Clinical trial NCT05108675: Microbiome and Malnutrition in Pregnancy (MMiP)
Official title: Elucidating the Dynamics and Impact of the Gut Microbiome on Maternal Nutritional Status During Pregnancy
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Weight Gain, Pregnancy
Microbial Colonization
Pregnancy Related
Pregnancy Loss
Pregnancy Complications
Pregnancy; Parasitic Disease
Parasitic Disease
Microbial Disease
Infant Malnutrition
Malnutrition
Malnutrition in Pregnancy
Breastfeeding
Keywords: Maternal Malnutrition, Gut Dysbiosis, Infant Health
Lead sponsor: Aga Khan University
Sponsor class: OTHER
Collaborators: name: The Hospital for Sick Children
name: University of Toronto
name: University of Calgary
name: Dalhousie University
name: University of Alberta
name: Canadian Institutes of Health Research (CIHR)
First posted: 2021-11-05
Enrollment: 400
Sex: FEMALE
Minimum age (years): 17
Maximum age (years): 24
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study will examine young, married women ≤24 years living in Matiari District, Pakistan. The investigators focus on younger women, due to the lack of knowledge about their microbiome and their vulnerability to undernutrition

Brief summary: Nutritional status during pregnancy plays an important role in maternal health and birth outcomes. While few factors impacting nutritional status during pregnancy have been identified, studies of undernutrition in children have revealed a key role for the gut microbiome. Remarkably, studies examining the dynamics of the maternal gut microbiome before and during pregnancy and its impact on birth outcomes are limited.

This study is being conducted to investigate how a mother's nutritional status and her gut microbiome during pregnancy contribute to the birth outcomes and health of her baby. The gut microbiome is the totality of microorganisms (e.g. bacteria, viruses, fungi) living in the gastrointestinal tract. This study will focus on married pregnant women 24 years and younger living in Matiari District in Pakistan. The focus is on younger women due to their vulnerability to undernutrition. Pregnant participants, and upon delivery, their newborns will be followed throughout pregnancy and for a year afterwards. Throughout this period, the investigators will collect stool samples, rectal swabs, blood samples, health assessments, nutritional and dietary assessments and birth/ labour details. The goal is to define the relationship between a mother's nutritional status and her microbiome dynamics during pregnancy and how they contribute to the birth outcomes and growth of her newborn. Investigators hypothesizes that alterations of the microbiota in the maternal gut (dysbiosis) is exacerbated by nutritional status or pathogen exposure during pregnancy. This impacts weight gain because of impaired nutrient absorption, and can lead to corresponding negative birth outcomes.

Detailed description: This project represents the first systematic investigation of the impact of the microbiome on nutritional status during pregnancy in young women and directly aligns with global health initiatives focused on this vulnerable cohort. The goal of the study is to define the relationships between host nutritional status and microbiome dynamics during pregnancy and how they contribute to birth outcomes. The gut microbiome has a profound influence on host nutritional status. Dysbiosis (loss of diversity/beneficial microbes and gain of pathobionts) has emerged as a major factor in the development of undernutrition. Despite the importance of nutrition during pregnancy, few studies have examined the role of the microbiome on maternal health and birth outcomes. Further, little is known concerning the influence of enteric eukaryotic microbes, such as parasites, on the bacterial microbiome and host nutrition.

At the core of this study are two complementary cohorts of young women that provide an exceptional opportunity to obtain longitudinal samples to monitor the dynamic relationships between microbiome community structure and function with gut health and host nutritional status. This registration is for the Matiari, Pakistan cohort of the study, where there is known to be a high prevalence of undernutrition among young women. This cohort is expected to yield insights into the influence of eukaryotic microbes that are often viewed as asymptomatic. The target demographic of the study is young, married mothers, ≤24 years in Matiari District within the province of Sindh, Pakistan. Matiari District is representative of rural settings in Pakistan The investigators have identified this younger demographic due to the lack of knowledge on the microbiome of young women, and their vulnerability to undernutrition. A second complementary cohort will be based Toronto, Canada. This project will yield insights into the relationships between prokaryotic and eukaryotic microbes in the gut and their associations with maternal health and birth outcomes.

The central hypothesis of the study is that alterations of the microbiota in the maternal gut (dysbiosis) exacerbated by nutritional status or pathogen exposure during pregnancy, impacts weight gain because of impaired nutrient absorption, leading to corresponding negative birth outcomes.

The study will be a prospective, longitudinal, observational study to investigate the impact and relationship between prokaryotic and eukaryotic microbes in the gut and their association with maternal health and birth outcomes among married young women ≤24 years residing in Matiari District. . The study will aim to recruit 400 women into two groups based on BMI at time of recruitment (normal BMI will be defined as between 20 and 24.9 kg/m2 and low BMI will be defined as less than 20 kg/m2). With a goal of having 200 participants within the normal BMI group and 200 participants within the low BMI group. Although this is the recruitment aim, in the event that the investigators are unable to recruit 200 women with a low BMI, more women will be recruited that fall within the normal BMI range. The study will follow women and their infants over the course of their pregnancy and for a year postpartum, collecting stool, rectal and blood samples, nutritional information, heath assessments, anthropometric measurements and empowerment metrics at different time points.

Eligibility criteria: Inclusion Criteria:

* Consent provided
* Married female aged 17-24 years
* In good general health, with no comorbidities
* Absence of COVID19 symptoms
* Intend to comply with study procedures and follow up

Exclusion Criteria:

* Women who do not meet the enrollment age criteria
* Women participating in interventional clinical trials
* Women who intend to leave the study area
* Women who cannot comply with study procedure's and follow-up
* Illness and other co-morbidities
* Signs of potential COVID19 infection
* BMI higher than 24.9 kg/m2
* Women who already have a member of their household participating
* Women who have taken antibiotics within the past 3 months
* Women who are past 16 weeks post- conception

Primary outcomes:
measure: To assess if alterations of the microbiota in the maternal gut (dysbiosis) are corelated with changes in maternal gestational weight gain
timeFrame: 8-20 weeks post-conception, 30-34 weeks post-conception
measure: To determine the correlation between maternal microbiome dysbiosis during pregnancy and birth weight.
timeFrame: At birth
measure: To determine the correlation between maternal microbiome dysbiosis during pregnancy and infant growth
timeFrame: 3month, 6month and 12month postpartum
Secondary outcomes:
measure: Anthropometrics
timeFrame: 8-16 weeks post-conception, 30-34 weeks post-conception, delivery, 3-months post-partum, 6 months post-partum and 12 months post-partum ]
measure: Anthropometrics: Maternal middle upper arm circumference
timeFrame: 8-16 weeks post-conception, 30-34 weeks post-conception, 3-months post-partum,and 12 months post-partum
measure: Anthropometrics: Maternal triceps skinfold thickness
timeFrame: 8-16 weeks post-conception, 30-34 weeks post-conception, 3-months post-partum, and 12 months post-partum
measure: Anthropometrics: Maternal height
timeFrame: 8-16 weeks post conception, 30-34 weeks post conception, delivery, 3 months post-partum and 12 months post partum
measure: Anthropometrics: Maternal weight
timeFrame: 8-16weeks post conception, 30-34 weeks post conception, delivery, 3 months post-partum and 12 months post-partum
measure: Maternal blood biomarker-1
timeFrame: 8-16 weeks post-conception, 30-34 weeks post-conception, and 12 months post-partum
measure: Maternal blood biomarker-2
timeFrame: 8-16 weeks post-conception, 30-34 weeks post-conception, and 12 months post-partum
measure: Maternal blood biomarker-3
timeFrame: 8-16 weeks post-conception, 30-34 weeks post-conception, and 12 months post-partum
measure: Maternal blood biomarker-4
timeFrame: 8-16 weeks post-conception, 30-34 weeks post-conception, and 12 months post-partum
measure: Infant blood biomarker-1
timeFrame: 1 year infant age
measure: Infant blood biomarker-2
timeFrame: 1 year infant age
measure: Infant blood biomarker-3
timeFrame: 1 year infant age
measure: Infant blood biomarker-4
timeFrame: 1 year infant age
measure: Infant sex
timeFrame: At birth
measure: Infant morbidity
timeFrame: at 3 months, 6 months and 12 months
measure: Maternal morbidity
timeFrame: 8-16 weeks post-conception, 30-34 weeks post-conception, 3 months post-partum, 6 months post-partum and 12 months post-partum
measure: Infant growth: weight
timeFrame: within 72 hours of birth, 3 months, 6 months and 12 months
measure: Infant growth: length
timeFrame: within 24 hours of birth, 3 months, 6 months and 12 months
measure: Infant growth: head circumference
timeFrame: within 72 hours of birth, 3 months, 6 months and 12 months
measure: Infant growth: mid upper arm circumference
timeFrame: within 72 hours of birth, 3 months, 6 months and 12 months
measure: Infant growth: triceps skinfold thickness
timeFrame: within 72 hours of birth, 3 months, 6 months and 12 months
measure: Gestational age at birth
timeFrame: Within 72 hours of birth
measure: Maternal age
timeFrame: 8-16 weeks post conception
measure: Breast feeding
timeFrame: at birth within 72 hours, 3 months, 6 months and 12 months
measure: Reported Maternal medicinal use
timeFrame: 8-16 weeks post-conception, 30-34 weeks post-conception, 3-months post-partum, 6 months post-partum and 12 months post-partum
measure: Reported Infant medication use
timeFrame: at birth within 72 hours, 3 months, 6 months and 12 months
measure: Maternal dietary intake Assessed through ASA 24 HR Dietary Recall system, completed 2x each time point
timeFrame: Baseline 8-16 weeks post conception, 30-34 weeks post conception and 12 months post partum
measure: Dietary diversity
timeFrame: Baseline 8-16 weeks post conception, 30-34 weeks post conception, 3 months post-partum and 12 months post partum
measure: Household annual food insecurity
timeFrame: 3 months post-partum and 12 months post-partum
measure: Generalized Self-efficacy
timeFrame: 3 months post-partum and 12 months post partum
measure: Perceived decision making
timeFrame: 3 months post-partum and 12 months post partum
measure: Perceived social support
timeFrame: 3 months post-partum and 12 months post partum
measure: Maternal demographics
timeFrame: Baseline 8-16 weeks post-conception
measure: Food insecurity
timeFrame: Baseline 8-16 weeks post conception, 3 months post partum and 12 months post partum
measure: Perceived parental stress
timeFrame: 3 months post-partum and 12 months post partum
measure: Preterm Births
timeFrame: At birth within 72 hours
measure: Small for gestational age
timeFrame: At birth within 72 hours
measure: Large for gestational age
timeFrame: At birth within 72 hours
measure: Delivery Assessment
timeFrame: at birth within 72 hours of birth
measure: Infant dietary intake
timeFrame: Infant age 1 year
measure: Maternal stool biomarkers-1
timeFrame: At baseline 8-16 weeks post conception and 30-34 weeks post conception
measure: Maternal stool biomarkers-2
timeFrame: At baseline 8-16 weeks post conception, 30-34 weeks post conception
measure: Maternal stool biomarkers-3
timeFrame: At baseline 8-16 weeks post conception and 30-34 weeks post conception
measure: Maternal: incidence of pathobionts
timeFrame: Baseline, 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum
measure: Infant: incidence of pathobionts
timeFrame: 3 and 12 month
measure: Maternal: metabolomic profile of stool [Metabolites involved in central metabolism as analysed by Mass Specttrometry]
timeFrame: Baseline, 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum
measure: Maternal gut bacteria profile
timeFrame: Baseline, 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum
measure: Maternal: blood metallomics profile
timeFrame: Baseline, 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum
measure: Infant: blood metallomics profile
timeFrame: Infant age 1 year
measure: Infant: gut bacterial profile
timeFrame: 3 month and 12 month
measure: Maternal metabolic pathway expression profile
timeFrame: Baseline 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum
measure: Infant eukaryotic microbiome profile
timeFrame: 3 & 12 Months
measure: Maternal eukaryotic microbiome profile
timeFrame: Baseline 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum ]
measure: Maternal bacterial gene expression profile
timeFrame: Baseline 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum ]
measure: Maternal: microbiome taxonomic alpha and beta diversity
timeFrame: Baseline 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum ]
measure: Infant: microbiome taxonomic alpha and beta diversity
timeFrame: 3 and 12 months postpartum
Other outcomes:
Locations:
city: Karachi
country: Pakistan
facility: Research and Training Centre Matiari, Aga Khan University
state: Sindh
Study officials:
affiliation: Aga Khan University
name: Zulfiqar Bhutta
role: PRINCIPAL_INVESTIGATOR
References: