Cohort profile: the Genetics of Glucose regulation in Gestation and Growth (Gen3G) - a prospective prebirth cohort of mother-child pairs in Sherbrooke, Canada, 3-year and 5-year follow-up visits.

Purpose: Initiated in 2010, the Genetics of Glucose regulation in Gestation and Growth (Gen3G) prospective cohort investigates the pathophysiology of impaired glycaemic regulation in pregnancy and evaluates its impact on both the mothers and her offspring health trajectory. Follow-up visits 3 and 5 years after delivery aimed to investigate pregnancy-related risk factors such as maternal obesity and gestational hyperglycaemia in relation to the mother's metabolic health after pregnancy, and with offspring health outcomes such as risk of obesity and neurodevelopmental problems in early childhood. We also investigated molecular mechanisms involved in the fetal programming of these later health outcomes.

Gut microbiota and microbial metabolites are associated with body composition in 5-year-old children: A cross-sectional study in the Gen3G cohort.

Objective: To examine gut microbiota diversity, composition and metabolites in relation to overall mass (OM), fat mass (FM) and lean soft tissue mass (LSTM) measured by dual x-ray absorptiometry (DXA) in 5-year-old children.

Methods: Mothers of the Gen3G cohort were enrolled prenatally in 2010-2013 in Quebec, Canada; 153 children from the cohort had data on gut microbiota and DXA scans at 5-6.4 years of age, and 140 also had plasma metabolite data.

Physical behaviours during pregnancy may alter the association of maternal insulin sensitivity with neonatal adiposity: a prospective pre-birth cohort of mother-child pairs.

Background: Lower maternal insulin sensitivity during pregnancy is associated with greater fetal adiposity. Physical activity can improve insulin sensitivity, but it is not known if physical behaviours influence the known association of maternal insulin sensitivity with offspring adiposity. This study aimed to investigate the moderating impact of physical behaviours on this association.

Associations of gut microbiota features and circulating metabolites with systemic inflammation in children.

Objective: Gut microbes and microbe-dependent metabolites (eg, tryptophan-kynurenine-serotonin pathway metabolites) have been linked to systemic inflammation, but the microbiota-metabolite-inflammation axis remains uncharacterised in children. Here we investigated whether gut microbiota features and circulating metabolites (both microbe-dependent and non-microbe-dependent metabolites) associated with circulating inflammation markers in children.

Methods: We studied children from the prospective Gen3G birth cohort who had data on untargeted plasma metabolome (n=321 children; Metabolon platform), gut microbiota (n=147; 16S rRNA sequencing), and inflammation markers (plasminogen activator inhibitor-1 (PAI-1), monocyte chemoattractant protein-1, and tumour necrosis factor-α) measured at 5-7 years.

Plasma metabolomic profile of adiposity and body composition in childhood: The Genetics of Glucose regulation in Gestation and Growth cohort.

Objective: This study identified metabolite modules associated with adiposity and body fat distribution in childhood using gold-standard measurements.

Methods: We used cross-sectional data from 329 children at mid-childhood (age 5.3 ± 0.

Effects of vanilla odor on hypoxia-related periodic breathing in premature newborns: A pilot study.

Background: Periodic breathing (PB)-related intermittent hypoxia can have long-lasting deleterious consequences in preterm infants. Olfactory stimulation using vanilla odor is beneficial for apnea of prematurity in the first postnatal days/weeks. We aimed to determine for the first time whether vanilla odor can also decrease PB-related intermittent hypoxia.

Pre-pregnancy body mass index and gut microbiota of mothers and children 5 years postpartum.

Background: Maternal pre-pregnancy body mass index (BMI) has been linked to altered gut microbiota in women shortly after delivery and in their offspring in the first few years of life. But little is known about how long these differences persist.

Methods: We followed 180 mothers and children from pregnancy until 5-year postpartum in the Gen3G cohort (Canada, enrolled 2010-2013).

Associations between Cord Blood Leptin Levels and Childhood Adiposity Differ by Sex and Age at Adiposity Assessment.

Lower cord blood leptin levels have been associated with lower and higher adiposity in childhood and associations seem to differ according to the child’s age, methods of adiposity assessment and sex. Our aim was to investigate sex-specific associations of cord blood leptinemia with childhood adiposity at birth, 3 and 5 years of age. We measured cord blood leptin using Luminex immunoassays in 520 offspring from the Gen3G cohort.

Associations of maternal insulin sensitivity during pregnancy with childhood central adiposity in the Genetics of Glucose regulation in Gestation and Growth (Gen3G) cohort.

Background: Childhood obesity has been associated with prenatal exposure to maternal hyperglycaemia, but we lack understanding about maternal insulin physiologic components that contribute to this association.

Objectives: Evaluate the association between maternal insulin sensitivity during pregnancy and adiposity measures in childhood.

Methods: In 422 mother-child pairs, we tested associations between maternal insulin sensitivity measures at ~26 weeks of pregnancy and child adiposity measures, including dual-energy X-ray absorptiometry body composition and anthropometry (body mass index and waist circumference) at ~5 years.

Associations of maternal glucose markers in pregnancy with cord blood glucocorticoids and child hair cortisol levels.

Exposure to maternal hyperglycemia has been associated with adverse metabolic outcomes in offspring. However, few studies have investigated the relationship between maternal hyperglycemia and offspring cortisol levels. We assessed associations of gestational diabetes mellitus (GDM) with cortisol biomarkers in two longitudinal prebirth cohorts: Project Viva included 928 mother-child pairs and Gen3G included 313 mother-child pairs.

DNA methylation mediates the association between breastfeeding and early-life growth trajectories.

Background: The role of breastfeeding in modulating epigenetic factors has been suggested as a possible mechanism conferring its benefits on child development but it lacks evidence. Using extensive DNA methylation data from the ALSPAC child cohort, we characterized the genome-wide landscape of DNA methylation variations associated with the duration of exclusive breastfeeding and assessed whether these variations mediate the association between exclusive breastfeeding and BMI over different epochs of child growth.

Results: Exclusive breastfeeding elicits more substantial DNA methylation variations during infancy than at other periods of child growth.

Associations of maternal insulin resistance during pregnancy and offspring inflammation at birth and at 5 years of age: A prospective study in the Gen3G cohort.

Background: Maternal insulin resistance is associated with greater maternal inflammation during pregnancy, but its relation to inflammation in offspring remains unclear. The goal of this study was to assess the relationship of gestational insulin resistance and other glycemic markers with offspring inflammation at birth and at 5 years of age.

Methods: We included 653 mother-child pairs from the prospective pre-birth Gen3G cohort.

Maternal glucose in pregnancy is associated with child's adiposity and leptin at 5 years of age.

Background: Exposure to maternal hyperglycaemia in pregnancy has been associated with childhood obesity. Leptin regulation might be involved in this 'adiposity programming' and may depend on timing of exposure.

Objectives: To investigate associations of maternal glycaemia at different periods in pregnancy with childhood adiposity and leptin levels at 5 years of age.

A prospective study of maternal adiposity and glycemic traits across pregnancy and mid-childhood metabolomic profiles.

Background: Fetal exposure to maternal excess adiposity and hyperglycemia is risk factors for childhood adverse metabolic outcomes. Using data from a prospective pre-birth cohort, we aimed to further understand the prenatal determinants of fetal metabolic programming based on analyses of maternal adiposity and glycemic traits across pregnancy with childhood metabolomic profiles.

Methods: This study included 330 mother-child pairs from the Gen3G cohort with information on maternal adiposity and glycemic markers at 5-16 (visit 1) and 24-30 (visit 2) weeks of pregnancy.

Potential interaction between timing of infant complementary feeding and breastfeeding duration in determination of early childhood gut microbiota composition and BMI.

Background: Introducing complementary foods other than breastmilk or formula acutely changes the infant gut microbiota composition. However, it is unknown whether the timing of introduction to complementary foods (early vs. late) in infancy is associated with early childhood gut microbiota and BMI, and if these associations depend on breastfeeding duration.

Interplay of Placental DNA Methylation and Maternal Insulin Sensitivity in Pregnancy.

The placenta participates in maternal insulin sensitivity changes during pregnancy; however, mechanisms remain unclear. We investigated associations between maternal insulin sensitivity and placental DNA methylation markers across the genome. We analyzed data from 430 mother-offspring dyads in the Gen3G cohort.

Associations of sleep duration, sedentary behaviours and energy expenditure with maternal glycemia in pregnancy.

Background: Women with high levels of physical activity (PA) are less likely to develop gestational diabetes mellitus (GDM), but the relations with sleep and sedentary behaviours (SB) are more controversial. We aimed to investigate all three components (sleep, PA, and SB) and their association with maternal glucose in pregnancy.

Methods: We included 766 pregnant women recruited at first trimester and that we followed at second trimester.

Association of Gestational Weight Gain With Adverse Maternal and Infant Outcomes.

Importance: Both low and high gestational weight gain have been associated with adverse maternal and infant outcomes, but optimal gestational weight gain remains uncertain and not well defined for all prepregnancy weight ranges.

Objectives: To examine the association of ranges of gestational weight gain with risk of adverse maternal and infant outcomes and estimate optimal gestational weight gain ranges across prepregnancy body mass index categories.

Design, Setting, And Participants: Individual participant-level meta-analysis using data from 196 670 participants within 25 cohort studies from Europe and North America (main study sample).

Maternal lipid profile differs by gestational diabetes physiologic subtype.

Aim: To characterize lipid profiles in women with different gestational diabetes mellitus (GDM) physiologic subtypes.

Methods: We measured seven lipid markers (total cholesterol, LDL, HDL, triglycerides, non-esterified fatty acids (NEFA), ApoA, ApoB) in fasting plasma collected in a prospective cohort of 805 pregnant women during second trimester. We estimated insulin sensitivity and secretion using oral glucose tolerance test-based validated indices.

Effect of gestational diabetes and insulin resistance on offspring's myocardial relaxation kinetics at three years of age.

Purpose: Scientific evidence on the long-term impact of gestational diabetes mellitus (GDM) on offspring's myocardial relaxation is scarce. Studies have linked GDM with transient ventricular hypertrophy in newborns resulting in diastolic dysfunction, but long-term assessment is lacking. The main objective of this study was to evaluate myocardial relaxation in 3-year-old children in relation to the degree of insulin resistance of their mother during pregnancy.

Gestational weight gain charts for different body mass index groups for women in Europe, North America, and Oceania.

Background: Gestational weight gain differs according to pre-pregnancy body mass index and is related to the risks of adverse maternal and child health outcomes. Gestational weight gain charts for women in different pre-pregnancy body mass index groups enable identification of women and offspring at risk for adverse health outcomes. We aimed to construct gestational weight gain reference charts for underweight, normal weight, overweight, and grades 1, 2 and 3 obese women and to compare these charts with those obtained in women with uncomplicated term pregnancies.

Associations of Maternal Leptin with Neonatal Adiposity Differ according to Pregravid Weight.

Background: During pregnancy, maternal circulating leptin is released by maternal adipose tissue and the placenta, and may have a role in fetal development.

Objectives: We investigated maternal leptinemia and glycemia associations with neonatal adiposity, taking into account pregravid weight status.

Methods: We included 235 pregnant women from the Genetics of Glucose Regulation in Gestation and Growth prospective cohort with data: blood samples collected during the 2nd trimester, an oral glucose tolerance test (OGTT), and the measured leptin and glucose levels.

Validation of a DNA methylation reference panel for the estimation of nucleated cells types in cord blood.

Cord blood is widely used as surrogate tissue in epigenome-wide association studies of prenatal conditions. Cell type composition variation across samples can be an important confounder of epigenome-wide association studies in blood that constitute a mixture of cells. We evaluated a newly developed cord blood reference panel to impute cell type composition from DNA methylation levels, including nucleated red blood cells (nRBCs).