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

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

Status
Completed
Phases
Unknown
Study type
Observational
Source
ClinicalTrials.gov
Registry ID
NCT05496712
Enrollment
230
Registered
2022-08-11
Start date
2014-07-01
Completion date
2023-06-30
Last updated
2024-08-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pregnancy, Physical Activity

Keywords

Human Milk Oligosaccharides

Brief summary

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

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.

Interventions

None listed

Sponsors

Medical University of Graz
Lead SponsorOTHER

Study design

Observational model
COHORT
Time perspective
PROSPECTIVE

Eligibility

Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes

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

Design outcomes

Primary

MeasureTime frameDescription
Human milk oligosaccharides (HMO) composition and concentration in maternal blood6 monthsHMOs will be analysed in maternal blood by high pressure liquid chromatography (HPLC) with fluorescence detection
Human milk oligosaccharides (HMO) composition and concentration in fetal blood6 monthsHMOs will be analysed in fetal (umbilical cord) blood by high pressure liquid chromatography (HPLC) with fluorescence detection
Human milk oligosaccharides (HMO) composition and concentration in maternal urine6 monthsHMOs will be analysed in maternal urine by high pressure liquid chromatography (HPLC) with fluorescence detection
Human milk oligosaccharides (HMO) composition and concentration in colostrum6 monthsHMOs will be analysed in colostrum by high pressure liquid chromatography (HPLC) with fluorescence detection

Secondary

MeasureTime frameDescription
Placental volume6 monthsplacental volume (ultrasound)
Placental outcomes - Cytokine mRNA6 monthsCytokine mRNA
Placental outcomes - Macrophage density6 monthsMacrophage density (number/tissue protein)
Placental outcomes - TREG density6 monthsTreg density (number/tissue protein)
Placental outcomes - placental volume6 monthsplacental volume
Fetal growth6 monthsfetal growth (longitudinal ultrasound measurements)
Birth weight6 monthsinfant weight at birth (scale)
Fetal body fat mass6 monthsFetal body fat mass (measured by air displacement plethysmography, PEAPOD)
Fetal fat free mass6 monthsFat free mass (measured by air displacement plethysmography, PEAPOD)
Subcutaneous adipose tissue thickness6 monthsSubcutaneous adipose tissue thickness (measured by lipometer at 15 defined body sites)
Cord blood metabolic parameters - Glucose6 monthsGlucose
Cord blood metabolic parameters- Insulin6 monthsInsulin
Cord blood metabolic parameters - C-Peptide6 monthsC-peptide
Placental outcomes- transcriptomic profile6 monthsTranscriptomic profile, RNAseq on a NovaSeq 6000 (Illumina)
Cord blood metabolic parameters - lipid profile6 monthslipid profile (triglycerides, phospholipids, free fatty acids, HDL proteome)
Cord blood metabolic parameters - Cytokines6 monthsCytokines
Maternal body composition - BMI6 monthsBody mass index (BMI)
Maternal body composition - weight gain6 monthsgestational weight gain
Maternal body composition - subcutaneous adipose tissue thickness6 monthssubcutaneous adipose tissue thickness (measured by lipometer at 15 defined body sites)
Maternal parameters - Glucose6 monthsglucose
Maternal parameters - Insulin6 monthsinsulin
Maternal parameters - C-Peptide6 monthsC-peptide
Maternal parameters - Leptin6 monthsLeptin
Maternal parameters - Adiponectin6 monthsAdiponectin
Maternal parameters - Liquid profile6 monthsLipid profile (triglycerides, phospholipids, free fatty acids, HDL/LDL/total cholesterol)
Maternal parameters - Cytokines6 monthsCytokines
Placental outcomes - Utero-placental blood flow6 monthsUtero-placental blood flow (ultrasound/Doppler)
Cord blood metabolic parameters - erythropoietin6 monthsErythropoietin (measure for fetal hypoxia)
Placental outcomes - epigenomic profile6 monthsEpigenomic profile measured by DNA methylation
Vaginal Microbiome6 monthsFrom 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.
Placental outcomes - fetal-placental blood flow6 monthsfetal-placental blood flow (ultrasound/Doppler)

Countries

Austria

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026