Introduction
Iron deficiency (ID) is the most common nutritional disorder worldwide, listed on the World Health Organisation’s (WHO) top 5 mental and physical disabilities.(1) ID is the leading underlying cause of anaemia, affecting approximately 45% of women of childbearing age in developed countries and up to 80% in lower resource settings.(2) As iron is necessary for many biological functions (3, 4) pregnant women with ID or iron deficiency anaemia (IDA) frequently suffer from cardiovascular problems, reduced physical activity, impaired cognitive performance, reduced immune function, fatigue and depressive episodes.(3, 5, 6) These women are at a higher risk of pregnancy complications, stillbirth, postpartum haemorrhage (PPH), peri-partum allogeneic red blood cell transfusion and death.(7-11) Infants of mothers with ID are at increased risk of preterm birth, growth restriction, low birth weight, perinatal death, low Apgar scores, neonatal infection, postnatal ID and impaired cognitive development.(4, 7, 9, 12) In recognition of these adverse outcomes, WHO targets 50% reduction of IDA in women of reproductive age by 2025.(13)
Women with inadequate iron stores are ill-prepared for the increased iron demand of pregnancy,(14) rendering up to 47% of pregnant women iron deficient.(15) ID is detectable, preventable and treatable,(3) with oral iron considered first-line treatment. Intravenous iron (IVI) is recommended when women are non-responsive, non-tolerant or non-compliant to oral iron, when ID/IDA is diagnosed late in pregnancy, or in women with severe anaemia or at risk of haemorrhage.(16-20)
Randomised controlled trials (RCTs) in pregnant women with IDA have demonstrated superior haematological outcomes after IVI compared with oral iron.(16, 21-23) Doses of IVI in RCTs and observational studies have ranged from 400mg to 1000mg, with all showing improvements in iron status without serious safety concerns.(16, 21-23) Higher doses come at a larger cost, and no data exist comparing adverse effects or the potential for iron excess with different doses.(24) In addition, accessibility to IVI and approved dosing schemes differ between countries, creating geographic, cultural and social barriers.(4, 25) Clinicians lack high quality data on the optimal dose to adequately improve and sustain iron status, and sufficiently protect against adverse obstetric, neonatal or mental health sequelae. We therefore conducted a RCT comparing two doses of IVI (500mg and 1000mg) using an equivalence design.