Elucidating the Dynamics and Impact of the Gut Microbiome on Maternal Nutritional Status During Pregnancy
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Weight Gain, Pregnancy
- Sponsor
- Aga Khan University
- Enrollment
- 400
- Locations
- 1
- Primary Endpoint
- To determine the correlation between maternal microbiome dysbiosis during pregnancy and birth weight.
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
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.
Investigators
Dr Zulfiqar Ahmed Bhutta
Professor Zulfiqar A Bhutta MBBS, FRCPCH, FAAP, PhD
Aga Khan University
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
Outcomes
Primary Outcomes
To determine the correlation between maternal microbiome dysbiosis during pregnancy and birth weight.
Time Frame: 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
Time Frame: 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).
To assess if alterations of the microbiota in the maternal gut (dysbiosis) are corelated with changes in maternal gestational weight gain
Time Frame: 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)
Secondary Outcomes
- Anthropometrics: Maternal height(8-16 weeks post conception, 30-34 weeks post conception, delivery, 3 months post-partum and 12 months post partum)
- Maternal blood biomarker-4(8-16 weeks post-conception, 30-34 weeks post-conception, and 12 months post-partum)
- 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 ])
- Infant blood biomarker-1(1 year infant age)
- Infant blood biomarker-3(1 year infant age)
- Perceived parental stress(3 months post-partum and 12 months post partum)
- Small for gestational age(At birth within 72 hours)
- Maternal stool biomarkers-1(At baseline 8-16 weeks post conception and 30-34 weeks post conception)
- 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)
- 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 ])
- 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)
- Maternal blood biomarker-3(8-16 weeks post-conception, 30-34 weeks post-conception, and 12 months post-partum)
- Infant blood biomarker-2(1 year infant age)
- Infant blood biomarker-4(1 year infant age)
- 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)
- 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)
- Household annual food insecurity(3 months post-partum and 12 months post-partum)
- Perceived social support(3 months post-partum and 12 months post partum)
- Preterm Births(At birth within 72 hours)
- Anthropometrics: Maternal triceps skinfold thickness(8-16 weeks post-conception, 30-34 weeks post-conception, 3-months post-partum, and 12 months post-partum)
- Anthropometrics: Maternal weight(8-16weeks post conception, 30-34 weeks post conception, delivery, 3 months post-partum and 12 months post-partum)
- Maternal blood biomarker-2(8-16 weeks post-conception, 30-34 weeks post-conception, and 12 months post-partum)
- Gestational age at birth(Within 72 hours of birth)
- Food insecurity(Baseline 8-16 weeks post conception, 3 months post partum and 12 months post partum)
- Maternal: incidence of pathobionts(Baseline, 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum)
- Maternal gut bacteria profile(Baseline, 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum)
- Maternal: blood metallomics profile(Baseline, 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum)
- Maternal eukaryotic microbiome profile(Baseline 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum ])
- Maternal blood biomarker-1(8-16 weeks post-conception, 30-34 weeks post-conception, and 12 months post-partum)
- Infant morbidity(at 3 months, 6 months and 12 months)
- Infant growth: weight(within 72 hours of birth, 3 months, 6 months and 12 months)
- Infant growth: length(within 24 hours of birth, 3 months, 6 months and 12 months)
- Infant growth: mid upper arm circumference(within 72 hours of birth, 3 months, 6 months and 12 months)
- Infant growth: triceps skinfold thickness(within 72 hours of birth, 3 months, 6 months and 12 months)
- Maternal age(8-16 weeks post conception)
- Breast feeding(at birth within 72 hours, 3 months, 6 months and 12 months)
- Reported Infant medication use(at birth within 72 hours, 3 months, 6 months and 12 months)
- 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)
- Perceived decision making(3 months post-partum and 12 months post partum)
- Maternal demographics(Baseline 8-16 weeks post-conception)
- Infant dietary intake(Infant age 1 year)
- Maternal stool biomarkers-2(At baseline 8-16 weeks post conception, 30-34 weeks post conception)
- Maternal stool biomarkers-3(At baseline 8-16 weeks post conception and 30-34 weeks post conception)
- Infant: incidence of pathobionts(3 and 12 month)
- 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)
- Infant eukaryotic microbiome profile(3 & 12 Months)
- Infant sex(At birth)
- Infant growth: head circumference(within 72 hours of birth, 3 months, 6 months and 12 months)
- Dietary diversity(Baseline 8-16 weeks post conception, 30-34 weeks post conception, 3 months post-partum and 12 months post partum)
- Generalized Self-efficacy(3 months post-partum and 12 months post partum)
- Infant: blood metallomics profile(Infant age 1 year)
- Infant: gut bacterial profile(3 month and 12 month)
- Large for gestational age(At birth within 72 hours)
- Delivery Assessment(at birth within 72 hours of birth)
- 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 ])
- Infant: microbiome taxonomic alpha and beta diversity(3 and 12 months postpartum)