Clinical trial NCT04992104: Microbiome and Malnutrition in Pregnancy
Official title: Elucidating the Dynamics and Impact of the Gut Microbiome on Maternal Nutritional Status During Pregnancy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Pregnancy Related
Pregnancy Loss
Pregnancy Complications
Pregnancy; Parasitic Disease
Microbial Colonization
Microbial Disease
Parasitic Disease
Metabolomics
Malnutrition
Malnutrition, Infant
Malnutrition Pregnancy
Breast Feeding
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
Collaborators: name: Unity Health Toronto
name: University of Toronto
name: University of Calgary
name: Dalhousie University
name: Aga Khan University
name: University of Alberta
name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Canadian Institutes of Health Research (CIHR)
First posted: 2021-08-05
Enrollment: 800
Sex: FEMALE
Maximum age (years): 28
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will consist of pregnant women, 28 years of age and younger, living in the Toronto and Greater Toronto Area. The investigators focus on younger women, due to the lack of knowledge about their microbiome and their vulnerability to undernutrition

Brief 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, 28 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.

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 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, 28 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, 28 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.

Eligibility criteria: Inclusion Criteria:

1. Consent provided
2. Participant is between 8-20 weeks post-conception
3. Female aged 28 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.

Primary outcomes:
measure: To assess if alterations of the microbiota in the maternal gut (dysbiosis) are associated with changes in maternal gestational weight gain.
timeFrame: 8-20 weeks post-conception, 30-34 weeks post conception
Secondary outcomes:
measure: Anthropometrics: Maternal BMI
timeFrame: 8-20 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: 8-20 weeks post-conception, 30-34 weeks post-conception, 3-months post-partum,and 12 months post-partum
measure: Anthropometrics: Maternal triceps skinfold thickness
timeFrame: 8-20 weeks post-conception, 30-34 weeks post-conception, 3-months post-partum, and 12 months post-partum
measure: Anthropometrics: Maternal height
timeFrame: 8-20 weeks post conception, 30-34 weeks post conception, delivery, 3 months post-partum and 12 months post partum
measure: Anthropometrics: Maternal weight
timeFrame: 8-20 weeks post conception, 30-34 weeks post conception, delivery, 3 months post-partum and 12 months post-partum
measure: Maternal blood biomarkers
timeFrame: 8-20 weeks post-conception, 30-34 weeks post-conception, and 12 months post-partum
measure: Infant blood biomarkers
timeFrame: 12 months
measure: Infant sex
timeFrame: Determined at delivery
measure: Infant morbidity
timeFrame: 3 months, 6 months and 12 months
measure: Maternal morbidity
timeFrame: 8-20 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 24 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 24 hours of birth, 3 months, 6 months and 12 months
measure: Infant growth: mid upper arm circumference
timeFrame: within 24 hours of birth, 3 months, 6 months and 12 months
measure: Infant growth: triceps skinfold thickness
timeFrame: within 24 hours of birth, 3 months, 6 months and 12 months
measure: Infant Gestational age
timeFrame: 8-20 weeks post conception
measure: Breast feeding: amount and initiation of complementary feeding
timeFrame: within 24 hours of birth, 3 months, 6 months and 12 months
measure: Maternal age
timeFrame: Documented at 8-20 weeks post-conception
measure: Reported maternal medication use
timeFrame: 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
measure: Reported Infant medication use
timeFrame: within 24 hours of birth, 3 months, 6 months and 12 months
measure: Maternal dietary intake
timeFrame: 8-20 weeks post conception, 30-34 weeks post conception and 12 months post partum
measure: Dietary diversity
timeFrame: 8-20 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: 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: 8-20 weeks post-conception
measure: Food insecurity
timeFrame: 8-20 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 birth
timeFrame: Within 24 hours of birth
measure: Stillbirth
timeFrame: Within 24 hours of birth
measure: Small for gestational age
timeFrame: Within 24 hours of birth
measure: Large for gestational age
timeFrame: Within 24 hours of birth
measure: Birth size: length
timeFrame: within 24 hours of birth
measure: Birth size: head circumference
timeFrame: within 24 hours of birth
measure: Birth size: weight
timeFrame: within 24 hours of birth
measure: Birth defects
timeFrame: within 24 hours of birth
measure: Delivery assessment
timeFrame: within 24 hours of birth
measure: Infant dietary intake: NutricheQ Questionnaire
timeFrame: 12 months
measure: Maternal stool biomarkers: Calprotectin, Lipocalin and Claudin 15
timeFrame: 8-20 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum
measure: Infant Stool biomarkers: Calprotectin, Lipocalin and Claudin 15
timeFrame: 3 months and 12 months
measure: Maternal: incidence of pathobionts
timeFrame: 8-20 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum
measure: Infant: incidence of pathobionts
timeFrame: 3 months and 12 months
measure: Maternal: metabolomic profile of stool (metabolites involved in central metabolism as analysed by Mass Spectrometry)
timeFrame: 8-20 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum
measure: Maternal gut bacteria profile as measured through 16S rDNA sequence surveys
timeFrame: 8-20 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum
measure: Maternal: blood metallomics profile as measured through ICP-MS (https://www.metabolomicscentre.ca/new_service/25)
timeFrame: 8-20 weeks post conception, 30-34 weeks post conception, and 12 months post partum
measure: Infant: blood metallomics profile as measured through ICP-MS (https://www.metabolomicscentre.ca/new_service/25)
timeFrame: 12 months
measure: Infant: gut bacterial profile as measured through 16S rDNA sequence surveys
timeFrame: 3 and 12 months post partum
measure: Maternal metabolic pathway expression profile as measured through whole microbiome RNASeq (metatranscriptomics)
timeFrame: 8-20 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum
measure: Infant eukaryotic microbiome profile as measured through 18S and ITS rDNA sequence surveys
timeFrame: 3 months and 12 months
measure: Maternal eukaryotic microbiome profile as measured through 18S and ITS rDNA sequence surveys
timeFrame: 8-20 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum
measure: Maternal bacterial gene expression profile as measured through whole microbiome RNASeq (metatranscriptomics)
timeFrame: 8-20 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: 8-20 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 months and 12 months
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: St. Michael's Hospital
city: Toronto
country: Canada
facility: The Hospital for Sick Children
Study officials:
affiliation: The Hospital for Sick Children
name: John Parkinson, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Unity Health Toronto
name: Shazeen Suleman, MD
role: PRINCIPAL_INVESTIGATOR
References: