Daily vs. intermittent iron therapy in pregnant patients

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Intermittent iron therapy is a reasonable option to treat iron deficiency anemia among pregnant women, according to a randomized non-inferiority trial.

The study, which was presented virtually at the 41st Annual Pregnancy Meeting of the Society for Maternal-Fetal Medicine (SMFM), concluded that intermittent iron therapy was non-inferior to daily iron therapy, with a mean standard deviation (SD) difference of 0.27 g/dL (95% confidence interval [CI]: -0.33 to 0.89).

Intermittent iron therapy also was associated with less nausea, but not with increased adherence.

Co-principal investigator Raminder Khangura, MD, a maternal fetal medicine physician at Henry Ford Health System in Detroit, is interested in obstetric quality improvement initiatives and research. During her fellowship at the University of Connecticut School of Medicine, she worked on implementation of Enhanced Recovery After Surgery (ERAS) for cesarean deliveries.

Raminder Khangura, MD

“As I reviewed ERAS protocols and perioperative optimization, I realized that anemia could have many maternal and fetal implications during pregnancy and postoperative recovery,” Khangura told Contemporary OB/GYN. “I observed that many women are anemic when they arrive for their procedure, so I began to research ways to improve anemia and thus improve ERAS optimization.”

The study was conducted at two medical sites, the University of Connecticut and Hartford Hospital, from October 2018 to March 2020.

A total of 58 pregnant women undergoing routine prenatal labs at 26 to 29 weeks gestation were equally randomized to supplemental iron daily (n = 29) or intermittent iron therapy every other day (n = 29).

The primary outcome was change in hemoglobin (Hgb) with treatment over a 4-to-6-week period with the non-inferiority margin set at 1 SD (0.5 g/dL Hgb).

“We assumed a mean increase of Hgb was 1 g/dL in the daily group,” Khangura said. A mean Hgb difference of at least 0.5 g/dL between the two groups was considered clinically significant.

Intermittent iron therapy was found non-inferior to daily therapy. Changes in other hematological indices like hematocrit, mean corpuscular volume, serums transferrin receptor molecule, hepcidin, ferritin and calculated body iron store were also not significant.

However, women in the daily group had more nausea compared to the intermittent group (P = 0.040).

But women in the intermittent group were no more likely to adhere to therapy (P = 0.244).

“I was surprised to learn that overall, women taking iron on an intermittent basis were not more adherent than women taking daily supplementation,” Khangura said.

Therefore, Khangura believes clinicians need to refrain from giving patients iron twice or three times a day because it does not improve outcomes. “Still, our study shows that giving patients iron on an intermittent basis may be a good option, especially patients who are concerned about gastrointestinal side effects,” she said.

Iron is best absorbed on an empty stomach, according to Khangura. “Milk, calcium and antacids should not be taken at the same time as iron supplements because this affects absorption,” she said. “Patients should be instructed to wait two hours after taking these medications before taking iron. Consuming iron with vitamin C has also been shown to improve absorption.”

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Khangura reports no relevant financial disclosures.