Hepcidin-guided screen-and-treat interventions against iron-deficiency anaemia in pregnancy: a randomised controlled trial in The Gambia

Abstract

Background WHO recommends daily iron supplementation for pregnant women, but adherence is poor because of side-effects, effectiveness is low, and there are concerns about possible harm. The iron-regulatory hormone hepcidin can signal when an individual is ready-and-safe to receive iron. We tested whether a hepcidin-guided screen-and-treat approach to combat iron-deficiency anaemia could achieve equivalent efficacy to universal administration, but with lower exposure to iron.Methods We did a three-arm, randomised, double-blind, non-inferiority trial in 19 rural communities in the Jarra West and Kiang East districts of The Gambia. Eligible participants were pregnant women aged 18-45 years at between 14 weeks and 22 weeks of gestation. We randomly allocated women to either WHO's recommended regimen (ie, a daily UN University, UNICEF, and WHO international multiple-micronutrient preparation [UNIMMAP] containing 60 mg iron), a 60 mg screen-and-treat approach (ie, daily UNIMMAP containing 60 mg iron for 7 days if weekly hepcidin was <2•5 µg/L or UNIMMAP without iron if hepcidin was ≥2•5 µg/L), or a 30 mg screen-and-treat approach (ie, daily UNIMMAP containing 30 mg iron for 7 days if weekly hepcidin was <2•5 µg/L or UNIMMAP without iron if hepcidin was ≥2•5 µg/L). We used a block design stratified by amount of haemoglobin at enrolment (above and below the median amount of haemoglobin on every enrolment day) and stage of gestation (14-18 weeks vs 19-22 weeks). Participants and investigators were unaware of the random allocation. The primary outcome was the amount of haemoglobin at day 84 and was measured as the difference in haemoglobin in each screen-and-treat group compared with WHO's recommended regimen; the non-inferiority margin was set at -5•0 g/L. The primary outcome was assessed in the per-protocol population, which comprised all women who completed the study. This trial is registered with the ISRCTN registry, number ISRCTN21955180.

Iron Deficiency and Iron Deficiency Anemia: Implications and Impact in Pregnancy, Fetal Development, and Early Childhood Parameters

“…An alternate approach to selective supplementation has been proposed using hepcidin as the indicator of early ID and a need for therapy. A recent report comparing a hepcidin-guided supplementation approach to a universal prophylaxis approach showed similar patient outcomes in both groups [71]. This study was performed in a high-risk population in Gambia, and this approach may have different outcomes in other venues.…”

“…Measurement of hepcidin for clinical purposes is not widely available at present but may become so in the next few years. Hepcidin appears to be an effective indicator of ID in pregnancy [69,70], but its specific role in management remains to be determined [71].…”

“…In a review of published reports, routine iron supplementation decreased the frequency of anemia at term by 73% and the frequency of IDA by 67% [97,98]. Table 4 summarizes results from a Cochrane Database systematic review comparing outcomes of daily iron supplementation to placebo or no iron supplementation [71,96]. Table 4.…”

First Trimester Ferritin Is Superior over Soluble Transferrin Receptor and Hepcidin in Predicting Anemia in the Third Trimester: Result from a Cohort Study in Indonesia

“…This had practically eliminated the two biomarkers as predictor for anemia. In a clinical trial, it was concluded that hepcidin-guided screen-and-treat approaches had no advantages over the WHO's recommended regimen in terms of adherence, side-effects, or safety outcomes [ 27 ]. In a review, it was concluded that hepcidin is a regulator of iron homeostasis and may be a useful biomarker to determine iron bioavailability in pregnancy, but there was no conclusive result for prediction of anemia [ 8 ].…”

Iron deficiency anaemia in pregnancy: A contemporary review

“…Newer laboratory indices of iron status such as hepcidin may ultimately help to guide iron therapy, but a recent study found no benefit of using a hepcidinguided screen-and-treat approach when compared with the WHO's recommended regimen. 98 Over a 5-year period, the Primary prevention of maternal ANaemia to avoid preterm Delivery and other Adverse outcomes (PANDA) 99 research programme, recently funded by the National Institute for Health Research (NIHR), will attempt to address some of the research uncertainties highlighted in this review. Initial work will include identifying barriers and enablers to iron supplementation, development of a behavioural intervention to promote compliance and a feasibility randomised controlled trial to identify the optimal dosing schedule for oral iron.…”