Pregnancy Complications, Hematologic Clinical Trial
Official title:
Iron Supplementation During Pregnancy - One Versus Two Ferrous Sulfate Capsules for Iron Deficient Pregnant Women
Since normal pregnancies are associated with dilutional anemia, due to a greater increase in
plasma volume with a smaller increase in RBC mass, it is important to properly diagnose IDA
according to the levels of serum ferritin. Previous studies examining the optimal iron dose
have shown that adjustment of iron supplementation according to serum ferritin levels in
early pregnancy could be beneficial. Nonetheless, there is no consensus regarding the
appropriate dose of iron during pregnancy, its dose-response curve and its effect on serum
ferritin levels.
In this trial the investigators sought to assess the efficacy of doubling the daily iron
supplement dose in pregnant women with IDA.
This study is a prospective randomized controlled trial performed at a women's health center
from April 2015 . All participants had a complete blood count performed during their initial
visit to the clinic during the first trimester of pregnancy. IDA was defined as a hemoglobin
concentration <10.5 g/dL and ferritin levels < 15 ng/ml.
Inclusion criteria were healthy pregnant women ages 18-42 with a singleton gestation and a
diagnosis of IDA between 16-19 weeks. The investigators included only women with full access
to medical computerized files. Exclusion criteria were: multiple pregnancies, hyperemesis
gravidarum continuing past 20 weeks of gestation, Thalassemia, abnormal blood smears,
vitamin D deficiency, mal-absorption disorders (inflammable bowel diseases; Crohn's,
Ulcerative Colitis) and chronic diseases associated with anemia (i.e SLE). Vitamin B12 and
blood smears were performed at the time of allocation. Additional inclusion criteria applied
after allocation were: deterioration in hemoglobin levels mandating IV iron administration,
more than 3 capsules missed at the 2 weeks check-up, diarrhea lasting more than 5 days,
vomiting lasting more than 5 days less than 2 hours after supplement , administration of
blood products during pregnancy, any use of multi-vitamin supplements containing iron,
hospitalization periods greater than two weeks and a time period shorter than 15 weeks from
allocation to delivery.
All participants diagnosed with IDA fulfilling the inclusion criteria were randomized by
"Randomizer" (http://www.randomizer.org) to receive either one or two capsules of aktiferrin
F (containing DL-Serine 129 mg; Iron (Ferrous Sulfate) 34 mg; Folic Acid 0.5 mg) or
Foliferrin (containing DL-Serine 120 mg; Iron (Ferrous Sulfate) 34 mg; Folic Acid 0.5 mg).
No cross-over was permitted between groups.
Participants were instructed to take one capsule at least 2 hours after consumption of dairy
products or two capsules 12 hours apart at least 2 hours after consumption of dairy
products. Validation of compliance to medical regimens was performed by a count of empty
pill packages every two weeks during regular check-ups. All participants were monitored for
weight, BP and urine dipstick measurements every 2-3 weeks until 34 weeks. Episodes of
vomiting, constipation and diarrhea were recorded. Constipation was defined as fewer than
three bowel movements a week or bowel movements consisting of hard, dry and small stool,
making it painful or difficult to pass. Fetal BPP and estimated weight were performed every
2-3 weeks until 34 weeks of gestation. Fetal monitor was performed every two weeks from 34
weeks of gestation.
Laboratory follow up was performed by measurements of ferritin and hemoglobin levels at
fixed time intervals during gestation: 15-20 weeks, 24 weeks, 35 weeks and also 6 weeks
post-partum. All lab studies were performed in a single central laboratory.
The data extracted included demographic data (age, parity, chronic disease, weight and BMI
at allocation and weight gain during the study period), obstetrical complications (GDM,
preeclampsia, IUGR, preterm labor, preterm delivery, IUFD and blood product transfusion) and
non obstetrical complications (diarrhea, thrombocytopenia, gastroenteritis, appendicitis,
hypo/hyperthyroidism, pre-gestational diabetes) and newborn outcome (birth-weight and Apgar
score and immediate post-partum complications). Any gastrointestinal symptoms, obstetrical
complications or hospital admissions were reported in real time to the PI
;
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment