Maternal anemia affects 613 million WRA globally and is associated with increased risk of adverse outcomes for both mothers and newborns. Targets set by the World Health Assembly aim to reduce anemia in WRA by 50% by 2025; however, progress to reduce maternal anemia has stagnated. Improved understanding of the causes and consequences, especially in LMICs, is vital to achieving Sustainable Development Goal 3: Ensure healthy lives and promote well-being for all at all ages.

Despite the importance of maternal anemia to individual health and policy goals, a 2017 WHO technical consultation identified four critical gaps in the use and interpretation of hemoglobin to assess anemia in pregnancy. Specifically, the consultation concluded that there was insufficient data to justify the current thresholds in pregnancy, questioned whether thresholds are the same globally, noted thresholds were not proven to be linked to functional health outcomes, and questioned how hemoglobin thresholds should be used for anemia diagnosis in the context of common gene mutations that affect hemoglobin function.

These critical gaps in the data and evidence lead to suboptimal clinical care and inadequate global burden estimation. Thus, there is an urgent need to generate high-quality data for pregnant women living in LMICs in order to redefine hemoglobin reference values and validate revised thresholds for anemia. The proposed study would contribute to a growing body of evidence that could inform new global guidelines for diagnosing maternal anemia and identifying high-risk pregnancies based on hemoglobin. 

The overarching objective of this study is to leverage the Antenatal/Postnatal Research Collective (ARC) network to advance clinical knowledge of anemia during pregnancy and contribute high quality, globally representative data toward establishing hemoglobin thresholds linked to functional outcomes.

Three primary aims will inform the study design:

Aim 1: To define normal hemoglobin values in healthy women during pregnancy and within 42 days postpartum and estimate related statistical thresholds for anemia diagnosis in these populations.

Aim 2: To establish hemoglobin thresholds for anemia diagnosis in pregnancy based on the link with adverse maternal, fetal, and newborn health outcomes.

Aim 3: To describe the underlying contributing factors of anemia during pregnancy.

It is an observational study, the services available in the study facility will be provided as per the Government guidelines. Additional tests for iron status, inflammation, communicable diseases, and hemoglobinopathies will be measured one time at the time of enrollment (gestational age <20 weeks) to identify clinically healthy participants per eligibility criteria for the Aim 1 sample. The same tests will be done on a subset of participants once in second or third trimester for Aim 3. Further, Indicators for micronutrient status, communicable diseases, and non-communicable diseases will be measured one time (in 1st, 2nd, or 3rd trimester) for the Aim 3 sample. The samples will be taken at the study facility (SDH Hodal), apart from the stool samples which will be collected from home.

The study is nested within a harmonized, multi-country research collaborative study, Pregnancy Risk, Infant Surveillance, and Measurement Alliance (PRISMA) Maternal and Newborn Health (MNH). PRISMA broadly endeavors to increase the quality of care for antenatal care (ANC) and postnatal care (PNC) services, to ensure early pregnancy registration and improve the continuity of care from antenatal to postnatal period. The PRISMA MNH study has the following objectives: 1) To improve the global understanding of key risk factors or vulnerabilities for morbidity and mortality among pregnant women and mother-infant pairs during antenatal care and postnatal care (up to one year), 2) To provide population-based baseline estimates of key maternal and child health outcomes. This may inform future interventions and randomized trial study designs and 3) To collect data to enable the application of novel analytical techniques (i.e., machine learning) to create risk prediction tools. As a harmonization effort, we are implementing the PRISMA activities as part of the ReMAPP study. These activities include conducting a house-to-house survey in the study catchment area to identify the pregnant women as early as possible, screening and enrollment in the study, encourage pregnant women to register early and get regular and complete at least 4-5 ANC check-ups from a government facility. Further, we are collecting data on maternal and infant hospitalization, maternal depression and fatigue, verbal autopsy, family care indicator, GSED short form, symptom survey, and infant bilirubin assessment.

Women are motivated to deliver in a government facility. Post-delivery, the study team visits their houses to provide home-based PNC care that include maternal and child anthropometrics, point of care Hb testing and bilirubin assessment through a non-invasive method. In case of any deviation of maternal or child health condition, they are being asked to visit referral facility for necessary consultation. In case of any adverse maternal, foetal or infant outcome, a designated person visits the house, verifies the event and report to the study investigator. The data is validated, and necessary information is being shared with the government officials for appropriate actions.

The knowledge generated from the study will help for better understanding of the normal hemoglobin values in healthy women during pregnancy and within 42 days postpartum and estimate related statistical thresholds for anemia diagnosis in these populations. Further, it will help establish hemoglobin thresholds for anemia diagnosis in pregnancy and to describe the underlying contributing factors of anemia during pregnancy.