An international registry of coronavirus exposure in pregnancy

ISRCTN	ISRCTN13539303
DOI	https://doi.org/10.1186/ISRCTN13539303
ClinicalTrials.gov number	NCT04366986

Submission date: 26/10/2020
Registration date: 30/10/2020
Last edited: 17/07/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
COVID-19 is a condition caused by the coronavirus (called SARS-CoV-2) that was first identified in late 2019. This virus can infect the respiratory (breathing) system. Some people do not have symptoms but can carry the virus and pass it on to others. People who have developed the condition may develop a fever and/or a continuous cough among other symptoms. This can develop into pneumonia. Pneumonia is a chest infection where the small air pockets of the lungs, called alveoli, fill with liquid and make it more difficult to breathe.

In 2020, the virus has spread to many countries around the world and neither a vaccine against the virus or specific treatment for COVID-19 has yet been developed. As of March 2020, it is advised that people minimize travel and social contact, and regularly wash their hands to reduce the spread of the virus.

Groups who are at a higher risk from infection with the virus, and therefore of developing COVID-19, include people aged over 70 years, people who have long-term health conditions (such as asthma or diabetes), people who have a weakened immune system and people who are pregnant. People in these groups, and people who might come into contact with them, can reduce this risk by following the up-to-date advice to reduce the spread of the virus.

There is insufficient information on the potential effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on pregnant women and their developing offspring. However, these populations are classified as vulnerable.
The International Registry of Coronavirus Exposure in Pregnancy (IRCEP) aims to describe the natural history of Coronavirus Disease 2019 (COVID-19) in pregnant women and to estimate the risk of major pregnancy-related outcomes among women with varying degrees of severity and of timing of COVID-19 exposure.

Who can participate?
Adult pregnant women with clinical confirmation of COVID-19 or tested for SARS-CoV-2 at any time during their pregnancy.

What does the study involve?
Registration and participation will be via the website or mobile app specially developed for the IRCEP. The IRCEP will collect data on the mother's social background, behaviors, reproductive history, chronic conditions, use of medications, and of healthcare utilization, on COVID-19 infection (symptoms, test results, treatment, and resolution), and information related to pregnancy, childbirth, and the health of the child. Follow-up will include questions at various time points during the pregnancy and will continue through the infant’s first 90 days of life.

What are the possible benefits and risks of participating?
Benefits: By joining the IRCEP and answering the questions, participants can help improve care for other pregnant women with COVID-19 in the future. Additionally, participants will be able to see how their pregnancy experiences compare to those of other women in the study, since aggregate results of the Registry will be reported to participants.
Risks: There are no known physical risks of taking part in the IRCEP. But, like any online activity, there is always a risk of loss of privacy.

Where is the study run from?
Pregistry LLC (USA)

When is the study starting and how long is it expected to run for?
March 2020 to June 2022

Who is funding the study?
Pregistry LLC (USA)

Who is the main contact?
Dr Diego Wyszynski, hello@pregistry.com

Study website

Contact information

Dr Diego Wyszynski
Public

1801 Century Park East
25th Floor
Los Angeles
90067
United States of America

ORCID ID	0000-0001-6293-3429
Phone	+1 (747) 200-5468
Email	hello@pregistry.com

Dr Sonia Hernandez-Diaz
Public

677 Huntington Avenue
Boston
02115
United States of America

ORCID ID	0000-0003-1458-7642
Phone	+1 (617) 432-3942
Email	shernan@hsph.harvard.edu

Study information

Study design	Prospective observational study
Primary study design	Observational
Secondary study design	Cohort study
Study setting(s)	Internet/virtual
Study type	Other
Participant information sheet	https://corona.pregistry.com/faq
Scientific title	International Registry of Coronavirus Exposure in Pregnancy (IRCEP)
Study acronym	IRCEP
Study objectives	COVID-19 during pregnancy increases the risk of obstetrical, neonatal, and infant abnormal outcomes.
Ethics approval(s)	Approved 08/06/2020, Institutional Review Board (IRB) of the Harvard T.H. Chan School of Public Health (90 Smith Street, 3rd Floor Boston, MA 02120, USA; +1 (617) 432-5132; kninsala@hsph.harvard.edu), ref: # IRB20-0622
Health condition(s) or problem(s) studied	COVID-19 (SARS-CoV-2 infection) during pregnancy
Intervention	The IRCEP will be an observational cohort study with prospective and retrospective components. Registration and participation via website or mobile app specially developed for the IRCEP will be voluntary. Women 18 years of age and older will be encouraged to enrol if at any time during pregnancy, they had a test performed for the coronavirus (regardless of the result) or if they had clinical confirmation of COVID-19 in the absence of a SARS-CoV-2 test. Women with confirmed COVID-19 via clinical or test methods will be included in the exposed group and women with a negative test will be included in the control group. Eligible women will be able to enrol at any time during gestation. Given the public health emergency due to the COVID-19 pandemic and the urgent need for data, the IRCEP will also enrol eligible women retrospectively during the first 180 days after delivery (if they delivered after December 2019). As numbers accumulate, the natural history of COVID-19 during pregnancy will be reported stratified by days since COVID-19 confirmation at enrollment (i.e., from prospective if immediate to retrospective if enrolled after resolution) and the risk of pregnancy outcomes by COVID-19 exposure group will be reported stratified by trimester at enrollment. For the assessment of miscarriages, only participants enrolled during the first trimester will be included and the analyses will be stratified by gestational week at enrollment. For other outcomes, the primary analysis will include all enrollees. However, sensitivity analyses of 1) teratogenicity will be restricted to participants enrolled before an informative prenatal screening was done; 2) late-pregnancy outcomes (e.g. preeclampsia) will be restricted to participants enrolled before the third trimester; and 3) delivery or neonatal outcomes will be restricted to participants enrolled before delivery. Information will be obtained directly from the participating women. Given the international nature of the IRCEP, the questionnaires will be available in 7 languages (English, Spanish, French, German, Italian, Mandarin, and Farsi). Participant confidentiality and anonymity will be strictly upheld. The IRCEP will collect data on potential confounding factors (such as maternal sociodemographic characteristics, behaviors, reproductive history, chronic conditions, use of medications, and measures of healthcare utilization), on COVID-19 infection (symptoms, test results, treatment, and resolution), and information related to obstetric and neonatal outcomes. Follow-up will include questions at various time points during the pregnancy and will continue through the infant’s first 90 days of life. There are two main data analyses: 1) a real-time descriptive surveillance that will report the COVID-19 characteristics and the frequency of outcomes in the exposed and control groups, and 2) hypothesis-based causal inference analyses that will investigate the potential effects of specific COVID-19 characteristics or treatments and will adjust through multivariate regression models or using propensity score (PS) matching to account for potential confounders, as appropriate.
Intervention type	Other
Primary outcome measure	Measured by maternal self-report using online questionnaire at baseline: 1. Pregnancy outcomes: 1.1. Miscarriage (or spontaneous abortion) 1.2. Elective termination 1.3. Stillbirth 1.4. Preterm delivery 2. Birth outcomes (measured at additional time points up to 90 days): 2.1. Major structural defects 2.2. Neonatal death 2.3. Admission into the Neonatal Intensive Care Unit 2.4. Maternal obstetric complications 2.5. Post-partum health
Secondary outcome measures	Measured by maternal self-report using online questionnaire: 1. Head circumference (cm) at each time point from baseline to 90 days. 2. Length at birth (cm)
Overall study start date	08/03/2020
Completion date	30/06/2022

Eligibility

Participant type(s)	All
Age group	Adult
Lower age limit	18 Years
Upper age limit	50 Years
Sex	Female
Target number of participants	20000
Total final enrolment	18000
Key inclusion criteria	Adult pregnant women with clinical confirmation of COVID-19 or tested for SARS-CoV-2 at any time during their pregnancy
Key exclusion criteria	Subjects who do not meet the inclusion criteria
Date of first enrolment	08/06/2020
Date of final enrolment	30/06/2022

Locations

Countries of recruitment

Afghanistan
Albania
Algeria
American Samoa
Andorra
Angola
Anguilla
Antarctica
Antigua and Barbuda
Argentina
Armenia
Aruba
Australia
Austria
Azerbaijan
Bahamas
Bahrain
Bangladesh
Barbados
Belarus
Belgium
Belize
Benin
Bermuda
Bhutan
Bolivia
Bonaire Saint Eustatius and Saba
Bosnia and Herzegovina
Botswana
Bouvet Island
Brazil
British Indian Ocean Territory
Brunei Darussalam
Bulgaria
Burkina Faso
Burundi
Cabo Verde
Cambodia
Cameroon
Canada
Cayman Islands
Central African Republic
Chad
Chile
China
Christmas Island
Cocos (Keeling) Islands
Colombia
Comoros
Congo
Congo, Democratic Republic
Cook Islands
Costa Rica
Croatia
Cuba
Curaçao
Cyprus
Czech Republic
Côte d'Ivoire
Denmark
Djibouti
Dominica
Dominican Republic
Ecuador
Egypt
El Salvador
Equatorial Guinea
Eritrea
Estonia
Eswatini
Ethiopia
Falkland Islands
Faroe Islands
Fiji
Finland
France
French Guiana
French Polynesia
French Southern Territories
Gabon
Gambia
Georgia
Germany
Ghana
Gibraltar
Greece
Greenland
Grenada
Guadeloupe
Guam
Guatemala
Guernsey
Guinea
Guinea-Bissau
Guyana
Haiti
Heard Island and McDonald Islands
Holy See (Vatican City State)
Honduras
Hong Kong
Hungary
Iceland
India
Indonesia
Iran
Iraq
Ireland
Isle of Man
Israel
Italy
Jamaica
Japan
Jersey
Jordan
Kazakhstan
Kenya
Kiribati
Korea, North
Korea, South
Kosovo
Kuwait
Kyrgyzstan
Lao People's Democratic Republic
Latvia
Lebanon
Lesotho
Liberia
Libya
Liechtenstein
Lithuania
Luxembourg
Macao
Madagascar
Malawi
Malaysia
Maldives
Mali
Malta
Marshall Islands
Martinique
Mauritania
Mauritius
Mayotte
Mexico
Micronesia, Federated States of
Moldova
Monaco
Mongolia
Montenegro
Montserrat
Morocco
Mozambique
Myanmar
Namibia
Nauru
Nepal
Netherlands
New Caledonia
New Zealand
Nicaragua
Niger
Nigeria
Niue
Norfolk Island
North Macedonia
Northern Ireland
Northern Mariana Islands
Norway
Oman
Pakistan
Palau
Palestine, State of
Panama
Papua New Guinea
Paraguay
Peru
Philippines
Pitcairn
Poland
Portugal
Puerto Rico
Qatar
Romania
Russian Federation
Rwanda
Réunion
Saint Barthélemy
Saint Helena, Ascension and Tristan da Cunha
Saint Kitts and Nevis
Saint Lucia
Saint Martin (French part)
Saint Pierre and Miquelon
Saint Vincent and the Grenadines
Samoa
San Marino
Sao Tome and Principe
Saudi Arabia
Scotland
Senegal
Serbia
Seychelles
Sierra Leone
Singapore
Sint Maarten (Dutch part)
Slovakia
Slovenia
Solomon Islands
Somalia
South Africa
South Georgia and the South Sandwich Islands
South Sudan
Spain
Sri Lanka
Sudan
Suriname
Svalbard and Jan Mayen
Sweden
Switzerland
Syria
Taiwan
Tajikistan
Tanzania
Thailand
Timor-Leste
Togo
Tokelau
Tonga
Trinidad and Tobago
Tunisia
Turkmenistan
Turks and Caicos Islands
Tuvalu
Türkiye
Uganda
Ukraine
United Arab Emirates
United Kingdom
United States Minor Outlying Islands
United States of America
Uruguay
Uzbekistan
Vanuatu
Venezuela
Viet Nam
Virgin Islands, British
Virgin Islands, U.S.
Wales
Wallis and Futuna
Western Sahara
Yemen
Zambia
Zimbabwe
Åland Islands

Study participating centre

Pregistry

1801 Century Park East, 25th Floor
Los Angeles
90067
United States of America

Sponsor information

Pregistry LLC
Other

1801 Century Park East, 25th Floor
Los Angeles
90067
United States of America

Phone	+1 (747) 200-5468
Email	hello@pregistry.com
Website	https://www.pregistry.com

Funders

Funder type

Industry

Pregistry LLC

No information available

Results and Publications

Intention to publish date	01/05/2024
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	Planned publication in a high-impact peer-reviewed journal.
IPD sharing plan	The datasets generated during and/or analysed during the current study will be available upon request from the International Registry of Coronavirus Exposure in Pregnancy (ircep@pregistry.com). De-identified data will be provided to applicants who submit a research study protocol approved by the Registry’s Leadership Team and the Scientific Advisory Committee.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		27/10/2022	17/07/2023	Yes	No

Editorial Notes

17/07/2023: The following changes were made to the study record:
1. The recruitment end date was changed from 30/04/2024 to 30/06/2022.
2. The overall study end date was changed from 30/04/2024 to 30/06/2022.
3. The target number of participants was changed from 25,000 to 20,000.
4. Total final enrolment and publication reference added.
21/10/2022: The contact details were updated.
28/10/2020: Trial’s existence confirmed by Harvard T.H. Chan School of Public Health.