Microbiome and Malnutrition in Pregnancy (MMiP)

Pregnancy Related Clinical Trial

— MMiP  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05108675
• Other study ID #: 51950
• Status: Active, not recruiting
• Start date: November 24, 2021
• Est. completion date: June 30, 2024

Study information

• Verified date: July 2023
• Source: Aga Khan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 400
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 17 Years to 24 Years

Eligibility

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

Related Conditions & MeSH terms

• Breastfeeding
• Communicable Diseases
• Gestational Weight Gain
• Infant Malnutrition
• Infant Nutrition Disorders
• Infections
• Malnutrition
• Malnutrition in Pregnancy
• Microbial Colonization
• Microbial Disease
• Parasitic Disease
• Parasitic Diseases
• Pregnancy Complications
• Pregnancy Loss
• Pregnancy Related
• Weight Gain

Locations

Country	Name	City	State
Pakistan	Research and Training Centre Matiari, Aga Khan University	Karachi	Sindh

Sponsors (7)

Lead Sponsor	Collaborator
Aga Khan University	Canadian Institutes of Health Research (CIHR), Dalhousie University, The Hospital for Sick Children, University of Alberta, University of Calgary, University of Toronto

Country where clinical trial is conducted

Pakistan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess if alterations of the microbiota in the maternal gut (dysbiosis) are corelated with changes in maternal gestational weight gain	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)	8-20 weeks post-conception, 30-34 weeks post-conception
Primary	To determine the correlation between maternal microbiome dysbiosis during pregnancy and birth weight.	The primary endpoint will be change in birthweight measured in kilograms.	At birth
Primary	To determine the correlation between maternal microbiome dysbiosis during pregnancy and infant growth	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).	3month, 6month and 12month postpartum
Secondary	Anthropometrics	Maternal BMI	8-16 weeks post-conception, 30-34 weeks post-conception, delivery, 3-months post-partum, 6 months post-partum and 12 months post-partum ]
Secondary	Anthropometrics: Maternal middle upper arm circumference	Measured in cm	8-16 weeks post-conception, 30-34 weeks post-conception, 3-months post-partum,and 12 months post-partum
Secondary	Anthropometrics: Maternal triceps skinfold thickness	Measured in mm	8-16 weeks post-conception, 30-34 weeks post-conception, 3-months post-partum, and 12 months post-partum
Secondary	Anthropometrics: Maternal height	measured in cm	8-16 weeks post conception, 30-34 weeks post conception, delivery, 3 months post-partum and 12 months post partum
Secondary	Anthropometrics: Maternal weight	measured in kg	8-16weeks post conception, 30-34 weeks post conception, delivery, 3 months post-partum and 12 months post-partum
Secondary	Maternal blood biomarker-1	Concentration of HB in g/dL, marker of anemia.	8-16 weeks post-conception, 30-34 weeks post-conception, and 12 months post-partum
Secondary	Maternal blood biomarker-2	Level of MCV in whole blood measured in femtoliters (fL).	8-16 weeks post-conception, 30-34 weeks post-conception, and 12 months post-partum
Secondary	Maternal blood biomarker-3	Concentration of Ferritin in serum measured in ng/mL, marker of iron stores in blood.	8-16 weeks post-conception, 30-34 weeks post-conception, and 12 months post-partum
Secondary	Maternal blood biomarker-4	Concentration of CRP in blood, measured in mg/dL, marker of inflammation .	8-16 weeks post-conception, 30-34 weeks post-conception, and 12 months post-partum
Secondary	Infant blood biomarker-1	Concentration of HB in g/dL, marker of anemia.	1 year infant age
Secondary	Infant blood biomarker-2	Level of MCV in whole blood measured in femtoliters (fL).	1 year infant age
Secondary	Infant blood biomarker-3	Concentration of Ferritin in serum measured in ng/mL, marker of iron stores in blood.	1 year infant age
Secondary	Infant blood biomarker-4	Concentration of CRP in blood, measured in mg/dL, marker of inflammation .	1 year infant age
Secondary	Infant sex	Male Female	At birth
Secondary	Infant morbidity	Assessed through infant health assessment questionnaire	at 3 months, 6 months and 12 months
Secondary	Maternal morbidity	Assessed through health assessment questionnaire	8-16 weeks post-conception, 30-34 weeks post-conception, 3 months post-partum, 6 months post-partum and 12 months post-partum
Secondary	Infant growth: weight	Measured in kg	within 72 hours of birth, 3 months, 6 months and 12 months
Secondary	Infant growth: length	Measured in cm	within 24 hours of birth, 3 months, 6 months and 12 months
Secondary	Infant growth: head circumference	Measured in cm	within 72 hours of birth, 3 months, 6 months and 12 months
Secondary	Infant growth: mid upper arm circumference	Measured in cm	within 72 hours of birth, 3 months, 6 months and 12 months
Secondary	Infant growth: triceps skinfold thickness	Measured in mm	within 72 hours of birth, 3 months, 6 months and 12 months
Secondary	Gestational age at birth	Measured in weeks	Within 72 hours of birth
Secondary	Maternal age	Age between 17-24 years documented through national ID card, school certificate or through maternal recall	8-16 weeks post conception
Secondary	Breast feeding	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)	at birth within 72 hours, 3 months, 6 months and 12 months
Secondary	Reported Maternal medicinal use	Questionnaire	8-16 weeks post-conception, 30-34 weeks post-conception, 3-months post-partum, 6 months post-partum and 12 months post-partum
Secondary	Reported Infant medication use	Questionnaire	at birth within 72 hours, 3 months, 6 months and 12 months
Secondary	Maternal dietary intake Assessed through ASA 24 HR Dietary Recall system, completed 2x each time point	Assessed through ASA 24 HR Dietary Recall system	Baseline 8-16 weeks post conception, 30-34 weeks post conception and 12 months post partum
Secondary	Dietary diversity	Minimum Dietary Diversity Score for Women (MDD-W)	Baseline 8-16 weeks post conception, 30-34 weeks post conception, 3 months post-partum and 12 months post partum
Secondary	Household annual food insecurity	Food insecurity will be assessed using the Household Food Insecurity Access Scale (HFIAS)	3 months post-partum and 12 months post-partum
Secondary	Generalized Self-efficacy	Self-efficacy will be measured using the Generalized Self-Efficacy scale, developed by Schwarzer and Jerusalem. A 10 item psychometric scale.	3 months post-partum and 12 months post partum
Secondary	Perceived decision making	Questions pertaining to perceived decision-making are from the Pakistan Demographic and Health Survey (PDHS)	3 months post-partum and 12 months post partum
Secondary	Perceived social support	Perceived social support will be measured using the Multi-dimensional Scale of Perceived Social Support (MSPSS), developed by Zimet et al.	3 months post-partum and 12 months post partum
Secondary	Maternal demographics	Questions pertaining to demographic data are adapted from the Pakistan Demographic and Health Survey (PDHS)	Baseline 8-16 weeks post-conception
Secondary	Food insecurity	Questionnaire developed by Hager, E.R., et al., Development and validity of a 2-item screen to identify families at risk for food insecurity.	Baseline 8-16 weeks post conception, 3 months post partum and 12 months post partum
Secondary	Perceived parental stress	Perceived parental stress will be measured using the Perceived Stress Scale (PSS-10)	3 months post-partum and 12 months post partum
Secondary	Preterm Births	Gestational age at birth in weeks	At birth within 72 hours
Secondary	Small for gestational age	Small-for-gestational-age (<10th percentile of weight-for-gestational-age and sex as defined by Intergrowth standards)	At birth within 72 hours
Secondary	Large for gestational age	>90th percentile of weight-for-gestational-age and sex as defined by Intergrowth standards)	At birth within 72 hours
Secondary	Delivery Assessment	Questionnaire, mode of delivery, place of birth and other description around delivery	at birth within 72 hours of birth
Secondary	Infant dietary intake	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	Infant age 1 year
Secondary	Maternal stool biomarkers-1	Level of Calprotectin in stool a marker of intestinal inflammation, measured in µg/g.	At baseline 8-16 weeks post conception and 30-34 weeks post conception
Secondary	Maternal stool biomarkers-2	Concentration of Claudin 15 in stool a marker of intestinal permeability measured in ng/mL.	At baseline 8-16 weeks post conception, 30-34 weeks post conception
Secondary	Maternal stool biomarkers-3	Concentration of Lipocalin in stool, a marker of gut inflammation, measured in µg/mL.	At baseline 8-16 weeks post conception and 30-34 weeks post conception
Secondary	Maternal: incidence of pathobionts	As identified through 16S, 18S and ITS rDNA surveys	Baseline, 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum
Secondary	Infant: incidence of pathobionts	As identified through 16S, 18S and ITS rDNA surveys	3 and 12 month
Secondary	Maternal: metabolomic profile of stool [Metabolites involved in central metabolism as analysed by Mass Specttrometry]	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	Baseline, 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum
Secondary	Maternal gut bacteria profile	Measured through 16S rDNA sequence surveys	Baseline, 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum
Secondary	Maternal: blood metallomics profile	Measured through ICP-MS (https://www.metabolomicscentre.ca/new_service/25) - TMIC platform of metabolmics	Baseline, 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum
Secondary	Infant: blood metallomics profile	as measured through ICP-MS (https://www.metabolomicscentre.ca/new_service/25) Through TMIC platform	Infant age 1 year
Secondary	Infant: gut bacterial profile	Measured through 16S rDNA sequence surveys	3 month and 12 month
Secondary	Maternal metabolic pathway expression profile	as measured through whole microbiome RNASeq (metatranscriptomics)	Baseline 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum
Secondary	Infant eukaryotic microbiome profile	as measured through 18S and ITS rDNA sequence surveys	3 & 12 Months
Secondary	Maternal eukaryotic microbiome profile	as measured through 18S and ITS rDNA sequence surveys	Baseline 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum ]
Secondary	Maternal bacterial gene expression profile	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.	Baseline 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum ]
Secondary	Maternal: microbiome taxonomic alpha and beta diversity	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.	Baseline 8-16 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum ]
Secondary	Infant: microbiome taxonomic alpha and beta diversity	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.	3 and 12 months postpartum