Breast Feeding, Malnutrition, Malnutrition, Infant, Malnutrition Pregnancy, Metabolomics, Microbial Colonization, Microbial Disease, Parasitic Disease, Pregnancy Complications, Pregnancy Loss, Pregnancy; Parasitic Disease, Pregnancy Related
Conditions
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.
Interventions
None listed
Sponsors
The Hospital for Sick Children
Unity Health Toronto
University of Toronto
University of Calgary
Dalhousie University
Aga Khan University
University of Alberta
National Institute of Allergy and Infectious Diseases (NIAID)
Canadian Institutes of Health Research (CIHR)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
No minimum to 28 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To assess if alterations of the microbiota in the maternal gut (dysbiosis) are associated 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 (8-20 weeks post-conception) and second time point (30-34 weeks post conception). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anthropometrics: Maternal BMI | 8-20 weeks post-conception, 30-34 weeks post-conception, delivery, 3-months post-partum, 6 months post-partum and 12 months post-partum | calculated using weight and height; BMI = kg/m2 |
| Anthropometrics: Maternal middle upper arm circumference | 8-20 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 | 8-20 weeks post-conception, 30-34 weeks post-conception, 3-months post-partum, and 12 months post-partum | Measured in cm |
| Anthropometrics: Maternal height | 8-20 weeks post conception, 30-34 weeks post conception, delivery, 3 months post-partum and 12 months post partum | Measured in cm |
| Anthropometrics: Maternal weight | 8-20 weeks post conception, 30-34 weeks post conception, delivery, 3 months post-partum and 12 months post-partum | Measured in kg |
| Maternal blood biomarkers | 8-20 weeks post-conception, 30-34 weeks post-conception, and 12 months post-partum | Concentration of HB + MCV, ferritin, and CRP |
| Infant blood biomarkers | 12 months | Concentration of HB + MCV, ferritin, and CRP |
| Infant sex | Determined at delivery | Female or Male |
| Infant morbidity | 3 months, 6 months and 12 months | Assessed through infant health assessment questionnaires |
| Maternal morbidity | 8-20 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 questionnaires |
| Infant growth: weight | within 24 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 24 hours of birth, 3 months, 6 months and 12 months | Measured in cm |
| Infant growth: mid upper arm circumference | within 24 hours of birth, 3 months, 6 months and 12 months | Measured in cm |
| Infant growth: triceps skinfold thickness | within 24 hours of birth, 3 months, 6 months and 12 months | Measured in cm |
| Infant Gestational age | 8-20 weeks post conception | Will be documented at baseline visit. |
| Breast feeding: amount and initiation of complementary feeding | within 24 hours of birth, 3 months, 6 months and 12 months | Based off of WHO 2010 Guidelines: Indicators for assessing infant and young child feeding practices (Part 2 Measurement) |
| Maternal age | Documented at 8-20 weeks post-conception | 28 years or younger |
| Reported maternal medication use | 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 | \[Questionnaire\] |
| Reported Infant medication use | within 24 hours of birth, 3 months, 6 months and 12 months | \[Questionnaire\] |
| Maternal dietary intake | 8-20 weeks post conception, 30-34 weeks post conception and 12 months post partum | Assessed through ASA 24 HR Dietary Recall system, completed 2x each time point |
| Dietary diversity | 8-20 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) |
| 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 |
| 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 | 8-20 weeks post-conception | Questions pertaining to demographic data are adapted from the Pakistan Demographic and Health Survey (PDHS) |
| Food insecurity | 8-20 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 birth | Within 24 hours of birth | noted in labor and birth chart review |
| Stillbirth | Within 24 hours of birth | noted in labor and birth chart review |
| Small for gestational age | Within 24 hours of birth | noted in labor and birth chart review |
| Large for gestational age | Within 24 hours of birth | noted in labor and birth chart review |
| Birth size: length | within 24 hours of birth | Measured in cm |
| Birth size: head circumference | within 24 hours of birth | Measured in cm |
| Birth size: weight | within 24 hours of birth | Measured in kg |
| Birth defects | within 24 hours of birth | Assessed within 24 hours of birth |
| Delivery assessment | within 24 hours of birth | Assessed within 24 hours of birth |
| Infant dietary intake: NutricheQ Questionnaire | 12 months | 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: Calprotectin, Lipocalin and Claudin 15 | 8-20 weeks post conception, 30-34 weeks post conception, 3 months post partum and 12 months post partum | Markers in the stool for intestinal mass, inflammation, and gut permeability and circulating lipopolysaccharide, among other markers |
| Infant Stool biomarkers: Calprotectin, Lipocalin and Claudin 15 | 3 months and 12 months | Markers in the stool for intestinal mass, inflammation, and gut permeability and circulating lipopolysaccharide, among other markers |
| Maternal: incidence of pathobionts | 8-20 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 months and 12 months | As identified through 16S, 18S and ITS rDNA surveys |
| Maternal: metabolomic profile of stool (metabolites involved in central metabolism as analysed by Mass Spectrometry) | 8-20 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 as 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 | measured through 16S rDNA sequence surveys |
| Maternal: blood metallomics profile as measured through ICP-MS (https://www.metabolomicscentre.ca/new_service/25) | 8-20 weeks post conception, 30-34 weeks post conception, and 12 months post partum | TMIC Metallomics Platform to be used. |
| Infant: blood metallomics profile as measured through ICP-MS (https://www.metabolomicscentre.ca/new_service/25) | 12 months | Through TMIC platform |
| Infant: gut bacterial profile as measured through 16S rDNA sequence surveys | 3 and 12 months post partum | measured through 16S rDNA sequence surveys |
| Maternal metabolic pathway expression profile as 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 | measured through whole microbiome RNASeq (metatranscriptomics) |
| Infant eukaryotic microbiome profile as measured through 18S and ITS rDNA sequence surveys | 3 months and 12 months | measured through 18S and ITS rDNA sequence surveys |
| Maternal eukaryotic microbiome profile as 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 | measured through 18S and ITS rDNA sequence surveys |
| Maternal bacterial gene expression profile as 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 | 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 | 8-20 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 months and 12 months | 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. |
Countries
Canada
Contacts
PRINCIPAL_INVESTIGATORJohn Parkinson, PHD
The Hospital for Sick Children
PRINCIPAL_INVESTIGATORShazeen Suleman, MD
Unity Health Toronto
Outcome results
None listed