Effect of Physical Activity in Pregnancy on Maternal and Fetal Human Milk Oligosaccharides: a Pilot Study
- Conditions
- Pregnancy, Physical Activity
- Registration Number
- NCT05496712
- Lead Sponsor
- Medical University of Graz
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 230
- ongoing pregnancy no later than 14 weeks of gestation
- giving informed consent
- 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
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Human milk oligosaccharides (HMO) composition and concentration in maternal blood 6 months HMOs will be analysed in maternal blood by high pressure liquid chromatography (HPLC) with fluorescence detection
Human milk oligosaccharides (HMO) composition and concentration in maternal urine 6 months HMOs will be analysed in maternal urine by high pressure liquid chromatography (HPLC) with fluorescence detection
Human milk oligosaccharides (HMO) composition and concentration in fetal blood 6 months HMOs 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 colostrum 6 months HMOs will be analysed in colostrum by high pressure liquid chromatography (HPLC) with fluorescence detection
- Secondary Outcome Measures
Name Time Method Fetal growth 6 months fetal growth (longitudinal ultrasound measurements)
Cord blood metabolic parameters - C-Peptide 6 months C-peptide
Cord blood metabolic parameters - Cytokines 6 months Cytokines
Maternal parameters - Liquid profile 6 months Lipid profile (triglycerides, phospholipids, free fatty acids, HDL/LDL/total cholesterol)
Placental outcomes - Cytokine mRNA 6 months Cytokine mRNA
Placental outcomes - Macrophage density 6 months Macrophage density (number/tissue protein)
Cord blood metabolic parameters- Insulin 6 months Insulin
Maternal body composition - subcutaneous adipose tissue thickness 6 months subcutaneous adipose tissue thickness (measured by lipometer at 15 defined body sites)
Maternal parameters - Glucose 6 months glucose
Maternal parameters - C-Peptide 6 months C-peptide
Maternal parameters - Leptin 6 months Leptin
Placental outcomes- transcriptomic profile 6 months Transcriptomic profile, RNAseq on a NovaSeq 6000 (Illumina)
Maternal body composition - BMI 6 months Body mass index (BMI)
Maternal body composition - weight gain 6 months gestational weight gain
Placental outcomes - fetal-placental blood flow 6 months fetal-placental blood flow (ultrasound/Doppler)
Placental outcomes - placental volume 6 months placental volume
Vaginal Microbiome 6 months 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.
Birth weight 6 months infant weight at birth (scale)
Fetal body fat mass 6 months Fetal body fat mass (measured by air displacement plethysmography, PEAPOD)
Fetal fat free mass 6 months Fat free mass (measured by air displacement plethysmography, PEAPOD)
Subcutaneous adipose tissue thickness 6 months Subcutaneous adipose tissue thickness (measured by lipometer at 15 defined body sites)
Cord blood metabolic parameters - erythropoietin 6 months Erythropoietin (measure for fetal hypoxia)
Cord blood metabolic parameters - lipid profile 6 months lipid profile (triglycerides, phospholipids, free fatty acids, HDL proteome)
Maternal parameters - Adiponectin 6 months Adiponectin
Maternal parameters - Cytokines 6 months Cytokines
Cord blood metabolic parameters - Glucose 6 months Glucose
Placental outcomes - Utero-placental blood flow 6 months Utero-placental blood flow (ultrasound/Doppler)
Placental volume 6 months placental volume (ultrasound)
Placental outcomes - TREG density 6 months Treg density (number/tissue protein)
Placental outcomes - epigenomic profile 6 months Epigenomic profile measured by DNA methylation
Maternal parameters - Insulin 6 months insulin
Trial Locations
- Locations (1)
Medical University of Graz
🇦🇹Graz, Styria, Austria