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

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.

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