Treating iron-deficiency anaemia (IDA) in pregnancy with intravenous (IV) iron results in better maternal and neonatal outcomes when compared with oral iron, according to a meta-analysis.
Pooled data from 29 randomized controlled trials involving 11,771 participants showed that maternal haemoglobin levels at delivery were significantly higher with IV vs oral iron therapy (weighted mean difference [WMD], 0.59 g/dL, 95 percent confidence interval [CI], 0.31–0.87; I2=95.2 percent; p<0.001), as were maternal ferritin levels (WMD, 50.93 ng/mL, 95 percent CI, 33.56–68.29; I2 values=96.4 percent; p<0.001). [JAMA Netw Open 2026;9:e2630657]
Compared with oral iron, IV iron therapy was also associated with a 37-percent lower risk of blood transfusion during delivery hospitalization (relative risk [RR], 0.63, 95 percent CI, 0.49–0.82; I2=1.6 percent; p<0.001) and higher neonatal ferritin levels at delivery (WMD, 21.38 ng/mL, 95 percent CI, 5.50–37.25; I2=63.9 percent; p=0.01).
The effect of IV iron therapy was notably higher among pregnant women with a mean pretreatment haemoglobin of ≤9 g/dL. This was true for haemoglobin levels (WMD, 0.70 g/dL, 95 percent CI, 0.19–1.21) and the risk of blood transfusion (RR, 0.58, 95 percent CI, 0.45–0.76) at delivery.
There were no serious adverse events reported. IV iron therapy was associated with a 43-percent lower risk of mild adverse effects (RR, 0.56, 95 percent CI, 0.41–0.76), driven by a significant reduction in mild gastrointestinal adverse effects (RR, 0.11, 95 percent CI, 0.05–0.23) compared with oral iron therapy.
Of the studies included in the meta-analysis, 21 were conducted in developing countries, and eight were conducted in developed countries. Ferrous sulfate (n=19) was the most common oral formulation, and iron sucrose (n=17) was the most common IV formulation.
Sixteen studies met the quality threshold and were of high quality, while 13 were deemed to be of lower quality. The mean pretreatment haemoglobin level was ≤9 g/dL in 15 studies and >9 g/dL in 14 studies.
Greater role for IV iron therapy
First author Ms Sarai Sales from Brown University, Providence, Rhode Island, US, and colleagues discussed the clinical implications of their findings.
In light of the maternal outcomes, “the increase in maternal haemoglobin and ferritin levels during delivery hospitalization should also reduce the risk of subsequent postpartum anaemia after childbirth,” they noted.
Fewer blood transfusions also matter for two reasons, Sales and colleagues continued. First, it lowers severe maternal morbidity scores based on the Centers for Disease Control and Prevention’s metrics. Second, it reduces “exposure to foreign red blood cell antigens, which can lead to maternal alloimmunization and potentially affect future pregnancies through haemolytic disease of the foetus and newborn,” they explained.
“From a neonatal perspective … the difference in neonatal ferritin level at childbirth may have long-term health implications because lower ferritin levels at delivery have been associated with impaired childhood growth and neurodevelopment,” Sales and colleagues pointed out.
The authors acknowledged substantial heterogeneity across the studies, and the funnel plot and Egger test for the primary outcome suggested publication bias. Nevertheless, the findings “support a greater role for IV iron therapy in clinical guidelines recommending optimal treatment of IDA in pregnancy, particularly among those with severe anaemia,” they said.
Paradigm changing
In an accompanying editorial, Drs Michael Auerbach and Helain Landy from Georgetown University School of Medicine, Washington, DC, US, echoed Sales and colleagues, noting that the findings from the meta-analysis challenge the American College of Obstetricians and Gynecologists (ACOG)’s recommendation of oral iron as first-line therapy for the treatment of IDA in pregnancy and reserving IV iron for those who are unresponsive to or intolerant of oral iron. [JAMA Netw Open 2026;9:e2630586]
“The fact that IV iron was associated with significant reductions in perinatal blood transfusion compared with oral iron, with improvement in maternal and neonatal haematologic parameters, presents an opportunity for ACOG to reconsider their recommendations,” they said.
Nevertheless, Auerbach and Landy acknowledged the challenges in changing the current treatment paradigm and discussed why transitioning from traditional oral iron to IV iron remains difficult.
“In making recommendations to its more than 62,000 members practicing in urban, suburban, and rural areas, ACOG relies on evidence-based literature as well as consideration of clinical feasibility. Challenges in providing IV iron infusions include supply and production shortages, insurance and financial barriers, and medical criteria,” they said.
“But perhaps more important are issues of clinician hesitancy related to historical concerns about serious adverse events and high rates of infusion reactions with older IV formulations,” they added.
Auerbach and Landy noted that newer formulations contain carbohydrate cores binding elemental iron more tightly to allow large complete replacement doses in a short, single visit. “These improve safety and efficacy while adding convenience for both patients and caregivers [and] could not be better corroborated by the results of the meta-analysis, which reports not only superior haematologic outcomes with IV iron but the virtual absence of serious adverse events,” they said.
Additional work is needed to assess neonatal outcomes comparing the two iron therapy modalities, according to Auerbach and Landy. “Findings could produce a dramatic change in our current treatment paradigm with far-reaching results,” they concluded.