Evaluating Hepcidin and sTfR in Pregnancy: Impact of Different Iron Supplementation Regimens
S. HAYNES 1, N.ROY 2, A. ARMITAGE3, A. DRAKESMITH3, J.HIRST1, D. CHURCHILL4, S.STANWORTH2
1. NUFFIELD DEPARTMENT OF WOMEN'S AND REPRODUCTIVE HEALTH, THE UNIVERSITY OF OXFORD
2. THE RADCLIFFE DEPARTMENT OF MEDICINE, THE UNIVERSITY OF OXFORD
3. WEATHERALL INSTITUTE FOR MOLECULAR MEDICINE, THE UNIVERSITY OF OXFORD AND JOHN RADCLIFFE HOSPITAL
4. THE ROYAL WOLVERHAMPTON NHS TRUST
Background:
•Anaemia affects 23–30% of pregnancies in the UK1.
•Iron deficiency is the primary cause2.
•The optimal dose and role of prophylactic oral iron in pregnancy remain unclear3,4.
•Hepcidin regulates iron metabolism and xx absorption.
•Soluble transferrin receptor (sTfR) reflects xxxxxx iron demand for red blood cell production.
Aim:
To evaluate whether different prophylactic iron supplementation frequencies (daily, alternate-day, 3x/week) affect iron biomarkers (hepcidin and sTfR) during pregnancy in non-anaemic women.
Methods:
Study Design
•A secondary analysis of the PANDA program dose-finding trial of 3 differing regimens of iron supplementation in non-anaemic pregnant women5.
•135 non-anaemic pregnant people randomised.
Treatment Groups (Ferrous Sulphate 200mg)
•Daily (n=45)
•Alternate-day (n=47)
•3x weekly (n=43)
Blood samples collected at:
•Baseline (9–13 weeks gestation)
•Follow-up (28–32 weeks gestation)
Hepcidin and sTfR Enzyme-Linked Immunosorbent Assays (ELISAs) performed.
Statistical Analysis
•Log-transformation
•Paired t-test (within-group)
•ANOVAs (between-group)
Results:
Haemoglobin & Ferritin
•Significant ↓ in Hb and ferritin within all groups (p<0.0001).
•No significant difference between groups.
•
sTfR
•↑ significantly in 3× weekly (p=0.0003) and alternate-day (p=0.0041).
•No significant ↑ in daily group (p=0.1223).
•↑ sTfR = ↑ iron demand.
•Daily dosing better meets iron demand.
Hepcidin
•↓ significantly in all groups (p<0.0001); no group differences (p=0.318).
•Reflects expected suppression in pregnancy.
•Suppression is consistent across regimens, unlike in non-pregnant populations6.
Limitations
•Sample Size.
•Variability in ELISA performance.
•No CRP levels, unable to control for inflammation.
Conclusions:
1.Only the daily group met their iron demands.
2.Hepcidin findings challenge the rationale for alternate-day dosing during pregnancy.
3.sTfR may be more sensitive than Hb & ferritin in detecting iron status during pregnancy.
Future Directions:
1.CRP Levels to Control for Inflammation.
2.Explore Associations Between Biomarkers & Side Effects.
3.PANDA Placebo RCT Now Recruiting.
Acknowledgements:
Serum samples were collected as part of the PANDA Programme, supported by DC, SS & NR. SH performed ELISAs under the supervision of AA & AD. SH is a PhD student funded by the Rhodes Scholarship.
No conflicts of interest declared.
References:
1.Churchill, D., Ali, H., Moussa, M., Donohue, C., Pavord, S., Robinson, S. E., Cheshire, K., Wilson, P., Grant-Casey, J., & Stanworth, S. J. (2022). Maternal iron deficiency anaemia in pregnancy: Lessons from a national audit. British Journal of Haematology, 199(2), 277–284. https://doi.org/10.1111/bjh.18391
2.Davidson, E. M., Scoullar, M. J. L., Peach, E., Morgan, C. J., Melepia, P., Opi, D. H., Supsup, H., Hezeri, P., Philip, W., Kabiu, D., Tokmun, K., Suruka, R., Fidelis, R., Elijah, A., Siba, P. M., Pomat, W., Kombut, B., Robinson, L. J., Crabb, B. S., … Fowkes, F. J. I. (2023). Quantifying differences in iron deficiency-attributable anemia during pregnancy and postpartum. Cell Reports Medicine, 4(7), 101097. https://doi.org/10.1016/j.xcrm.2023.101097
3.Fisher, A. L., & Nemeth, E. (2017). Iron homeostasis during pregnancy†‡. The American Journal of Clinical Nutrition, 106, 1567S-1574S. https://doi.org/10.3945/ajcn.117.155812
4.Rusch, J. A., van der Westhuizen, D. J., Gill, R. S., & Louw, V. J. (2023). Diagnosing iron deficiency: Controversies and novel metrics. Best Practice & Research Clinical Anaesthesiology, 37(4), 451–467. https://doi.org/10.1016/j.bpa.2023.11.001
5.Stanworth, S. J., Churchill, D., Sweity, S., Holmes, T., Hudson, C., Brown, R., Lax, S. J., Murray, J., Spiby, H., Roy, N., Farmer, A., Gale, C., Crayton, E., Lorencatto, F., Griffiths, J., Mullings, J., Last, S., Knight, M., & On behalf of the PANDA Collaborator Group. (2024). The impact of different doses of oral iron supplementation during pregnancy: A pilot randomized trial. Blood Advances, 8(21), 5683–5694.
https://doi.org/10.1182/bloodadvances.20240134086.Auerbach, M. (2023). Optimizing diagnosis and treatment of iron deficiency and iron deficiency anemia in women and girls of reproductive age: Clinical opinion. International Journal of Gynecology & Obstetrics, 162(S2), 68–77. https://doi.org/10.1002/ijgo.14949
