Main Findings
This randomised controlled trial, comparing two pragmatic doses of
intravenous iron for treating ID in pregnancy, demonstrated 500 mg of
intravenous FCM was not equivalent to the 1000 mg dose. To achieve
initial and sustained correction of ID, participants in the lower dose
arm received more than twice the rate of repeat infusions compared to
the higher dose arm. Participants in the higher dose arm had
significantly higher ferritin levels up to 6 months postpartum, coupled
with a significantly greater increase in haemoglobin, reflecting
favourable iron availability and utilisation. While participants in the
lower arm also remained iron replete for the duration of the study, this
occurred under close monitoring with appropriate treatment administered
where declining iron stores were observed, as per our study protocol.
Given the rate of persistent ID observed in this group, we would suggest
that continued monitoring after infusion of 500g IVI is essential to
ensure adequate iron stores are accomplished in pregnancy.
The ability of IVI to improve antenatal and postpartum haematological
outcomes in pregnant women has been demonstrated in several previous
randomised controlled trials.(16, 21-23) These studies have used a range
of IVI dosing strategies to achieve vital short-term iron repletion and
haemoglobin restoration in anaemic women, using doses ranging from 400mg
to 1000mg.(16) The current study, is to our knowledge, the first
prospective RCT to compare intravenous iron doses for successful and
persistent correction of ID in pregnancy and over the first postpartum
year. Recent concerns have been raised whether IVI prescribing practice
for women of reproductive age is appropriate and cost effective.(24) Our
data suggest administration of 1000mg can significantly reduce the need
for repeat IVI, thereby improving patient health while reducing clinical
load and cost. The importance has become even more apparent during the
COVID-19 pandemic. Globally, antenatal services were disrupted and fear
of contracting the virus led to a decrease of antenatal visits.(29)
Australia saw a 8.3% reduction in face-to-face antenatal care services
for 2020 compared with 2019.(30) However, it is imperative that
clinicians and patient do no become complacent after IVI administration,
given over 20% of participants in both arms required additional
infusions at 12 months postpartum to sustain satisfactory iron stores.
ID and IDA are significant medical
conditions with serious consequences for maternal and fetal outcomes.(3,
7, 8, 13) Our study found no differences in pregnancy, birth- or infant
related outcomes between the 500mg and 1000mg IVI arms, with the
exception of PPROM, which occurred only in participants receiving
1000mg. Although the pathways leading to PPROM are complex and
multifaceted, increased oxidative stress appears to play a role. It is
possible that first or second trimester IDA itself, or exposure to
increased iron, or differences in ferritin levels after IVI, may have
contributed to oxidative stress leading to PPROM in the current
study.(31) However, this must be interpreted with caution given the
present study was not powered to examine this outcome.
Pregnancy represents a time of increased iron demand.(4) The prevalence
of ID is high, and progression from ID to IDA common.(20) Ensuring iron
stores are optimal throughout pregnancy can avoid any adverse
physiological and psychological outcomes associated with ID and IDA
.(20, 32) Further, should women experience a PPH, which remains the
leading cause of maternal morbidity and mortality, optimal iron stores
will boost Hb, which can provide a buffer to help protect against
serious anaemia.(33) Although routine in our obstetrics unit, screening
for ID is rarely incorporated into routine antenatal care.(34) Recent
obstetrics guidelines on the management of ID and obstetric patient
blood management guidelines have emphasised the need for more
attentiveness and potential actions to detect and treat ID in
pregnancy.(19, 20) Despite this, IVI therapy has continued to be met
with fear, scepticism, and criticism, resulting in large uptake
variations. (16, 22, 23, 35-38)