Condition category
Pregnancy and Childbirth
Date applied
23/10/2018
Date assigned
28/12/2018
Last edited
28/12/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
More than 7 million children have been born after assisted reproductive technology (ART) since the first baby was born after ART in 1978. The significant decrease in twin births has caused a tremendous drop in the twin birth rates and the associated preterm birth rate. However, single births conceived by ART also have a slightly higher risk of adverse outcomes depending on the ART technology used. The aim of this study is to assess the short- and long-term health risks in children conceived after ART.

Who can participate?
Women who delivered after ART treatment and children born after ART conception in 1985-2015 in Sweden, Norway, Denmark and Finland, and women delivering after spontaneous conception during the same time period and their children

What does the study involve?
This study only includes only register data that are routinely recorded in all private and public clinics in Denmark. This data recording is compulsory and there is no other involvement for the patients. The main categories of data are type of ART treatment, pregnancy and perinatal outcomes, selected diagnosis from specialised health care including detailed information on malignancies, diabetes, imprinting diseases, cardiovascular diseases, neurodevelopmental health and school performance and causes of death.

What are the possible benefits and risks of participating?
Possible benefits are the new knowledge obtained, which may lead to altering or abandoning certain ART methods such as freezing and lead to more safe ART treatments. Further if increased long-term health risks are seen in ART children screening programs may be set up for the patients to prevent further disease development. There are no risks for patients related to the trial.

Where is the study run from?
1. Fertility Clinic, Rigshospitalet (Denmark)
2. National Institute for Health and Welfare (Finland)
3. Hvidovre Hospital (Denmark)
4. Helsinki University Hospital (Finland)
5. Sahlgrenska University Hospital, Inst of Clinical Sciences, University of Gothenburg (Sweden)
6. Norwegian University of Science and Technology (NTNU) (Norway)

When is the study starting and how long is it expected to run for?
October 2016 to October 2028

Who is funding the study?
1. NordForsk
2. Sahlgrenska Universitetssjukhuset
3. NFOG fund
4. Reprounion EU/Interreg
5. The Research Fund of Helsinki University Hospital
6. Kreftforeningen
7. Helse Midt-Norge
8. Norges Teknisk-Naturvitenskapelige Universitet

Who is the main contact?
Prof. Anja Pinborg

Trial website

http://www.conartas.com

Contact information

Type

Scientific

Primary contact

Prof Anja Pinborg

ORCID ID

http://orcid.org/0000-0002-8340-104X

Contact details

Fertility Clinic
Rigshospitalet
Copenhagen University Hospital
Blegdamsvej 9
Copenhagen
2100
Denmark

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

706005

Study information

Scientific title

Health in mothers and children after assisted reproductive technology - Committee of Nordic ART and Safety (CoNARTaS)

Acronym

CoNARTaS

Study hypothesis

Short- and long-term health in children conceived by assisted reproductive technology and in their mothers differs from health in children and mothers after spontaneous conception. Specific ART methods influence short and long-term health in children and mothers differently and give rise to altered health risk profiles.

Ethics approval

Approvals for data retrieval and linkage were obtained in each country. In Denmark and Finland, ethical approval is not required for research solely based on registry data. In Norway, ethical approval was given by the Regional Committee for Medical and Health Research Ethics (REC North, 2010/1909-13-20, 05/09/2016). In Sweden approval was obtained from the Ethical committee in Gothenburg, Dnr 214-12 (22/05/2012), T422-12, T516-15, T233-16, T300-17, T1144-17, T121-18.

Study design

Nordic controlled register-based cohort study including all children born after assisted reproductive technology and their mothers in Finland, Norway, Sweden and Denmark from 1985 to 2015. Control groups comprise the national birth cohorts born during the same period in the four Nordic countries, as well as their mothers.

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Other

Trial type

Other

Patient information sheet

Condition

Reproductive medicine, infertility
Morbidity, cognitive development, and mortality in mothers and children after assisted reproductive technology treatment

Intervention

The cohort consists of 173,148 children conceived by ART and their mothers, identified from the Medical Birth Registries in Denmark (1994 to 2015), Finland (October 1992 to 2015), Norway (1984 to 2015) and Sweden (1985 to 2015). The control cohorts are the background populations of children born during the same time periods in the four countries and their mothers.

Data are individual-level data on all residents that are routinely collected by the national health and socio-economic registries in each country and may be linked using the unique personal identity number of each resident.

Main categories of data are on type of ART treatment herein IVF, ICSI, frozen embryo transfer and oocyte donation, pregnancy and perinatal outcomes, selected diagnosis from specialised health care including detailed information on malignancies, diabetes, imprinting diseases, cardiovascular diseases, neurodevelopmental health and school performance and causes of death are available for all individuals in the cohort.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measure

1. Short and long-term health in children born after ART (perinatal outcomes, imprinting diseases, diabetes, pubertal diseases, malignancies, cardiovascular diseases, cognitive development, mental health, mortality)
2. Short and long-term health in women who give birth after ART (pregnancy complications, mental health, metabolic diseases, cardiovascular disease, cancer, mortality)

Data are routinely collected by the national health and socio-economic registries in each country. Data are entered continuously in the database and the primary outcome will be measured at different child ages with the relevant statistical adjustments for this in the analyses.

Secondary outcome measures

There are no secondary outcome measures

Overall trial start date

01/10/2016

Overall trial end date

01/10/2028

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Women who delivered after ART treatment and children born after ART conception 1985-2015 in Sweden, Norway, Denmark and Finland
2. Control group: all mothers delivering after spontaneous conception during the same time period and their children

Participant type

Mixed

Age group

Mixed

Gender

Both

Target number of participants

7,000,000

Participant exclusion criteria

Does not meet inclusion criteria

Recruitment start date

01/01/1985

Recruitment end date

31/12/2015

Locations

Countries of recruitment

Denmark, Finland, Norway, Sweden

Trial participating centre

Fertility Clinic, Rigshospitalet
Blegdamsvej 9
Copenhagen
2100
Denmark

Trial participating centre

National Institute for Health and Welfare
Mannerheimintie 166
Helsinki
FI-00271
Finland

Trial participating centre

Dept Obstetrics/Gynecology, Hvidovre Hospital
Kettegaard Allé 30
Hvidovre
2650
Denmark

Trial participating centre

Dept Obstetrics/Gynecology, Helsinki University Hospital
Haartmaninkatu 2
Helsinki
00029 HUS
Finland

Trial participating centre

Dept Obst/Gynecology, Sahlgrenska University Hospital, Inst of Clinical Sciences, University of Gothenburg
Journalvägen 6
Gothenburg
41685
Sweden

Trial participating centre

Department of Public Health and Nursing , Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU)
Håkon Jarls Gate 11
Trondheim
7030
Norway

Sponsor information

Organisation

Fertility Clinic, Rigshospitalet

Sponsor details

Blegdamsvej 9
Copenhagen
2100
Denmark

Sponsor type

Hospital/treatment centre

Website

https://www.rigshospitalet.dk/afdelinger-og-klinikker/julianemarie/fertilitetsklinikken/Sider/default.aspx

Funders

Funder type

Government

Funder name

NordForsk

Alternative name(s)

Funding Body Type

government organisation

Funding Body Subtype

government non-federal

Location

Norway

Funder name

Sahlgrenska Universitetssjukhuset

Alternative name(s)

Sahlgrenska University Hospital, SU

Funding Body Type

private sector organisation

Funding Body Subtype

academic

Location

Sweden

Funder name

NFOG fund

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Reprounion EU/Interreg

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

The Research Fund of Helsinki University Hospital

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Kreftforeningen

Alternative name(s)

Norwegian Cancer Society

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

Norway

Funder name

Helse Midt-Norge

Alternative name(s)

Central Norway Regional Health Authority

Funding Body Type

government organisation

Funding Body Subtype

government non-federal

Location

Norway

Funder name

Norges Teknisk-Naturvitenskapelige Universitet

Alternative name(s)

Norwegian University of Science and Technology, NTNU

Funding Body Type

private sector organisation

Funding Body Subtype

academic

Location

Norway

Results and Publications

Publication and dissemination plan

Results will be published in peer-reviewed high ranking scientific journals and at Nordic and international scientific congresses. Thirteen scientific publications have already been published based on the Nordic cohort data up to 2007 primarily on short term health outcomes i.e. perinatal morbidity and mortality and malformations. The trialists are now planning another 10 to 15 publications on long-term health outcomes including also the children born after ART conception up to 2015. Results of general interest will be published in the lay press, broadcast, television and social media.

IPD sharing statement
The datasets generated during and/or analysed during the current study are/will be available upon request from Prof. Anja Pinborg. As these are national health care data hosted in Statistics Denmark, data cannot be transported to other research institutions or hospitals.dk. Request for working with the database should be send to the investigator and the request will be brought up on the first coming CoNARTas board meeting. The board will look at each application individually. If approval is given the trialists will prepare a specific database for the purpose of the new study and researcher(s) will have login to Statistics Denmark with limited access to this specific role.

Intention to publish date

01/01/2019

Participant level data

Available on request

Basic results (scientific)

Publication list

1. 2011 results in: https://www.ncbi.nlm.nih.gov/pubmed/21477001
2. 2013 results in: https://www.ncbi.nlm.nih.gov/pubmed/23832793
3. 2014 results in: https://www.ncbi.nlm.nih.gov/pubmed/24990274
4. 2014 results in: https://www.ncbi.nlm.nih.gov/pubmed/24578477
5. 2014 results in: https://www.ncbi.nlm.nih.gov/pubmed/25267782
6. 2015 results in: https://www.ncbi.nlm.nih.gov/pubmed/25605701
7. 2015 results in: https://www.ncbi.nlm.nih.gov/pubmed/25924655
8. 2016 results in: https://www.ncbi.nlm.nih.gov/pubmed/27399261
9. 2017 results in: https://www.ncbi.nlm.nih.gov/pubmed/28057876
10. 2018 results in: https://www.ncbi.nlm.nih.gov/pubmed/29572867
11. 2018 results in: https://www.ncbi.nlm.nih.gov/pubmed/30276983
12. 2018 results in: https://www.ncbi.nlm.nih.gov/pubmed/30124838
13. 2018 results in: https://www.ncbi.nlm.nih.gov/pubmed/30165380

Publication citations

Additional files

Editorial Notes