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Comment & Response
January 13, 2020

Extrapolation Pitfalls and Methodology Flaws in Curing Anemia via Parental Education and Counseling—Reply

Author Affiliations
  • 1Sickle Cell Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland
  • 2Schulich School of Medicine and Dentistry, Department of Family Medicine, Western University, London, Ontario, Canada
  • 3Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden
  • 4Centre for Epidemiology and Community Medicine, Stockholm Health Care District, Stockholm, Sweden
JAMA Pediatr. Published online January 13, 2020. doi:10.1001/jamapediatrics.2019.5054

In Reply We thank Zhou and Niu for their comments regarding our pragmatic cluster randomized trial. The authors raise 2 specific issues that they believe are legitimate. First, Zhou and Niu question the generalizability of the trial conducted in Chamarajnagar district, South India, to rural children from the rest of India. In support of their concern is cited evidence for genetic diversity among Indian individuals and documentation of rare germline mutations in TMPRSS6, which encodes a type II transmembrane serine protease produced by the liver that regulates the expression of the systemic iron regulatory hormone hepcidin that can cause iron-refractory iron-deficiency anemia.1 This concern is unfounded for the following reasons. In spite of genetic diversity, anemia prevalence in children younger than 5 years between rural Indian provinces is remarkably similar.2 Moreover, genetic mutations causally associated with iron deficiency anemia in the general population are likely to be randomly distributed. Besides, regardless of heterogeneity in anemia prevalence among genetically diverse individuals, there is no logical reason to think that the relative effect of our intervention would be different because the effect is obtained via education and counselling, mechanisms that are social and cultural rather than genetic.

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