Clinical trial NCT06925815: Pregnancy Cohort Study: Pregnancy as a Window to Future Health
Official title: Pregnancy Cohort Study: Pregnancy as a Window to Future Health
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Healthy Pregnant Women
Obese Pregnant Women
Gestational Diabetes
Keywords: pregnancy
deep phenotyping
maternal metabolism
body composition
longitudinal pregnancy cohort study
fetal growth
obesity in pregnancy
neonatal adiposity
gestational weight gain
gestational diabetes
cardiovascular health
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
First posted: 2025-04-13
Enrollment: 800
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Eligible for participation are women with child wish and women with an on-going pregnancy who are planning to give birth at the university hospital in Graz, Austria. Women will be recruited as soon as possible in their pregnancy, but not after the 14th week of gestation. They will be recruited through the outpatient clinics and, in case of women with child wish, at the center for assisted reproductive technologies at the Department of Obstetrics and Gynecology, at Medical University Graz.

Brief summary: The goal of this observational cohort study is to gain deep insights into how metabolic disorders such as obesity or diabetes during pregnancy affect the metabolic and cardiovascular health of mother and child in the short and long term.

It will investigate the following questions:

* How do maternal metabolic disorders affect pregnancy outcomes?
* How do maternal metabolic disorders affect fetal growth?
* How do maternal metabolic disorders affect the newborn's metabolism and body composition?
* How do maternal metabolic disorders during pregnancy affect breast milk composition?
* How do maternal metabolic disorders during pregnancy affect the metabolic health of the mother after birth? Participants in this study are pregnant women who will be asked to come to the clinics for three visits during their pregnancy, as well as for the delivery of their baby, and one time 2-3 months thereafter. At each visit, researchers will perform physical examinations (such as body composition measurements) and collect biological samples (blood, urine, saliva), clinical information, and lifestyle data. At birth, researchers will collect cord blood and breast milk as well as clinical data of the delivery and the health of the baby. Researchers will measure body fat in newborn babies and at 2-3 months of age.

Detailed description: 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®.

Eligibility criteria: Inclusion Criteria:

* ongoing pregnancy prior to 14th gestational week, women with child wish; above 18 years of age, giving informed consent

Exclusion Criteria:

* gestational age \> 14th week of gestation; below 18 years of age; fetal genetic anomalies /malformation

Primary outcomes:
measure: Maternal adiposity
timeFrame: From enrolment to 8-12 weeks post partum
measure: Maternal fasting blood glucose
timeFrame: from enrollment to 8-12 weeks postpartum
measure: Maternal blood pressure
timeFrame: From enrolment to 8-12 weeks postpartum
measure: Maternal lipid profiles - triglycerides
timeFrame: From enrolment to 8-12 weeks post partum
measure: Maternal lipid profiles: phospholipids
timeFrame: From enrolment to 8-12 weeks post partum
measure: Maternal lipid profiles: free fatty acids
timeFrame: From enrolment to 8-12 weeks post partum
measure: Maternal lipid profiles: total cholesterol
timeFrame: From enrolment to 8-12 weeks post partum
measure: Maternal lipid profiles: HDL cholesterol
timeFrame: From enrolment to 8-12 weeks post partum
measure: Maternal lipid profiles: LDL cholesterol
timeFrame: From enrolment to 8-12 weeks post partum
measure: Maternal endothelial function
timeFrame: From enrolment to 8-12 weeks post partum
measure: Maternal cytokine profile
timeFrame: From enrolment to 8-12 weeks postpartum
measure: Gestational diabetes
timeFrame: From enrolment to child birth; 6 months
measure: Hypertensive disorders of pregnancy
timeFrame: From enrolment to child birth; 6 months
measure: Neonatal body composition at birth
timeFrame: between delivery and 48h postpartum
measure: Neonatal C-peptide in cord blood
timeFrame: at birth
measure: Neonatal cytokine profile
timeFrame: at birth
measure: Neonatal epigenetic profile
timeFrame: at birth
Secondary outcomes:
measure: Human milk oligosaccharide (HMO) profile in maternal blood
timeFrame: From enrolment to 8-12 weeks postpartum
measure: Human milk oligosaccharide (HMO) profile in maternal urine
timeFrame: From enrolment to 8-12 weeks post partum
measure: Human milk oligosaccharide (HMO) profile in cord blood
timeFrame: at birth
measure: Human milk oligosaccharide (HMO) profile in breast milk
timeFrame: from child birth to 8-12 weeks postpartum
measure: Adverse pregnancy outcome
timeFrame: From enrolment to child birth; 6 months
Other outcomes:
measure: Maternal vaginal microbiome
timeFrame: From enrolment to 8-12 weeks postpartum
Locations:
city: Graz
country: Austria
facility: Department of Obstetrics and Gynecology, Medical University of Graz
state: Styria
Study officials:
affiliation: Medical University of Graz
name: Evelyn Jantscher-Krenn, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of Graz
name: Herbert Fluhr, Univ.-Prof. Dr. med.
role: STUDY_DIRECTOR
References: