certain factors that warrant interventions to reduce aflatoxin-related stunting in Nepal. This study was registered at ClinicalTrials.gov as NCT03312049.

Keywords

aflatoxins, children, dried blood spots, gestation, growth, Nepal, mycotoxins

Copyright

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References

[1]	Wells JCK, Briend A, Boyd EM, Berkely JA, Hall A, Isanaka S, et al. Beyond wasted and stunted—a major shift to fight child undernutrition. Lancet Child Adolesc Heal. 2019.
[2]	International Food Policy Research Institute, Bill & Melinda Gates Foundation. Aflatoxin : Impact on Stunting in Children and Interventions to Reduce Exposure. 2012; 1-55.
[3]	Koirala KS, BK Y, KC P. Occurrence of aflatoxin in some of the food and feed in Nepal. Indian J Med Sci. 2005; 59(8): 331-6.
[4]	Caruana EJ, Roman M, Hernández-Sánchez J, Solli P. Longitudinal studies. J Thorac Dis [Internet]. 2015; 7(11): E537-40. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26716051%0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4669300
[5]	Turner PC, Collinson AC, Cheung YB, Gong Y, Hall AJ, Prentice AM, et al. Aflatoxin exposure in utero causes growth faltering in Gambian infants. Int J Epidemiol. 2007; 36(5): 1119-25.
[6]	Thorne-Lyman AL, Shrestha M, Fawzi WW, Pasqualino M, Strand TA, Kvestad I, et al. Dietary Diversity and Child Development in the Far West of Nepal: A Cohort Study. Nutrients. 2019; 11(8): 1799.
[7]	WHO Multicentre Growth Reference Study Group. WHO Child Growth Standards: Length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age: Methods and development. Geneva; 2006.
[8]	Denno DM, VanBuskirk K, Nelson ZC, Musser CA, Hay Burgess DC, Tarr PI. Use of the lactulose to mannitol ratio to evaluate childhood environmental enteric dysfunction: A systematic review. Clin Infect Dis. 2014;
[9]	Wang JS, Qian GS, Zarba A, He X, Zhu YR, Zhang BC, et al. Temporal patterns of aflatoxin-albumin adducts in hepatitis B surface antigen-positive and antigen-negative residents of Daxin, Qidong County, People’s Republic of China. Cancer Epidemiol Biomarkers Prev [Internet]. 1996; 5(4): 253-61. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8722216
[10]	Qian G, Tang L, Wang F, Guo X, Massey ME, Williams JH, et al. Physiologically based toxicokinetics of serum aflatoxin B1-lysine adduct in F344 rats. Toxicology [Internet]. 2013; 303: 147-51. Available from: http://dx.doi.org/10.1016/j.tox.2012.10.020
[11]	Turner PC, Burley VJ, Rothwell JA, White KLM, Cade JE, Wild CP. Dietary wheat reduction decreases the level of urinary deoxynivalenol in UK adults. J Expo Sci Environ Epidemiol. 2008;
[12]	Sugita-Konsihi Y, Tanaka T, Tabata S, Nakajima M, Nouno M, Nakaie Y, et al. Validation of an HPLC analytical method coupled to a multifunctional clean-up column for the determination of deoxynivalenol. Mycopathologia. 2006.
[13]	Shulman RJ, Schanler RJ, Lau C, Heitkemper M, Ou CN, O’Brian Smith E. Early feeding, antenatal glucocorticoids, and human milk decrease intestinal permeability in preterm infants. Pediatr Res. 1998.
[14]	Gong Y, Cardwell K, Hounsa A, Egal S, Turner PC, Hall AJ, et al. Dietary aflatoxin exposure and impaired growth in young children from Benin and Togo: cross sectional study. 2002; 325 (July): 20-1.
[15]	Hoffmann V, Jones K, Leroy JL. The impact of reducing dietary aflatoxin exposure on child linear growth: A cluster randomised controlled trial in Kenya. BMJ Glob Heal. 2018; 3(6): 1-8.