Trial: IV, Oral Iron Provide Similar Effect on Fatigue Despite Different Lab Parameters

Miha Lučovnik, MD, PhD
Credit: Association for Perinatal Medicine of Slovenia

A new trial of women with postpartum maternal fatigue suggests treatment adherence may be more important than choice of treatment when it comes to iron supplementation.

Results of the trial, which compared intravenous ferric carboxymaltose, intravenous ferric derisomaltose, and oral ferrous sulphate, concluded had comparable effects on maternal fatigue at 6 weeks postpartum, even though the intravenous groups exhibited improved laboratory parameters at end of study.¹

“Our results confirm that effective iron therapy, regardless of the medication type and route of administration, effectively corrects anemia and is associated with a reduction in maternal fatigue postpartum,” wrote investigators.¹

With the condition impacting an estimated 37% of pregnant women and 30% of women 15–49 years of age worldwide, management of iron defieincy anemia can be a significant contributor to realizing desired outcomes and quality of life.² Citing rising popularity of intravenous iron formulations and a lack of randomized controlled trials comparing intravenous formulations against oral alternatives, a team from Ljubljana University Medical Centre in Slovenia designed a single-center, open-label, randomized controlled trial to compare the effects of postpartum anemia treatment on maternal fatigue with intravenous ferric carboxymaltose, intravenous ferric derisomaltose, and oral ferrous sulfate.¹

Conducted at the Ljubljana University Medical Centre’s Department of Perinatology, the trial enrolled 300 women with hemoglobin levels less than 100 g/L within 48 hours postpartum and randomized them in a 1:1:1 ratio to the aforementioned treatments. Of note, major exclusion criteria included having a history of anemia due to known causes other than iron deficiency or blood loss, renal or hepatic impairment, and preexisting depression. Per trial protocol, intravenous iron was given in 1 or 2 doses and ferrous sulfate was given as 2, 80 mg tablets once daily.¹

The primary outcome of interest for the trial was change in maternal fatigue at 6 weeks. For the purpose of analysis, maternal fatigue was measured using the Multidimensional Fatigue Inventory (MFI). Secondary outcomes of interest included changes in hemoglobin, ferritin, and transferrin saturation levels.¹

Of the 300 who underwent randomization, 35 did not have primary outcome data, 16 failed to attend their 6-week study visit, and 19 failed to complete the MFI questionnaire at 6 weeks despite attending the visit. Overall, 39 women were excluded from the primary analysis.¹

Upon analysis, results suggested there was no statistically significant difference in MFI at 6 weeks postpartum between the groups, with median MFI scores of 38 (Interquartile Range [IQR], 29-47) for intravenous ferric carboxymaltose, 34 (IQR 26–42) for intravenous ferric derisomaltose, and 36 (IQR 25–47) for ferrous sulfate (P = .26). Analysis of secondary outcomes revealed those receiving oral iron therapy had reduced levels of hemoglobin (135 g/L [131–139] vs. 134 g/L [129–139] vs 131 g/L [125–137]; P = .008), ferritin (273 µg/L[198–377] vs. 187 µg/L [155–246] vs. 24 µg/L [17–37]; P <.001), and transferrin saturation (34% [28–38] vs 30% [23–37] vs 24% [17–37]; P <.001) than those receiving ferric carboxymaltose or ferric derisomaltose.¹

“The lack of effects of intravenous vs. oral iron treatments on maternal fatigue in our study could be explained by numerous factors that impact the sense of fatigue besides anemia,” investigators wrote.¹ “Sleep deprivation, pain, and postpartum mood disorders have all been associated with maternal fatigue and were not accounted for in the present study.”

Investigators called attention to multiple limitations within their trial to consider before overinterpretation of the results. These limitations included, but were not limited to, the open-label design of the trial, lack of generalizability as a single-center study, and lack of long-term follow-up.¹

References:

1. _{^{Bombač Tavčar L, Hrobat H, Gornik L, et al. Maternal Fatigue after Postpartum Anemia Treatment with Intravenous Ferric Carboxymaltose vs. Intravenous Ferric Derisomaltose vs. Oral Ferrous Sulphate: A Randomized Controlled Trial. J Clin Med. 2024;13(3):758. Published 2024 Jan 28. doi:10.3390/jcm13030758}}
2. _{^{World Health Organization. Anaemia. World Health Organization. May 1, 2023. Accessed February 12, 2024. https://www.who.int/news-room/fact-sheets/detail/anaemia.}}