Clinical trial NCT04012177: Nutritional Support and Prophylaxis Doses of Azithromycin for Pregnant Women - Mumta Pregnant Women Trial
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Undernutrition
Lead sponsor: Vital Pakistan Trust
Sponsor class: OTHER
Collaborators: name: Aga Khan University
First posted: 2019-07-09
Enrollment: 1884
Sex: FEMALE
Minimum age (years): 13
Maximum age (years): 49
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Birth weight of newborn
timeFrame: To be assessed within 72 hours of birth
Secondary outcomes:
measure: Birth length of newborn
timeFrame: To be assessed within 72 hours of birth
Other outcomes:
measure: Maternal hemoglobin
timeFrame: At enrollment and 32 weeks of pregnancy
measure: Maternal Ferritin level
timeFrame: At enrollment and 32 weeks of pregnancy
measure: Maternal Vitamin D level
timeFrame: At enrolment and 32 weeks of pregnancy
measure: Cord blood
timeFrame: At birth
measure: Plasma for proteomic analysis
timeFrame: At week 19 and 32 of pregnancy
measure: Plasma for Niacin metabolites
timeFrame: At enrolment and 32 weeks of pregnancy
measure: Urine for Choline metabolites
timeFrame: At enrolment and 32 weeks of pregnancy
measure: Magnetic resonance imaging (MRI) of infants (post birth outcomes)
timeFrame: 6 and 12 months of infant's age
measure: Global Scale for Early Development assessment
timeFrame: 6 and 12 months of infant's age
measure: Mullen assessment
timeFrame: 6 and 12 months of infant's age
measure: Hammersmith Neurological Examinations
timeFrame: 6 and 12 months of infant's age
measure: Maternal depression
timeFrame: At week 19 and 32 of pregnancy and then at 6 and 12 month post-partum
measure: Maternal and infant stool microbiome
timeFrame: At week 19 and 32 of pregnancy for mother, and then at 1-2, 3-4 and 5-6 and 12 months post-partum for mother-infant dyad
measure: Maternal and infant stool Lipocalin-2
timeFrame: At week 19 and 32 of pregnancy for mother, and then at 1-2, 3-4 and 5-6 and 12 months post-partum for mother-infant dyad
measure: Maternal and infant stool Carlprotectin
timeFrame: At week 19 and 32 of pregnancy for mother, and then at 1-2, 3-4 and 5-6 and 12 months post-partum for mother-infant dyad
measure: Maternal and infant stool Myeloperoxidase (MPO)
timeFrame: At week 19 and 32 of pregnancy for mother, and then at 1-2, 3-4 and 5-6 and 12 months post-partum for mother-infant dyad
measure: Maternal and infant stool TaqMan assay
timeFrame: At week 19 and 32 of pregnancy for mother, and then at 1-2, 3-4 and 5-6 and 12 months post-partum for mother-infant dyad
measure: Maternal and infant stool Bifido species
timeFrame: At week 19 and 32 of pregnancy for mother, and then at 1-2, 3-4 and 5-6 and 12 months post-partum for mother-infant dyad
measure: Metabolomic work - Maternal during pregnancy
timeFrame: At enrolment and 32 week of pregnancy
measure: Metabolomic work - Mother-Infant dyad
timeFrame: 1-2, 3-4 and 5-6 and 12 months post-partum for mother-infant dyad
measure: Human milk oligosaccharides
timeFrame: within 72 hours of birth
measure: Breastmilk quality
timeFrame: within 72 hours of birth
measure: Breastmilk microbiome
timeFrame: within 72 hours of birth
measure: Breastmilk immunoglobulin
timeFrame: within 72 hours of birth
Locations:
city: Karachi
country: Pakistan
facility: Peri-urban slum (Rehri Goth)
state: Sindh
Study officials:
affiliation: Vital Pakistan Trust
name: Yasir Shafiq, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Vital Pakistan Trust
name: Ameer Muhammad, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Aga Khan University
name: Fyezah Jehan, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Aga Khan University
name: Muhammad Imran Nisar, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Muhammad A, Fazal ZZ, Baloch B, Nisar I, Jehan F, Shafiq Y. Nutritional support and prophylaxis of azithromycin for pregnant women to improve birth outcomes in peri-urban slums of Karachi, Pakistan-a protocol of multi-arm assessor-blinded randomized controlled trial (Mumta PW trial). Trials. 2022 Jan 3;23(1):2. doi: 10.1186/s13063-021-05960-9.