Abstract
Background
The persistent high prevalence of anaemia among Indian women of reproductive age (WRA) despite aggressive long-term iron supplementation could be related to over-diagnosis from an inappropriately high haemoglobin (Hb) diagnostic cut-off. To develop an appropriate cut-off for Indian WRA, we hypothesized that during iron-folic acid (IFA) supplementation to a mixed (anaemic/non-anaemic) WRA population, the positive slope of the Hb-plasma ferritin (PF) response in anaemic women would inflect into a plateau (zero-response) as a non-anaemic status is reached. The 2.5th percentile of the Hb distribution at this inflection point will be the diagnostic Hb cut-off for iron-responsive anaemia.
Method
A hierarchical mixed effects model, with a polynomial mean and variance model to account for intraclass correlation due to repeated measures, was used to estimate the response curve of Hb to PF, or body iron stores, in anaemic and non-anaemic WRA (without inflammation), who were receiving a 90-day IFA supplementation.
Results
The Hb response curve at low PF values showed a steep increase, which inflected into a plateau at a PF of 10.1 µg/L and attained a steady state at a PF of 20.6 µg/L. The Hb distribution at the inflection was a normal probability distribution, with a mean of 12.3 g/dL. The 2.5th percentile value of this distribution, or the putative diagnostic Hb cut-off for anaemia, was 10.8 g/dL (~11 g/dL).
Conclusion
The derived Hb cut-off is lower than the current adult values of 12 g/dL and could partly explain the persistently high prevalence of anaemia.
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Data availability
The datasets generated and analysed during the current study are available from the corresponding author on reasonable request.
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Funding
This secondary analysis was not funded. The human data came from a study that was funded by the Indian Council of Medical Research (ICMR), Government of India to BK, in turn nested in a larger study supported by a grant from the Systems Biology Research Initiative from the International Crops Research Institute for the Semi-Arid Tropics (ICRISAT) to RKV. The ICRISAT funding contributed to some activities related to data collection in the present study.
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SG and AVK wrote the first draft of the paper. All authors commented and edited draft versions and then approved the final version of the paper. SG, HSS, AVK and BK had primary responsibility for final content.
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No separate ethical approval was required for this secondary analysis. The original study was nested within a trial (CTRI No: 2019/02/017806, http://ctri.nic.in/) to evaluate the effect of IFA supplementation on the gut microbiome and Hb. The original study was approved by the ethics committee of ICMR-National Institute of Nutrition (IEC: 06/II/2018). Prior informed consent from the participants and approval of the college authorities was taken for the study participation.
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Ghosh, S., Palika, R., Dasi, T. et al. Haemoglobin diagnostic cut-offs for anaemia in Indian women of reproductive age. Eur J Clin Nutr 77, 966–971 (2023). https://doi.org/10.1038/s41430-023-01308-5
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DOI: https://doi.org/10.1038/s41430-023-01308-5