This prospective observational study investigates the interaction of maternal physical activity (PA) and body composition during pregnancy with prenatal Human Milk Oligosaccharide (HMO) concentrations, and assesses associations of HMOs with fetal/neonatal outcomes.
Maternal obesity is a known risk factor for adverse short- and long-term health outcomes for the offspring. In non-pregnant individuals, obesity can alter glucose and fat metabolism, and induce a low-grade inflammation. Pregnancy is a natural state of low-grade inflammation in the mother and the feto-placental unit, and the severity of this inflammation increases with higher pre-gravid BMI. Consequently, in pregnant women, obesity could account for an altered intrauterine environment that might affect fetal development and programming. Regular physical activity (PA) is associated with a reduced inflammatory state. PA has been determined as a major factor contributing to fetal growth and body composition, besides maternal nutrition, gestational diabetes and obesity. Human milk oligosaccharides (HMOs), highly bioactive factors in breast milk, but also present in the systemic circulation of pregnant women, may be one of the factors altered by metabolic changes seen in obesity, which might have an impact on the health of the offspring. HMOs have been implicated in multiple beneficial effects for the breast-fed infant, and also have anti-inflammatory and immuno-modulating effects. HMOs are found in the urine of pregnant and lactating women, indicating that HMO circulate in the maternal blood system during pregnancy and throughout lactation. HMOs can also be detected in umbilical cord blood, suggesting either transplacental transfer or fetal production and release, raising the question whether maternal and fetal HMOs have a health impact on mother and fetus and, consequently, could be monitored as potential biomarkers for adverse pregnancy outcomes. More than 150 HMO structures are known, and HMO composition and concentration in breast milk vary significantly between mothers and also within one mother due to different stages of lactation. Genetic factors and potentially also environmental factors contribute to the composition of HMOs in an individual. Different prenatal HMO profiles could potentially affect maternal and fetal health. Whether HMO composition and concentrations are different in women with overweight or obesity is not known. Exposure to a changed intrauterine environment could potentially pose a risk factor for certain pregnancy outcomes or cause aberrant fetal programming. At the same time, lifestyle factors that can counteract some obesity-induced metabolic changes such as physical activity and diet could potentially also have an effect on HMO concentration/composition. The overall objective of the study is to investigate the interaction of maternal physical activity on HMOs in maternal and fetal circulation. Specific Aims are: * To longitudinally determine maternal HMO concentration and composition during gestation to describe variability and temporal changes. * To assess fetal HMO concentration and composition to gain insight about origin: comparison arterial vs. venous cord blood; maternal vs. fetal HMOs. * To investigate associations of maternal and fetal HMOs with maternal body mass index/physical activity, and fetal growth/body composition.
Study Type
OBSERVATIONAL
Enrollment
230
Medical University of Graz
Graz, Styria, Austria
Human milk oligosaccharides (HMO) composition and concentration in maternal blood
HMOs will be analysed in maternal blood by high pressure liquid chromatography (HPLC) with fluorescence detection
Time frame: 6 months
Human milk oligosaccharides (HMO) composition and concentration in fetal blood
HMOs will be analysed in fetal (umbilical cord) blood by high pressure liquid chromatography (HPLC) with fluorescence detection
Time frame: 6 months
Human milk oligosaccharides (HMO) composition and concentration in maternal urine
HMOs will be analysed in maternal urine by high pressure liquid chromatography (HPLC) with fluorescence detection
Time frame: 6 months
Human milk oligosaccharides (HMO) composition and concentration in colostrum
HMOs will be analysed in colostrum by high pressure liquid chromatography (HPLC) with fluorescence detection
Time frame: 6 months
Fetal growth
fetal growth (longitudinal ultrasound measurements)
Time frame: 6 months
Birth weight
infant weight at birth (scale)
Time frame: 6 months
Fetal body fat mass
Fetal body fat mass (measured by air displacement plethysmography, PEAPOD)
Time frame: 6 months
Fetal fat free mass
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Fat free mass (measured by air displacement plethysmography, PEAPOD)
Time frame: 6 months
Subcutaneous adipose tissue thickness
Subcutaneous adipose tissue thickness (measured by lipometer at 15 defined body sites)
Time frame: 6 months
Cord blood metabolic parameters - Glucose
Glucose
Time frame: 6 months
Cord blood metabolic parameters- Insulin
Insulin
Time frame: 6 months
Cord blood metabolic parameters - C-Peptide
C-peptide
Time frame: 6 months
Cord blood metabolic parameters - erythropoietin
Erythropoietin (measure for fetal hypoxia)
Time frame: 6 months
Cord blood metabolic parameters - lipid profile
lipid profile (triglycerides, phospholipids, free fatty acids, HDL proteome)
Time frame: 6 months
Cord blood metabolic parameters - Cytokines
Cytokines
Time frame: 6 months
Maternal body composition - BMI
Body mass index (BMI)
Time frame: 6 months
Maternal body composition - weight gain
gestational weight gain
Time frame: 6 months
Maternal body composition - subcutaneous adipose tissue thickness
subcutaneous adipose tissue thickness (measured by lipometer at 15 defined body sites)
Time frame: 6 months
Maternal parameters - Glucose
glucose
Time frame: 6 months
Maternal parameters - Insulin
insulin
Time frame: 6 months
Maternal parameters - C-Peptide
C-peptide
Time frame: 6 months
Maternal parameters - Leptin
Leptin
Time frame: 6 months
Maternal parameters - Adiponectin
Adiponectin
Time frame: 6 months
Maternal parameters - Liquid profile
Lipid profile (triglycerides, phospholipids, free fatty acids, HDL/LDL/total cholesterol)
Time frame: 6 months
Maternal parameters - Cytokines
Cytokines
Time frame: 6 months
Placental outcomes - Utero-placental blood flow
Utero-placental blood flow (ultrasound/Doppler)
Time frame: 6 months
Placental outcomes - fetal-placental blood flow
fetal-placental blood flow (ultrasound/Doppler)
Time frame: 6 months
Placental volume
placental volume (ultrasound)
Time frame: 6 months
Placental outcomes - Cytokine mRNA
Cytokine mRNA
Time frame: 6 months
Placental outcomes - Macrophage density
Macrophage density (number/tissue protein)
Time frame: 6 months
Placental outcomes - TREG density
Treg density (number/tissue protein)
Time frame: 6 months
Placental outcomes - placental volume
placental volume
Time frame: 6 months
Placental outcomes- transcriptomic profile
Transcriptomic profile, RNAseq on a NovaSeq 6000 (Illumina)
Time frame: 6 months
Placental outcomes - epigenomic profile
Epigenomic profile measured by DNA methylation
Time frame: 6 months
Vaginal Microbiome
From the extracted DNA, 16S rRNA genes will be amplified using specific primers for bacterial and archaeal communities. The amplicons obtained will be prepared for Illumina MiSeq Sequencing.
Time frame: 6 months