Normal range and predictors of serum erythroferrone in infants.

"Competing interests The authors declare no competing interests."

"Funding This secondary study was funded by Wallenberg Centre for Molecular Medicine, The Västerbotten County Council and Swedish Research Council (ref. 2019-01005). Open access funding provided by Umea University."

"The first set of samples included sera from Swedish normal birth weight (NBW), breastfed infants, originally included as a reference population in the LIME study (Swedish acronym), a randomized controlled infant formula intervention trial. Briefly, the breastfed reference infants were not assigned to any intervention and the original inclusion criteria were birth weight 2500–4500 g, gestational age at birth ≥37 weeks, absence of chronic illness and neonatal diagnosis likely to affect any iron status outcome, no previous blood transfusion or iron supplementation, and exclusive breastfeeding at the inclusion with the intention to exclusively breastfeed until 6 months of age. In the present study, the first 45 breastfed infants included between 2014 and 2017 in the LIME study were analyzed for ERFE as a healthy NBW control group to the LBW at-risk group with regards to iron deficiency, and as a cohort on which to base reference values for ERFE serum concentrations. The LIME study was approved by the Regional Ethical Review Board in Umeå and registered at clinicaltrials.gov (NCT02103205). The second set of samples included stored serum from Swedish marginally LBW infants (2000–2500 g), previously included in a randomized controlled trial of iron supplements, the JOHN study (Swedish acronym). Briefly, 285 LBW infants were included between 2004 and 2007 and randomized to receive placebo (n = 95), or iron supplementation at doses 1 mg (n = 95) or 2 mg/kg/day (n = 95) from 6 weeks to 6 months of age. Inclusion criteria were birth weight 2000–2500 g, no chronic diseases diagnosed at inclusion, and no previous blood transfusion or iron supplementation. Exclusion criteria in the present analyses were infants randomized to 1 mg/kg/day (n = 95), hematological disorder diagnosed during the study (n = 1), drop out from original study before 6 months of age (n = 17), poor compliance to the intervention (n = 21), infants unblinded from the randomized trial due to iron deficiency anemia (n = 15). Remaining LBW infants, randomized to placebo (LBW/no iron, n = 78) and 2 mg/kg/day (LBW/iron, n = 58), were analyzed for ERFE in the present secondary study. The JOHN study was approved by the Ethical Review Board in Umeå and registered at clinicaltrials.gov (NCT00558454). As previously published from the JOHN study, the placebo treated group had a high prevalence of ID at 6 months of age and thereby represents a high-risk population for iron depletion, while the iron supplemented LBW infants had an overall low ID prevalence."