A Study of Multiple Micronutrient Supplementation (MMS) to Increase Adherence With Digital Technology

Adherence, Pregnancy

MMS, Pregnancy, Digitalization, adherence, Antenatal Care

The goal of this randomized clinical trial is to learn whether a digital health intervention can improve adherence to Multiple Micronutrient Supplementation (MMS) among pregnant women in Lombok Island. The study also aims to understand how individual characteristics, socio-economic factors, maternal health status, and antenatal care services influence adherence to MMS. The main questions it aims to answer are: 1. Does a digitally supported intervention increase adherence to MMS compared to standard care? 2. Does the type of MMS packaging (bottle vs. blister) affect adherence? 3. In the second stage, does adding calcium supplementation affect adherence to MMS? Researchers will compare four groups to see if digital support and packaging type improve MMS adherence: 1. Standard care with MMS in bottles 2. Standard care with MMS in blister packs 3. Digital intervention with MMS in bottles 4. Digital intervention with MMS in blister packs Approximately 10,012 pregnant women will be randomly assigned to one of these four groups using a 2×2 factorial design. Participants will: 1. Receive MMS through either bottle or blister packaging 2. Receive either standard care or a digital health intervention (such as reminders or digital support tools) 3. Attend routine antenatal care services 4. Be followed throughout pregnancy, delivery, and up to 42 days after childbirth In the second stage of the study, participants from community health posts (Posyandu) will also receive calcium supplementation in addition to MMS. Additional 900 pregnant women will be enrolled from the same Puskesmas areas participating in the MMS study to evaluate the addition of calcium supplementation. These participants will be recruited outside of the main MMS cohort and will be equally distributed across the four study arms. This stage aims to assess whether adding calcium supplementation influences adherence to MMS among pregnant women. Participants will be monitored during pregnancy, at delivery, and during the postnatal care period up to 42 days after birth. This study represents an early implementation of Multiple Micronutrient Supplementation (MMS) in Lombok Island, where MMS is not yet routinely available through government programs. Only selected primary healthcare centers (Puskesmas) that are randomized into the study will provide MMS to eligible participants. While the government has begun introducing MMS in other areas, it has not yet been implemented in Lombok. The digital health intervention will only be provided to pregnant women who agree to participate in the study and provide informed consent. All participants will continue to receive standard antenatal care (ANC) services in accordance with existing government programs. This study is also integrated with the ongoing distribution of iron and folic acid supplementation (TTD) in Lombok. Pregnant women who do not consent to participate in the study or do not receive MMS will continue to receive TTD as part of routine care outside of the study.

This study is a nested (two-stage) cluster-randomized controlled trial conducted in Lombok Island, designed to evaluate strategies to improve adherence to Multiple Micronutrient Supplementation (MMS) among pregnant women, as well as to assess the feasibility of integrating calcium supplementation into the MMS program within routine health systems. The first stage of the study consists of a cluster randomized trial at the puskesmas (primary healthcare center) level. Puskesmas are randomized into four intervention arms to evaluate the effectiveness of different delivery approaches for MMS, specifically comparing combinations of digital and non-digital strategies, as well as packaging formats. The digital intervention includes mobile-based tools such as WhatsApp reminders, chatbot-assisted education, call center support, and a gamified alert system to encourage adherence. Artificial intelligence-based approaches, including adherence monitoring and prediction models, will also be explored. The non-digital group receives standard antenatal and postnatal care services, including routine health promotion and printed educational materials. The second stage involves a cluster randomized trial at the posyandu (community health post) level within selected puskesmas. This stage evaluates the addition of calcium supplementation to MMS compared with MMS alone. Additional pregnant women will be enrolled outside the main MMS cohort and distributed across study arms. This component aims to assess the feasibility, acceptability, and operational considerations of co-administering calcium alongside MMS within the existing health system. To support implementation across both study components, several operational and digital systems will be applied. Each supplement package will be labeled with a unique QR code to enable real-time tracking of supplement distribution and consumption through KoboToolbox. A Dynamic Worker Support (DWS) system will be implemented to assist Community Health Promoters in automated scheduling, task management, and field activity optimization. Sample Size and Statistical Considerations The sample size has been calculated based on the primary outcome of MMS adherence, accounting for clustering effects at both puskesmas and posyandu levels. Approximately 10,012 pregnant women will be enrolled in Stage 1 across 60 puskesmas clusters. In Stage 2, approximately 900 additional participants will be recruited to evaluate calcium co-supplementation. The sample size is designed to ensure adequate statistical power to detect meaningful differences between study groups. A comprehensive quality assurance framework will be implemented to ensure data integrity, accuracy, and consistency across all study sites. Electronic data capture systems (KoboToolbox) will incorporate built-in validation rules, including range checks, consistency checks, and logical constraints across related variables. In addition, data validation will be strengthened through a double data entry process, whereby selected records are entered independently by two data entry personnel and discrepancies are identified and resolved through predefined verification procedures. Routine centralized data monitoring will be conducted to assess data completeness, timeliness, and internal consistency. In addition, quality assurance (QA) activities will be implemented to assess field staff performance through direct verification. This includes periodic visits by QA staff to pregnant women to validate home visit activities conducted by field workers. QA may also be conducted through HealthComm by contacting participants to confirm services received and ensure consistency with reported data. These procedures aim to ensure adherence to study protocols, verify implementation fidelity, and maintain overall data quality. A standardized data management system will be implemented, including a comprehensive data dictionary that defines all study variables, formats, permissible values, coding structures, and data sources. Where applicable, standardized coding approaches will be applied to ensure consistency. All study procedures will be guided by Standard Operating Procedures (SOPs) and a detailed field manual to ensure standardized implementation across sites. The field manual provides step-by-step operational guidance for field staff, including participant recruitment, informed consent procedures, home visit protocols, supplement distribution, digital system utilization, and data collection processes. It also outlines procedures for data management, adverse event reporting, and communication workflows between field teams and supervisors. Field staff, including Community Health Promoters, will receive structured training and ongoing supervision based on the field manual to ensure consistent, accurate, and high-quality implementation throughout the study. Data quality checks during data collection will aim to minimize missingness. During analysis, appropriate statistical techniques, such as multiple imputation or sensitivity analyses, will be applied as specified in the statistical analysis plan. All analyses will follow the intention-to-treat principle. Primary analyses will assess adherence to MMS across intervention arms using mixed-effects regression models to account for cluster randomization and potential confounders. The factorial design allows estimation of the independent and interaction effects of digital intervention and packaging type. Secondary analyses will examine factors influencing adherence, maternal and neonatal outcomes, and the impact of calcium co-supplementation. Depending on the nature of the outcome variables, appropriate generalized linear (mixed-effects) models will be employed. Binary outcomes will be analyzed using mixed-effects logistic regression models, continuous outcomes using linear mixed-effects models, and count or proportion outcomes using Poisson or binomial-based models with appropriate link functions. All models will account for clustering at the study design level and adjust for relevant covariates. Subgroup and sensitivity analyses will be conducted to assess the robustness and generalizability of the findings.

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