International Journal of Human and Health Sciences Vol. 06 No. 04 October’22 372 Original Article Injectable Iron and Blood Transfusion for Correction of Anemia in Pregnancy in a Peripheral Tertiary Hospital in Bangladesh: A Quasi-Experimental Study Syed Muhammad Baqui Billah1, Fatema Kamrun Naher2 Abstract Background: Anemia in pregnancy is one of the most commonly encountered medical disorders. Objective: To compare the effects of injectable iron and blood transfusion for correction of anemia in pregnancy. Methods: This quasi-experimental study was conducted in the Obstetrics & Gynaecology outpatient department (OPD) of Shaheed Ziaur Rahman Medical College Hospital, Bogura, Bangladesh, between April and December of 2020on 100 expecting mothers through interviews, investigation of hemoglobin (Hb) level at 16 weeks, 24-28 weeks and 36 weeks. The injectable iron and blood transfusion were the experiments given to the pregnant women around 24-28 weeks.The effect of the experiment along with other factors were assessed over the change of Hb level from 24-28 weeks to 36 weeks. Results: Only iron injection singly significantly improved Hb level (1.4 mg/ dl, p<0.001) though it improved a little in combination with blood transfusion (0.472 mg/ dl, p=0.15) too, but blood alone was associated with decreased Hb level (-0.414 mg/dl, p=0.07). Other factors were not related to the change. Conclusion: Iron injection improves hemoglobin status and should be given to all anemic women irrespective of presence or absence or other risk factors. Keywords: Anemia, pregnancy, injectable iron, blood transfusion, anemia correction Correspondence to: Dr. Syed Muhammad Baqui Billah, Department of Community Medicine, Sher-E-Bangla Medical College, Barishal, Bangladesh. Email: sbbillah@gmail.com 1. Department of Community Medicine, Sher-E-Bangla Medical College, Barishal, Bangladesh 2. Department of Obstetrics & Gynaecology, Naogaon Medical College, Naogaon, Bangladesh Introduction Anemia in pregnancy is one of the most commonly encountered medical disorders with an overall global prevalence of around 56%1. Females are usually found to be anemic2, which becomes obvious during pregnancy, contributing to 20-40% of maternal deaths3. In this situation, the risk of death is double in developing countries4. Albeit the intervention options are limited to oral iron therapy, injectable iron and blood transfusion5 or a combination of any or all of these, the prevalence of anemia during pregnancy in Bangladesh remains over 25%6,7. The treatment options include dietary sources, oral, intravenous or intramuscular iron therapy, blood transfusion of the combination of any of the above8. Study shows that anemia is more prevalent in second trimester hence focus the importance of intervention during this period of time3,9. With a high prevalence of anemia in pregnancy6,7,10, the need to assess the effective intervention has become a necessity in a recourse-compromised country like Bangladesh. World Health Organization (WHO)11 targeted a 50% reduction of anemia in women of reproductive age. Oral iron therapy has been a common treatment option during pregnancy, though non-adherence, infection, coexisting morbidity or incorrect diagnoses have led to treatment failure8. Besides oral iron, researchers have tried intravenous, intramuscular, blood transfusion or other intervention options8,12-17 to correct anemia in pregnancy. We find information of post-partum anemia correction18, but there is a knowledge gap comparing blood transfusion and intravenous iron therapy, or a combination of these two to the patients, the effectiveness of these two interventions for improvement of anemia needs to be examined. We aimed to compare the effect International Journal of Human and Health Sciences Vol. 06 No. 04 October’22 Page : 372-376 DOI: http://dx.doi.org/10.31344/ijhhs.v6i4.475 373 International Journal of Human and Health Sciences Vol. 06 No. 04 October’22 of injectable iron and blood transfusion to correct anemia in pregnancy in a peripheral tertiary health care facility, to refute the null hypothesis that the intervention is not effective. Methods This quasi-experimental study was conducted in the Obstetrics & Gynaecology outpatient department (OPD) of Shaheed Ziaur Rahman Medical College Hospital, Bogura, Bangladesh, between April and December of 2020 on 100 willing pregnant women who completed a minimum of three antenatal visits. Expecting mothers who declined to participate, or who had severe co-morbidities were excluded. We recorded age (completed years), education level, address, religion, gravida, blood group, Rh typingand serum hemoglobin at 16, 24-28 and 36 weeks. History of iron intake, sun exposure, progesterone therapy, eggs and fruits consumed per week, thalassemia, iron injection, blood transfusion were among the suspected factors. The questionnaire was developed based on the important factors from different studies and reviewed afterwards by an expert panel of clinicians and epidemiologists.The experiments consisted of iron supplementation and/or blood transfusion, after first trimester as indicated by their Hb concentration, so we took 24-28 weeks as baseline and checked whether iron supplement and/or blood transfusion could improve their blood Hb at 36 weeks of pregnancy or not. We recorded the data in excel after collection and cleaned to remove any stroke or data error. After data management in excel, the product was exported to SPSS where the final analysis was done, the figures were constructed in excel though. We operationalized Hb category taking ≥11 mg/dl as normal, 10.1-10.9 mg/dl as mild, 7.0 to 10.0 mg/dl as moderate, and <7 mg/dl as severe anemia respectively. We assessed numeric and categorical anemia variable with the demographic and other related variables using Mann Whitney U and Kruskal-Wallis test. We deducted Hb level of 24-28 weeks from 36 weeks to compute the change as outcome variable. Because the interventions were mixed up as some patients got only iron injection, some only blood transfusion and some both, we computed a new variable of intervention classifying those who took only iron injection, those who took only blood transfusion and those who took both the intervention. We applied non-parametric test to assess the variables as the sample size was small and also continuous variables showed skewed distribution. Finally, we conducted generalized linear model analysis taking the significant factors from the univariate and bivariate analysis. We also included some clinically important though non-significant variables like iron intake, thalassemia, assumed to be confounding with the Hb concentration. Because almost invariably we advise for oral iron to all patients, as happened here too, added with the clinical experience and practice, we did not assess the oral iron with injectable one in the model. The quantitative variables are presented as mean±standard deviation (SD), minimum (Min) and maximum (Max), while the qualitative variables are presented as frequency and percentage. We considered a p value of ≤0.05 to be significant in our study. Results Table 1 shows the baseline information of the respondents. The respondents were 25.04±4.27 years of age, almost 50% of them had secondary education. There was a nearly homogeneous distribution of their address. A half of them were primigravida. Around 90% of them were Muslims; A+ve, B +ve and O +ve blood group were almost equally distributed around 30% each. Figure 1 depicts the anemia status before and after intervention that the intervention significantly (p<0.001) shifted the severe and moderate anemia to mild and normal anemia. There were only 2 severe anemia which turned to moderate anemia after intervention. While looking at the hemoglobin status, we observed that the hemoglobin level decreased from first to second trimester, which again increased in third trimester. The minimum and maximum Hb level in third trimester roamed around the level of first trimester, though the mean Hb was a little higher than that of first trimester. Looking at the category of anemia in Table 2, we detected that the Hb level improved from second to third trimester indicating the effectiveness of the intervention. We constructed a general linear model to assess the change of Hb status by the intervention and other significant factors keeping age as covariate (Table 4). The model showed that only iron injection was significantly associated with improvement of Hb level by 1.4 mg/dl adjusting for other variables. Only blood transfusion was associated with a reduction of Hb level by 0.414 mg/dl. Other variables could not show any significant relation with the change. International Journal of Human and Health Sciences Vol. 06 No. 04 October’22 374 Table 1.Basic demographic information of the respondents Variables Mean ± SD / N Min-Max / % Age 25.01 ± 4.26 18-36 Education Illiterate 2 2.0 Primary 29 28.7 Secondary 48 47.5 Graduate and above 22 21.8 Address Rural 58 57.4 Urban 43 42.6 Gravida 1 52 51.5 2 25 24.7 >2 24 24.8 Religion Muslim 88 87.1 Non-Muslim 13 12.9 Blood group O +ve 32 31.7 A -ve 3 3.0 A +ve 28 27.7 B -ve 1 1.0 B +ve 30 29.7 AB +ve 7 6.9 Fig. 1.Status of anemia before and after intervention Table 2.Hemoglobin status at first, second and third trimester including change from second to third trimester after the intervention (N=100) Weeks of pregnancy Mean SD Min Max 16 weeks 9.80 1.10 7 12.7 24-28 weeks 9.50 1.09 6.4 7.1 36 weeks 9.92 0.99 7.1 12.4 Weeks of pregnancy Normal Mild Moderate Severe 16 weeks 14 23 63 0 24-28 weeks 11 21 66 2 36 weeks 15 30 55 0 We evaluated several factors with Hb change, but none of those were associated with the Hb change except for the intervention variable (p<0.001) and Thalassemia (p=0.03). Table 3 showed that only iron injection significantly improved the Hb level by 1.5 mg/dl. Strikingly, only blood transfusion could not improve the Hb, rather the Hb decreased from 24-28 weeks to 36 weeks by 0.24 mg/dl even after blood transfusion. Similarly, oral iron intake couldn’t improve the Hb level rather it was almost significantly higher in those who didn’t take iron therapy. The significance was being contributed by iron injection only as appeared in post hoc test (data not shown). Table 3.Second to third trimester change of hemoglobin with the factors Variables N Mean SD p value Religion Muslim 88 0.38 0.92 0.25Non-Muslim 13 0.70 1.23 Address Rural 58 0.51 1.01 0.26Urban 43 0.29 0.88 Education Illiterate 2 -0.35 0.49497 0.64Primary 29 0.52 1.11Secondary 48 0.37 0.93 Graduate and above 22 0.45 0.85 Gravida 1 52 0.39 0.93 0.622 25 0.57 1.21 >2 24 0.31 0.71 Blood group O +ve 32 0.365 0.91 0.86 A -ve 3 0.97 0.45 A +ve 28 0.45 1.20 B -ve 1 0.50 . B +ve 30 0.47 0.88 AB +ve 7 0.11 0.67 Sun exposure No 54 0.47 1.07 0.52Yes 47 0.35 0.82 Egg/week 0 9 0.27 0.57 0.50 3 7 0.00 0.79 4 4 0.98 0.75 5 1 -0.20 . 7 80 0.45 1.01 Fruits/week 0 10 0.39 0.67 0.59 2 1 0.80 . 3 8 -0.05 0.74 4 3 1.03 0.91 5 1 -0.20 . 7 78 0.45 1.01 Oral iron intake No 17 0.81 0.92 0.06Yes 84 0.34 0.95 Progesterone therapy No 54 0.38 0.96 0.67Yes 47 0.46 0.96 Thalassemia No 95 0.45 0.98 0.03Yes 6 -0.02 0.35 Intervention No intervention 51 0.08 0.69 <0.001 Iron injection 27 1.47 0.89 Blood transfusion 18 -0.24 0.43 Both 5 0.54 0.52 375 International Journal of Human and Health Sciences Vol. 06 No. 04 October’22 Table 4.General linear model to predict hemoglobin change Parameter Coefficient p value Α (Intercept) 0.541 0.28 Blood + iron* 0.472 0.15 Only blood -0.414 0.07 Only iron* 1.400 <0.001 Thalassemia 0.314 0.37 Age -0.006 0.72 * Iron = injectable iron Discussion Our study excavated that fact that injectable iron can be a key management option to correct anemia in pregnancy. Other interventions like blood transfusion only and mixed intervention (blood transfusion and iron injection) cannot be regarded as treatment of choice to manage anemia in pregnancy, though we adopt these intervention preferences in our clinical setting. The present study is unique as we compared injectable iron and blood transfusion with and without combination, while other researchers compared oral iron with injectable iron, intravascular iron with intramuscular iron and other different combinations12,13,17,19-21. Though oral iron has been the first line of management choice in pregnancy22, the clinical experts experienced that intravenous iron works better than oral iron. Even researchers found that oral therapy throughout the pregnancy failed to meet the purpose of iron therapy12. They advocated to assess the factors related to anemia so that proper treatment decision can be made23. Of the different interventions tried by different researchers, intravenous iron therapy proved to improve the Hb better than other intervention options16. Our study and other study findings bring about a question on rationality of the decision for blood transfusion. If the blood transfusion has got a small or no role as evidenced in our study, we should be more cautious about the cause of anemia before deciding for transfusion. Out of different determinants of anemia, iron deficiency has been common in developing world so far research has been explored1,9,23-25 with adverse pre, intra and post-natal outcomes4,26. As the pregnant women commonly suffer from this problem3,7,12,23, researchers recommended for iron therapy to prevent the adverse outcome during and after pregnancy. Though age has been identified a risk factor related with anemia in pregnancy1, we didn’t find any relation with the improvement of Hb in our study. Antenatal care (ANC) and gestation age at first ANC were related to anemia24. Researchers in Ghana showed that regular ANC visit can significantly improve the Hb level. This brings us an addressable limitation in our study which we learned after the collection of data and analysis. Researchers recommended different prevention strategies to prevent anemia in pregnancy. Of the options, women education especially nutrition education, deworming, diagnosing and treating chronic diseases in early pregnancy, government and non-government initiative through long term policy have been the key steps suggested by them27. Though our study significantly established the iron therapy to improve the Hb status of the pregnant women, we can’t claim the strength of this study as it was not a randomized controlled trial (RCT). Being a quasi-experimental study, we should have adjusted other confounding factors such as ANC history, helminthic infestation and comorbidities. Conclusion Our study finding emphasized the fact to investigate the cause of anemia before initiating any treatment to correct anemia. As different study suggested that iron deficiency is the main cause of anemia in pregnancy in our population, we should keep in mind to prefer injectable iron over blood transfusion during pregnancy. Conflict of Interest:The authors declare no conflict of interest. Ethical approval:Ethical approval was obtained from Ethical Review Committee of Shaheed Ziaur Rahman Medical College, Bogura, Bangladesh. Funding statement:Self-funded. Authors’contribution:SMBB and FKN designed the study; FKN collected data and entered in excel; SMBB analyzed data in SPSS;SMBB and FKN wrote the manuscript, reviewed, and finalized the draft. International Journal of Human and Health Sciences Vol. 06 No. 04 October’22 376 References 1. Ababiya T, Gabriel T. Prevalence of Anemia among Pregnant Women in Ethiopia and Its Management: A Review. Int Res J Pharmacy. 2014;5(10):737-750. 2. Chathuranga G, Balasuriya T, Perera R. Anaemia among Female Undergraduates Residing in the Hostels of University of Sri Jayewardenepura, Sri Lanka. Anemia. 2014;2014:526308. 3. Prakash S, Yadav K. Maternal Anemia in Pregnancy: An Overview. Int J Pharmacy Pharmaceutical Res. 2015;4(3):174-179. 4. Daru J, Zamora J, Fernández-Félix BM, et al. Risk of maternal mortality in women with severe anaemia during pregnancy and post partum: a multilevel analysis. The Lancet Global Health. 2018;6(5):e548-e554. 5. Munoz M, Pena-Rosas JP, Robinson S, et al. Patient blood management in obstetrics: management of anaemia and haematinic deficiencies in pregnancy and in the post-partum period: NATA consensus statement. Transfus Med. 2018;28(1):22-39. 6. Lindstrom E, Hossain MB, Lonnerdal B, Raqib R, El Arifeen S, Ekstrom EC. Prevalence of anemia and micronutrient deficiencies in early pregnancy in rural Bangladesh, the MINIMat trial. Acta Obstet Gynecol Scand. 2011;90(1):47-56. 7. Ahmed F, Khan MR, Shaheen N, et al. Anemia and iron deficiency in rural Bangladeshi pregnant women living in areas of high and low iron in groundwater. Nutrition. 2018;51-52:46-52. 8. Baird-Gunning J, Bromley J. Correcting iron deficiency. Aust Prescr. 2016;39(6):193-199. 9. Mortaz R, Ahmed M, Sultana A, et al. Pattern of Anemia during Pregnancy among Patients in Selected Hospital in Bangladesh. MOJ Public Health. 2015;2(4). 10. Merrill R, Shamim A, Ali H, et al. High prevalence of anemia with lack of iron deficiency among women in rural Bangladesh: a role for thalassemia and iron in groundwater. Asia Pac J Clin Nutr. 2012;21(3):416- 424. 11. World Health Organization (WHO). WHA Global Nutrition Targets: 2025: Anaemia Policy Brief. Geneva. 2014. 12. Wali A, Mushtaq A, Nilofer. Comparative Stydy - Efficacy, Safety and Compliance of Intravenous Iron Sucrose and Intramuscular Iron Sorbitol in Iron Deficiency Anemia of Pregnancy. J Pak Med Assoc. 2002;52(9):392-395. 13. Krafft A, Breymann C. Iron sucrose with and without recombinant erythropoietin for the treatment of severe postpartum anemia: a prospective, randomized, open- label study. J Obstet Gynaecol Res. 2011;37(2):119- 124. 14. Bhavi SB, Jaju PB. Intravenous iron sucrose v/s oral ferrous fumarate for treatment of anemia in pregnancy. A randomized controlled trial. BMC Pregnancy Childbirth. 2017;17(1):137. 15. Naqash A, Ara R, Bader GN. Effectiveness and safety of ferric carboxymaltose compared to iron sucrose in women with iron deficiency anemia: phase IV clinical trials. BMC Womens Health. 2018;18(1):6. 16. Qassim A, Mol BW, Grivell RM, Grzeskowiak LE. Safety and efficacy of intravenous iron polymaltose, iron sucrose and ferric carboxymaltose in pregnancy: A systematic review. Aust NZ J Obstet Gynaecol. 2018;58(1):22-39. 17. Das SN, Devi A, Mohanta BB, Choudhury A, Swain A, Thatoi PK. Oral versus intravenous iron therapy in iron deficiency anemia: An observational study. J Family Med Prim Care. 2020;9(7):3619-3622. 18. Chua S, Gupta S, Curnow J, Gidaszewski B, Khajehei M, Diplock H. Intravenous iron vs blood for acute post-partum anaemia (IIBAPPA): a prospective randomised trial. BMC Pregnancy Childbirth. 2017;17(1):424. 19. Darwish AM, Khalifa EE, Rashad E, Farghally E. Total dose iron dextran infusion versus oral iron for treating iron deficiency anemia in pregnant women: a randomized controlled trial. J Matern Fetal Neonatal Med. 2019;32(3):398-403. 20. Darwish AM, Fouly HA, Saied WH, Farah E. Lactoferrin plus health education versus total dose infusion (TDI) of low-molecular weight (LMW) iron dextran for treating iron deficiency anemia (IDA) in pregnancy: a randomized controlled trial. J Matern Fetal Neonatal Med. 2019;32(13):2214-2220. 21. Chughtai F, Syed H, Shams M, Akhter A, Munir A, Rana S. Intravenous Iron Treatment in Pregnancy: Comparison of High Dose Carboxymaltose vs Iron Sucrose. Pak Armed Forces Med J. 2020;70(5):1469- 1473. 22. Garzon S, Cacciato PM, Certelli C, Salvaggio C, Magliarditi M, Rizzo G. Iron Deficiency Anemia in Pregnancy: Novel Approaches for an Old Problem. Oman Med J. 2020;35(5):e166. 23. Richards T, Breymann C, Brookes MJ, et al. Questions and answers on iron deficiency treatment selection and the use of intravenous iron in routine clinical practice. Ann Med. 2021;53(1):274-285. 24. Anlaakuu P, Anto F. Anaemia in pregnancy and associated factors: a cross sectional study of antenatal attendants at the Sunyani Municipal Hospital, Ghana. BMC Res Notes. 2017;10(1):402. 25. Rahman MM, Abe SK, Rahman MS, et al. Maternal anemia and risk of adverse birth and health outcomes in low- and middle-income countries: systematic review and meta-analysis. Am J Clin Nutr. 2016;103(2):495-504. 26. Stephen G, Mgongo M, Hussein Hashim T, Katanga J, Stray-Pedersen B, Msuya SE. Anaemia in Pregnancy: Prevalence, Risk Factors, and Adverse Perinatal Outcomes in Northern Tanzania. Anemia. 2018;2018:1846280. 27. Sifakis S, Pharmakides G. Anemia in pregnancy. Ann NY Acad Sci. 2000;900:125-36.