Effect of Physical Activity in Pregnancy on Maternal and Fetal Human Milk Oligosaccharides: a Pilot Study

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Effect of Physical Activity in Pregnancy on Maternal and Fetal Human Milk Oligosaccharides: a Pilot Study

Conditions
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Pregnancy, Physical Activity

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ongoing pregnancy no later than 14 weeks of gestation giving informed consent Exclusion Criteria: not wanting to give birth at the university hospital gestational age > 14th week of gestation multiple pregnancy 3 or more consecutive miscarriages increased risk ≥ 1:100 after combined test (minimum parameters: maternal age, Fetal CRL, nuchal translucency, nasal bone and maternal biochemistry - free-ß-hCG and PAPP-A) and no NIPT (Non-Invasive Prenatal Testing) or no invasive testing for chromosomal anomalies fetal anomalies which are associated with possible growth or genetic anomalies smoking pre-pregnancy diabetes type 1 or 2 (T1D, T2D) maternal metabolic risk factors (autoimmune conditions, increased risk for thromboembolic events needing anticoagulative therapy) pre-pregnancy hypertension

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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 | 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 | 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 | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fetal growth | fetal growth (longitudinal ultrasound measurements) | 6 months | 
| Birth weight |  | 6 months | 
| Fetal body fat mass | Fetal body fat mass (measured by air displacement plethysmography, PEAPOD) | 6 months | 
| Fetal fat free mass | Fat free mass (measured by air displacement plethysmography, PEAPOD) | 6 months | 
| Subcutaneous adipose tissue thickness | Subcutaneous adipose tissue thickness (measured by lipometer at 15 defined body sites) | 6 months | 
| Cord blood metabolic parameters - Glucose | Glucose | 6 months | 
| Cord blood metabolic parameters- Insulin | Insulin | 6 months | 
| Cord blood metabolic parameters - C-Peptide | C-peptide | 6 months | 
| Cord blood metabolic parameters - erythropoietin | Erythropoietin (measure for fetal hypoxia) | 6 months | 
| Cord blood metabolic parameters - lipid profile | lipid profile (triglycerides, phospholipids, free fatty acids, HDL proteome) | 6 months | 
| Cord blood metabolic parameters - Cytokines | Cytokines | 6 months | 
| Maternal body composition - BMI | Body mass index (BMI) | 6 months | 
| Maternal body composition - weight gain | gestational weight gain | 6 months | 
| Maternal body composition - subcutaneous adipose tissue thickness | subcutaneous adipose tissue thickness (measured by lipometer at 15 defined body sites) | 6 months | 
| Maternal parameters - Glucose | glucose | 6 months | 
| Maternal parameters - Insulin | insulin | 6 months | 
| Maternal parameters - C-Peptide | C-peptide | 6 months | 
| Maternal parameters - Leptin | Leptin | 6 months | 
| Maternal parameters - Adiponectin | Adiponectin | 6 months | 
| Maternal parameters - Liquid profile | Lipid profile (triglycerides, phospholipids, free fatty acids, HDL/LDL/total cholesterol) | 6 months | 
| Maternal parameters - Cytokines | Cytokines | 6 months | 
| Placental outcomes - Utero-placental blood flow | Utero-placental blood flow (ultrasound/Doppler) | 6 months | 
| Placental outcomes - fetal-placental blood flow | fetal-placental blood flow (ultrasound/Doppler) | 6 months | 
| Placental outcomes - placental volume | placental volume (ultrasound) | 6 months | 
| Placental outcomes - Cytokine mRNA | Cytokine mRNA | 6 months | 
| Placental outcomes - Macrophage density | Macrophage density (number/tissue protein) | 6 months | 
| Placental outcomes - TREG density | Treg density (number/tissue protein) | 6 months | 
| Placental outcomes - placental volume | placental volume | 6 months | 
| Placental outcomes- transcriptomic profile | Transcriptomic profile | 6 months | 
| Placental outcomes - epigenomic profile | Epigenomic profile | 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. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Human Milk Oligosaccharides