Randomised controlled trial of daily versus alternate day oral iron for the treatment of anaemia in pregnancy

Congratulations to Professor Fionnuala McAuliffe and all those involved from the UCD School of Medicine, UCD Perinatal Research Centre and National Maternity Hospital, Dublin, on their recently published research titled, ‘IronMother- Protocol for a Randomised Controlled Trial of Daily versus Alternate Day Ferrous Fumarate for the treatment of Iron Deficiency Anaemia in Pregnancy’.

The team hypothesise that alternate day iron in pregnancy will be as effective as daily iron for the treatment of iron deficiency anaemia.

Highlights:

• Randomized controlled trial of daily versus alternate day oral iron for the treatment of anaemia in pregnancy
• Inclusion criteria: singleton pregnancies with haemoglobin <10.5g/dL and ferritin <30μg/L between 14+0 and 34+0 weeks gestation
• Non-inferiority study with a non-inferior margin of -0.4g/dL haemoglobin difference between the two arms
• Secondary outcomes include compliance, tolerance, serum ferritin, haemoglobin at term

Abstract

Objective

Iron deficiency anaemia (IDA) is the commonest haematological problem in pregnancy and has implications for maternal, fetal, and childhood health. Treatment, despite being inexpensive and readily available, remains challenging with issues relating to compliance, tolerability, and effectiveness. There is a lack of consensus regarding the optimal dosing of oral iron replacement in pregnancy. Emerging evidence from non-pregnant populations suggest that alternate day dosing may be as effective.

Methods

We propose a phase IV open label randomised controlled non-inferiority trial of daily versus alternate day ferrous fumarate for a 4-week period for the treatment of confirmed iron deficiency anaemia in pregnancy. Our study population comprises singleton pregnancies between 14+0- and 34+0-weeks’ gestation with a haemoglobin (Hb) of <10.5g/dL and a ferritin of <30ug/L. The intervention is alternate day ferrous fumarate 305mg (100mg elemental iron) and the comparator is daily ferrous fumarate 305mg. The primary endpoint, change in Hb from randomisation to week 4, will be analysed by linear regression, adjusting for baseline Hb level. Analysis will be conducted by intention-to-treat analysis with per protocol sensitivity analysis. Sample size was calculated on the assumption of no difference between primary endpoint means, a Type 1 error rate of 0.025, a power of 90%, a standard deviation of 0.83g/dL and a non-inferiority margin of -0.4g/dL. Under these assumptions, 92 subjects per treatment arm would be required to test for non-inferiority.

Conclusion

We hypothesise that alternate day iron in pregnancy will be as effective as daily iron for the treatment of iron deficiency anaemia.

Read the full paper here.