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.