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

Pregnancy, Physical Activity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05496712
• Other study ID #: 26-380 ex 13/14
• Status: Recruiting
• Start date: July 1, 2014
• Est. completion date: July 2023

Study information

• Verified date: August 2022
• Source: Medical University of Graz
• Contact: Evelyn Jantscher-Krenn, PhD
• Email: evelyn.jantscher-krenn[@]medunigraz.at
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: July 2023
• Est. primary completion date: August 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pregnancy, Physical Activity

Locations

Country	Name	City	State
Austria	Medical University of Graz	Graz	Styria

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Graz

Country where clinical trial is conducted

Austria, 

Outcome

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