The MOM-CARE Trial : Evaluating Antenatal and Postnatal MMSPlus for Improved Infant Birth and Growth Outcomes

A Phase III Double-Blind, Adaptive Randomized Trial of Antenatal MMSPlus Versus UNIMAPP MMS and Postnatal MMSPlus Versus UNIMAPP MMS or IFA to Improve Infant Birth Outcomes and Growth at 6 Months

This clinical trial aims to learn if MMS Plus improves infant health compared to standard MMS during pregnancy and the postnatal period in women living in peri-urban areas of Karachi, Pakistan. It will also evaluate how MMS Plus affects infant growth during the first 6 months of life.

The main questions it aims to answer are:

1. Does MMS Plus during pregnancy reduce the risk of poor infant outcomes compared to standard MMS, as measured on a 5-point ordinal scale ranging from perinatal mortality to term birth with appropriate, small, or large-for-gestational-age infants?
2. Does postnatal MMS Plus improve infant length velocity at 6 months of age among exclusively breastfed infants compared to standard MMS and iron/folic acid (IFA) supplementation?

Researchers will compare:

1. MMS Plus versus standard MMS during pregnancy (antenatal phase)
2. MMS Plus versus standard MMS versus IFA after birth (postnatal phase)

Participants will:

1. Be randomly assigned to receive either MMS Plus or standard MMS during pregnancy
2. Be re-randomized after delivery to receive either MMS Plus, standard MMS, or IFA supplements during the postnatal period
3. Receive supplements under double-blind conditions
4. Be followed through childbirth and until the infant is 6 months of age
5. Attend regular clinic visits for health monitoring, infant assessments, and data collection.

This phase III adaptive randomized controlled trial will occur in three peri-urban catchment areas of Karachi, Pakistan.

This is a two-phase, Phase III double-blind, adaptive randomized controlled trial designed to evaluate the effects of enhanced multiple micronutrient supplementation (MMS Plus) compared to standard UNIMMAP MMS and iron/folic acid (IFA) supplementation on maternal and infant health outcomes in peri-urban Karachi, Pakistan. The trial is being conducted by The Aga Khan University and is funded by the Bill Gates Foundation.

Study Phases and Design:

Antenatal Phase:

Pregnant women between 8-14 weeks of gestation will be enrolled and randomized (1:1) into one of two arms:

MMS Plus (enhanced formulation) Standard MMS (UNIMMAP formulation)

Both groups will also receive standard antenatal care (ANC) and nutrition counseling. The primary endpoint is a composite 5-point ordinal scale of infant health at 28 days post-birth, which includes perinatal mortality and growth-for-gestational-age outcomes - Small for gestational age (SGA), Appropriate for Gestational Age (AGA) and Large for Gestational Age (LGA), along with preterm or term. The trial employs a Bayesian adaptive design, with interim analyses beginning after 500 participants have birth outcomes, and subsequent evaluations every 250 outcomes. The design allows early stopping for superiority or continuation based on posterior probabilities.

Postnatal Phase:

Women with live births will be re-randomised (1:1:1) within one week postpartum into one of three arms:

MMS Plus Standard MMS IFA (standard care)

All groups receive standard postnatal care and nutrition counselling. The primary endpoint is infant length velocity (cm/month) at 6 months among exclusively breastfed infants. Secondary outcomes include additional anthropometric measures and neurodevelopmental assessments. Adaptive analyses in this phase also begin after 500 infants have outcome data.

Interventions:

MMS Plus includes 22 micronutrients with additional components: choline (450 mg), DHA (200 mg), calcium (500 mg), and a higher dose of nicotinamide (118 mg NE).

Standard MMS follows the UNIMMAP formulation with 15 micronutrients. IFA includes 60 mg of iron and 400 mcg folic acid.

All supplements are administered daily via single-dose sachets, indistinguishable in packaging and taste to preserve blinding. Products are manufactured by Remington Pharma.

Setting and Recruitment:

The trial is implemented through the Clinical Trials Unit (CTU) of Aga Khan University. Recruitment will occur in three peri-urban catchment communities: Ali Akbar Shah Goth (AG), Bhains Colony (BH), and Qayyumabad (QB). Two sites (AG and BH) are located in District Malir and one (QB) in District East. These communities have been selected due to high burdens of maternal undernutrition and established surveillance systems through the Integrated Research Platform (IRP).

Pregnant women will be recruited during Antenatal Care (ANC) visits and confirmed eligible via ultrasound. Postnatal re-randomization occurs for women with eligible live-born infants. Follow-up includes scheduled home and clinic visits until 6 months postpartum. Participants will receive all clinical services and transportation free of charge.

Data Management and Monitoring:

Data will be collected using a digital platform developed on OpenSRP, enabling longitudinal tracking of mother-child dyads. Unique IDs link all clinical encounters and supplement adherence records. Data quality assurance includes weekly field audits, double-entry verification, and remote monitoring by the trial coordination team.

A Data Safety Monitoring Board (DSMB) will review interim results and safety data. Trial governance includes a Trial Management Group (TMG) and an independent Trial Steering Committee. All adverse events will be reported following institutional and national regulatory guidelines.

Scientific Rationale:

Despite global efforts to improve maternal and infant nutrition, Pakistan continues to report high levels of maternal anaemia, low birth weight, and childhood stunting. While MMS is being piloted for national scale-up, the evidence base for extended formulations remains limited, especially regarding postnatal supplementation. MMS Plus is hypothesised to offer superior outcomes due to its inclusion of neurodevelopmentally and metabolically relevant nutrients (choline, DHA, calcium, and high-dose nicotinamide). These additions are based on recent findings from the MUMTA trial and other global data highlighting their role in fetal brain development, infant growth, and maternal health.

This trial addresses critical knowledge gaps in the timing (antenatal vs. postnatal), formulation, and impact of micronutrient interventions, using robust adaptive methodologies to optimise power, efficiency, and ethical participant exposure.

Antenatal Phase::

Inclusion Criteria:

• Gestational age confirmed by ultrasound to be 8-14 weeks
• Singleton and viable fetus on ultrasound
• A resident of the catchment area for at least the last six months
• Plans to stay within the catchment area during the pregnancy duration, during delivery and after birth of the baby.
• Has provided voluntary written informed consent

Exclusion Criteria:

• Women with known allergies or intolerance to any components of the MMS or MMS PLUS being studied
• Women with pre-existing health conditions such as history of uncontrolled diabetes and hypertension or other chronic illnesses
• Substance abuse, such as recreational drugs or smoking tobacco. Women chewing tobacco will not be excluded.

Postnatal Phase::

Inclusion Criteria:

• Birth weight available within 72 hours
• Intention to breastfeed for 6 months
• Resides in the study area for the duration of the trial
• Has provided voluntary written informed consent

Exclusion Criteria:

• Congenital anomalies, birth defects, or severe neonatal complications
• Infants who are already receiving supplemental formula feeding or other nutritional supplements (except pre-lacteal feeding, vitamins, and medications)
• Infants whose mothers have conditions that significantly affect breastfeeding, such as severe postpartum depression, insufficient milk supply, or maternal use of medications that contraindicate breastfeeding