The HUN-PER Study

The Need...

is huge, since miscarriages affect 50-70% of all conceptions and 15-20% of clinically recognized pregnancies, and approximately 25% of pregnant women have obstetrical syndromes that may have severe impact on the health of both mother and child. In every year, tens of millions of women worldwide lose their babies or encounter often life-threatening pregnancy complications.

In spite of the considerable developments in the clinical management and biological understanding of these severe pregnancy complications, our knowledge on their complex molecular pathways, early biomarkers and targeted therapies are still scarce.

The first big challenge for the research of these molecular disease pathways and early biomarkers and the development of novel diagnostic and therapeutic tools for pregnancy complications is obtaining sufficient number and good quality biospecimens for well-powered studies.

Our Aims are to…

collect a large number of high-quality biological specimens and related clinical data and archive these according to international biobank standards,
provide these samples and data to academic and industrial partners, nationally and internationally,
characterize the molecular pathways key in the development of miscarriages and obstetrical syndromes using our biobank samples,
identify, test and validate novel biomarkers that can predict these complications in early pregnancy,
identify drug-targets in the centre of disease pathways,
contribute to the development of novel type of predictive tests for accurate risk assessment and subsequent personalized therapies.

The Hungarian Perinatal (HUN-PER) Study…

has been conducted in two phases. The first phase was directed by Olga Török MD, DSci and conducted by the Department of Obstetrics and Gynaecology of the University of Debrecen between 2010 and 2012. The study received ethics approval from the University of Debrecen Research Ethics Committee (DEOEC RKEB/IKEB: 3092-2010).

The recruitment and sample collection was based at two hospitals: 1) Department of Obstetrics and Gynaecology, University of Debrecen and 2) Department of Obstetrics and Gynaecology, András Jósa Hospital in Nyíregyháza. Together these maternity services deliver around 8,500 newborns a year.

Maternal blood and urine samples as well as related demographic and clinical data was taken between weeks 11 and 14 from a cohort of 2,545 patients. Patients were followed up, and delivery and medication records were also obtained.

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The ongoing second phase of the HUN-PER Study has been directed by Nándor Gábor Than MD, PhD and conducted by the Maternity Clinic in Budapest and the Research Centre for Natural Sciences since 2014. The study received ethics approval from the Hungarian Research Ethics Committee (ETT-TUKEB, 4834-0/2011-1018EKU (130/PI/11)), which was strengthened by the approval from the Ministry of Human Capabilities (4013-1/2019/EKU and 2430-9/2019/EÜIG).

The recruitment and sample collection has been based at three hospitals:
1) Maternity Clinic, Budapest,
2) Dept. of Obstetrics and Gynaecology, Aladár Petz County Teaching Hospital in Győr, and
3) Department of Obstetrics and Gynaecology, University of Debrecen.
Together these maternity services deliver around 8,200 newborns a year.

In the first arm of the study, maternal blood and urine samples as well as related demographic and clinical data has been taken between weeks 11 and 14 from a second cohort of patients. Patients have been followed up and delivery and medication records have also been obtained.

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In the second arm of the study, maternal blood and placental specimens have been collected from women with miscarriages and those undergoing elective termination of pregnancy in the first trimester.

Biospecimens and Data…

have been collected and stored according to international biobanking and research standards in the HUN-PER study.

The biobank already contains >25,000 first trimester maternal biological specimens and paired data from >1,000 women. The clinical data collection and review is ongoing for the identification of preeclampsia, small-for-gestational age, foetal growth restriction, spontaneous preterm birth and stillbirth cases as well as ‘normal’ control pregnancies with no recorded problems associated with the mothers' health, pregnancy, or delivery.

The biobank also contains >1,500 placental and maternal biospecimens from 145 pregnancies with first trimester miscarriage or termination. The clinical data collection and review is ongoing.

Biobank location information on coded biospecimens are stored in an electronic database. Pseudo-anonymised patient data, gathered by the recruitment team from patients and electronic clinical records, is stored in a secure database..

Sample collection sites

Systems Biological Investigations

Maternity Clinic
Budapest, Hungary

Department of Obstetrics and Gynecology
Semmelweis University, Faculty of Medicine
Budapest, Hungary

Petz Aladár County Teaching Hospital
Győr, Hungary

Miscarriages and obstetrical syndromes represent a spectrum of disorders, which are syndromic in nature. Distinct disease pathways can trigger their development due to the combined and varying effects of the maternal and foetal genotype, intrauterine environment, clinical and environmental factors.

An increasing body of scientific evidence has started to show the heterogeneous molecular signatures of these pregnancy complications. In parallel, the need has risen for biomarker combinations instead of single biomarkers in screening tests which latter are not specific or sensitive enough to predict complex diseases.

The Systems Biology of Reproduction research group has been using the HUN-PER study samples for its omics studies to discover molecular signatures of pregnancy complications. Using integrated transcriptomics, proteomics and advanced bioinformatics methods, we are aiming to explore the complex disease pathways and discover novel biomarker combinations. Our aim is to promote early and effective screening and personalized preventive therapies for the radical improvement of maternal and foetal health.