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
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
Funders
Funder type
Government
Funder name
NordForsk
Alternative name(s)
Funding Body Type
government organisation
Funding Body Subtype
Local government
Location
Norway
Funder name
Sahlgrenska Universitetssjukhuset
Alternative name(s)
Sahlgrenska University Hospital, SU
Funding Body Type
private sector organisation
Funding Body Subtype
Universities (academic only)
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, The Norwegian Cancer Society, NCS
Funding Body Type
private sector organisation
Funding Body Subtype
Other non-profit organizations
Location
Norway
Funder name
Helse Midt-Norge
Alternative name(s)
Central Norway Regional Health Authority
Funding Body Type
government organisation
Funding Body Subtype
Local government
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
Universities (academic only)
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
14. 2020 results in: https://www.ncbi.nlm.nih.gov/pubmed/31976535 (added 27/01/2020)