Iron deficiency anaemia in pregnancy: Evaluation of the effectiveness and safety of intravenous ferric carboxymaltose and oral ferrous sulphate in a low-middle income country

Background: Anaemia in pregnancy is a public health burden especially in African countries where a larger proportion of women are of lower socioeconomic status with resultant nutritional deficiencies. This is further worsened by the increased demand and physiological changes that occur in pregnancy. Iron deficiency is the commonest nutritional deficiency with a higher incidence in the rural regions compared to the urban regions in Nigeria (1). It has adverse consequences on the mother and/or baby such as increased incidence of spontaneous abortion, premature delivery, intrauterine growth restriction and intrauterine fetal death. Iron deficiency anaemia (IDA) occurs in 25 – 45.6% of pregnant Nigerian women (2). Iron supplementation is carried out routinely in pregnancy, yet some women still approach or go into delivery in a state of IDA, either because of inaccessibility of antenatal care, poor health seeking behaviour, illiteracy, misconceptions, or noncompliance with oral haematinics. The compliance rate with the use of oral iron in Nigeria was found to be as low as 65.9% and the commonest reasons for non-compliance were side effects (often gastrointestinal symptoms such as abdominal pain and constipation), non-affordability of drugs and forgetfulness (3) In most low-middle income countries (LMICs), including Nigeria, routine treatment of IDA in pregnancy is with oral iron preparations, due to fears of serious adverse reactions from parenteral iron, including anaphylaxis, and the belief that oral iron is equally effective (4,5). Newer parenteral drugs such as iron isomaltoside and ferric carboxymaltose have been found to be associated with a lower risk of anaphylactic reactions. This study will focus on comparing the effectiveness, side effects and tolerability profile of intravenous ferric carboxymaltose (FCM) and oral ferrous sulphate (FS) in treatment of IDA in pregnancy. Study rationale: A survey among 220 pregnant women in late pregnancy (37 weeks and above) earlier conducted at the Lagos University Teaching Hospital (LUTH) found 20.0% (n=44) of women with Haemoglobin (Hb) concentration <10 g/dl, and 12.3% (n=27) had IDA (serum ferritin less than 15ng/L) (6). IDA was found to be associated with a higher risk of blood transfusion, wound infection, and puerperal sepsis, compared to non-anaemic women with Hb concentration ≥11g/dl. A recent systematic review comparing intravenous iron to oral iron, found a lower incidence of blood transfusion, higher maternal quality of life, and higher infant birth weights. Of the 15 studies included in this review, 10 were studies conducted in LMICs. However, the authors assessed all included studies as having low or very low-quality evidence, outcomes were susceptible to bias and there was some heterogeneity with different doses of oral iron used (7). A more recent systematic review focusing on endpoints of maternal haemoglobin, serum ferritin and haematocrit reported superior outcomes for intravenous vs. oral iron for IDA in pregnancy (8). Given that IDA in pregnancy is highly prevalent in Nigeria, and in the context of high maternal and perinatal mortality rates, a randomized controlled trial examining the effectiveness and safety of parenteral versus oral iron is critically needed. Study setting: The research will be conducted in 10 purposively selected health facilities located within 2 densely populated states in Nigeria – Lagos and Kano. These will comprise 4 primary health centres, 4 secondary health facilities, and 2 tertiary health facilities. References1. Okafor IM, Okpokam DC, Antai AB, Usanga EA. Iron Status of Pregnant Women in Rural and Urban Communities of Cross River State, South-South Nigeria. Niger J Physiol Sci. 2016;31:121-1252. Ugwu NI, Uneke CJ. Iron deficiency anaemia in pregnancy in Nigeria – A systematic review. Niger J Clin Pract. 2020;23:889-963. Ugwu EO, Olibe AO, Obi SN, Ugwu AO. Determinants of compliance to iron supplementation among pregnant women in Enugu, Southeastern Nigeria. Niger J Clin Pract. 2014;17:608-12.4. Balarajan Y, Ramakrishnan U, Özaltin E, Shankar AH, Subramanian SV. Anaemia in low-income and middle-income countries. The Lancet. 2011;378(9809):2123-35.5. Auerbach M, Gafter-Gvili A, Macdougall IC. Intravenous iron: a framework for changing the management of iron deficiency. Lancet Haematol. 2020;7(4):e342-e50.6. Ajepe AA, Okunade KS, Sekumade AI, Daramola ES, Beke MO, Ijasan O, et al. Prevalence and foetomaternal effects of iron deficiency anaemia among pregnant women in Lagos, Nigeria. PLoS One. 2020;15(1):e0227965.7. Qassim A, Grivell RM, Henry A, Kidson-Gerber G, Shand A, Grzeskowiak LE. Intravenous or oral iron for treating iron deficiency anaemia during pregnancy: systematic review and meta-analysis. Med J Aust. 2019;211(8):367-73.8. Radhika AG, Sharma AK, Perumal V, Sinha A, Sriganesh V, Kulshreshtha V, et al. Parenteral Versus Oral Iron for Treatment of Iron Deficiency Anaemia During Pregnancy and post-partum: A Systematic Review. J Obstet Gynaecol India. 2019;69(1):13-24.

Keywords:B680-public-health