Low-Dose Prophylactic Iron Supplementation in Pregnancy Not Associated With Gastrointestinal Complaints: Study
During pregnancy, the demand for iron is markedly increased due to the expansion of the pregnant woman's hemoglobin mass and the concomitant need for iron in the growing fetus. In many European and developed countries, oral iron supplementation is now routinely recommended to pregnant women because studies have shown that women not taking iron supplements suffer a high frequency of iron deficiency (ID) and many display ID anemia (IDA).
A Danish randomized study found that a low dose (i.e., a dose being considerably lower than the dose used for treatment of IDA) of 40mg of elemental iron as ferrous fumarate daily is sufficient to prevent ID and IDA in 90% and 95%, respectively, of all pregnancies. Thus, in 2013, the Danish Health Authorities changed their recommendation on prophylactic oral iron supplementation from 50–70 mg of elemental ferrous iron/day to 40–50 mg/day without recommending any specific iron formula.
However, many women are still reluctant to follow the recommendation, as they are worried about gastrointestinal (GI) discomfort or side effects of oral iron supplements.
Uncomplicated pregnancy is accompanied by “physiological” GI discomfort, with considerable individual variation between the women. The GI complaints are partly due to hormonal changes, for example, increased production of progesterone inhibiting GI motility resulting in constipation, increased levels of prostaglandins causing diarrhea, and increased fetoplacental production of GDF15, which appears to be linked to the maternal risk of nausea and vomiting during pregnancy. Furthermore, the pressure of the growing uterus on the abdominal organs, the ventricle, and the intestines provokes gastroesophageal reflux with symptoms such as epigastric pain, pyrosis, heartburn, cardialgia, and constipation. Due to these physiologically induced changes in GI function in uncomplicated pregnancy, it is difficult to evaluate the possible GI side effects of oral iron supplements during gestation.
To assess the frequency of GI complaints during low-dose oral iron prophylaxis and compare three iron formulas in equipotent doses: ferrous fumarate versus ferrous bisglycinate versus ferrous sulphate, in healthy women with an uncomplicated single pregnancy, study was carried out by Nils Thorm Milman and Thomas Bergholt. Results from two randomized, double-blind studies are reported: the Gentofte study comprising 404 women allocated into four groups taking 20, 40, 60, and 80 mg of elemental iron as ferrous fumarate/day and the Naestved study comprising 78 women allocated into two groups: 25 mg of elemental iron as ferrous bisglycinate/day and 50 mg of elemental iron as ferrous sulphate/day between meals from 15 to 19 weeks of gestation to delivery. GI complaints (nausea, vomiting, epigastric pain/ pyrosis, belching, meteorism, borborygmi, intestinal colic, flatulence, loose stools, constipation, and use of laxatives), as well as black stools, were recorded by interview at the time of inclusion and at regular intervals during gestation.
At inclusion, the frequency of total combined GI complaints in all women (n = 482) was 21%. The Gentofte study showed that in the groups taking 20–60 mg iron/day as fumarate, there was no association between the iron dose and the frequency of GI side effects. An iron dose of 80 mg as fumarate was associated with significantly higher frequencies of constipation and the use of laxatives. Comparing the three equipotent doses of iron formulas, which can prevent iron deficiency, ferrous bisglycinate 25 mg iron had the most favourable GI side effect profile, while ferrous fumarate 40 mg iron and ferrous sulphate 50 mg iron had higher but similar GI side effect profiles. The frequency of black stools increased with the iron dose. Ferrous bisglycinate 25 mg iron had a lower frequency of black stools (8%) than ferrous fumarate 40 mg iron (22%) and ferrous sulphate 50 mg iron (31%).
This study showed that low-dose iron supplementation for pregnant women appears to have no clinically significant GI side effects. However, an iron dose above 60 mg of elemental ferrous iron as fumarate/day, for example, 80 mg/ day, most likely causes an increased frequency of specific GI complaints. Comparing the three iron formulas in doses that can prevent ID and IDA, ferrous bisglycinate 25 mg iron had the most favourable GI side effect profile, while ferrous fumarate 40 mg iron and ferrous sulphate 50 mg iron had somewhat higher but similar GI side effect profiles. Ferrous bisglycinate may be considered for iron prophylaxis, especially in women experiencing GI side effects when taking conventional iron formulas.
Source: Nils Thorm Milman and Thomas Bergholt; Wiley Journal of Pregnancy Volume 2024, Article ID 1716798, 10 pages https://doi.org/10.1155/2024/1716798
