Pregnancy Cohort Study: Pregnancy as a Window to Future Health

Pregnancy is a sensitive and determining period in life where maternal and environmental cues can influence mother and offspring health short and long term. Negative exposures in pregnancy can have long term consequences, such as higher risk for development or aggravation of obesity, metabolic and cardiovascular diseases. However, preventive measures such as life style interventions can be particularly effective (window of opportunity) and could mitigate disease trajectories.

During a healthy pregnancy, a multitude of fine-tuned physiological adaptations takes place to meet the demands of the developing fetus and prepare maternal organism for delivery and lactation. These physiological changes affect the maternal metabolism, cardiovascular system, immune system, microbiome, or endocrine system. Unfavorable or adverse maternal factors (e.g. endocrine, genetic, metabolic, lifestyle factors) may compromise these adaptations, promoting pregnancy complications such as gestational diabetes (GDM), hypertensive pregnancy diseases, fetal growth restriction, fetal overgrowth, or preterm birth. These pregnancy pathologies not only pose an immediate health risk to both mother and child, but also may negatively impact the longer-term cardiovascular, endocrine, and metabolic health of both.

Offspring exposed in utero to maternal diabetes, hypertensive diseases or maternal obesity are at higher risk of developing obesity, diabetes of cardiovascular disorders later in life. For the mother, each pregnancy loads a metabolic burden, which is aggravated by pregnancy complications, also increasing the mother's risk of developing metabolic or cardiovascular disease later in life.

Therefore, prediction and risk evaluation, early diagnosis and prognosis, safe (non-invasive) therapeutic strategies are urgently needed to provide intervention as early as possible (pre-conceptional, during pregnancy and postpartum) to avoid potential manifestations of long-term health problems. Due to the relatively short duration of pregnancy and the often increased health awareness of expectant mothers, pregnancy is an ideal phase to identify origins of disease, evaluate personalized diagnostic and predictive markers, as well as preventive strategies.

In the recent years, the concept of deep phenotyping during pregnancy has emerged as a means to tackle the current inadequate understanding on the pathobiology of pregnancy related diseases and heath trajectories.

The proposed pregnancy and birth cohort aims to meet this need providing comprehensive sets of biological samples, clinical data, physical measurements and life style information for deep phenotyping of pregnancy and early life. Special focus will be put on monitoring glucose metabolism throughout pregnancy and postpartum, since the standard care oGTT at 24 to 28 weeks merely detects an already manifest glucose intolerance without giving any information on potentially preconceptionally existing impaired glucose tolerance/pre-diabetes or predicting maternal hyperglycemia thereafter, in late pregnancy.

This study will be a monocentric, prospective cohort with the goal of recruiting 80-100 participants per year. The study will be conducted at the LKH Graz University Hospital, Department of Gynecology and Obstetrics, Outpatient Clinic. Women with child wish will be recruited at the Center for Assisted Reproductive Technologies (Center for Gynecologic Endocrinology and Reproductive Medicine, Kinderwunsch-Zentrum) or pregnant women attending their routine first trimester screening visits will be enrolled and followed throughout their pregnancy until 8-12 weeks postpartum. There will be up to 6 visits: (T0 preconceptional enrollment), T1 (10-14 weeks of gestation, first trimester screening/enrollment), T2 (24-28 weeks of gestation, time of routine care oGTT); T3 (34-37 weeks of gestation, late pregnancy control visit in preparation for delivery), T4 (delivery), T5 (8-12 weeks postpartum; follow-up after pregnancy complications). The study is designed to closely monitor glucose metabolism and requires participants to be fasting for blood sampling. Women will be offered an oGTT at each visit (at T2 standard of care), but may opt out.

The study will collect clinical markers and measurements of metabolic and hemodynamic parameters, as well as a comprehensive collection of biospecimens and metadata on lifestyle factors (nutrition, physical activity). Advanced methods such as maternal and infant air displacement plethysmography (BODPOD /PEAPOD) will provide accurate body composition measurements. Endothelial/vascular function is assessed by hemodynamic parameters, including pulse wave velocity measured with a Vicorder®.

• Human milk oligosaccharide (HMO) profile in maternal blood [Time frame: From enrolment to 8-12 weeks postpartum]
• Human milk oligosaccharide (HMO) profile in maternal urine [Time frame: From enrolment to 8-12 weeks post partum]
• Human milk oligosaccharide (HMO) profile in cord blood [Time frame: at birth]
• Human milk oligosaccharide (HMO) profile in breast milk [Time frame: from child birth to 8-12 weeks postpartum]
• Adverse pregnancy outcome [Time frame: From enrolment to child birth; 6 months]