Reference cut-offs to define low serum zinc concentrations in healthy 1-19 year old Indian children and adolescents

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Zinc (Zn) deficiency, which is linked to stunting and a higher risk of morbidity, is thought to be widely prevalent in India, which warrants interventional policies to supplement its intake. This may not be true, as the biomarker used to define Zn deficiency at the population level is the serum zinc concentration (SZC), which could be region or country-specific. At present, age-, sex- and fasting status-specific SZC cut-offs have been derived by the International Zinc Nutrition Consultative Group (IZiNCG), based on the 2•5th centiles of the SZC distributions of healthy populations from a dated National Health and Nutrition Examination Survey (NHANES-II) survey (1).  This is a ‘one size fits all’ biomarker which is globally applied (2, 3). However, even though the SZC is tightly regulated, it can change from 3-15% (mean 9%) when Zn intakes change two-fold in children (4), by about 22% in daily circadian excursions (5), and by 11% during long-term dietary adaptation to a vegetarian diet (6, 7).  It is then possible that in a healthy population with lower, but still adequate, habitual Zn intakes, the left shifted SZC distribution can result in 10-15% lower SZC cut-offs, which while entirely appropriate for such populations, can substantially lower the estimated prevalence of Zn deficiency in these settings. Therefore, in Low- and Middle-Income Countries (LMICs), a re-examination of the existing IZINCG cut-offs from SZC distributions of ‘healthy’ populations is warranted, since a falsely high Zn deficiency will result in unnecessary interventional policies. While such data are scarce in LMICs, in 2019, a nationally representative, quality-controlled survey, the Comprehensive National Nutrition Survey (CNNS), measured SZCs of Indian children and adolescents aged 0–19 years along with plethora of socio-demographic, anthropometric and biomarkers indicators (8, 9). This offered an opportunity for a formal re-examination of the SZC in carefully selected, healthy children from this survey to define age-, sex- and fasting status-specific cut-offs (2·5th centile); these were then used to compared the prevalence of zinc deficiency Zn deficiency in the entire CNNS population with estimates based on IZINCG cut-offs.

What did we find in the study

In our manuscript 10 entitled “Reference cut-offs to define low serum zinc concentrations in healthy 1-19 year old Indian children and adolescents”, we reported the, age-, sex-, and fasting status-specific SZC cut-offs from a representative, healthy, Indian children, aged 1-19 years (10). Healthy children were stringently defined in the present study, by excluding stunted and obese children, those with CRP >5mg/L, anemia, hypoalbuminemia, recent diarrhea, elevated HbA1C and a history of smoking as well as those belonging to the lower 3 wealth quintiles (analytical sample 1). In a sensitivity analysis, we further excluded, children with underweight and thin children, as well as those in households with poor water, sanitation and hygiene (analytical sample 2), or only including those belonging to the richest wealth quintile (analytical sample 3).  The 2.5th centile of SZC distribution for each age, sex and fasting status were then derived as the reference cutoff to indicate zinc deficiency, and these values are comparable across all the analytical samples.  The SZC cut-offs for Zn deficiency of the present study were lower by 10–18 µg/dL than the IZiNCG cut-offs, more so in adolescents. The prevalence of Zn deficiency was 2·7 to 5·5 times lower than that estimated by IZINCG cut-offs in different age- and sex-groups, the difference being highest in adolescents. In all states, Zn deficiency was not a serious public health problem, as its prevalence was always less than 20%.

This study has important implications: First, this study shows that Zn deficiency in Indian children is not widely prevalent as previously thought. The follow-on implication is that there is no need for universal Zn supplementation policies, and this concurs with evidence from previous trials of Zn supplementation that failed to prevent stunting in Indian children. Second, this study suggests that there is a need for re-examining the applicability of the ‘one size fits all’ definition of SZC cut-offs for different regions and populations. Third, these contemporary age-, sex- and fasting status-specific SZC cut-offs for 1–19 year old children and adolescents are suitable for national use in India, and indeed, for any LMIC with similar Zn intakes and social conditions.

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