Microbiome and Malnutrition in Pregnancy

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: Recruiting

Administrative data

• NCT number: NCT04992104
• Other study ID #: CTOREB3512
• Secondary ID: MRT-168043
• Status: Recruiting
• Start date: February 22, 2023
• Est. completion date: December 2024

Study information

• Verified date: April 2023
• Source: The Hospital for Sick Children
• Contact: Jessie Hulst, MD
• Phone: 416-813-7735
• Email: jessie.hulst[@]sickkids.ca
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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 pregnant women, 24 years and younger living in the Toronto and greater Toronto area. 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. With the hypothesis 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.

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 the Toronto cohort of the study, which will focus on refugee and young adult obstetric clinics in Toronto, a population of specific relevance to undernutrition. 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 mothers, 24 years of age and younger, in the Toronto and Greater Toronto Area. 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 in the Matiari district of Pakistan. This project will yield unprecedented 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 young women, 24 years of age and younger in the Toronto and Greater Toronto Area. 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 post-partum, collecting stool, rectal and blood samples, nutritional information, heath assessments, anthropometric measurements and empowerment metrics at different time points.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 800
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A to 24 Years

Eligibility

Inclusion Criteria:

1. Consent provided

2. Participant is between 8-20 weeks post-conception

3. Female aged 24 years of age and younger

4. Confirmation of pregnancy

5. Intend to comply with study procedures and follow up

Exclusion Criteria:

1. Women who do not meet the enrolment age criteria

2. Women who are 20 + weeks post-conception

3. Women who have taken antibiotics within the past 3 months Note: it is common practice to give the mother penicillin in perinatal period if they are GBS positive; because this is standardized across the board it would not act as an exclusion factor.

Related Conditions & MeSH terms

• Breast Feeding
• Communicable Diseases
• Infant Nutrition Disorders
• Infections
• Malnutrition
• Malnutrition, Infant
• Metabolomics
• Microbial Colonization
• Microbial Disease
• Parasitic Disease
• Parasitic Diseases
• Pregnancy Complications
• Pregnancy Loss
• Pregnancy Related

Locations

Country	Name	City	State
Canada	St. Michael's Hospital	Toronto
Canada	The Hospital for Sick Children	Toronto

Sponsors (9)

Lead Sponsor	Collaborator
The Hospital for Sick Children	Aga Khan University, Canadian Institutes of Health Research (CIHR), Dalhousie University, National Institute of Allergy and Infectious Diseases (NIAID), Unity Health Toronto, University of Alberta, University of Calgary, University of Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess if alterations of the microbiota in the maternal gut (dysbiosis) are associated 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 (8-20 weeks post-conception) and second time point (30-34 weeks post conception).	8-20 weeks post-conception, 30-34 weeks post conception
Secondary	Anthropometrics: Maternal BMI	calculated using weight and height; BMI = kg/m2	8-20 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	8-20 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 cm	8-20 weeks post-conception, 30-34 weeks post-conception, 3-months post-partum, and 12 months post-partum
Secondary	Anthropometrics: Maternal height	Measured in cm	8-20 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	8-20 weeks post conception, 30-34 weeks post conception, delivery, 3 months post-partum and 12 months post-partum
Secondary	Maternal blood biomarkers	Concentration of HB + MCV, ferritin, and CRP	8-20 weeks post-conception, 30-34 weeks post-conception, and 12 months post-partum
Secondary	Infant blood biomarkers	Concentration of HB + MCV, ferritin, and CRP	12 months
Secondary	Infant sex	Female or Male	Determined at delivery
Secondary	Infant morbidity	Assessed through infant health assessment questionnaires	3 months, 6 months and 12 months
Secondary	Maternal morbidity	Assessed through health assessment questionnaires	8-20 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 24 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 24 hours of birth, 3 months, 6 months and 12 months
Secondary	Infant growth: mid upper arm circumference	Measured in cm	within 24 hours of birth, 3 months, 6 months and 12 months
Secondary	Infant growth: triceps skinfold thickness	Measured in cm	within 24 hours of birth, 3 months, 6 months and 12 months
Secondary	Infant Gestational age	Will be documented at baseline visit.	8-20 weeks post conception
Secondary	Breast feeding: amount and initiation of complementary feeding	Based off of WHO 2010 Guidelines: Indicators for assessing infant and young child feeding practices (Part 2 Measurement)	within 24 hours of birth, 3 months, 6 months and 12 months
Secondary	Maternal age	24 years or younger	Documented at 8-20 weeks post-conception
Secondary	Reported maternal medication use	[Questionnaire]	8-20 weeks post-conception, 30-34 weeks post-conception, within 24 hours of delivery, 3-months post-partum, 6 months post-partum and 12 months post-partum
Secondary	Reported Infant medication use	[Questionnaire]	within 24 hours of birth, 3 months, 6 months and 12 months
Secondary	Maternal dietary intake	Assessed through ASA 24 HR Dietary Recall system, completed 2x each time point	8-20 weeks post conception, 30-34 weeks post conception and 12 months post partum
Secondary	Dietary diversity	Minimum Dietary Diversity Score for Women (MDD-W)	8-20 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	Self-efficacy	Self-efficacy will be measured using the Generalized Self-Efficacy scale, developed by Schwarzer and Jerusalem	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)	8-20 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.	8-20 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 birth	noted in labor and birth chart review	Within 24 hours of birth
Secondary	Stillbirth	noted in labor and birth chart review	Within 24 hours of birth
Secondary	Small for gestational age	noted in labor and birth chart review	Within 24 hours of birth
Secondary	Large for gestational age	noted in labor and birth chart review	Within 24 hours of birth
Secondary	Birth size: length	Measured in cm	within 24 hours of birth
Secondary	Birth size: head circumference	Measured in cm	within 24 hours of birth
Secondary	Birth size: weight	Measured in kg	within 24 hours of birth
Secondary	Birth defects	Assessed within 24 hours of birth	within 24 hours of birth
Secondary	Delivery assessment	Assessed within 24 hours of birth	within 24 hours of birth
Secondary	Infant dietary intake: NutricheQ Questionnaire	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	12 months
Secondary	Maternal stool biomarkers: Calprotectin, Lipocalin and Claudin 15	Markers in the stool for intestinal mass, inflammation, and gut permeability and circulating lipopolysaccharide, among other markers	8-20 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum
Secondary	Infant Stool biomarkers: Calprotectin, Lipocalin and Claudin 15	Markers in the stool for intestinal mass, inflammation, and gut permeability and circulating lipopolysaccharide, among other markers	3 months and 12 months
Secondary	Maternal: incidence of pathobionts	As identified through 16S, 18S and ITS rDNA surveys	8-20 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 months and 12 months
Secondary	Maternal: metabolomic profile of stool (metabolites involved in central metabolism as analysed by Mass Spectrometry)	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	8-20 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum
Secondary	Maternal gut bacteria profile as measured through 16S rDNA sequence surveys	measured through 16S rDNA sequence surveys	8-20 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum
Secondary	Maternal: blood metallomics profile as measured through ICP-MS (https://www.metabolomicscentre.ca/new_service/25)	TMIC Metallomics Platform to be used.	8-20 weeks post conception, 30-34 weeks post conception, 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	12 months
Secondary	Infant: gut bacterial profile as measured through 16S rDNA sequence surveys	measured through 16S rDNA sequence surveys	3 and 12 months post partum
Secondary	Maternal metabolic pathway expression profile as measured through whole microbiome RNASeq (metatranscriptomics)	measured through whole microbiome RNASeq (metatranscriptomics)	8-20 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	measured through 18S and ITS rDNA sequence surveys	3 months and 12 months
Secondary	Maternal eukaryotic microbiome profile as measured through 18S and ITS rDNA sequence surveys	measured through 18S and ITS rDNA sequence surveys	8-20 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.	8-20 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.	8-20 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 months and 12 months