1. What data in particular will be shared?
   Response - Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices).
   


2. What additional supporting information will be shared?
   Response -  Study Protocol
   Response -  Statistical Analysis Plan
   Response - Informed Consent Form
   Response - Clinical Study Report
   
   
3. Who will be able to view these files?
   Response (Others) -  Researchers whose proposed use of the data has been approved by Trial Steering Committee.


4. For what types of analyses will this data be available?
   Response - To achieve aims in the approved proposal.
   


5. By what mechanism will data be made available?
   Response (Others) -  Communication with representatives of Trial by email: Dr. Shivaprasad S. Goudar (sgoudar@jnmc.edu) and Dr Richard Derman (Richard.Derman@jefferson.edu)


6. For how long will this data be available start date provided 01-04-2024 and end date provided 31-03-2029?
   Response - Beginning 3 months and ending 5 years following article publication.
   


7. Any URL or additional information regarding plan/policy for sharing IPD? 
   Additional Information - NIL

Background

Over the past 40 years rates of anemia among reproductive age women, especially in low and middle-income countries (reported range 20-60%) have not decreased despite a multitude of governmental campaigns and funded programs. While many women suffer from multiple micronutrient deficiencies, iron is considered most important and is associated with increases in mortality and morbidity in both non-pregnant as well as pregnant women and their offspring. Additionally, iron deficiencies that present at various stages of a woman’s life have been associated with poorer life-quality. The degree of anemia has been shown in many studies to be associated with the worst health outcomes. There are a number of times during a woman’s reproductive period that effective interventions might preferentially be employed -- pre-pregnancy, during gestation or post-partum. Iron deficiency anemia is an intergenerational condition and the initiation of menses adds further burden to already reduced iron stores. A number of initiatives employing a single infusion of IV Iron, as compared to the usual standard of care oral iron, have shown promise. Large definitive studies are currently ongoing in pregnant women, and a Global Network trial is soon to begin in women with moderate anemia diagnosed immediately post-delivery. It would be ideal if one could identify women already suffering from anemia and determine its severity pre-pregnancy, thus allowing focused public health or personalized interventions to be implemented. Such programs may have more impact and be more cost-effective than intervening during pregnancy or in the post-partum period. Health agencies often recommend a course of oral iron for those who are mildly anemic, a single dose intravenous iron infusion for those suffering from moderate anemia, and referral for a complete medical and hematologic work-up prior to treatment for those diagnosed with severe anemia.  Additionally, hormonal therapy and the use of other nutritional supplements could be considered. Regardless of the proposed intervention, an instrument that exhibits good correlation with grade of anemia is likely to be widely utilized. During a woman’s pre-pregnancy reproductive years, heavy menstrual bleeding (HUB) is likely a most important contributor to high rates of anemia. The majority of women suffering from HUB have no underlying pathology, thus allowing for focused interventions to replete iron stores. Religious beliefs and customs often prevent women from speaking about issues related to menstruation, even if their flow is abnormal, often viewing heavy menstrual bleeding as “normal” or a necessary burden.

To our knowledge, there does not exist a validated instrument that could be easily utilized in LMICs that would convey meaningful associations between a woman’s response to a series of focused questions and her hematologic findings referable to anemia. A small trial conducted in Spain utilized a questionnaire that focused almost exclusively on descriptive menstrual blood loss and is likely not applicable to use in LMICs.

Study Aim

To develop and validate the PREPSA scoring instrument in women of reproductive age prior to pregnancy.

Study Design

The proposed pilot study incorporates 23 individual questions (Appendix A) which will be provided to village/rural women by female community health workers. We wish to sample 500 pre-pregnancy women (ages 18-25). Subsequent to the completion of responses to the questionnaire (and within four weeks) all previously consented participants will have blood drawn to obtain hemoglobin, ferritin, and transferrin saturation values. The responses that most closely align with low hemoglobin indices will be identified and become the basis of a scored, validated instrument which may be weighted based upon the strength of the associations found. Results will inform future health-outcome trials; interest among funders has already been confirmed.

The timeline includes a 2–3-month approval window and a four-month intervention, with 1-2 months to review study data and generate a primary publication.

Data Analyses

We plan to analyze the data in three steps. First, we will use a two-parameter logistic item response model to calibrate the scale and obtain information about the best items to include in a revised measure. Second, we will confirm the one-dimensionality of the scale using confirmatory factor analytic methods appropriate for binary and categorical outcomes. Third, the predictive validity of the revised scale will be tested via linear regression using the metrics gleamed from the blood samples as outcomes. While calibration, refinement, and validation of the PREPSA instrument will be an important outcome of this trial, the results will also facilitate future health-outcome trials in LMICs.