High-dose iron infusion corrects deficiency, maintains iron stores in pregnancy

A single 1,000-mg infusion of ferric carboxymaltose (FCM) effectively resolves iron deficiency in pregnancy, preserving iron stores and reducing the need for repeat infusions as compared with the lower FCM dose, as shown in a study.

“This randomised controlled trial, comparing two pragmatic doses of intravenous iron for treating iron deficiency in pregnancy, demonstrated [that] 500 mg of intravenous FCM was not equivalent to the 1,000-mg dose,” the investigators said.

“To achieve initial and sustained correction of iron deficiency, participants in the lower-dose arm received more than twice the rate of repeat infusions compared to the higher-dose arm… [T]he 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 utilization,” they added.

The study population included 278 pregnant women (median age 27 years) with iron deficiency, among whom 152 were in the 500-mg arm and 126 were in the 1,000-mg arm, with treatment administered in either the second or third trimester. The average gestational age at enrolment was 32 weeks, with about half of the participants being anaemic.

At 4 weeks after infusion, 26 out of 73 (36 percent) participants in the 500-mg arm required a repeat infusion as opposed to only five out of 67 (8 percent) in the 1,000-mg arm. Those who received the lower dose were given twice the repeat infusion rate prior to delivery, after delivery, and overall (0.81 vs 0.40; rate ratio, 2.05, 95 percent confidence interval [CI], 1.45–2.91; p<0.001).

Ferritin levels were significantly higher in the 1,000-mg arm for up to 6 months postpartum, as were serum iron and transferrin saturation at 4 weeks postinfusion.

“Importantly, transferrin saturations remained within normal limits in both groups, safeguarding the foetus from unnecessary transplacental iron transfer. Between-group differences had disappeared for all markers of iron status by 12 months postpartum,” according to the investigators.

None of the women developed serious adverse events. Minor adverse events were observed in 3 percent of participants during the first infusion, with the most common being dizziness, hypotension, nausea, and chest tightness. There were no adverse events reported during subsequent infusions.

“The outcomes of this trial suggest that successful treatment of iron deficiency can occur with a single 1,000-mg dose, with no adverse outcomes for antenatal progression, neonatal, or child outcomes. This represents an effective treatment modality to shield from the detrimental short- and potential long-term impacts of iron deficiency and iron-deficiency anaemia,” the investigators pointed out.

“Due to the close monitoring provided in this study, women with declining iron stores were able to receive subsequent treatment. Given the higher rate of persistent iron deficiency observed in the low-dose arm, we would suggest that continued monitoring after infusion of 500-g intravenous iron is essential to ensure adequate iron stores are accomplished in pregnancy,” they added.

The investigators also noted that ensuring optimal iron stores throughout pregnancy can put the women at lower risk of any adverse physiological and psychological outcomes associated with iron deficiency and iron-deficiency anaemia. [Br J Haematol 2020;188:819-830; Acta Obstet Gynecol Scand 2016;95:555-564)

“Further, should women experience postpartum haemorrhage, which remains the leading cause of maternal morbidity and mortality, optimal iron stores will boost haemoglobin, which can provide a buffer to help protect against serious anaemia,” they said. [BJA Educ 2022;22:238-244]

More studies are needed to optimize intravenous iron dose, which may be particularly relevant to those countries where 1,000 mg is not currently routinely used.