Dosing Recommendations

• Clinically effective dose: at least 15 mg/day of elemental iron as iron amino acid chelate. Note: If supplementing more than 60 mg/day of elemental iron, dose every second day as high dose iron supplementation can raise serum hepcidin, decreasing absorption and utilisation of iron.¹
• Duration: 12 weeks, and the assess 
• Form: Iron amino acid chelate (such as iron bisglycinate) is the preferred form as it has shown to have fewer side effects compared to other forms of iron (e.g. ferrous fumarate).
• Drug interactions:
  • Iron & dolutegravir: Pharmacokinetic research shows that iron can decrease the absorption of dolutegravir from the gastrointestinal tract through chelation. Separate doses by a minimum of 2 hours.²
  • Iron may decrease absorption of methyldopa, levodopa & levothyroxine. Separate doses by a minimum of 2 hours.^3,4,5
• Safe dosing:
  • Studies suggest doses up to 100 mg/day of elemental iron are considered safe in pregnancy.⁶

Iron deficiency anaemia (IDA) is the most common micronutrient deficiency among pregnant women and is associated with a variety of impaired maternal and foetal outcomes. For the mother, this can include, reduced physical and cognitive performance, premature labour, reduced lactation and increased risk of spontaneous abortion.⁷ In the developing foetus, IDA in the mother can cause low birth weight, neonatal anaemia and neurologic impairment;⁸ potentially leading to delays in language and motor development, reduced neurotransmitter function and myelination and impaired cognitive function in later life.⁷

For these reasons, effective treatment of IDA in pregnant women is essential to improve maternal and foetal health.

While oral iron is considered to be important to correct IDA and replenish iron stores, gastrointestinal side effects occur in around 50% of patients taking oral iron preparations, with constipation being the main side effect. This is further compounded as pregnant women frequently suffer from constipation due to hormonal and physiological changes during this time.¹

In a randomised controlled trial by Makled et al. 2020,⁹ 150 pregnant women (14 to 18 weeks of gestation) with haemoglobin (HB) levels 8 to 10.5 g/dL and serum ferritin <15 µg/L were randomised into 2 groups:

• Group 1: Iron amino acid chelate (IAAC) [as ferrotron], 15 mg elemental iron once daily.
• Group 2: Ferrous fumarate (FF) 350 mg (elemental iron 115 mg) once daily.

Researchers investigated a variety of haematological parameters including, haemoglobin levels, blood indices, serum iron, and serum ferritin levels at baseline, and at weeks 4, 8, and 12 of treatment.

After 12 weeks of supplementation, IAAC was found to increase haematological parameters at a faster rate than FF in pregnant women with IDA (mean HB and serum ferritin level) [Table 1]. Importantly, IAAC was also associated with fewer gastrointestinal side effects than FF (Table 2).

Table 1: Anaemia (<11.0 gm/dL) among the studied groups.

Table 2: Gastrointestinal side effects of iron supplementation.

Improvements in Haematological Parameters

Haemoglobin

At weeks 4, 8 and 12 there was a significant increase in mean HB level in both groups. However, researchers found this was marginally higher in the IAAC group (11.6±0.8) compared to the FF group (11.3±0.9). Furthermore, after 12 weeks of treatment 15.5% of the IAAC group had HB levels below 11.0 gm/dL compared to 30% of the FF group (Table 1).⁹

Ferritin

As with haemoglobin, treatment with IAAC and FF showed a significant increase in serum ferritin levels in both groups. At 12 weeks the mean serum ferritin level in the IAAC group was 29.5±3.5 (mean change 18.5±3.1), while in the FF group the mean ferritin level was 28.2±3.2 (mean change 17.7±2.9).⁹

Reduced Gastrointestinal Side Effects with Iron Amino Acid Chelate Supplementation

Due to an increase in gastrointestinal disturbances experienced by women during pregnancy, using iron supplementation with reduced side effects is of utmost importance. In this study, maternal side effects were significantly less frequent in the IAAC group compared to the FF group (Table 2).⁹

Clinical Take-Aways

Iron deficiency anaemia is a common health problem during pregnancy that can have both short- and long-term effects on the mother, foetus and infant. Some forms of iron supplementation can exacerbate constipation (e.g. FF), an already common complaint in pregnancy due to hormonal and physiological changes occurring at this time. Providing iron supplementation associated with reduced side effects is therefore paramount. IAAC has been shown to have rapid effects on restoring optimal iron status in pregnant women and is associated with less gastrointestinal side effects compared to FF.⁹ Supplementation of IAAC is therefore recommended to increase serum iron and limit gastrointestinal side effects in pregnant women.

References

1. Juul SE, Derman RJ, Auerbach M. Perinatal iron deficiency: implications for mothers and infants. Neonatology. 2019;115(3):269-74.
2. Jalloh MA, Gregory PJ et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AID. 2017;28(1):4-15.
3. Campbell NR, Campbell RR, Hasinoff BB. Ferrous sulfate reduces methyldopa absorption: methyldopa: iron complex formation as a likely mechanism. J Clin Invest. 1990;13(6):329-32.
4. Campbell NR, Hasinoff B. Ferrous sulfate reduces levodopa bioavailability: chelation as a possible mechanism. Clin Pharmacol Ther. 1989;45(3):220-5.
5. Campbell NR, Hasinoff BB et al. Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism. Ann Intern Med. 1992;117(12):1010-3.
6. Peña‐Rosas JP, De‐Regil LM et al. Intermittent oral iron supplementation during pregnancy. Cochrane Database of Syst Rev. 2015(10).
7. Abu-Ouf NM, Jan MM. The impact of maternal iron deficiency and iron deficiency anemia on child’s health. Saudi Med J. 2015;36(2):146.
8. Zhang Q, Lu XM et al. Adverse effects of iron deficiency anemia on pregnancy outcome and offspring development and intervention of three iron supplements. Scientific reports. 2021;11(1):1347.
9. Makled AK, Abuelghar WM, El-Shahawy AA. Amino Acid Chelated Iron versus Ferrous Fumarate in the Treatment of Iron Deficiency Anemia with Pregnancy: Randomized Controlled Trial. Evidence Based Women's Health Journal. 2020;10(1):95-103.