Microbiome and Malnutrition in Pregnancy (MMiP)

Sponsor

Aga Khan University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05108675

Collaborator

The Hospital for Sick Children (Other), University of Toronto (Other), University of Calgary (Other), Dalhousie University (Other), University of Alberta (Other), Canadian Institutes of Health Research (CIHR) (Other)

400

Enrollment

Location

31.2

Anticipated Duration (Months)

12.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

400 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Elucidating the Dynamics and Impact of the Gut Microbiome on Maternal Nutritional Status During Pregnancy

Actual Study Start Date :

Nov 24, 2021

Anticipated Primary Completion Date :

Jun 30, 2024

Anticipated Study Completion Date :

Jun 30, 2024

Outcome Measures

Primary Outcome Measures

To assess if alterations of the microbiota in the maternal gut (dysbiosis) are corelated with changes in maternal gestational weight gain [8-20 weeks post-conception, 30-34 weeks post-conception]
The primary endpoint will be the change in maternal gestational weight gain (GWG) during pregnancy, measured between the first (8-16 weeks post-conception) and second time point (30-34 weeks post-conception)
To determine the correlation between maternal microbiome dysbiosis during pregnancy and birth weight. [At birth]
The primary endpoint will be change in birthweight measured in kilograms.
To determine the correlation between maternal microbiome dysbiosis during pregnancy and infant growth [3month, 6month and 12month postpartum]
The primary endpoint will be change in WHO z-scores during first year of infant's life. These z-scores will be calculated for weight (measured in kg), length and head circumference (measured in cm).

Secondary Outcome Measures

Anthropometrics [8-16 weeks post-conception, 30-34 weeks post-conception, delivery, 3-months post-partum, 6 months post-partum and 12 months post-partum ]]
Maternal BMI
Anthropometrics: Maternal middle upper arm circumference [8-16 weeks post-conception, 30-34 weeks post-conception, 3-months post-partum,and 12 months post-partum]
Measured in cm
Anthropometrics: Maternal triceps skinfold thickness [8-16 weeks post-conception, 30-34 weeks post-conception, 3-months post-partum, and 12 months post-partum]
Measured in mm
Anthropometrics: Maternal height [8-16 weeks post conception, 30-34 weeks post conception, delivery, 3 months post-partum and 12 months post partum]
measured in cm
Anthropometrics: Maternal weight [8-16weeks post conception, 30-34 weeks post conception, delivery, 3 months post-partum and 12 months post-partum]
measured in kg
Maternal blood biomarker-1 [8-16 weeks post-conception, 30-34 weeks post-conception, and 12 months post-partum]
Concentration of HB in g/dL, marker of anemia.
Maternal blood biomarker-2 [8-16 weeks post-conception, 30-34 weeks post-conception, and 12 months post-partum]
Level of MCV in whole blood measured in femtoliters (fL).
Maternal blood biomarker-3 [8-16 weeks post-conception, 30-34 weeks post-conception, and 12 months post-partum]
Concentration of Ferritin in serum measured in ng/mL, marker of iron stores in blood.
Maternal blood biomarker-4 [8-16 weeks post-conception, 30-34 weeks post-conception, and 12 months post-partum]
Concentration of CRP in blood, measured in mg/dL, marker of inflammation .
Infant blood biomarker-1 [1 year infant age]
Concentration of HB in g/dL, marker of anemia.
Infant blood biomarker-2 [1 year infant age]
Level of MCV in whole blood measured in femtoliters (fL).
Infant blood biomarker-3 [1 year infant age]
Concentration of Ferritin in serum measured in ng/mL, marker of iron stores in blood.
Infant blood biomarker-4 [1 year infant age]
Concentration of CRP in blood, measured in mg/dL, marker of inflammation .
Infant sex [At birth]
Male Female
Infant morbidity [at 3 months, 6 months and 12 months]
Assessed through infant health assessment questionnaire
Maternal morbidity [8-16 weeks post-conception, 30-34 weeks post-conception, 3 months post-partum, 6 months post-partum and 12 months post-partum]
Assessed through health assessment questionnaire
Infant growth: weight [within 72 hours of birth, 3 months, 6 months and 12 months]
Measured in kg
Infant growth: length [within 24 hours of birth, 3 months, 6 months and 12 months]
Measured in cm
Infant growth: head circumference [within 72 hours of birth, 3 months, 6 months and 12 months]
Measured in cm
Infant growth: mid upper arm circumference [within 72 hours of birth, 3 months, 6 months and 12 months]
Measured in cm
Infant growth: triceps skinfold thickness [within 72 hours of birth, 3 months, 6 months and 12 months]
Measured in mm
Gestational age at birth [Within 72 hours of birth]
Measured in weeks
Maternal age [8-16 weeks post conception]
Age between 17-24 years documented through national ID card, school certificate or through maternal recall
Breast feeding [at birth within 72 hours, 3 months, 6 months and 12 months]
amount and initiation of breast feeding, top milk, formula milk and complementary feeding Based off of WHO 2010 Guidelines: Indicators for assessing infant and young child feeding practices (Part 2 Measurement)
Reported Maternal medicinal use [8-16 weeks post-conception, 30-34 weeks post-conception, 3-months post-partum, 6 months post-partum and 12 months post-partum]
Questionnaire
Reported Infant medication use [at birth within 72 hours, 3 months, 6 months and 12 months]
Questionnaire
Maternal dietary intake Assessed through ASA 24 HR Dietary Recall system, completed 2x each time point [Baseline 8-16 weeks post conception, 30-34 weeks post conception and 12 months post partum]
Assessed through ASA 24 HR Dietary Recall system
Dietary diversity [Baseline 8-16 weeks post conception, 30-34 weeks post conception, 3 months post-partum and 12 months post partum]
Minimum Dietary Diversity Score for Women (MDD-W)
Household annual food insecurity [3 months post-partum and 12 months post-partum]
Food insecurity will be assessed using the Household Food Insecurity Access Scale (HFIAS)
Generalized Self-efficacy [3 months post-partum and 12 months post partum]
Self-efficacy will be measured using the Generalized Self-Efficacy scale, developed by Schwarzer and Jerusalem. A 10 item psychometric scale.
Perceived decision making [3 months post-partum and 12 months post partum]
Questions pertaining to perceived decision-making are from the Pakistan Demographic and Health Survey (PDHS)
Perceived social support [3 months post-partum and 12 months post partum]
Perceived social support will be measured using the Multi-dimensional Scale of Perceived Social Support (MSPSS), developed by Zimet et al.
Maternal demographics [Baseline 8-16 weeks post-conception]
Questions pertaining to demographic data are adapted from the Pakistan Demographic and Health Survey (PDHS)
Food insecurity [Baseline 8-16 weeks post conception, 3 months post partum and 12 months post partum]
Questionnaire developed by Hager, E.R., et al., Development and validity of a 2-item screen to identify families at risk for food insecurity.
Perceived parental stress [3 months post-partum and 12 months post partum]
Perceived parental stress will be measured using the Perceived Stress Scale (PSS-10)
Preterm Births [At birth within 72 hours]
Gestational age at birth in weeks
Small for gestational age [At birth within 72 hours]
Small-for-gestational-age (<10th percentile of weight-for-gestational-age and sex as defined by Intergrowth standards)
Large for gestational age [At birth within 72 hours]
>90th percentile of weight-for-gestational-age and sex as defined by Intergrowth standards)
Delivery Assessment [at birth within 72 hours of birth]
Questionnaire, mode of delivery, place of birth and other description around delivery
Infant dietary intake [Infant age 1 year]
NutricheQ Questionnaire: a tool designed for toddlers aged 1 to 3 years of age, with a focus on markers for inadequate or excessive intake and dietary imbalances
Maternal stool biomarkers-1 [At baseline 8-16 weeks post conception and 30-34 weeks post conception]
Level of Calprotectin in stool a marker of intestinal inflammation, measured in μg/g.
Maternal stool biomarkers-2 [At baseline 8-16 weeks post conception, 30-34 weeks post conception]
Concentration of Claudin 15 in stool a marker of intestinal permeability measured in ng/mL.
Maternal stool biomarkers-3 [At baseline 8-16 weeks post conception and 30-34 weeks post conception]
Concentration of Lipocalin in stool, a marker of gut inflammation, measured in μg/mL.
Maternal: incidence of pathobionts [Baseline, 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum]
As identified through 16S, 18S and ITS rDNA surveys
Infant: incidence of pathobionts [3 and 12 month]
As identified through 16S, 18S and ITS rDNA surveys
Maternal: metabolomic profile of stool [Metabolites involved in central metabolism as analysed by Mass Specttrometry] [Baseline, 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum]
Analysis of the core metabolites involved in central metabolism. These metabolites will be analysed through Mass Spec and include short chain fatty acids, amino acids, intermediates in energy metabolism and nucleotide biosynthesis
Maternal gut bacteria profile [Baseline, 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum]
Measured through 16S rDNA sequence surveys
Maternal: blood metallomics profile [Baseline, 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum]
Measured through ICP-MS (https://www.metabolomicscentre.ca/new_service/25) - TMIC platform of metabolmics
Infant: blood metallomics profile [Infant age 1 year]
as measured through ICP-MS (https://www.metabolomicscentre.ca/new_service/25) Through TMIC platform
Infant: gut bacterial profile [3 month and 12 month]
Measured through 16S rDNA sequence surveys
Maternal metabolic pathway expression profile [Baseline 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum]
as measured through whole microbiome RNASeq (metatranscriptomics)
Infant eukaryotic microbiome profile [3 & 12 Months]
as measured through 18S and ITS rDNA sequence surveys
Maternal eukaryotic microbiome profile [Baseline 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum ]]
as measured through 18S and ITS rDNA sequence surveys
Maternal bacterial gene expression profile [Baseline 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum ]]
as measured through whole microbiome RNASeq (metatranscriptomics) - The output of these analyses are readouts of microbial gene expression detailing biochemical activities as well as the taxa responsible.
Maternal: microbiome taxonomic alpha and beta diversity [Baseline 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum ]]
To define taxonomic diversity, species profiles from 16S, 18S and ITS rDNA data will be clustered to identify differences in community structure across samples. Alpha diversity will be measured through indices such as Chao, Shannon and Simpson indices. Beta diversity will be measured through standard indices such as Bray-Curtis distances.
Infant: microbiome taxonomic alpha and beta diversity [3 and 12 months postpartum]
To define taxonomic diversity, species profiles from 16S, 18S and ITS rDNA data will be clustered to identify differences in community structure across samples. Alpha diversity will be measured through indices such as Chao, Shannon and Simpson indices. Beta diversity will be measured through standard indices such as Bray-Curtis distances.