Effect Of Multiple Micronutrient Supplementation and Iron-Folic Acid Supplementation on Hemoglobin Levels of Pregnant Women, Fetal Growth and Birth Outcome in Ogbomoso: Protocol of A Randomized Control Trial

Effect Of Multiple Micronutrient Supplementation and Iron-Folic Acid Supplementation on Hemoglobin Levels of Pregnant Women, Fetal Growth and Birth Outcome in Ogbomoso: Protocol of A Randomized Control Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effect Of Multiple Micronutrient Supplementation and Iron-Folic Acid Supplementation on Hemoglobin Levels of Pregnant Women, Fetal Growth and Birth Outcome in Ogbomoso: Protocol of A Randomized Control Trial Omobolaji Olawale Adewuyi, Ayobami A. Alabi, Gbenga Olorunfemi, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5608899/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Background Maternal nutrition during pregnancy is critical for both maternal and fetal health, with inadequate intake of essential nutrients linked to adverse outcomes such as maternal anemia, intrauterine growth restriction, and low birth weight. Maternal malnutrition is a major public health issue in low- and middle-income countries, contributing to high maternal and infant mortality rates. While iron and folic acid (IFA) supplementation is a standard intervention to prevent anemia and neural tube defects, micronutrient deficiencies often extend beyond iron and folic acid, necessitating a broader approach. Multiple micronutrient supplementation (MMS), which includes vitamins and minerals like vitamin A, D, zinc, and selenium, has shown promise in improving maternal and neonatal outcomes. Objective The objective of this study is to assess the effect of Multiple Micronutrient Supplementation (MMS) and Iron-Folic Acid (IFA) supplementation on maternal hemoglobin levels during pregnancy, fetal growth, and birth outcomes in Ogbomosho, Oyo State, Nigeria. Methods:- This is a 2-study arm double-blind, multi-stage Randomized Control Trial. It is a double centered study involving pregnant women with recruitment of participants into the study commencing at 24 gestation weeks with 2 study arms, a group would be on IFA while another group would be on MMS. Maternal Hemoglobin, Fetal growth (fetal weight, fetal length, fetal adnominal circumference) would be measured and monitored at baseline (24 weeks of gestation), 4 weeks follow up and at delivery. The study plan to recruit a maximum of 120 participants from both study centers. Discussion The study would determine the effect of MMS and IFA supplementation on maternal hemoglobin levels, fetal growth and birth outcome. The findings of this study will contribute to the growing body of evidence on the role of multiple micronutrient supplementation (MMS) in improving maternal and fetal health outcomes. Trial Registration The study has also been registered with the Pan African Clinical Trial Registry with approval number ( https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=31868). PACTR202409756247389, registered on 19th September 2024. Multiple Micronutrient Supplementation Iron Folic Acid Supplementation Hemoglobin fetal growth birth weight Figures Figure 1 INTRODUCTION Background and Rationale: - Maternal nutrition during pregnancy is crucial for both the health of the mother and the developing fetus. Adequate intake of essential nutrients plays a vital role in optimizing fetal growth, reducing complications, and improving birth outcomes (1,2).Pregnancy is a period of increased physiological demands, necessitating an increased intake of specific nutrients to support both maternal health and fetal development. Inadequate nutrition can lead to poor maternal and child health outcomes, including maternal anaemia, intrauterine growth restriction, low birth weight, preterm birth, and increased neonatal mortality (3). According to (4), micronutrient deficiencies affect two out of every three women of reproductive age worldwide. In Nigeria, maternal malnutrition remains a significant public health challenge, contributing to high rates of maternal and infant mortality. According to the Nigeria Demographic and Health Survey (NDHS), maternal malnutrition is a key factor in the country's high maternal mortality rate, which stands at 512 deaths per 100,000 live births (5). Maternal anemia, a common consequence of inadequate iron intake during pregnancy, affects approximately 40% of pregnant women globally and is associated with adverse pregnancy outcomes such as low birth weight (6), preterm birth, small for gestational age (SGA) and neonatal mortality. (7,8,9). Iron and folic acid (IFA) supplementation is a standard antenatal care intervention aimed at preventing maternal anemia and neural tube defects (6). IFA supplementation is recommended by the World Health Organization (WHO) as part of routine prenatal care to improve maternal hemoglobin levels and reduce the risk of iron deficiency anemia (10). However, micronutrient deficiencies in pregnant women often extend beyond iron and folic acid, necessitating a broader approach to maternal nutrition. Multiple micronutrient supplementation (MMS), which includes a combination of essential vitamins and minerals beyond iron and folic acid, is emerging as a potential strategy to address these deficiencies (11). MMS formulations typically include vitamins and minerals such as vitamin A, vitamin D, zinc, and selenium, in addition to IFA. Previous studies in Nigeria explored MMS during lactation (12) and reported that MMS had no impact on human milk copper, iron and zinc after 10 weeks of supplementation and there is the need for longer duration of RCT. Micronutrients play essential roles in immune function, antioxidant defense, and fetal development (13). Emerging evidence suggests that MMS may offer additional benefits over IFA alone, including improved maternal and neonatal outcomes, such as increased birth weight and reduced incidence of low birth weight (14,15,16). Given the high burden of micronutrient deficiencies in low- and middle-income countries (LMICs) and the potential benefits of MMS, it is crucial to explore the impact of MMS on maternal and fetal health outcomes in resource-limited settings like Nigeria. Objectives/Hypothesis:- This study aims to evaluate the effects of MMS compared to IFA supplementation on maternal hemoglobin levels, fetal growth, and birth outcomes among pregnant women in Ogbomosho, Nigeria. The study hypothesis is that Multiple Micronutrient Supplementation (MMS) when compared with Iron Folic Acid (IFA) supplementation would improve maternal hemoglobin levels, fetal growth and birth weight. Outcome Evaluation The Primary Objective is to assess the effect of multiple micronutrient supplementation (MMS) compared to iron-folic acid (IFA) supplementation on the hemoglobin levels of pregnant women. The Secondary Objectives is to evaluate the effect of MMS and IFA on fetal weight, femur length, fetal head circumference and birth weight. Trial Design. The trial design I shown in figure 1 METHODS: Participants, Interventions and Outcomes Study Design This study is a Randomized Control Trial to investigate the impact of Multiple Micronutrient Supplementation (MMS) versus Iron and Folic Acid (IFA) supplementation during pregnancy on maternal and fetal health outcomes. Participants will be randomly assigned to either the MMS group or the IFA group. This design allows for the comparison of outcomes between the two groups while accounting for potential confounding factors. Eligibility Criteria Inclusion Criteria: Pregnant women in their third trimester (<24 weeks gestation). Age between 18 to 45 years. Willingness to participate and provide informed consent. Attendance at Primary Health Care, Ibrahim Taiwo or Bowen University Teaching Hospital for Antenatal care. Exclusion Criteria: Pre-existing medical conditions such as diabetes or hypertension. Multiple pregnancies (e.g., twins). History of substance abuse. Inability to understand study procedures or communicate effectively. Severe anemia (hemoglobin level < 7 g/dL). Explanation for the Choice of Comparators The MMS dose is from KIRK Humanitarian, USA while the IFA dose is the regular regime given to pregnant women during antenatal clinic visits in Nigeria. Both MMS and placebos would be provided at recruitment and replenished at 4 weeks during the participant visit to the healthcare facility for follow up. Nutrient MMS - Dose IFA - Dose Vitamin A (ug) 800 µg Vitamin D (IU) 200 IU Vitamin E (mg) 10 mg Vitamin C (mg) 70 mg Thiamine (mg) 1.4 mg Riboflavin (mg) 1.4 mg Niacin (mg) 18 mg Vitamin B6 (mg) 1.9 mg Folic acid (µg) 400 µg 400 µg Vitamin B12 (µg) 2.6 µg Copper (mg) 2.0 mg Iodine (µg) 150 µg Iron (mg) 30 mg 60 mg Zinc (mg) 15 mg Selenium (µg) 65 µg Intervention Description Participants in the intervention group will receive weekly supplementation of multiple micronutrient supplements (MMS) containing a combination of essential vitamins and minerals, including vitamin A, vitamin B1, vitamin B2, niacin, vitamin B6, vitamin B12, folic acid, vitamin C, vitamin D, vitamin E, iron (30 mg), zinc (15 mg), copper, selenium, and iodine. The supplementation will start upon obtaining informed consent and will continue until delivery. Control Description The control group (IFA group) will follow the standard antenatal care protocol, receiving iron and folic acid supplements. Participants in this group will receive standard weekly supplementation of iron (60 mg) and folic acid (400 µg). This regimen aligns with the WHO's recommendations for preventing maternal anemia and neural tube defects. Criteria for discontinuing or modifying allocated intervention Safety Concerns: The participating pregnant women may be withdrawn if they experience siginificant adverse reactions, such as severe such as severe gastrointestinal disturbances like excessive vomiting, diarrhoea or noticeable allergic reactions to the supplements. The participants will be regularly monitored to identify any potential side effects early. The research team will review any adverse events and determine if discontinuation or modification of the intervention is necessary. Non-compliance with supplement dosing: Consistent non-adherence to the supplementation schedule, such as missing more than 20% of doses, may lead to discontinuation. Participants will be encouraged to maintain a simple diary to track adherence, and regular follow-ups by phone calls and during antenatal visits will be conducted to address challenges. Pregnancy Complications: If participants develop pregnancy-related complications such as pre-eclampsia, gestational diabetes, or other significant medical issues requiring specialized treatment, the intervention may be modified or stopped prioritizing the mother's health. The decision to modify or discontinue the intervention will be made collaboratively with the participant and their healthcare provider. Voluntary Withdrawal: Participants have the right to withdraw from the trial at any point without facing any consequences. They will be informed about this right at the outset and reminded periodically to ensure they feel comfortable making this decision. Withdrawal will not deny the participants best of care that the facility offers. Participants Timeline Baseline Assessment Pregnant women who meet the eligibility criteria would be administered the consent form, after which socio-demography data would be collected. 24hr recall and MDDQ questionnaire would be administered to collect the dietary intake data of the pregnant women. Maternal hemoglobin levels and blood pressure as well as fetal weight, fetal head circumference, femur length would be measured at baseline. 4 weeks At 4 weeks, another 24hr recall and MDDQ would be administered to the mother. Maternal hemoglobin levels, blood pressure, fetal weight, fetal head circumference and femur length would be measured. Delivery At delivery, mothers’ hemoglobin levels at delivery would be measured. Serum and human milk samples would be collected from the mothers by a trained mid-wife/nurse. Infant birth weight would be recorded as well. Data Collection Data will be collected from baseline, at 4 weeks follow-up and at the delivery. The following key domains will be assessed. Household Characteristics: Socioeconomic status, education level, household size, and access to healthcare services. Maternal Diet: Dietary intake will be assessed using a validated 24hr recall and MDDQ questionnaire to evaluate nutrient intake and dietary diversity at baseline and at 4 weeks follow up. Anthropometric Measurements: Maternal weight, height, and body mass index (BMI) will be measured using standardized procedures at baseline and at 4 weeks follow up. Fetal Growth Assessments: Ultrasound will be used to measure fetal growth parameters, including fetal weight, fetal head circumference, fetal abdominal circumference, and femur length. Hemoglobin measurements: Venous blood samples will be collected via accessible vein into capillary tube. This is minimally invasive and suitable for repeated measures throughout pregnancy. The capillary sample will be spun at about 3000 revolution per minute to ensure a well packed sample. This will then be read against hematocrit reader to determine the packed cell volume. Quality control procedures will be in place to ensure accuracy and reliability of the measurements. Blood Pressure – Mothers blood pressure would be measured at baseline and at 4 weeks Strategy to Improve adherence to Intervention. To aid compliance with the study regimen, at each follow up visits, the trained research assistant would check the sachet of the mothers to validate compliance of supplements used and this would also be used for replenishment. The study also has an education component embedded into it, where mothers in the MMS group are given education on Exclusive breastfeeding and the benefits of supplementation during pregnancy and the impact it has on birth outcome. Trained research assistants also put phone calls to the mothers participating in the study once a week to remind them to take their supplements daily. Relevant concomitant care permitted or prohibited during the trial. Participants on MMS are not permitted to be on IFA and vice visa. Foetus in the pregnant women would also be monitored for stability and any risk whatsoever and any mother/foetus pair at any risk would be discontinued from the study. Permitted Care: Standard prenatal care will be offered to include regular check-ups, ultrasound scans for mother and foetus well-being, and routine blood tests, is encouraged. Nutritional counseling sessions will be available to all participants to support healthy eating practices during pregnancy. Treatment for common pregnancy symptoms, such as morning sickness, with approved medications. Prohibited Care: Participants will be instructed not to take additional micronutrients or vitamins containing iron, folic acid that could confound the study results and prevent interference with study outcomes. The same will apply to herbal supplements or traditional remedies that have not been approved by the study team due to potential interactions with the interventions. Ancillary and Post-Trial Care This study doesn’t anticipate any post-trial care, however the participating pregnant women in the study would be advised to contact the PI or Co-PIs via the email in the consent form if any symptoms is felt during the study that would warrant any mother withdrawing from the study. Outcomes Primary Outcome The Primary Objective is the effect of multiple micronutrient supplementation (MMS) compared to iron-folic acid (IFA) supplementation on the hemoglobin levels of pregnant women. Secondary Outcome The Secondary Objectives is to evaluate the influence of MMS and IFA on fetal weight, femur length, fetal head circumference and birth weight. Sample Size Calculation. The sample size for the study was determined using sample size estimation for 2 independent study groups with a continuous endpoint. The study is powered at 80% for a 2-sided test with a 0.05 level of significance, Z α = 1.96. Use the sample size formula for comparing two means: n = Sample size per group Z α/2 = Z-score corresponding to the significance level (1.96 for α = 0.05) Z β. = Z-score corresponding to the desired power (e.g., 0.84 for 80% power) σ = Estimated standard deviation of hemoglobin levels = 1.5 g/dL Δ. = Expected difference in mean hemoglobin levels between groups = 0.6 g/dL Based on the effect size and expected mean difference in hemoglobin from (16) sample size required is 34 participants in each group, 68. Adjusting for a 20% attrition rate = [34 + (20% * 34)] = 41 Sample size = 41 mother – child pair per group, In total 82 mother to child pair. Recruitment Strategy The study participants will consist of pregnant women residing in Ogbomosho, Oyo State, Nigeria, who seek antenatal care at Primary Health Care, Ibrahim Taiwo and Bowen University Teaching Hospital. These hospitals provide comprehensive maternity and prenatal care services to many pregnant women in the region. Eligible participants will be pregnant women in their third trimester (approximately 24-32 weeks of gestation) who voluntarily participate in the study. P regnant women meeting the inclusion criteria will be randomly selected from the study site into MMS or IFA group. Assignment of Interventions Randomization Process: Participants will be randomly assigned to either the MMS or IFA group using a computer-generated sequence to ensure impartiality. This ensures that each participant has an equal chance of being placed in any group, reducing bias and ensuring comparability between groups. Randomization will be stratified based on key demographic variables such as maternal age, parity, and baseline hemoglobin levels to enhance group comparability. Participant Enrolment: Eligible participants will be recruited from local antenatal clinics of the selected centres Informed consent will be obtained prior to enrollment, ensuring participants understand the study's purpose, procedures, and potential benefit and risks. Allocation, Concealment, Implementation Allocation: The allocation sequence will be generated by an independent statistician and kept secure to maintain confidentiality and prevent bias. Concealment: Allocation will be concealed using sequentially numbered, opaque, sealed envelopes (SNOSE) prepared in advance to prevent selection bias. These envelopes will only be opened by the study coordinator at the time of assignment to ensure blinding. Implementation: The research team will be responsible for enrolling participants and ensuring proper allocation according to the pre-determined sequence. Training sessions will be conducted for all staff involved in the trial to ensure consistent implementation of the protocol. Blinding Participants and Researchers: The trial will employ a double-blind design where both participants and researchers are unaware of which supplement group the participants belong to, minimizing bias in reporting and observation. Outcome Assessors: Individuals responsible for measuring outcomes such as hemoglobin levels and assessing birth outcomes will be blinded to the group assignments to ensure objective evaluation. Compliance with Supplementation: Compliance will be monitored through self-reports and tablet counts during antenatal visits. Serum sample collection at delivery Venous blood samples will be collected from participants shortly after delivery by trained phlebotomists to ensure consistency and safety. At delivery, 10 mL of whole blood will be drawn from the participant. The blood will be collected in Ethylenediaminetetraacetic acid (EDTA) bottle, centrifuged for 15 minutes at 2200-2500 RPM, and the serum will be pipetted into clean plastic screw-cap vials for analysis. Samples will be processed within two hours to separate serum components, reducing the risk of degradation. Serum samples will be stored at -80°C freezer to maintain integrity until analysis is carried out. Human milk samples collection immediately after birth Colostrum samples approximately 2 - 5ml, will be collected from mothers within the first 24 hours postpartum for assessment of micronutrient (Copper, Iron, Zinc content) content. This timing is crucial as colostrum is rich in nutrients and antibodies, providing insights into the nutritional status influenced by supplementation. Samples will be collected using sterile techniques to prevent contamination. Manual expression or breast pumps may be used, depending on the mother's preference and comfort. Mothers will be instructed and supported by trained nurses and midwives to ensure proper collection techniques. Collected samples will be immediately placed in sterile, labeled containers and stored at -80°C to preserve nutrient content and prevent spoilage. Sample Analysis Samples will be analyzed for micronutrient concentrations in the human milk samples. Data Quality Management To ensure the accuracy and reliability of the data, the following measures will be implemented, all research staff involved in data collection will receive comprehensive training on study protocols, ethical considerations, and data collection methods. Validated and standardized instruments will be used for data collection, including questionnaires and measurement tools. Data quality control checks/review will be done regularly for completeness, consistency, and accuracy. Data Analysis Quantitative data will be analyzed using STATA. The following analytical techniques will be employed, to summarize baseline characteristics of participants and key study variables. T-tests and chi-square tests will be used to compare maternal hemoglobin levels, fetal growth parameters, and birth outcomes between the MMS and IFA groups. Multivariable regression analysis will be conducted to assess the impact of MMS versus IFA on maternal and fetal outcomes, adjusting for potential confounders such as maternal age, parity, and baseline nutritional status. Discussion The findings of this study will contribute to the growing body of evidence on the role of multiple micronutrient supplementation (MMS) in improving maternal and fetal health outcomes. Previous studies have shown that MMS can reduce the risk of low birth weight, preterm birth, and maternal anemia (18). The results from this study also have the potential to inform prenatal nutritional guidelines and improve maternal and neonatal health outcomes in similar settings. According to a meta-analysis by (19) it suggested that MMS could reduce the risk of low birth weight and small-for-gestational-age births more effectively than IFA alone. However, the implementation of MMS as a standard intervention across different regions of the world raises practical and economic considerations, especially in low-resource settings (18). This study could generate context-specific data that could help determine whether the potential benefits of MMS justify its wider adoption over IFA even in low- and middle-income countries (LMICs). The design of the trial, including the proper randomization, allocation, concealment and blinding, aims to minimize bias and enhance the validity of the findings. By measuring outcomes such as hemoglobin levels and birth metrics, the study will contribute valuable evidence to the ongoing debate regarding optimal prenatal supplementation (20). The implications of this study could extend beyond the immediate health outcomes on mother and the newborn. By potentially demonstrating the superiority of MMS over IFA, the findings could encourage shift in policy formulation tending towards prioritization of comprehensive nutritional strategies in prenatal care. This is particularly relevant in LMICCs regions with high rates of malnutrition and limited healthcare resources, where improving maternal nutrition could have a cascading effect on overall community health (18). By focusing on pregnant women in primary health care and tertiary facilities in Ogbomoso, this trial underscores the importance of identifying the nutritional needs across different populations, and interventions must be tailored to address these unique challenges. Furthermore, the study provides insights that are directly applicable to similar demographic and socioeconomic settings in Nigeria and potentially other parts of sub-Saharan Africa. Limitations may include potential challenges in adherence to supplementation and the generalizability of findings beyond the study population. Addressing these limitations through participant thorough education and proper follow up through phone call during the study could mitigate against this. In conclusion, this study seeks to fill critical gaps in the literature regarding prenatal nutrition. By providing robust evidence on the impact of MMS versus IFA, it aims to inform and potentially transform nutritional guidelines to better support maternal and child health in resource-limited settings. Study Participants Protocol Involvement The study participants were not involved in the development of the protocol Protocol Amendments. If there would be any need for protocol amendments, the researchers would seek for approval from the Oyo State Ministry of Health ethics committee and an update protocol would be made available. The amended copy would then be also made available to the clinical trial registry site, study sites, consents forms and the entire research team. Consent for Publication, Dissemination and Access to Data. All the authors have agreed to the publication and scientific dissemination of the findings from the study at international conferences and in scientific journals. Data request can be submitted to the Principal Investigator (PI) – OOA upon trial completion and scientific publication. Strategic Plan for Storage and Laboratory Analysis of Biological Specimens: Current and Future Applications Samples will be clearly labeled to ensure seamless identification of participants and differentiation between baseline, 4-week, and delivery time points. Each set of samples will be stored in designated compartments for organization. Milk and serum samples will be preserved at -80°C to maintain their integrity. Any analysis of samples for purposes beyond the scope of this trial will require prior approval from the Ethics Committee to ensure compliance with ethical guidelines. Declarations Ethical Approval/Study Status Recruitment and data collection for the study began on 27 th August 2024 and are still ongoing. The recruitment phase commenced following the receipt of ethical approval. The study protocol has been approved by the Institutional review boards (IRBs) of Oyo state ministry of health with approval number NHREC/OYOSHRIEC/10/11/22. The study has also been registered with the Pan African Clinical Trial Registry with approval number PACTR202409756247389 ( https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=31868). Authors’ contributions Conceptualization: Omobolaji O. Adewuyi Methodology: Omobolaji O. Adewuyi, Ayobami A. Alabi, Olumiyiwa Ogunlaja Investigation: Omobolaji O. Adewuyi, Eniola A. Ayemonisan, Deborah U. Akpanusong, Deborah O. Iwunna,Favour O. Afolabi, Ayobami A. Alabi, Olumiyiwa Ogunlaja Funding Acquisition: Omobolaji O. Adewuyi and Ayobami A. Alabi Supervision and validation: Omobolaji O. Adewuyi, Ayobami A. Alabi, Olumiyiwa Ogunlaja Analysis: Omobolaji O. Adewuyi, Gbenga Olorunfemi Writing: Original draft: Omobolaji O. Adewuyi, Eniola A. Ayemonisan and Oyeduntan A. Adediran Writing: Review and Editing: Omobolaji O. Adewuyi, Ayobami A. Alabi, Olumiyiwa Ogunlaja, Eniola A. Ayemonisan and Oyeduntan A. Adediran Funding Multiple Micronutrient supplements for the study was provided by Vitamin Angels. Trial Status The protocol version is 1.4, 28 th February 2025. Study recruitment started on 27 th August 2024 with baseline recruitment completed, expected completion date for study is 31 st April 2025. References Black RE, Victora CG, Walker SP, Bhutta ZA, Christian P, De Onis M, Uauy R. Maternal and child undernutrition and overweight in low-income and middle-income countries. lancet. 2013;382(9890):427–51. King JC. The risk of maternal nutritional depletion and poor outcomes increases in early or closely spaced pregnancies. J Nutr. 2003;133(5):S1732–6. Black RE, Victora CG, Walker SP, Bhutta ZA, Christian P, de Onis M, Ezzati M, Grantham-McGregor S, Katz J, Martorell R, Uauy R. Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet. 2021;399(10321):604–16. 10.1016/S0140-6736(21)01590-7 . Stevens, Gretchen S et al. A Micronutrient deficiencies among preschool-aged children and women of reproductive age worldwide: a pooled analysis of individual-level data from population-representative surveys. The Lancet. Global health vol. 10,11 (2022): e1590-e1599. 10.1016/S2214-109X(22)00367-9 National Population Commission (NPC) [Nigeria] and ICF. Nigeria Demographic and Health Survey 2018. Nigeria, and Rockville, Maryland, USA: NPC and ICF: Abuja; 2019. Balarajan Y, Ramakrishnan U, Özaltin E, Shankar AH, Subramanian SV. Anaemia in low-income and middle-income countries. lancet. 2011;378(9809):2123–35. Bourassa MW, Osendarp SJ, Adu-Afarwuah S, Ahmed S, Ajello C, Bergeron G, Zlotkin S. Review of the evidence regarding the use of antenatal multiple micronutrient supplementation in low-and middle-income countries. Volume 1444. Annals of the New York Academy of Sciences; 2019. pp. 6–21. 1. Gernand AD, Schulze KJ, Stewart CP, West KP Jr, Christian P. Micronutrient deficiencies in pregnancy worldwide: health effects and prevention. Nat Reviews Endocrinol. 2016;12(5):274–89. 10.1038/nrendo.2016.37 . Allen LH. Biological mechanisms that might underlie iron's effects on fetal growth and preterm birth. J Nutr. 2001;131(2):S581–9. World Health Organization (WHO). WHO guidelines on maternal nutrition. World Health Organization; 2012. Haider BA, Bhutta ZA. Multiple-micronutrient supplementation for women during pregnancy. Cochrane Database Syst Reviews. 2017;410.1002/14651858.CD004905.pub6. Adewuyi OO, Geddes D, Samuel F. (2024). Multiple Micronutrient Supplementation and Its Association with Copper, Iron & Zinc Levels in Human Milk of Lactating Mothers and Infant Nutritional Status in Jos, Nigeria. Current Developments in Nutrition, 8. https://cdn.nutrition.org/article/S2475-2991(24)00959-4/fulltext Christian, P., West, K. P., Khatry, S. K., Leclerq, S. C., Pradhan, E. K., Katz, J.,… Sommer, A. (2003). Effects of maternal micronutrient supplementation on fetal loss and infant mortality: a cluster-randomized trial in Nepal. The American journal of clinical nutrition, 78(6), 1194–1202. Keats EC, Haider BA, Tam E, Bhutta ZA. (2019). Multiple-micronutrient supplementation for women during pregnancy. Cochrane Database of Systematic Reviews, (3). Christian P, Khatry SK, Katz J, Pradhan EK, LeClerq SC, Shrestha SR, et al. Effects of alternative maternal micronutrient supplements on low birth weight in rural Nepal: double blind randomised community trial. BMJ. 2003;326:571. Zeng L, Cheng Y, Dang S, Yan H, Dibley MJ, Chang S, Kong L. (2008). Impact of micronutrient supplementation during pregnancy on birth weight, duration of gestation, and perinatal mortality in rural western China: double blind cluster randomised controlled trial. BMJ 2008;337:a2001. West, K. P., Shamim, A. A., Mehra, S., Labrique, A. B., Ali, H., Shaikh, S., … Christian,P. (2014). Effect of maternal multiple micronutrient vs iron–folic acid supplementation on infant mortality and adverse birth outcomes in rural Bangladesh: the JiVitA-3 randomized trial. Jama, 312(24), 2649–2658.. Bhutta ZA, Das JK, Rizvi A, Gaffey MF, Walker N, Horton S, Black RE. Evidence-based interventions for improvement of maternal and child nutrition: what can be done and at what cost? lancet. 2013;382(9890):452–77. Haider BA, Bhutta ZA. Multiple-micronutrient supplementation for women during pregnancy. Cochrane Database Syst Reviews. 2017;410.1002/14651858.CD004905.pub6. Ramakrishnan U, Grant FK, Goldenberg T, et al. Effect of multiple micronutrient supplementation on pregnancy and infant outcomes: a systematic review. Paediatr Perinat Epidemiol. 2012;26(Supp1):153–67. 10.1111/j.1365-3016.2012.01276.x . Supplementary Files CONSORT2010checklistofinformationtoincludewhenreportingarandomisedtrial.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 10 Mar, 2025 Reviewers agreed at journal 04 Mar, 2025 Reviewers invited by journal 04 Mar, 2025 Editor invited by journal 03 Mar, 2025 Editor assigned by journal 02 Mar, 2025 First submitted to journal 28 Feb, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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Alabi","email":"","orcid":"","institution":"Ladoke Akintola University of Technology Teaching Hospital: LAUTECH Teaching Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ayobami","middleName":"A.","lastName":"Alabi","suffix":""},{"id":423858280,"identity":"7a67a894-5e09-4ea2-aecd-8a2ae6e795c4","order_by":2,"name":"Gbenga Olorunfemi","email":"","orcid":"","institution":"Wits University: University of the Witwatersrand Johannesburg","correspondingAuthor":false,"prefix":"","firstName":"Gbenga","middleName":"","lastName":"Olorunfemi","suffix":""},{"id":423858281,"identity":"bbc7db49-c67e-4dba-a9a5-ba147a574c36","order_by":3,"name":"Eniola A. Ayemonisan","email":"","orcid":"","institution":"Ladoke Akintola University of Technology","correspondingAuthor":false,"prefix":"","firstName":"Eniola","middleName":"A.","lastName":"Ayemonisan","suffix":""},{"id":423858282,"identity":"0190b303-acce-4a7b-9a78-9d7fe57c6c77","order_by":4,"name":"Deborah U. Akpanusong","email":"","orcid":"","institution":"Ladoke Akintola University of Technology","correspondingAuthor":false,"prefix":"","firstName":"Deborah","middleName":"U.","lastName":"Akpanusong","suffix":""},{"id":423858283,"identity":"07d4266a-c424-47cb-bb10-9454c159e9a9","order_by":5,"name":"Deborah O. Iwunna","email":"","orcid":"","institution":"Ladoke Akintola University of Technology","correspondingAuthor":false,"prefix":"","firstName":"Deborah","middleName":"O.","lastName":"Iwunna","suffix":""},{"id":423858284,"identity":"0a0f972c-903d-4b2c-add9-c3aa6d394b11","order_by":6,"name":"Favour O. Afolabi","email":"","orcid":"","institution":"Ladoke Akintola University of Technology","correspondingAuthor":false,"prefix":"","firstName":"Favour","middleName":"O.","lastName":"Afolabi","suffix":""},{"id":423858285,"identity":"617c16ac-9459-4690-bc1e-923bedef46f5","order_by":7,"name":"Olumiyiwa Ogunlaja","email":"","orcid":"","institution":"Bowen University","correspondingAuthor":false,"prefix":"","firstName":"Olumiyiwa","middleName":"","lastName":"Ogunlaja","suffix":""},{"id":423858286,"identity":"91511699-7f40-460d-8185-b0621ef05f67","order_by":8,"name":"Oyeduntan A. Adediran","email":"","orcid":"","institution":"University of Ibadan Faculty of Veterinary Medicine","correspondingAuthor":false,"prefix":"","firstName":"Oyeduntan","middleName":"A.","lastName":"Adediran","suffix":""}],"badges":[],"createdAt":"2024-12-09 12:19:44","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5608899/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5608899/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":78240694,"identity":"e020ba5f-bef3-4ea5-8a97-a5072ed901c6","added_by":"auto","created_at":"2025-03-11 08:59:07","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":351970,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eStudy flow chart.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5608899/v1/f1d0e9b7af67cb42392a31a7.jpg"},{"id":78245138,"identity":"819658c6-9a60-42e6-b548-d3a52135b254","added_by":"auto","created_at":"2025-03-11 09:23:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1574166,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5608899/v1/9b4ad974-4ad0-4bf6-ae6e-21bf6649648c.pdf"},{"id":78241786,"identity":"00b270b0-bfe3-4833-a7de-e16624601699","added_by":"auto","created_at":"2025-03-11 09:07:15","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":28221,"visible":true,"origin":"","legend":"","description":"","filename":"CONSORT2010checklistofinformationtoincludewhenreportingarandomisedtrial.docx","url":"https://assets-eu.researchsquare.com/files/rs-5608899/v1/811eaa69785336f806fa4b9d.docx"}],"financialInterests":"","formattedTitle":"Effect Of Multiple Micronutrient Supplementation and Iron-Folic Acid Supplementation on Hemoglobin Levels of Pregnant Women, Fetal Growth and Birth Outcome in Ogbomoso: Protocol of A Randomized Control Trial","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003e\u003cstrong\u003eBackground and Rationale: -\u0026nbsp;\u003c/strong\u003eMaternal nutrition during pregnancy is crucial for both the health of the mother and the developing fetus. Adequate intake of essential nutrients plays a vital role in optimizing fetal growth, reducing complications, and improving birth outcomes (1,2).Pregnancy is a period of increased physiological demands, necessitating an increased intake of specific nutrients to support both maternal health and fetal development. Inadequate nutrition can lead to poor maternal and child health outcomes, including maternal anaemia, intrauterine growth restriction, low birth weight, preterm birth, and increased neonatal mortality (3).\u003c/p\u003e\n\u003cp\u003eAccording to (4), micronutrient deficiencies affect two out of every three women of reproductive age worldwide. In Nigeria, maternal malnutrition remains a significant public health challenge, contributing to high rates of maternal and infant mortality. According to the Nigeria Demographic and Health Survey (NDHS), maternal malnutrition is a key factor in the country's high maternal mortality rate, which stands at 512 deaths per 100,000 live births (5). Maternal anemia, a common consequence of inadequate iron intake during pregnancy, affects approximately 40% of pregnant women globally and is associated with adverse pregnancy outcomes such as low birth weight (6), preterm birth, small for gestational age (SGA) and neonatal mortality. (7,8,9).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIron and folic acid (IFA) supplementation is a standard antenatal care intervention aimed at preventing maternal anemia and neural tube defects (6). IFA supplementation is recommended by the World Health Organization (WHO) as part of routine prenatal care to improve maternal hemoglobin levels and reduce the risk of iron deficiency anemia (10). However, micronutrient deficiencies in pregnant women often extend beyond iron and folic acid, necessitating a broader approach to maternal nutrition. Multiple micronutrient supplementation (MMS), which includes a combination of essential vitamins and minerals beyond iron and folic acid, is emerging as a potential strategy to address these deficiencies (11).\u003c/p\u003e\n\u003cp\u003eMMS formulations typically include vitamins and minerals such as vitamin A, vitamin D, zinc, and selenium, in addition to IFA. Previous studies in Nigeria explored MMS during lactation (12) and reported that MMS had no impact on human milk copper, iron and zinc after 10 weeks of supplementation and there is the need for longer duration of RCT. Micronutrients play essential roles in immune function, antioxidant defense, and fetal development (13). Emerging evidence suggests that MMS may offer additional benefits over IFA alone, including improved maternal and neonatal outcomes, such as increased birth weight and reduced incidence of low birth weight (14,15,16). Given the high burden of micronutrient deficiencies in low- and middle-income countries (LMICs) and the potential benefits of MMS, it is crucial to explore the impact of MMS on maternal and fetal health outcomes in resource-limited settings like Nigeria.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjectives/Hypothesis:-\u0026nbsp;\u003c/strong\u003eThis study aims to evaluate the effects of MMS compared to IFA supplementation on maternal hemoglobin levels, fetal growth, and birth outcomes among pregnant women in Ogbomosho, Nigeria. The study hypothesis is that Multiple Micronutrient Supplementation (MMS) when compared with Iron Folic Acid (IFA) supplementation would improve maternal hemoglobin levels, fetal growth and birth weight. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcome Evaluation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Primary Objective is to assess the effect of multiple micronutrient supplementation (MMS) compared to iron-folic acid (IFA) supplementation on the hemoglobin levels of pregnant women. The Secondary Objectives is to evaluate the effect of MMS and IFA on fetal weight, femur length, fetal head circumference and birth weight.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial Design.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe trial design I shown in figure 1\u003c/p\u003e"},{"header":"METHODS: Participants, Interventions and Outcomes","content":"\u003cp\u003e\u003cstrong\u003eStudy Design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is a Randomized Control Trial to investigate the impact of Multiple Micronutrient Supplementation (MMS) versus Iron and Folic Acid (IFA) supplementation during pregnancy on maternal and fetal health outcomes. Participants will be randomly assigned to either the MMS group or the IFA group. This design allows for the comparison of outcomes between the two groups while accounting for potential confounding factors.\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003eEligibility Criteria\u003c/h3\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;Inclusion Criteria:\u003c/strong\u003e\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003ePregnant women in their third trimester (\u0026lt;24 weeks gestation).\u003c/li\u003e\n \u003cli\u003eAge between 18 to 45 years.\u003c/li\u003e\n \u003cli\u003eWillingness to participate and provide informed consent.\u003c/li\u003e\n \u003cli\u003eAttendance at Primary Health Care, Ibrahim Taiwo or Bowen University Teaching Hospital for Antenatal care.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp; Exclusion Criteria:\u003c/strong\u003e\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003ePre-existing medical conditions such as diabetes or hypertension.\u003c/li\u003e\n \u003cli\u003eMultiple pregnancies (e.g., twins).\u003c/li\u003e\n \u003cli\u003eHistory of substance abuse.\u003c/li\u003e\n \u003cli\u003eInability to understand study procedures or communicate effectively.\u003c/li\u003e\n \u003cli\u003eSevere anemia (hemoglobin level \u0026lt; 7 g/dL).\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eExplanation for the Choice of Comparators\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe MMS dose is from KIRK Humanitarian, USA while the IFA dose is the regular regime given to pregnant women during antenatal clinic visits in Nigeria. Both MMS and placebos would be provided at recruitment and replenished at 4 weeks during the participant visit to the healthcare facility for follow up.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"330\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNutrient\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMMS - Dose\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIFA - Dose\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eVitamin\u0026nbsp;A (ug)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e800 \u0026micro;g\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eVitamin\u0026nbsp;D (IU)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e200\u0026nbsp;IU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eVitamin\u0026nbsp;E (mg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e10 mg\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eVitamin\u0026nbsp;C\u0026nbsp;(mg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e70\u0026nbsp;mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eThiamine (mg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1.4 mg\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eRiboflavin (mg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1.4\u0026nbsp;mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eNiacin\u0026nbsp;(mg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e18 mg\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eVitamin B6 (mg)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e1.9 mg\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eFolic acid \u0026nbsp;(\u0026micro;g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e400 \u0026micro;g\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e400 \u0026micro;g\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eVitamin\u0026nbsp;B12 (\u0026micro;g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e2.6 \u0026micro;g\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eCopper (mg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e2.0\u0026nbsp;mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eIodine\u0026nbsp;(\u0026micro;g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e150 \u0026micro;g\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eIron (mg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e30\u0026nbsp;mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e60\u0026nbsp;mg\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eZinc (mg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e15\u0026nbsp;mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eSelenium (\u0026micro;g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e65 \u0026micro;g\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eIntervention Description\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants in the intervention group will receive weekly supplementation of multiple micronutrient supplements (MMS) containing a combination of essential vitamins and minerals, including vitamin A, vitamin B1, vitamin B2, niacin, vitamin B6, vitamin B12, folic acid, vitamin C, vitamin D, vitamin E, iron (30 mg), zinc (15 mg), copper, selenium, and iodine. The supplementation will start upon obtaining informed consent and will continue until delivery.\u003c/p\u003e\n\u003ch3\u003eControl Description\u003c/h3\u003e\n\u003cp\u003eThe control group (IFA group) will follow the standard antenatal care protocol, receiving iron and folic acid supplements. Participants in this group will receive standard weekly supplementation of iron (60 mg) and folic acid (400 \u0026micro;g). This regimen aligns with the WHO\u0026apos;s recommendations for preventing maternal anemia and neural tube defects. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCriteria for discontinuing or modifying allocated intervention\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSafety Concerns: \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe participating pregnant women may be withdrawn if they experience siginificant adverse reactions, such as severe such as severe gastrointestinal disturbances like excessive vomiting, diarrhoea or noticeable allergic reactions to the supplements. The participants will be regularly monitored to identify any potential side effects early. The research team will review any adverse events and determine if discontinuation or modification of the intervention is necessary.\u003c/p\u003e\n\u003ch3\u003eNon-compliance with supplement dosing:\u003c/h3\u003e\n\u003cp\u003eConsistent non-adherence to the supplementation schedule, such as missing more than 20% of doses, may lead to discontinuation. Participants will be encouraged to maintain a simple diary to track adherence, and regular follow-ups by phone calls and during antenatal visits will be conducted to address challenges.\u003c/p\u003e\n\u003ch3\u003ePregnancy Complications:\u003c/h3\u003e\n\u003cp\u003eIf participants develop pregnancy-related complications such as pre-eclampsia, gestational diabetes, or other significant medical issues requiring specialized treatment, the intervention may be modified or stopped prioritizing the mother\u0026apos;s health. The decision to modify or discontinue the intervention will be made collaboratively with the participant and their healthcare provider.\u003c/p\u003e\n\u003ch3\u003eVoluntary Withdrawal:\u003c/h3\u003e\n\u003cp\u003eParticipants have the right to withdraw from the trial at any point without facing any consequences. They will be informed about this right at the outset and reminded periodically to ensure they feel comfortable making this decision. Withdrawal will not deny the participants best of care that the facility offers.\u003c/p\u003e\n\u003ch3\u003eParticipants Timeline\u003c/h3\u003e\n\u003cp\u003e\u003cstrong\u003eBaseline Assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePregnant women who meet the eligibility criteria would be administered the consent form, after which socio-demography data would be collected. 24hr recall and MDDQ questionnaire would be administered to collect the dietary intake data of the pregnant women. Maternal hemoglobin levels and blood pressure as well as fetal weight, fetal head circumference, femur length would be measured at baseline.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e4 weeks\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAt 4 weeks, another 24hr recall and MDDQ would be administered to the mother. Maternal hemoglobin levels, blood pressure, fetal weight, fetal head circumference and femur length would be measured.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDelivery\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAt delivery, mothers\u0026rsquo; hemoglobin levels at delivery would be measured. Serum and human milk samples would be collected from the mothers by a trained mid-wife/nurse. Infant birth weight would be recorded as well.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Collection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData will be collected from baseline, at 4 weeks follow-up and at the delivery. The following key domains will be assessed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHousehold Characteristics:\u003c/strong\u003e Socioeconomic status, education level, household size, and access to healthcare services.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaternal Diet:\u003c/strong\u003e Dietary intake will be assessed using a validated 24hr recall and MDDQ questionnaire to evaluate nutrient intake and dietary diversity at baseline and at 4 weeks follow up.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnthropometric Measurements:\u003c/strong\u003e Maternal weight, height, and body mass index (BMI) will be measured using standardized procedures at baseline and at 4 weeks follow up.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFetal Growth Assessments:\u003c/strong\u003e Ultrasound will be used to measure fetal growth parameters, including fetal weight, fetal head circumference, fetal abdominal circumference, and femur length.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHemoglobin measurements:\u003c/strong\u003e Venous blood samples will be collected via accessible vein into capillary tube. This is minimally invasive and suitable for repeated measures throughout pregnancy. The capillary sample will be spun at about 3000 revolution per minute to ensure a well packed sample. This will then be read against hematocrit reader to determine the packed cell volume. Quality control procedures will be in place to ensure accuracy and reliability of the measurements.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBlood Pressure \u0026ndash;\u003c/strong\u003e Mothers blood pressure would be measured at baseline and at 4 weeks\u003c/p\u003e\n\u003ch3\u003eStrategy to Improve adherence to Intervention.\u003c/h3\u003e\n\u003cp\u003eTo aid compliance with the study regimen, at each follow up visits, the trained research assistant would check the sachet of the mothers to validate compliance of supplements used and this would also be used for replenishment. The study also has an education component embedded into it, where mothers in the MMS group are given education on Exclusive breastfeeding and the benefits of supplementation during pregnancy and the impact it has on birth outcome. Trained research assistants also put phone calls to the mothers participating in the study once a week to remind them to take their supplements daily.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRelevant concomitant care permitted or prohibited during the trial.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants on MMS are not permitted to be on IFA and vice visa. Foetus in the pregnant women would also be monitored for stability and any risk whatsoever and any mother/foetus pair at any risk would be discontinued from the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePermitted Care:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStandard prenatal care will be offered to include regular check-ups, ultrasound scans for mother and foetus well-being, and routine blood tests, is encouraged.\u003c/p\u003e\n\u003cp\u003eNutritional counseling sessions will be available to all participants to support healthy eating practices during pregnancy. Treatment for common pregnancy symptoms, such as morning sickness, with approved medications.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProhibited Care:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants will be instructed not to take additional micronutrients or vitamins containing iron, folic acid that could confound the study results and prevent interference with study outcomes.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe same will apply to herbal supplements or traditional remedies that have not been approved by the study team due to potential interactions with the interventions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAncillary and Post-Trial Care\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study doesn\u0026rsquo;t anticipate any post-trial care, however the participating pregnant women in the study would be advised to contact the PI or Co-PIs via the email in the consent form if any symptoms is felt during the study that would warrant any mother withdrawing from the study.\u003c/p\u003e"},{"header":"Outcomes","content":"\u003cp\u003e\u003cstrong\u003ePrimary Outcome\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Primary Objective is the effect of multiple micronutrient supplementation (MMS) compared to iron-folic acid (IFA) supplementation on the hemoglobin levels of pregnant women.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSecondary Outcome\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Secondary Objectives is to evaluate the influence of MMS and IFA on fetal weight, femur length, fetal head circumference and birth weight.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSample Size Calculation.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe sample size for the study was determined using sample size estimation for 2 independent study groups with a continuous endpoint. The study is powered at 80% for a 2-sided test with a 0.05 level of significance, Z\u003csub\u003e\u0026alpha; =\u003c/sub\u003e1.96.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eUse the sample size formula for comparing two means:\u003c/p\u003e\n\u003cp\u003e\u003cimg width=\"212\" 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\" alt=\"image\"\u003e\u003c/p\u003e\n\u003cp\u003en \u0026nbsp; \u0026nbsp; = Sample size per group\u003c/p\u003e\n\u003cp\u003eZ\u003csub\u003e\u0026alpha;/2\u003c/sub\u003e = Z-score corresponding to the significance level (1.96 for \u0026alpha; = 0.05)\u003c/p\u003e\n\u003cp\u003eZ\u003csub\u003e\u0026beta;.\u0026nbsp;\u003c/sub\u003e = Z-score corresponding to the desired power (e.g., 0.84 for 80% power)\u003c/p\u003e\n\u003cp\u003e\u0026sigma; \u0026nbsp; \u0026nbsp;= Estimated standard deviation of hemoglobin levels = 1.5 g/dL\u003c/p\u003e\n\u003cp\u003e\u0026Delta;. \u0026nbsp;= Expected difference in mean hemoglobin levels between groups = 0.6 g/dL\u003c/p\u003e\n\u003cp\u003eBased on the effect size and expected mean difference in hemoglobin from \u003cem\u003e(16)\u0026nbsp;\u003c/em\u003esample size required is 34 participants in each group, 68.\u003c/p\u003e\n\u003cp\u003eAdjusting for a 20% attrition rate = [34 + (20% * 34)] = 41\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSample size = 41 mother \u0026ndash; child pair per group, In total 82 mother to child pair.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRecruitment Strategy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study participants will consist of pregnant women residing in Ogbomosho, Oyo State, Nigeria, who seek antenatal care at Primary Health Care, Ibrahim Taiwo and Bowen University Teaching Hospital. These hospitals provide comprehensive maternity and prenatal care services to many pregnant women in the region. Eligible participants will be pregnant women in their third trimester (approximately 24-32 weeks of gestation) who voluntarily participate in the study.\u003cstrong\u003e\u0026nbsp;P\u003c/strong\u003eregnant women meeting the inclusion criteria will be randomly selected from the study site into MMS or IFA group.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssignment of Interventions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRandomization Process:\u003c/strong\u003e Participants will be randomly assigned to either the MMS or IFA group using a computer-generated sequence to ensure impartiality. This ensures that each participant has an equal chance of being placed in any group, reducing bias and ensuring comparability between groups.\u003c/p\u003e\n\u003cp\u003eRandomization will be stratified based on key demographic variables such as maternal age, parity, and baseline hemoglobin levels to enhance group comparability.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eParticipant Enrolment:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEligible participants will be recruited from local antenatal clinics of the selected centres\u003c/p\u003e\n\u003cp\u003eInformed consent will be obtained prior to enrollment, ensuring participants understand the study\u0026apos;s purpose, procedures, and potential benefit and risks.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAllocation, Concealment, Implementation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAllocation:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe allocation sequence will be generated by an independent statistician and kept secure to maintain confidentiality and prevent bias.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConcealment:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAllocation will be concealed using sequentially numbered, opaque, sealed envelopes (SNOSE) prepared in advance to prevent selection bias. These envelopes will only be opened by the study coordinator at the time of assignment to ensure blinding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImplementation:\u003c/strong\u003e\u0026nbsp; \u0026nbsp;The research team will be responsible for enrolling participants and ensuring proper allocation according to the pre-determined sequence. Training sessions will be conducted for all staff involved in the trial to ensure consistent implementation of the protocol.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBlinding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eParticipants and Researchers:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe trial will employ a double-blind design where both participants and researchers are unaware of which supplement group the participants belong to, minimizing bias in reporting and observation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcome Assessors:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIndividuals responsible for measuring outcomes such as hemoglobin levels and assessing birth outcomes will be blinded to the group assignments to ensure objective evaluation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompliance with Supplementation:\u003c/strong\u003e Compliance will be monitored through self-reports and tablet counts during antenatal visits.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSerum sample collection at delivery\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eVenous blood samples will be collected from participants shortly after delivery by trained phlebotomists to ensure consistency and safety.\u003c/p\u003e\n\u003cp\u003eAt delivery, 10 mL of whole blood will be drawn from the participant. The blood will be collected in Ethylenediaminetetraacetic acid (EDTA) bottle, centrifuged for 15 minutes at 2200-2500 RPM, and the serum will be pipetted into clean plastic screw-cap vials for analysis. \u0026nbsp;Samples will be processed within two hours to separate serum components, reducing the risk of degradation. Serum samples will be stored at -80\u0026deg;C freezer to maintain integrity until analysis is carried out.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHuman milk samples collection immediately after birth\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eColostrum samples approximately 2 - 5ml, will be collected from mothers within the first 24 hours postpartum for assessment of micronutrient (Copper, Iron, Zinc content) content. This timing is crucial as colostrum is rich in nutrients and antibodies, providing insights into the nutritional status influenced by supplementation.\u003c/p\u003e\n\u003cp\u003eSamples will be collected using sterile techniques to prevent contamination. Manual expression or breast pumps may be used, depending on the mother\u0026apos;s preference and comfort. Mothers will be instructed and supported by trained nurses and midwives to ensure proper collection techniques.\u003c/p\u003e\n\u003cp\u003eCollected samples will be immediately placed in sterile, labeled containers and stored at -80\u0026deg;C to preserve nutrient content and prevent spoilage.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSample Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSamples will be analyzed for micronutrient concentrations in the human milk samples.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Quality Management\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo ensure the accuracy and reliability of the data, the following measures will be implemented, all research staff involved in data collection will receive comprehensive training on study protocols, ethical considerations, and data collection methods. Validated and standardized instruments will be used for data collection, including questionnaires and measurement tools. Data quality control checks/review will be done regularly for completeness, consistency, and accuracy.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eQuantitative data will be analyzed using STATA. The following analytical techniques will be employed, to summarize baseline characteristics of participants and key study variables. T-tests and chi-square tests will be used to compare maternal hemoglobin levels, fetal growth parameters, and birth outcomes between the MMS and IFA groups. Multivariable regression analysis will be conducted to assess the impact of MMS versus IFA on maternal and fetal outcomes, adjusting for potential confounders such as maternal age, parity, and baseline nutritional status.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe findings of this study will contribute to the growing body of evidence on the role of multiple micronutrient supplementation (MMS) in improving maternal and fetal health outcomes. Previous studies have shown that MMS can reduce the risk of low birth weight, preterm birth, and maternal anemia (18).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe results from this study also have the potential to inform prenatal nutritional guidelines and improve maternal and neonatal health outcomes in similar settings. According to a meta-analysis by (19) it suggested that MMS could reduce the risk of low birth weight and small-for-gestational-age births more effectively than IFA alone. However, the implementation of MMS as a standard intervention across different regions of the world raises practical and economic considerations, especially in low-resource settings\u0026nbsp;(18). This study could generate context-specific data that could help determine whether the potential benefits of MMS justify its wider adoption over IFA even in low- and middle-income countries (LMICs).\u003c/p\u003e\n\u003cp\u003eThe design of the trial, including the proper randomization, allocation, concealment and blinding, aims to minimize bias and enhance the validity of the findings. By measuring outcomes such as hemoglobin levels and birth metrics, the study will contribute valuable evidence to the ongoing debate regarding optimal prenatal supplementation (20).\u003c/p\u003e\n\u003cp\u003eThe implications of this study could extend beyond the immediate health outcomes on mother and the newborn. By potentially demonstrating the superiority of MMS over IFA, the findings could encourage shift in policy formulation tending towards prioritization of comprehensive nutritional strategies in prenatal care. This is particularly relevant in LMICCs regions with high rates of malnutrition and limited healthcare resources, where improving maternal nutrition could have a cascading effect on overall community health (18). By focusing on pregnant women in primary health care and tertiary facilities in Ogbomoso, this trial underscores the importance of identifying the nutritional needs across different populations, and interventions must be tailored to address these unique challenges. Furthermore, the study provides insights that are directly applicable to similar demographic and socioeconomic settings in Nigeria and potentially other parts of sub-Saharan Africa.\u003c/p\u003e\n\u003cp\u003eLimitations may include potential challenges in adherence to supplementation and the generalizability of findings beyond the study population. Addressing these limitations through participant thorough education and proper follow up through phone call during the study could mitigate against this.\u003c/p\u003e\n\u003cp\u003eIn conclusion, this study seeks to fill critical gaps in the literature regarding prenatal nutrition. By providing robust evidence on the impact of MMS versus IFA, it aims to inform and potentially transform nutritional guidelines to better support maternal and child health in resource-limited settings.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Participants Protocol Involvement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study participants were not involved in the development of the protocol\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProtocol Amendments.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIf there would be any need for protocol amendments, the researchers would seek for approval from the Oyo State Ministry of Health ethics committee and an update protocol would be made available. The amended copy would then be also made available to the clinical trial registry site, study sites, consents forms and the entire research team.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication, Dissemination and Access to Data.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the authors have agreed to the publication and scientific dissemination of the findings from the study at international conferences and in scientific journals. Data request can be submitted to the Principal Investigator (PI) – OOA upon trial completion and scientific publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStrategic Plan for Storage and Laboratory Analysis of Biological Specimens: Current and Future Applications\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSamples will be clearly labeled to ensure seamless identification of participants and differentiation between baseline, 4-week, and delivery time points. Each set of samples will be stored in designated compartments for organization. Milk and serum samples will be preserved at -80°C to maintain their integrity. Any analysis of samples for purposes beyond the scope of this trial will require prior approval from the Ethics Committee to ensure compliance with ethical guidelines.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval/Study Status\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRecruitment and data collection for the study began on 27\u003csup\u003eth\u003c/sup\u003e August 2024 and are still ongoing. The recruitment phase commenced following the receipt of ethical approval. The study protocol has been approved by the Institutional review boards (IRBs) of Oyo state ministry of health with approval number NHREC/OYOSHRIEC/10/11/22. The study has also been registered with the Pan African Clinical Trial Registry with approval number PACTR202409756247389 ( https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=31868).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConceptualization:\u003c/strong\u003e Omobolaji O. Adewuyi\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethodology:\u003c/strong\u003e Omobolaji O. Adewuyi, Ayobami A. Alabi, Olumiyiwa Ogunlaja\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInvestigation:\u003c/strong\u003e Omobolaji O. Adewuyi, Eniola A. Ayemonisan, Deborah U. Akpanusong, Deborah O. Iwunna,Favour O. Afolabi, Ayobami A. Alabi, Olumiyiwa Ogunlaja\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Acquisition:\u003c/strong\u003e Omobolaji O. Adewuyi and Ayobami A. Alabi\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupervision and validation:\u003c/strong\u003e Omobolaji O. Adewuyi, Ayobami A. Alabi, Olumiyiwa Ogunlaja\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnalysis:\u003c/strong\u003e Omobolaji O. Adewuyi, Gbenga Olorunfemi\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWriting:\u003c/strong\u003e \u003cstrong\u003eOriginal draft:\u003c/strong\u003e Omobolaji O. Adewuyi, Eniola A. Ayemonisan and Oyeduntan A. Adediran\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWriting:\u003c/strong\u003e \u003cstrong\u003eReview and Editing:\u003c/strong\u003e Omobolaji O. Adewuyi, Ayobami A. Alabi, Olumiyiwa Ogunlaja, Eniola A. Ayemonisan and Oyeduntan A. Adediran\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMultiple Micronutrient supplements for the study was provided by Vitamin Angels.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial Status\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe protocol version is 1.4, 28\u003csup\u003eth\u003c/sup\u003e February 2025. Study recruitment started on 27\u003csup\u003eth\u003c/sup\u003e August 2024 with baseline recruitment completed, expected completion date for study is 31\u003csup\u003est\u003c/sup\u003e April 2025.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBlack RE, Victora CG, Walker SP, Bhutta ZA, Christian P, De Onis M, Uauy R. Maternal and child undernutrition and overweight in low-income and middle-income countries. lancet. 2013;382(9890):427\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKing JC. The risk of maternal nutritional depletion and poor outcomes increases in early or closely spaced pregnancies. J Nutr. 2003;133(5):S1732\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBlack RE, Victora CG, Walker SP, Bhutta ZA, Christian P, de Onis M, Ezzati M, Grantham-McGregor S, Katz J, Martorell R, Uauy R. Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet. 2021;399(10321):604\u0026ndash;16. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S0140-6736(21)01590-7\u003c/span\u003e\u003cspan address=\"10.1016/S0140-6736(21)01590-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStevens, Gretchen S et al. A Micronutrient deficiencies among preschool-aged children and women of reproductive age worldwide: a pooled analysis of individual-level data from population-representative surveys. The Lancet. Global health vol. 10,11 (2022): e1590-e1599. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S2214-109X(22)00367-9\u003c/span\u003e\u003cspan address=\"10.1016/S2214-109X(22)00367-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNational Population Commission (NPC) [Nigeria] and ICF. Nigeria Demographic and Health Survey 2018. Nigeria, and Rockville, Maryland, USA: NPC and ICF: Abuja; 2019.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBalarajan Y, Ramakrishnan U, \u0026Ouml;zaltin E, Shankar AH, Subramanian SV. Anaemia in low-income and middle-income countries. lancet. 2011;378(9809):2123\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBourassa MW, Osendarp SJ, Adu-Afarwuah S, Ahmed S, Ajello C, Bergeron G, Zlotkin S. Review of the evidence regarding the use of antenatal multiple micronutrient supplementation in low-and middle-income countries. Volume 1444. Annals of the New York Academy of Sciences; 2019. pp. 6\u0026ndash;21. 1.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGernand AD, Schulze KJ, Stewart CP, West KP Jr, Christian P. Micronutrient deficiencies in pregnancy worldwide: health effects and prevention. Nat Reviews Endocrinol. 2016;12(5):274\u0026ndash;89. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/nrendo.2016.37\u003c/span\u003e\u003cspan address=\"10.1038/nrendo.2016.37\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAllen LH. Biological mechanisms that might underlie iron's effects on fetal growth and preterm birth. J Nutr. 2001;131(2):S581\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWorld Health Organization (WHO). WHO guidelines on maternal nutrition. World Health Organization; 2012.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaider BA, Bhutta ZA. Multiple-micronutrient supplementation for women during pregnancy. Cochrane Database Syst Reviews. 2017;410.1002/14651858.CD004905.pub6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAdewuyi OO, Geddes D, Samuel F. (2024). Multiple Micronutrient Supplementation and Its Association with Copper, Iron \u0026amp; Zinc Levels in Human Milk of Lactating Mothers and Infant Nutritional Status in Jos, Nigeria. Current Developments in Nutrition, 8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://cdn.nutrition.org/article/S2475-2991(24)00959-4/fulltext\u003c/span\u003e\u003cspan address=\"https://cdn.nutrition.org/article/S2475-2991(24)00959-4/fulltext\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChristian, P., West, K. P., Khatry, S. K., Leclerq, S. C., Pradhan, E. K., Katz, J.,\u0026hellip; Sommer, A. (2003). Effects of maternal micronutrient supplementation on fetal loss and infant mortality: a cluster-randomized trial in Nepal. The American journal of clinical nutrition, 78(6), 1194\u0026ndash;1202.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKeats EC, Haider BA, Tam E, Bhutta ZA. (2019). Multiple-micronutrient supplementation for women during pregnancy. Cochrane Database of Systematic Reviews, (3).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChristian P, Khatry SK, Katz J, Pradhan EK, LeClerq SC, Shrestha SR, et al. Effects of alternative maternal micronutrient supplements on low birth weight in rural Nepal: double blind randomised community trial. BMJ. 2003;326:571.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZeng L, Cheng Y, Dang S, Yan H, Dibley MJ, Chang S, Kong L. (2008). Impact of micronutrient supplementation during pregnancy on birth weight, duration of gestation, and perinatal mortality in rural western China: double blind cluster randomised controlled trial. BMJ 2008;337:a2001.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWest, K. P., Shamim, A. A., Mehra, S., Labrique, A. B., Ali, H., Shaikh, S., \u0026hellip; Christian,P. (2014). Effect of maternal multiple micronutrient vs iron\u0026ndash;folic acid supplementation on infant mortality and adverse birth outcomes in rural Bangladesh: the JiVitA-3 randomized trial. Jama, 312(24), 2649\u0026ndash;2658..\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBhutta ZA, Das JK, Rizvi A, Gaffey MF, Walker N, Horton S, Black RE. Evidence-based interventions for improvement of maternal and child nutrition: what can be done and at what cost? lancet. 2013;382(9890):452\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaider BA, Bhutta ZA. Multiple-micronutrient supplementation for women during pregnancy. Cochrane Database Syst Reviews. 2017;410.1002/14651858.CD004905.pub6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRamakrishnan U, Grant FK, Goldenberg T, et al. Effect of multiple micronutrient supplementation on pregnancy and infant outcomes: a systematic review. Paediatr Perinat Epidemiol. 2012;26(Supp1):153\u0026ndash;67. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.1365-3016.2012.01276.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1365-3016.2012.01276.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"trials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"trls","sideBox":"Learn more about [Trials](http://trialsjournal.biomedcentral.com/)","snPcode":"13063","submissionUrl":"https://www.editorialmanager.com/trls","title":"Trials","twitterHandle":"MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Multiple Micronutrient Supplementation, Iron Folic Acid Supplementation, Hemoglobin, fetal growth, birth weight","lastPublishedDoi":"10.21203/rs.3.rs-5608899/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5608899/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMaternal nutrition during pregnancy is critical for both maternal and fetal health, with inadequate intake of essential nutrients linked to adverse outcomes such as maternal anemia, intrauterine growth restriction, and low birth weight. Maternal malnutrition is a major public health issue in low- and middle-income countries, contributing to high maternal and infant mortality rates. While iron and folic acid (IFA) supplementation is a standard intervention to prevent anemia and neural tube defects, micronutrient deficiencies often extend beyond iron and folic acid, necessitating a broader approach. Multiple micronutrient supplementation (MMS), which includes vitamins and minerals like vitamin A, D, zinc, and selenium, has shown promise in improving maternal and neonatal outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe objective of this study is to assess the effect of Multiple Micronutrient Supplementation (MMS) and Iron-Folic Acid (IFA) supplementation on maternal hemoglobin levels during pregnancy, fetal growth, and birth outcomes in Ogbomosho, Oyo State, Nigeria. Methods:- This is a 2-study arm double-blind, multi-stage Randomized Control Trial. It is a double centered study involving pregnant women with recruitment of participants into the study commencing at 24 gestation weeks with 2 study arms, a group would be on IFA while another group would be on MMS. Maternal Hemoglobin, Fetal growth (fetal weight, fetal length, fetal adnominal circumference) would be measured and monitored at baseline (24 weeks of gestation), 4 weeks follow up and at delivery. The study plan to recruit a maximum of 120 participants from both study centers.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study would determine the effect of MMS and IFA supplementation on maternal hemoglobin levels, fetal growth and birth outcome. The findings of this study will contribute to the growing body of evidence on the role of multiple micronutrient supplementation (MMS) in improving maternal and fetal health outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial Registration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study has also been registered with the Pan African Clinical Trial Registry with approval number ( https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=31868). PACTR202409756247389, registered on 19th September 2024.\u003c/p\u003e","manuscriptTitle":"Effect Of Multiple Micronutrient Supplementation and Iron-Folic Acid Supplementation on Hemoglobin Levels of Pregnant Women, Fetal Growth and Birth Outcome in Ogbomoso: Protocol of A Randomized Control Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-11 08:59:01","doi":"10.21203/rs.3.rs-5608899/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2025-03-10T17:11:37+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-03-04T09:30:12+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-04T09:14:48+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"Trials","date":"2025-03-03T13:44:35+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-02T07:39:20+00:00","index":"","fulltext":""},{"type":"submitted","content":"Trials","date":"2025-02-28T15:08:43+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"trials","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"trls","sideBox":"Learn more about [Trials](http://trialsjournal.biomedcentral.com/)","snPcode":"13063","submissionUrl":"https://www.editorialmanager.com/trls","title":"Trials","twitterHandle":"MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"de95ae2c-96aa-47b5-8dbe-5cf83216a1c0","owner":[],"postedDate":"March 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-07-18T21:40:36+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-11 08:59:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5608899","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5608899","identity":"rs-5608899","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}