Ferrous sulfate drops
A trial comparing ferrous sulfate with iron polysaccharide complex to treat infants and young children with nutritional iron-deficiency anemia (IDA) has shown ferrous sulfate to be more effective at raising hemoglobin levels in this population, according to researchers.
Dozens of oral iron supplements exist for IDA treatment, ferrous sulfate being the most commonly used. Iron polysaccharide complex, however, may be better tolerated.
Investigators undertook the BESTIRON study (NCT01904864) to determine whether the iron complex was more efficacious than ferrous sulfate in increasing hemoglobin concentrations in infants and young children aged 9 to 48 months.
Up to 3% of children aged 1 to 2 years in the United States have IDA, as do millions worldwide. IDA is associated with impaired neurodevelopment in the young.
Inadequate dietary iron intake in this group is the most common cause of IDA. It most often results from excessive cow milk consumption and/or prolonged breastfeeding without appropriate iron supplementation.
For this study, investigators randomized 80 infants and young children with nutritional IDA to receive 3 mg/kg of ferrous sulfate (n=40) or iron complex (n=40) drops once daily for 12 weeks.
Patients had to have hemoglobin concentrations of 10 g/dL or less, mean corpuscular volumes of 70 fL or less, reticulocyte hemoglobin equivalents of 25 pg or less, and either serum ferritin level of 15 ng/mL or less or total iron-binding capacity of 425 μg/dL or greater.
And they could have no clinical or laboratory evidence of other causes of anemia.
All 80 patients were included in the primary analysis evaluating change in hemoglobin concentration during the 12 weeks after starting oral iron therapy.
Patient characteristics
Patient characteristics were similar between the groups. The mean age was 23 months and 55% were male.
Most patients (61%) were Hispanic white, 9% were non-Hispanic white, and 11% were black.
Ten patients in the ferrous sulfate group and 8 in the iron complex group had received a packed red blood cell transfusion prior to study enrollment.
Results
Fifty-nine patients completed all study visits, 28 in the ferrous sulfate group and 31 in the iron complex group.
Patients’ mean hemoglobin level in the ferrous sulfate group increased from 7.9 g/dL to 11.9 g/dL over the 12 weeks. In the iron complex group, the patients’ hemoglobin level increased from 7.7 g/dL to 11.1 g/dL.
Using a linear mixed model, the primary outcome demonstrated a significant difference in the change in hemoglobin concentration of 1.0 g/dL (95% CI, 0.4-1.6; P < .001) between the groups, favoring ferrous sulfate.
IDA completely resolved in 8 of 28 (29%) patients in the ferrous sulfate group and 2 of 31 (6%) in the iron complex group (P=0.04).
However, successful administration of the supplement—meaning he child did not spit out the medication—was higher in the iron complex group (94%) than the iron sulfate group (82%), P=0.009.
The median serum ferritin level increased from 3.0 ng/mL to 15.6 ng/mL in the ferrous sulfate arm, which was significantly better than in the iron complex arm, which increased from 2.0 ng/mL to 7.5 ng/mL, P<0.001.
And the mean total iron binding capacity significantly increased in the ferrous sulfate group compared with the iron oxide group (P<0.001).
Safety
The investigators reported that patients treated with iron complex had significantly more diahrrea, while patients treated with ferrous sulfate had more vomiting, although the latter was not statistically significant.
A gastrointestinal adverse effect profile created at the end of the study showed no significant differences between the groups.
The investigators noted a few limitations of the study.
First, it was conducted in a single tertiary-care children’s hospital, the Children’s Medical Center in Dallas, Texas.
Second, a disproportionate number of patients were from lower income and minority families and frequently had severe anemia, with approximately 23% requiring blood transfusion prior to study start.
And third, the trial had a high lost-to-follow-up rate of 25% at the final visit.
So the results may not be generalizable to the general pediatric population.
Nevertheless, the investigators concluded, “Once daily, low-dose ferrous sulfate should be considered for children with nutritional iron-deficiency anemia.”
The team reported their findings in JAMA.
The study was an investigator-initiated trial with sponsorship from Gensavis Pharmaceuticals LLC, the manufacturer of the iron polysaccharide complex used in the trial. The company provided funding for both trial drugs.
The study received additional grant support from the National Center for Advancing Translational Sciences and the National Heart, Lung, and Blood Institute.
