Nutritional Support and Prophylaxis Doses of Azithromycin for Pregnant Women - Mumta Pregnant Women Trial

Study Overview
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Brief Summary
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This four arm trial envisions to generate robust evidence for use of a fortified balanced energy-protein supplement to pregnant women for at least 6 months, alone versus in combination of Azithromycin (AZM) prophylaxis (two prophylaxis oral doses) versus in combination with both AZM prophylaxis (two prophylaxis oral doses) plus oral Choline and Nicotinamide supplementation; to see the impact on birth weight and length of newborn soon after birth (approximately within 72 hours). This is an open label, community-based, randomized controlled trial in peri-urban settings of Karachi, Pakistan, where the outcome assessor will be blinded. The comparison groups are control arm (only routine ANC care and nutritional counseling), nutrition only arm, nutrition plus AZM arm, and nutrition plus Choline and Nicotinamide arm.

Detailed Description
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Maternal under nutrition has a critical role in etiology of poor perinatal outcomes like low birth weight (LBW), accounting for 60-80% of all neonatal deaths and impacting nearly 20 million newborns overall. In Pakistan, nearly half of the households are food insecure with or without hunger. Great disparities exist between urban-rural and within urban disadvantaged populations living in the poorest of slums. In Sindh province alone, 72% of households are food insecure and 50% are with moderate to severe hunger. Around 18% of the married woman of reproductive age in Pakistan, are underweight and deficient of different micronutrients for example, 42% and 41% of women are Vitamin A and Zinc deficient, respectively.. This impacts childhood stunting, wasting, and underweight, prevalence of which, among under-five children is around 44%, 15% and 31%, respectively in Pakistan. WHO antenatal care (ANC) guidelines recommend the use of fortified balanced energy-protein supplements during pregnancy, but there is a lack of guidance on the best product/supplement for use in a particular setting. Until recently, the WHO ANC guidelines has made no recommendations on the use of these supplements in food insecure and undernourished settings. This is an area that required further research. Additionally, there is emerging literature on use of Choline and Nicotinamide during pregnancy and its potential additional impact on birth outcomes including growth and development after prenatal supplementation with Choline and Nicotinamide. Apart from nutrition supplement, the prophylaxis use of antibiotics, especially AZM is also under strong debate, as many studies have shown improvements in birth outcomes in low middle income settings. The possible mechanism of AZM may be explained through reduction in the risk of maternal infections during pregnancy. A systematic review showed that prophylaxis may reduce the risk of postpartum endometritis, preterm rupture of membranes and gonococcal infection when given routinely to all pregnant women With no effect on birth outcome but there were several biases reported such as high loss to follow-ups and limited numbers of included studies.. Therefore, robust evidence is needed via a field trial in the local context to evaluate the efficacy and effectiveness of the locally-produced, balanced energy-protein supplement alone or in combination with prophylaxis dose of AZM or balanced energy-protein supplement alone or in combination with Choline and Nicotinamide to pregnant woman on maternal and birth outcomes in low-income and food insecure settings. This could help to draw inferences for larger public health policy-making. This investment is specifically aiming to look at what impact a newly formulated nutritional supplement for pregnant and lactating women (PLW) can have on improving birth outcomes and as well as its potential to reduce wasting, stunting and underweight in infants.

Official Title
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Nutritional Support and Prophylaxis Doses of Azithromycin for Pregnant Women to Improve Birth Outcomes in the Peri-urban Slums of Karachi, Pakistan -a Randomized Controlled Trial

Conditions
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Undernutrition

Intervention / Treatment
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* Dietary Supplement: Balanced-energy protein (BEP)
* Drug: Azithromycin Tablets
* Drug: Choline Bitartrate
* Drug: Nicotinamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gestational age between ≥8 and < 19 weeks confirmed by ultrasound Able to give written voluntary informed consent. Permanent resident within the surveillance area, i.e. woman should be resident of the area for last 6 months at least to be considered as part of surveillance. Willing to spend the whole pregnancy duration after registration in trial within surveillance area until the birth outcome. Singleton and viable fetus on ultrasound Not working woman, and available for ANC and compliance visits at home. Previously not enrolled in pregnant woman trial. Previously not enrolled in Lactating woman trials. Exclusion Criteria: Having Mid-upper-arm-circumference of pregnant of ≥30.5 cm Having known food allergies if reported by woman (like peanut, lentils)

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control Arm<br>Arm-A: Standard antenatal care (ANC) counseling, service provision and nutrition counseling (World Health Organization (WHO) standard) | |
| Experimental: Nutrition only Arm<br>Arm-B:Balanced-energy protein (BEP), ready-to-use utrition supplement for at least 6 months + Standard ANC counseling, service provision and nutrition counseling (WHO standard) | Dietary Supplement: Balanced-energy protein (BEP)<br>* Pregnant women in the intervention arms will receive approximately 800 Kcal/day and around 16-21 gram of protein in a day in the form of ready-to-use supplement.<br>* Other names: Ready-to-use-supplementary food (RUSF);|
| Experimental: Nutrition plus Azithromycin Arm<br>Arm-C:Balanced-energy protein (BEP), ready-to-use nutrition supplement for at least 6 months + 2000 mg of Azithromycin at week 20 and 28 of pregnancy + Standard ANC counseling, service provision and nutrition counseling (WHO standard). | Dietary Supplement: Balanced-energy protein (BEP)<br>* Pregnant women in the intervention arms will receive approximately 800 Kcal/day and around 16-21 gram of protein in a day in the form of ready-to-use supplement.<br>* Other names: Ready-to-use-supplementary food (RUSF);Drug: Azithromycin Tablets<br>* Pregnant women randomized in Arm C will received two doses of 2000 mg of Azithromycin (4 tablets of 500 mg) oral at week 20 and 28 of pregnancy.<br>* Other names: Zetro;|
| Experimental: Nutrition plus Choline and Nicotinamide Arm<br>Arm-D: Balanced-energy protein (BEP), ready-to-use nutrition supplement for at least 6 months + Choline 450 and Nicotinamide 100 mg (1 each once daily orally starting from week 20 until birth outcome) + Standard ANC counseling, service provision and nutrition counseling (WHO standard). | Dietary Supplement: Balanced-energy protein (BEP)<br>* Pregnant women in the intervention arms will receive approximately 800 Kcal/day and around 16-21 gram of protein in a day in the form of ready-to-use supplement.<br>* Other names: Ready-to-use-supplementary food (RUSF);Drug: Azithromycin Tablets<br>* Pregnant women randomized in Arm C will received two doses of 2000 mg of Azithromycin (4 tablets of 500 mg) oral at week 20 and 28 of pregnancy.<br>* Other names: Zetro;Drug: Choline Bitartrate<br>* Pregnant women randomized in Arm D will received 450 mg of Choline orally once daily, starting from week 20 weeks of pregnancy until birth outcome<br>* Other names: Choline;Drug: Nicotinamide<br>* Pregnant women randomized in Arm D will received 100 mg of Nicotinamide orally once daily, starting from week 20 weeks of pregnancy until birth outcome<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Birth weight of newborn | Weight of the newborn assess in gram to assess the difference among four arms | To be assessed within 72 hours of birth | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Birth length of newborn | Length of the newborn assess in cm to assess the difference among four arms | To be assessed within 72 hours of birth |