Ignite Creation Date:
2024-05-06 @ 3:12 PM
Last Modification Date:
2024-10-26 @ 1:45 PM
Study NCT ID:
NCT04558996
Status:
UNKNOWN
Last Update Posted:
2020-09-22
First Post:
2020-09-18
Brief Title:
Spanish Registry of Pregnant Women With COVID-19
Sponsor:
Puerta de Hierro University Hospital
Organization:
Puerta de Hierro University Hospital
Study Overview
Official Title:
REGISTRO EPIDEMIOLOGICO DE COVID 19 EN GESTANTES
Status:
UNKNOWN
Status Verified Date:
2020-09
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
OBS COVID
Brief Summary:
Study title Spanish Registry of Pregnant Women with COVID-19 Protocol number and version Number 5520 Version V8 Sponsors This registry is a project promoted by Dr Oscar Martínez Pérez of the Obstetrics and Gynaecology department of the Puerta de Hierro University Hospital
Principal investigator of the registry National coordinator Dr Óscar Martínez Pérez Obstetrics and Gynaecology Department Puerta de Hierro University Hospital Majadahonda
Epidemiologist Maria Luisa de la Cruz Conti Researchers for each site 100 sites from 32 Spanish provinces are included Appendix 1 Funding Neither the hospitals nor the participating investigators will receive any financial compensation for their collaboration A bank account has been opened at the hospitals Biomedical Research Foundation to receive donations COV2000021 - SARS-COV-2 and the COVID-19 disease Call financed by the Carlos III Institute of Health and co-financed with ERDF funds
Abstract Rationale Knowledge about the impact of the SARS-CoV-2 virus on pregnancy is still scarce and all current recommendations are based on less than 100 cases published in the literature To identify moderate effects such as vertical transmission obstetric morbidity foetal death maternal or neonatal death and to allow accurate risk estimates larger sample sizes than those currently available are required
Methods Prospective observational study of pregnant women in whom SARS-CoV-2 infection is suspected at any time during pregnancy with positive test results for SARS-CoV-2 in order to create a registry of baseline characteristics of the pregnant woman aspects related to the course of pregnancy and delivery and related to the new-born with an observation period of up to 14 days after delivery Subsequently several phased studies will be conducted to help establish and monitor the set of measures to improve the care of pregnant women
Discussion The national registry for COVID-19 in pregnancy described here is a tool for sharing and centralizing data related to exposures to SARS-CoV-2 during pregnancy in a structured way It should speed up the process of prospectively obtaining a large unbiased data set and will collect information at national level
Principal investigator of the registry National coordinator Dr Óscar Martínez Pérez Obstetrics and Gynaecology Department Puerta de Hierro University Hospital Majadahonda
Epidemiologist Maria Luisa de la Cruz Conti Researchers for each site 100 sites from 32 Spanish provinces are included Appendix 1 Funding Neither the hospitals nor the participating investigators will receive any financial compensation for their collaboration A bank account has been opened at the hospitals Biomedical Research Foundation to receive donations COV2000021 - SARS-COV-2 and the COVID-19 disease Call financed by the Carlos III Institute of Health and co-financed with ERDF funds
Abstract Rationale Knowledge about the impact of the SARS-CoV-2 virus on pregnancy is still scarce and all current recommendations are based on less than 100 cases published in the literature To identify moderate effects such as vertical transmission obstetric morbidity foetal death maternal or neonatal death and to allow accurate risk estimates larger sample sizes than those currently available are required
Methods Prospective observational study of pregnant women in whom SARS-CoV-2 infection is suspected at any time during pregnancy with positive test results for SARS-CoV-2 in order to create a registry of baseline characteristics of the pregnant woman aspects related to the course of pregnancy and delivery and related to the new-born with an observation period of up to 14 days after delivery Subsequently several phased studies will be conducted to help establish and monitor the set of measures to improve the care of pregnant women
Discussion The national registry for COVID-19 in pregnancy described here is a tool for sharing and centralizing data related to exposures to SARS-CoV-2 during pregnancy in a structured way It should speed up the process of prospectively obtaining a large unbiased data set and will collect information at national level
Detailed Description:
Rationale To date few studies have described the impact of the SARS-CoV-2 virus on pregnancy particularly infection occurring during the third trimester of pregnancy The impact of the virus during the first and second trimesters of pregnancy remains unknown and must be urgently determined All current recommendations are based on less than 50 cases published in the literature with speculations on different aspects of management To identify moderate effects such as vertical transmission foetal death maternal or neonatal death larger sample sizes than those currently available are required to allow accurate risk estimates The national registry for COVID-19 in pregnancy described here is a tool for sharing and centralizing data related to exposures to SARS-CoV-2 during pregnancy in a structured way It should speed up the process of prospectively obtaining a large unbiased data set and will collect information at national level
Study hypothesis and objectives Hypothesis The COVID 19 disease affects pregnancy and has an influence on maternal and perinatal morbidity and mortality Objectives This study focuses on the creation of a registry of pregnant women with COVID-19 infection which will help establish and monitor the set of measures to improve their care
Primary objective Collect and analyse COVID-19 cases in pregnant and postpartum women at associated health centres
Secondary objectives
1 Establish incidence of COVID-19 infections diagnosed in pregnant women in the Spanish population
2 Determine the variables that are associated with more maternal and neonatal morbidity
3 Determine if there is vertical transmission
4 Evaluate the risk of SARS-CoV-2 infection during pregnancy
5 Characterize the clinical course of SARS-CoV-2 infection during pregnancy for example severity of maternal symptoms distribution of gestational age at onset ICU admission mechanical ventilation death
6 Quantify the risk of adverse pregnancy outcomes eg miscarriage stillbirth growth restriction and neonatal outcomes eg NICU prematurity death birth defects
7 Identify additional risk factors and risk modifiers eg symptomatic infection SARS-CoV-2 positive amniotic fluid co-infections
8 Develop a responsive data collection tool across a network of healthcare facilities to ensure rapid assessment of risks associated with future emerging pathogens and to help develop guidelines on this disease
9 Strengthen capacity-building in data exchange against emerging pathogens The collected dataset will allow a comprehensive characterization of the risks associated with SARS-CoV-2 infection in pregnancy In the future the developed structure will allow a rapid assessment of the risks linked to future emerging pathogens
Study design Prospective observational registry study of pregnant women with suspected SARS-CoV-2 infection at any time during pregnancy with positive test results for SARS-CoV-2
A specific database will be developed which will include the baseline characteristics of the pregnant women aspects related to the course of pregnancy and childbirth and the new-born Vertical transmission will be analysed only by means of a nasopharyngeal swab from the new-born before contact with the mother This registry sets an observation deadline of up to 14 days after birth for the new-born and 6 weeks postpartum for the mother The registry will be hosted on a secure https server this server will be physically located at OBS Covid Spain of the company ReserArch which has a contract with the Puerta de Hierro-Majadahonda University Hospital Research Foundation
Recruitment period will be between 1st March 2020 and 1st March 2021 After that different sub-analyses will be carried out with the data extracted in the registry and the secondary objectives will be addressed
Definitions Definition of case and healthy patient for the study The result in the PCR test on a sample of nasopharyngeal andor oropharyngeal swab was considered synonymous with exposurenon-exposure defining a case as any pregnant woman with a positive result regardless of the symptoms Those cases with clinical presentation of COVID-19 were classified according to the WHO division for adults into mild symptoms mild-moderate pneumonia severe pneumonia and septic shock 16
The recommended samples for diagnosis are samples from the upper respiratory tract nasopharyngeal andor oropharyngeal swab
A healthy patient is considered to have a negative PCR in the absence of symptoms Patients with positive IgM or IgG serology cannot be included The absence of serology does not prevent classifying the patient as healthy if the PCR is negative
Definitions of symptomatic and asymptomatic patient
Acute symptomatic patient Positive PCR Manifests any of the symptoms compatible with COVID-19 at the time of the study or analysis or during admission These symptoms may vary based on new findings
Symptomatic patient Patients with symptoms before 14 days of delivery even if they no longer have symptoms at the time of delivery
Asymptomatic patient Positive PCR No symptoms compatible with COVID-19 were observed at the time of the study or analysis
Ex-symptomatic or cured patient Positive or negative PCR The patient was symptomatic PCR more than 14 days before delivery and no longer has any of the symptoms compatible with COVID-19 at the time of the study or analysis Patient can be IgM positive or negative but shall be IgG if serology is available
Symptomatic patient with sequelae Positive or negative PCR The patient was symptomatic PCR and has any of the sequelae recognized after COVID-19 at the time of data analysis These sequelae may vary based on new findings
Overall sample size Currently the percentage of pregnant patients who are being diagnosed with COVID-19 is unknown this being one of the objectives of the study The registry includes 100 sites that in 2019 cared for a total of 172000 deliveries Appendix 1 and 3
Data sources and work plan Patient referral sources If the doctor in charge considers it appropriate to inform the patient about the existence and purpose of this registry heshe may do so At this time consent will be requested so that the information derived from the regular monitoring of these patients is incorporated into the data registry and that said information can be analysed and disclosed for scientific purposes in accord with the confidentiality provisions of the current legislation
Data collection Encrypted health-related personal data is collected prospectively using the OBS Covid Spain database of the company ReserArch
The collection of data on each pregnant woman is planned from the diagnosis of a case in a pregnancy up to 6 weeks after delivery and up to 14 days postpartum in the case of the new-born based on a manual prepared for the collection of data and for the investigator
Hospitals enrol their pregnant patients on an ongoing basis and the information is collected and stored anonymously in two separate phases the first phase during the inclusion period that occurs at the time of the SARS-CoV-2 test in the pregnant woman the second phase throughout the 2 weeks after birth
For sites with existing cohorts using methods that comply with registry data collection methods ie systematic inclusion of women screened for SARS-CoV-2 regardless of test results prospective follow-up and information requested as shown in the variables table of appendix 5 the data collected will be entered at the time they join the registry
Delivery monitoring the outcomes include perinatal and neonatal events which were collected at the time of delivery and the days immediately afterward These perinatal events included gestational age type of delivery presence of prepartum or premature rupture of membranes before delivery as well as any medical complications thromboembolic events admission to ICU maternal death and obstetric complications hemorrhagic events and hypertensive disorders while neonatal events included the 5-minute Apgar score the pH of the umbilical artery and possible complications such as admission to the NICU and neonatal death in the follow-up period or intrauterine foetal death The definitions of obstetric pathology follow the international criteria of the ACOG and RCOG 18-21
Follow-up after delivery Patient follow-up is carried out by the local investigator over the phone and the medical history is consulted from the time the patient is discharged up to 6 weeks later in order to detect late postpartum complications related to COVID 19 In the case of the new-born the follow-up is 14 days by the investigating neonatology department by telephone and consultation of the patients medical history to detect symptoms of COVID 19 symptoms Complications recorded in the mother during this period mastitis endometritis pulmonary embolism as well as neonatal death or readmission of the new-born due to COVID 19 were considered outcomes of interest and analysed together with those previously described
Data quality assurance plan Several strategies have been implemented to reduce data errors including a limited number of open questions a predefined range of values where applicable an easy-to-use case report form build that uses branching logic to reduce fields to complete one person per site assigned to data collection correction of systematic inconsistencies and verification of outliers The different forms that will be used to collect the data in a systematic way are shown in appendix 1
Heterogeneity tests Populations from diverse genetic socio-cultural and socio-economic backgrounds can be quite different in their characteristics Additionally there may be some disparities between sites with respect to the quality and quantity of data items that each site can measure This is expected regarding a data collection that allows any site to contribute Consequently heterogeneity in effect estimates may be due to clinical differences between pregnant women andor site-level differences in terms of exposure and outcome determination reporting or assessment bias We will formally assess heterogeneity taking into account variations in exposure covariates and significant outcomes and use meta-analysis methods Q or I2 statistics meta-regression and subgroup analysis to unravel heterogeneity at central and individual levels Briefly we will incorporate individual-level interaction terms in one-stage analysis and random intercepts to account for central-level factors not measured in the regression models mentioned above
EXTRACTION OF DATA FROM THE REGISTRY SUBSTUDIES Based on the registry prepared data extraction will be carried out to carry out four sub-studies that address the secondary objectives
Substudy 1 Prospective observational study on delivery and vertical transmission to the new-born
Objectives
1 Determine the variables that are associated with more maternal and neonatal morbidity
2 Determine if there is vertical transmission
3 Evaluate the risk of SARS-CoV-2 infection during pregnancy
4 Characterize the clinical course of SARS-CoV-2 infection during delivery
5 Identify additional risk factors and risk modifiers eg symptomatic infection SARS-CoV-2 positive amniotic fluid co-infections
Design Prospective observational study in 100 Spanish sites Recruitment 1st March 2020 to 1st March 2021 Spanish sites collected in Appendix 1
Patients Patients eligible for follow-up or target population will be any pregnant woman who is suspected of or needs to be ruled out as having SARS-CoV-2 infection at any time during pregnancy with positive test results for SARS-CoV-2 by PCR
The result of the PCR test on a sample of nasopharyngeal andor oropharyngeal swab was considered synonymous with exposurenon-exposure defining a case as any pregnant woman with a positive result regardless of the symptoms Those cases with clinical presentation of COVID19 were classified according to the WHO division for adults into mild symptoms mild-moderate pneumonia severe pneumonia and septic shock 16
The recommended samples for diagnosis are samples from the upper respiratory tract nasopharyngeal andor oropharyngeal swab
Primary variables Maternal characteristics Age mean years range Age groups n 20 20-34
35 Time between COVID-19 diagnosis and delivery mean days range Symptomatology n Showing COVID-19 symptoms Asymptomatic
Delivery characteristics Gestational age mean weeks range Preterm deliveries 37 weeks n Start of delivery n Spontaneous Induced Elective caesarean Type of delivery n Normal Instrumental Caesarean Weight at birth mean grams range Neonatal tests for COVID-19 n 12 hours from delivery Positive ones 12-48 hours from delivery Positive ones Skin-to-skin within first 24 hours n Breastfeeding at immediate postpartum n Arterial pH mean value range 5-minute Apgar score n 5
5 ICU admission n
Evaluation 14 days after delivery N
Symptomatology n Showing COVID-19 symptoms Asymptomatic COVID-19 symptoms Mild symptoms Symptoms reported at birth Cough Fever Dyspnoea New olfactory or taste disorder Fatiguemalaise Altered consciousness Headache Nauseavomiting Diarrhoea Mild-moderate pneumonia Severe pneumonia Septic shockmaternal mortality
The rest of the variables are defined in appendix 5 Statistics For the statistical analysis the SAS v94 software will be used The set of groups of variables requested and collected for each enrolled patient will be the same The demographic and clinical characteristics of the population included will be summarized Mean standard deviation minimum and maximum or median and interquartile intervals will be used for continuous variables according to the distribution The corresponding absolute and relative frequency will be reported for the discrete variables
An analysis of the possible association of both the characteristics of the patients and the outcomes collected with COVID-19 infection will be carried out using Pearsons Chi-square test or Fishers exact test and the Mann-Whitney U test after verification of the absence of normal data by the Kolmogorov-Smirnov test See section on Data Quality Plan and sample size Statistical significance was established with P 005
Substudy 2 Prospective observational study on maternal and neonatal morbidity in pregnant women with COVID-19 Objectives
1 Determine the variables that are associated with more maternal and neonatal morbidity
2 Characterize the clinical course of SARS-CoV-2 infection during pregnancy for example severity of maternal symptoms distribution of gestational age at onset ICU admission mechanical ventilation death
3 Identify additional risk factors and risk modifiers eg symptomatic infection SARS-CoV-2 positive amniotic fluid co-infections
Design Descriptive Observational Study Recruitment 1st March 2020 to 1st March 2021 Spanish sites collected in Appendix 1
Patients Patients eligible for follow-up or target population will be any pregnant woman who is suspected of or needs to be ruled out as having SARS-CoV-2 infection at any time during pregnancy with positive test results for SARS-CoV-2 by PCR
The result in the PCR test on a sample of nasopharyngeal andor oropharyngeal swab was considered synonymous with exposurenon-exposure defining a case as any pregnant woman with a positive result regardless of the symptoms Those cases with clinical presentation of COVID19 were classified according to the WHO division for adults into mild symptoms mild-moderate pneumonia severe pneumonia and septic shock 16
The recommended samples for diagnosis are samples from the upper respiratory tract nasopharyngeal andor oropharyngeal swab
Primary variables
Age Premature rupture of membranes PRM Race Preterm PRM Weight at the beginning of pregnancy NICU admission BMI Body Mass Index NICU admission days Single or Multiple Gestation APGAR 5 IVF with egg donation and IVF without egg donation Arterial pH Medical comorbidity Postpartum haemorrhage Blood group and Rh Abruptio placentae Maternal mortality Severe preeclampsia ICU admission HELLP Intrauterine foetal mortality Pulmonary embolism COVID 19 diagnosis date Endometritis Delivery 37 weeks Mastitis Delivery Type
COVID-19 symptoms Mild symptoms Symptoms reported at birth Cough Fever Dyspnoea New olfactory or taste disorder Fatiguemalaise Altered consciousness Headache Nauseavomiting Diarrhoea Mild-moderate pneumonia Severe pneumonia Septic shockmaternal mortality
The rest of the variables are defined in appendix 5 Statistics For the statistical analysis the SAS v94 software will be used The set of groups of variables requested and collected for each enrolled patient will be the same The demographic and clinical characteristics of the population included will be summarized Mean standard deviation minimum and maximum or median and interquartile intervals will be used for continuous variables according to the distribution The corresponding absolute and relative frequency will be reported for the discrete variables
An analysis of the possible association of both the characteristics of the patients and the outcomes collected with COVID-19 infection will be carried out using Pearsons Chi-square test or Fishers exact test and the Mann-Whitney U test after verification of the absence of normal data by the Kolmogorov-Smirnov test See section on Data Quality Plan and sample size Statistical significance was established with P 005 All statistical analyses were carried out with SAS 94 software
Substudy 3 Cohort study on obstetric pathology Objectives The purpose of this study was to test if pregnant patients with COVID-19 have more obstetrical morbidity than those non-infected
Determine the variables that are associated with more maternal and neonatal morbidity
Quantify the risk of adverse pregnancy outcomes eg miscarriage stillbirth growth restriction and neonatal outcomes eg NICU prematurity death birth defects
Design Longitudinal cohort case study to quantify the obstetrical and perinatal morbi-mortality throughout all hospitals in Spain with a universal consecutive PCR based screening program
Recruitment 1st March 2020 to 1st March 2021 Spanish sites collected in Appendix 1
Patients Case eligibility criteria included individuals with laboratory confirmation of COVID-19 infection irrespective of clinical signs and symptoms or the result of another serological test Positive RNA PCR test from maternal nasopharyngeal swabs
The selection of the control group will be collected in the same database considering patients with negative COVID-19 delivery diagnosed by PCR screening at the time of delivery or less than 3 days before
The delivery or deliveries that were treated in this site and that occurred within the same day before and after the case maximum 3 per case are included in the control group If the case were the last delivery of the day the first ones of the following day could be recruited If the case were the first of that day the last one of the previous day could be recruited
The data collected will be entered at the time they join the registry Delivery monitoring the outcomes include perinatal and neonatal events which were collected at the time of delivery and the days immediately afterward These perinatal events included gestational age type of delivery presence of prepartum or premature rupture of membranes before delivery as well as any medical complications thromboembolic events admission to ICU maternal death and obstetric complications hemorrhagic events and hypertensive disorders while neonatal events included the 5-minute Apgar score the pH of the umbilical artery and possible complications such as admission to the NICU and neonatal death in the follow-up period or intrauterine foetal death The definitions of obstetric pathology follow the international criteria of the ACOG and RCOG 18-21
Follow-up after delivery Patient follow-up is carried out by the local investigator over the phone and the medical history is consulted from the time the patient is discharged up to 6 weeks later in order to detect late postpartum complications related to COVID 19 In the case of the new-born the follow-up is 14 days by the investigating neonatology department by telephone and consultation of the patients medical history to detect symptoms of COVID 19 symptoms Complications recorded in the mother during this period mastitis endometritis pulmonary embolism as well as neonatal death or readmission of the new-born due to COVID were considered outcomes of interest and analysed together with those described above
Primary variables Maternal characteristics
Maternal age years meanrange Age range 18-24 25-34 34-49 Ethnicity White European Latino Americans Black non-Hispanic Asian non-Hispanic Arab Nulliparous Smoking ICU admission COVID 19 diagnosis date Delivery 37 weeks
Maternal comorbidities Obesity BMI 30 kgm2
Cardiovascular comorbidities Chronic Cardiac Disease Pre-pregnancy HT Pulmonary comorbidities Chronic Pulmonary Disease not asthma Asthma Hematologic comorbidities Chronic Blood Disease Thrombophilia Antiphospholipid syndrome
COVID-19 symptoms Mild symptoms Symptoms reported at birth Cough Fever Dyspnoea New olfactory or taste disorder Fatiguemalaise Altered consciousness Headache Nauseavomiting Diarrhoea Mild-moderate pneumonia Severe pneumonia Septic shockmaternal mortality
Delivery Type Premature rupture of membranes Preterm PRM NICU admission NICU admission days Postpartum haemorrhage Abruptio placentae Severe Preeclampsia HELLP Pulmonary embolism
The rest of the variables are described in appendix 5 Statistics For the descriptive analysis categorical variables were expressed as absolute and relative frequencies whereas quantitative ones were expressed as mean and range minimum-maximum values Analysis of the possible association of both the characteristics of the patients and the outcomes collected with COVID-19 infection is carried out using the Pearson Chi-square test or Fishers exact test and the Mann-Whitney U test after checking the absence of normal data using the Kolmogorov-Smirnov test See sections of Data Quality Plan and sample size Statistical significance was established with P 005 All statistical analyses were carried out with SAS 94 software
For each response variable outcome a multiple logistic regression model has been carried out refined with the backward conditional stepwise method
The response variables are those described in the previous section The subset of explanatory variables is different for each model and is specified in the text
It will only be of interest the Odds Ratio OR its 95 CI and the significance of the COVID factor The information on the rest of the explanatory variables is irrelevant since they only act as adjustment variables
Substudy 4 Epidemiological prevalence study Objectives Determine the prevalence of SARS_COV2 infection in Spanish pregnant women Design Cross-sectional study The nQuery Advisor Release 70 software was used to calculate the sample size based on the available data As we do not have data on the prevalence of COVID-19 we set an expected percentage of 50 a situation that maximizes the sample size of asymptomatic women during delivery We determined the sample size for a COVID-19 delivery prevalence study with an expected prevalence of 50 a 95 confidence level and 5 accuracy resulting in a sample size of 1056 pregnant women
The selection of pregnant women in the sample will follow the distribution of the delivery rate by communities and hospitals in Spain according to the INE data for 2018 Appendix 3 15 Subsequently a simple random selection procedure will be carried out in each site creating a numerical list of the women to be included in the sample Appendix 1 Pregnant women will be assigned a consecutive number from one onwards according to their due date Subsequently the pregnant women who will be part of the sample will be chosen when the number that identifies them is within the table previously created through the random procedure
Recruitment 1st March 2020 to 1st March 2021 Spanish sites collected in the Appendix 1 Patients Delivery of pregnant women in Spanish maternity wards with a diagnostic test for COVID-19
Inclusion criteria
Single or multiple gestations of 24 weeks or more without a positive laboratory test for COVID-19 prior to delivery
Delivery in a public or private maternity hospital in Spain with a diagnostic test for COVID-19 using PCR Kits within 72 hours prior to delivery or 24 hours after delivery
The presence of comorbidity is not an exclusion criterion asthma diabetes mellitus hypertension-preeclampsia endocrine disorder dermatological pathology or other obstetric or medical-surgical pathologies
Acceptance by the pregnant woman to participate in the study by means of informed consent for group study
The result of the PCR test on a sample of nasopharyngeal andor oropharyngeal swab was considered synonymous with exposurenon-exposure defining a case as any pregnant woman with a positive result regardless of the symptoms Those cases with clinical presentation of COVID-19 were classified according to the WHO division for adults into mild symptoms mild-moderate pneumonia severe pneumonia and septic shock 16
The recommended samples for diagnosis are samples from the upper respiratory tract nasopharyngeal andor oropharyngeal swab
A healthy patient is considered to have a negative PCR in the absence of symptoms Patients with positive IgM or IgG serology cannot be included The absence of serology does not prevent classifying the patient as healthy if the PCR is negative
Primary variables
Age Delivery 37 weeks Race Delivery Type Weight at the beginning of pregnancy Premature rupture of membranes Body Mass Index BMI Preterm PRM Blood type NICU admission Single or Multiple NICU admission days IVF Postpartum haemorrhage Obesity BMI 30 Abruptio placentae Vascular comorbidities Severe Preeclampsia Pulmonary comorbidity HELLP Maternal mortality Pulmonary embolism ICU admission COVID 19 diagnosis date
The rest of the variables are described in appendix 5 Statistics For the statistical analysis the SAS v94 software will be used The set of groups of variables requested and collected for each enrolled patient will be the same The demographic and clinical characteristics of the population included will be summarized Mean standard deviation minimum and maximum or median and interquartile intervals will be used for continuous variables according to the distribution The corresponding absolute and relative frequency will be reported for the discrete variables
The possible association of both the characteristics of the patients and the outcomes collected with COVID-19 infection using the Pearson Chi-square test or Fishers exact test and the Mann-Whitney U test after checking the absence of normal data using the Kolmogorov-Smirnov test Statistically significant associations were considered when the p value was less than 005 For those categorical variables in which statistically significant differences were identified the corresponding Odds Ratio OR and 95 Confidence Intervals 95 CI were estimated using univariate logistic regression models
Logistic regressions both univariate and multivariate will be performed determining the odd ratio and its 95 confidence interval
Management and reporting of adverse reactions As it is an epidemiological study without a drug under study the provisions on Pharmacovigilance in Ministerial Order SAS34702009 and Royal Decree 5772013 in relation to reporting adverse reactions to approved drugs will be followed Investigators who are aware of possible adverse reactions during the study should notify them as quickly as possible to the Autonomous Center for Pharmacovigilance corresponding to their healthcare area through any of the channels that the institution makes available through the yellow card system or via online through the SINAEM website It is also recommended that the Investigator or reporting doctor reports all adverse reactions to the marketing authorization holder of the drugs involved Additionally the conditions of use outside the marketing authorization of the drug must be reported eg off-label use overdose misuse abuse and medication errors or occupational exposure as well as cases of suspected drug interactions pregnancy exposure during breastfeeding and lack of efficacy
Ethical aspects This study will be carried out under conditions of respect for the fundamental rights of the person and the ethical principles that affect biomedical research with human beings following the international recommendations contained in the Declaration of Helsinki and its subsequent revisions Likewise national recommendations will be followed in accordance with the Biomedical Research Law 142007
During the completion of this study the investigators will strictly adhere to the provisions of this protocol fully completing the Case Report Form
Informed consent In accordance with the criteria of good clinical practice the subjects will be duly informed of all those details concerning their participation in the study and will freely give their consent in writing or orally recording this fact in their medical records
Preferably written or oral consent will be sought for cases and controls chosen at random from among pregnant women who have given birth in each centre and who have COVID-19 The patient may sign the consent electronically See appendix 7
Safety Measures and Confidentiality Protection of human subjects Pregnant women and newborns participate in the registry as mentioned above No biological samples are collected for specific analysis in this study
The laboratory tests collected in the registry will be those carried out in each site according to its protocol No extra lab tests will be carried out for this study and there is no handling of biological tests The data collected through the national registry for SARS-CoV-2 in pregnancy does not contain personally identifiable information
The data of the subjects included in it will be treated in accordance with Organic Law 32018 of 5th December on the Protection of Personal Data and guarantee of digital rights
Use of the data contained in the registry
The use of the data contained in this registry within any scientific research project will previously require
Approval by the local Clinical Research Ethics Committee CREC of the study site
Approval by the Scientific Committee a body that will be constituted to give scientific output to the database
Signing of the data protection law contract A citation policy will be established for the registry as well as for the authorship order of the different sites providing patients to each research project
Study hypothesis and objectives Hypothesis The COVID 19 disease affects pregnancy and has an influence on maternal and perinatal morbidity and mortality Objectives This study focuses on the creation of a registry of pregnant women with COVID-19 infection which will help establish and monitor the set of measures to improve their care
Primary objective Collect and analyse COVID-19 cases in pregnant and postpartum women at associated health centres
Secondary objectives
1 Establish incidence of COVID-19 infections diagnosed in pregnant women in the Spanish population
2 Determine the variables that are associated with more maternal and neonatal morbidity
3 Determine if there is vertical transmission
4 Evaluate the risk of SARS-CoV-2 infection during pregnancy
5 Characterize the clinical course of SARS-CoV-2 infection during pregnancy for example severity of maternal symptoms distribution of gestational age at onset ICU admission mechanical ventilation death
6 Quantify the risk of adverse pregnancy outcomes eg miscarriage stillbirth growth restriction and neonatal outcomes eg NICU prematurity death birth defects
7 Identify additional risk factors and risk modifiers eg symptomatic infection SARS-CoV-2 positive amniotic fluid co-infections
8 Develop a responsive data collection tool across a network of healthcare facilities to ensure rapid assessment of risks associated with future emerging pathogens and to help develop guidelines on this disease
9 Strengthen capacity-building in data exchange against emerging pathogens The collected dataset will allow a comprehensive characterization of the risks associated with SARS-CoV-2 infection in pregnancy In the future the developed structure will allow a rapid assessment of the risks linked to future emerging pathogens
Study design Prospective observational registry study of pregnant women with suspected SARS-CoV-2 infection at any time during pregnancy with positive test results for SARS-CoV-2
A specific database will be developed which will include the baseline characteristics of the pregnant women aspects related to the course of pregnancy and childbirth and the new-born Vertical transmission will be analysed only by means of a nasopharyngeal swab from the new-born before contact with the mother This registry sets an observation deadline of up to 14 days after birth for the new-born and 6 weeks postpartum for the mother The registry will be hosted on a secure https server this server will be physically located at OBS Covid Spain of the company ReserArch which has a contract with the Puerta de Hierro-Majadahonda University Hospital Research Foundation
Recruitment period will be between 1st March 2020 and 1st March 2021 After that different sub-analyses will be carried out with the data extracted in the registry and the secondary objectives will be addressed
Definitions Definition of case and healthy patient for the study The result in the PCR test on a sample of nasopharyngeal andor oropharyngeal swab was considered synonymous with exposurenon-exposure defining a case as any pregnant woman with a positive result regardless of the symptoms Those cases with clinical presentation of COVID-19 were classified according to the WHO division for adults into mild symptoms mild-moderate pneumonia severe pneumonia and septic shock 16
The recommended samples for diagnosis are samples from the upper respiratory tract nasopharyngeal andor oropharyngeal swab
A healthy patient is considered to have a negative PCR in the absence of symptoms Patients with positive IgM or IgG serology cannot be included The absence of serology does not prevent classifying the patient as healthy if the PCR is negative
Definitions of symptomatic and asymptomatic patient
Acute symptomatic patient Positive PCR Manifests any of the symptoms compatible with COVID-19 at the time of the study or analysis or during admission These symptoms may vary based on new findings
Symptomatic patient Patients with symptoms before 14 days of delivery even if they no longer have symptoms at the time of delivery
Asymptomatic patient Positive PCR No symptoms compatible with COVID-19 were observed at the time of the study or analysis
Ex-symptomatic or cured patient Positive or negative PCR The patient was symptomatic PCR more than 14 days before delivery and no longer has any of the symptoms compatible with COVID-19 at the time of the study or analysis Patient can be IgM positive or negative but shall be IgG if serology is available
Symptomatic patient with sequelae Positive or negative PCR The patient was symptomatic PCR and has any of the sequelae recognized after COVID-19 at the time of data analysis These sequelae may vary based on new findings
Overall sample size Currently the percentage of pregnant patients who are being diagnosed with COVID-19 is unknown this being one of the objectives of the study The registry includes 100 sites that in 2019 cared for a total of 172000 deliveries Appendix 1 and 3
Data sources and work plan Patient referral sources If the doctor in charge considers it appropriate to inform the patient about the existence and purpose of this registry heshe may do so At this time consent will be requested so that the information derived from the regular monitoring of these patients is incorporated into the data registry and that said information can be analysed and disclosed for scientific purposes in accord with the confidentiality provisions of the current legislation
Data collection Encrypted health-related personal data is collected prospectively using the OBS Covid Spain database of the company ReserArch
The collection of data on each pregnant woman is planned from the diagnosis of a case in a pregnancy up to 6 weeks after delivery and up to 14 days postpartum in the case of the new-born based on a manual prepared for the collection of data and for the investigator
Hospitals enrol their pregnant patients on an ongoing basis and the information is collected and stored anonymously in two separate phases the first phase during the inclusion period that occurs at the time of the SARS-CoV-2 test in the pregnant woman the second phase throughout the 2 weeks after birth
For sites with existing cohorts using methods that comply with registry data collection methods ie systematic inclusion of women screened for SARS-CoV-2 regardless of test results prospective follow-up and information requested as shown in the variables table of appendix 5 the data collected will be entered at the time they join the registry
Delivery monitoring the outcomes include perinatal and neonatal events which were collected at the time of delivery and the days immediately afterward These perinatal events included gestational age type of delivery presence of prepartum or premature rupture of membranes before delivery as well as any medical complications thromboembolic events admission to ICU maternal death and obstetric complications hemorrhagic events and hypertensive disorders while neonatal events included the 5-minute Apgar score the pH of the umbilical artery and possible complications such as admission to the NICU and neonatal death in the follow-up period or intrauterine foetal death The definitions of obstetric pathology follow the international criteria of the ACOG and RCOG 18-21
Follow-up after delivery Patient follow-up is carried out by the local investigator over the phone and the medical history is consulted from the time the patient is discharged up to 6 weeks later in order to detect late postpartum complications related to COVID 19 In the case of the new-born the follow-up is 14 days by the investigating neonatology department by telephone and consultation of the patients medical history to detect symptoms of COVID 19 symptoms Complications recorded in the mother during this period mastitis endometritis pulmonary embolism as well as neonatal death or readmission of the new-born due to COVID 19 were considered outcomes of interest and analysed together with those previously described
Data quality assurance plan Several strategies have been implemented to reduce data errors including a limited number of open questions a predefined range of values where applicable an easy-to-use case report form build that uses branching logic to reduce fields to complete one person per site assigned to data collection correction of systematic inconsistencies and verification of outliers The different forms that will be used to collect the data in a systematic way are shown in appendix 1
Heterogeneity tests Populations from diverse genetic socio-cultural and socio-economic backgrounds can be quite different in their characteristics Additionally there may be some disparities between sites with respect to the quality and quantity of data items that each site can measure This is expected regarding a data collection that allows any site to contribute Consequently heterogeneity in effect estimates may be due to clinical differences between pregnant women andor site-level differences in terms of exposure and outcome determination reporting or assessment bias We will formally assess heterogeneity taking into account variations in exposure covariates and significant outcomes and use meta-analysis methods Q or I2 statistics meta-regression and subgroup analysis to unravel heterogeneity at central and individual levels Briefly we will incorporate individual-level interaction terms in one-stage analysis and random intercepts to account for central-level factors not measured in the regression models mentioned above
EXTRACTION OF DATA FROM THE REGISTRY SUBSTUDIES Based on the registry prepared data extraction will be carried out to carry out four sub-studies that address the secondary objectives
Substudy 1 Prospective observational study on delivery and vertical transmission to the new-born
Objectives
1 Determine the variables that are associated with more maternal and neonatal morbidity
2 Determine if there is vertical transmission
3 Evaluate the risk of SARS-CoV-2 infection during pregnancy
4 Characterize the clinical course of SARS-CoV-2 infection during delivery
5 Identify additional risk factors and risk modifiers eg symptomatic infection SARS-CoV-2 positive amniotic fluid co-infections
Design Prospective observational study in 100 Spanish sites Recruitment 1st March 2020 to 1st March 2021 Spanish sites collected in Appendix 1
Patients Patients eligible for follow-up or target population will be any pregnant woman who is suspected of or needs to be ruled out as having SARS-CoV-2 infection at any time during pregnancy with positive test results for SARS-CoV-2 by PCR
The result of the PCR test on a sample of nasopharyngeal andor oropharyngeal swab was considered synonymous with exposurenon-exposure defining a case as any pregnant woman with a positive result regardless of the symptoms Those cases with clinical presentation of COVID19 were classified according to the WHO division for adults into mild symptoms mild-moderate pneumonia severe pneumonia and septic shock 16
The recommended samples for diagnosis are samples from the upper respiratory tract nasopharyngeal andor oropharyngeal swab
Primary variables Maternal characteristics Age mean years range Age groups n 20 20-34
35 Time between COVID-19 diagnosis and delivery mean days range Symptomatology n Showing COVID-19 symptoms Asymptomatic
Delivery characteristics Gestational age mean weeks range Preterm deliveries 37 weeks n Start of delivery n Spontaneous Induced Elective caesarean Type of delivery n Normal Instrumental Caesarean Weight at birth mean grams range Neonatal tests for COVID-19 n 12 hours from delivery Positive ones 12-48 hours from delivery Positive ones Skin-to-skin within first 24 hours n Breastfeeding at immediate postpartum n Arterial pH mean value range 5-minute Apgar score n 5
5 ICU admission n
Evaluation 14 days after delivery N
Symptomatology n Showing COVID-19 symptoms Asymptomatic COVID-19 symptoms Mild symptoms Symptoms reported at birth Cough Fever Dyspnoea New olfactory or taste disorder Fatiguemalaise Altered consciousness Headache Nauseavomiting Diarrhoea Mild-moderate pneumonia Severe pneumonia Septic shockmaternal mortality
The rest of the variables are defined in appendix 5 Statistics For the statistical analysis the SAS v94 software will be used The set of groups of variables requested and collected for each enrolled patient will be the same The demographic and clinical characteristics of the population included will be summarized Mean standard deviation minimum and maximum or median and interquartile intervals will be used for continuous variables according to the distribution The corresponding absolute and relative frequency will be reported for the discrete variables
An analysis of the possible association of both the characteristics of the patients and the outcomes collected with COVID-19 infection will be carried out using Pearsons Chi-square test or Fishers exact test and the Mann-Whitney U test after verification of the absence of normal data by the Kolmogorov-Smirnov test See section on Data Quality Plan and sample size Statistical significance was established with P 005
Substudy 2 Prospective observational study on maternal and neonatal morbidity in pregnant women with COVID-19 Objectives
1 Determine the variables that are associated with more maternal and neonatal morbidity
2 Characterize the clinical course of SARS-CoV-2 infection during pregnancy for example severity of maternal symptoms distribution of gestational age at onset ICU admission mechanical ventilation death
3 Identify additional risk factors and risk modifiers eg symptomatic infection SARS-CoV-2 positive amniotic fluid co-infections
Design Descriptive Observational Study Recruitment 1st March 2020 to 1st March 2021 Spanish sites collected in Appendix 1
Patients Patients eligible for follow-up or target population will be any pregnant woman who is suspected of or needs to be ruled out as having SARS-CoV-2 infection at any time during pregnancy with positive test results for SARS-CoV-2 by PCR
The result in the PCR test on a sample of nasopharyngeal andor oropharyngeal swab was considered synonymous with exposurenon-exposure defining a case as any pregnant woman with a positive result regardless of the symptoms Those cases with clinical presentation of COVID19 were classified according to the WHO division for adults into mild symptoms mild-moderate pneumonia severe pneumonia and septic shock 16
The recommended samples for diagnosis are samples from the upper respiratory tract nasopharyngeal andor oropharyngeal swab
Primary variables
Age Premature rupture of membranes PRM Race Preterm PRM Weight at the beginning of pregnancy NICU admission BMI Body Mass Index NICU admission days Single or Multiple Gestation APGAR 5 IVF with egg donation and IVF without egg donation Arterial pH Medical comorbidity Postpartum haemorrhage Blood group and Rh Abruptio placentae Maternal mortality Severe preeclampsia ICU admission HELLP Intrauterine foetal mortality Pulmonary embolism COVID 19 diagnosis date Endometritis Delivery 37 weeks Mastitis Delivery Type
COVID-19 symptoms Mild symptoms Symptoms reported at birth Cough Fever Dyspnoea New olfactory or taste disorder Fatiguemalaise Altered consciousness Headache Nauseavomiting Diarrhoea Mild-moderate pneumonia Severe pneumonia Septic shockmaternal mortality
The rest of the variables are defined in appendix 5 Statistics For the statistical analysis the SAS v94 software will be used The set of groups of variables requested and collected for each enrolled patient will be the same The demographic and clinical characteristics of the population included will be summarized Mean standard deviation minimum and maximum or median and interquartile intervals will be used for continuous variables according to the distribution The corresponding absolute and relative frequency will be reported for the discrete variables
An analysis of the possible association of both the characteristics of the patients and the outcomes collected with COVID-19 infection will be carried out using Pearsons Chi-square test or Fishers exact test and the Mann-Whitney U test after verification of the absence of normal data by the Kolmogorov-Smirnov test See section on Data Quality Plan and sample size Statistical significance was established with P 005 All statistical analyses were carried out with SAS 94 software
Substudy 3 Cohort study on obstetric pathology Objectives The purpose of this study was to test if pregnant patients with COVID-19 have more obstetrical morbidity than those non-infected
Determine the variables that are associated with more maternal and neonatal morbidity
Quantify the risk of adverse pregnancy outcomes eg miscarriage stillbirth growth restriction and neonatal outcomes eg NICU prematurity death birth defects
Design Longitudinal cohort case study to quantify the obstetrical and perinatal morbi-mortality throughout all hospitals in Spain with a universal consecutive PCR based screening program
Recruitment 1st March 2020 to 1st March 2021 Spanish sites collected in Appendix 1
Patients Case eligibility criteria included individuals with laboratory confirmation of COVID-19 infection irrespective of clinical signs and symptoms or the result of another serological test Positive RNA PCR test from maternal nasopharyngeal swabs
The selection of the control group will be collected in the same database considering patients with negative COVID-19 delivery diagnosed by PCR screening at the time of delivery or less than 3 days before
The delivery or deliveries that were treated in this site and that occurred within the same day before and after the case maximum 3 per case are included in the control group If the case were the last delivery of the day the first ones of the following day could be recruited If the case were the first of that day the last one of the previous day could be recruited
The data collected will be entered at the time they join the registry Delivery monitoring the outcomes include perinatal and neonatal events which were collected at the time of delivery and the days immediately afterward These perinatal events included gestational age type of delivery presence of prepartum or premature rupture of membranes before delivery as well as any medical complications thromboembolic events admission to ICU maternal death and obstetric complications hemorrhagic events and hypertensive disorders while neonatal events included the 5-minute Apgar score the pH of the umbilical artery and possible complications such as admission to the NICU and neonatal death in the follow-up period or intrauterine foetal death The definitions of obstetric pathology follow the international criteria of the ACOG and RCOG 18-21
Follow-up after delivery Patient follow-up is carried out by the local investigator over the phone and the medical history is consulted from the time the patient is discharged up to 6 weeks later in order to detect late postpartum complications related to COVID 19 In the case of the new-born the follow-up is 14 days by the investigating neonatology department by telephone and consultation of the patients medical history to detect symptoms of COVID 19 symptoms Complications recorded in the mother during this period mastitis endometritis pulmonary embolism as well as neonatal death or readmission of the new-born due to COVID were considered outcomes of interest and analysed together with those described above
Primary variables Maternal characteristics
Maternal age years meanrange Age range 18-24 25-34 34-49 Ethnicity White European Latino Americans Black non-Hispanic Asian non-Hispanic Arab Nulliparous Smoking ICU admission COVID 19 diagnosis date Delivery 37 weeks
Maternal comorbidities Obesity BMI 30 kgm2
Cardiovascular comorbidities Chronic Cardiac Disease Pre-pregnancy HT Pulmonary comorbidities Chronic Pulmonary Disease not asthma Asthma Hematologic comorbidities Chronic Blood Disease Thrombophilia Antiphospholipid syndrome
COVID-19 symptoms Mild symptoms Symptoms reported at birth Cough Fever Dyspnoea New olfactory or taste disorder Fatiguemalaise Altered consciousness Headache Nauseavomiting Diarrhoea Mild-moderate pneumonia Severe pneumonia Septic shockmaternal mortality
Delivery Type Premature rupture of membranes Preterm PRM NICU admission NICU admission days Postpartum haemorrhage Abruptio placentae Severe Preeclampsia HELLP Pulmonary embolism
The rest of the variables are described in appendix 5 Statistics For the descriptive analysis categorical variables were expressed as absolute and relative frequencies whereas quantitative ones were expressed as mean and range minimum-maximum values Analysis of the possible association of both the characteristics of the patients and the outcomes collected with COVID-19 infection is carried out using the Pearson Chi-square test or Fishers exact test and the Mann-Whitney U test after checking the absence of normal data using the Kolmogorov-Smirnov test See sections of Data Quality Plan and sample size Statistical significance was established with P 005 All statistical analyses were carried out with SAS 94 software
For each response variable outcome a multiple logistic regression model has been carried out refined with the backward conditional stepwise method
The response variables are those described in the previous section The subset of explanatory variables is different for each model and is specified in the text
It will only be of interest the Odds Ratio OR its 95 CI and the significance of the COVID factor The information on the rest of the explanatory variables is irrelevant since they only act as adjustment variables
Substudy 4 Epidemiological prevalence study Objectives Determine the prevalence of SARS_COV2 infection in Spanish pregnant women Design Cross-sectional study The nQuery Advisor Release 70 software was used to calculate the sample size based on the available data As we do not have data on the prevalence of COVID-19 we set an expected percentage of 50 a situation that maximizes the sample size of asymptomatic women during delivery We determined the sample size for a COVID-19 delivery prevalence study with an expected prevalence of 50 a 95 confidence level and 5 accuracy resulting in a sample size of 1056 pregnant women
The selection of pregnant women in the sample will follow the distribution of the delivery rate by communities and hospitals in Spain according to the INE data for 2018 Appendix 3 15 Subsequently a simple random selection procedure will be carried out in each site creating a numerical list of the women to be included in the sample Appendix 1 Pregnant women will be assigned a consecutive number from one onwards according to their due date Subsequently the pregnant women who will be part of the sample will be chosen when the number that identifies them is within the table previously created through the random procedure
Recruitment 1st March 2020 to 1st March 2021 Spanish sites collected in the Appendix 1 Patients Delivery of pregnant women in Spanish maternity wards with a diagnostic test for COVID-19
Inclusion criteria
Single or multiple gestations of 24 weeks or more without a positive laboratory test for COVID-19 prior to delivery
Delivery in a public or private maternity hospital in Spain with a diagnostic test for COVID-19 using PCR Kits within 72 hours prior to delivery or 24 hours after delivery
The presence of comorbidity is not an exclusion criterion asthma diabetes mellitus hypertension-preeclampsia endocrine disorder dermatological pathology or other obstetric or medical-surgical pathologies
Acceptance by the pregnant woman to participate in the study by means of informed consent for group study
The result of the PCR test on a sample of nasopharyngeal andor oropharyngeal swab was considered synonymous with exposurenon-exposure defining a case as any pregnant woman with a positive result regardless of the symptoms Those cases with clinical presentation of COVID-19 were classified according to the WHO division for adults into mild symptoms mild-moderate pneumonia severe pneumonia and septic shock 16
The recommended samples for diagnosis are samples from the upper respiratory tract nasopharyngeal andor oropharyngeal swab
A healthy patient is considered to have a negative PCR in the absence of symptoms Patients with positive IgM or IgG serology cannot be included The absence of serology does not prevent classifying the patient as healthy if the PCR is negative
Primary variables
Age Delivery 37 weeks Race Delivery Type Weight at the beginning of pregnancy Premature rupture of membranes Body Mass Index BMI Preterm PRM Blood type NICU admission Single or Multiple NICU admission days IVF Postpartum haemorrhage Obesity BMI 30 Abruptio placentae Vascular comorbidities Severe Preeclampsia Pulmonary comorbidity HELLP Maternal mortality Pulmonary embolism ICU admission COVID 19 diagnosis date
The rest of the variables are described in appendix 5 Statistics For the statistical analysis the SAS v94 software will be used The set of groups of variables requested and collected for each enrolled patient will be the same The demographic and clinical characteristics of the population included will be summarized Mean standard deviation minimum and maximum or median and interquartile intervals will be used for continuous variables according to the distribution The corresponding absolute and relative frequency will be reported for the discrete variables
The possible association of both the characteristics of the patients and the outcomes collected with COVID-19 infection using the Pearson Chi-square test or Fishers exact test and the Mann-Whitney U test after checking the absence of normal data using the Kolmogorov-Smirnov test Statistically significant associations were considered when the p value was less than 005 For those categorical variables in which statistically significant differences were identified the corresponding Odds Ratio OR and 95 Confidence Intervals 95 CI were estimated using univariate logistic regression models
Logistic regressions both univariate and multivariate will be performed determining the odd ratio and its 95 confidence interval
Management and reporting of adverse reactions As it is an epidemiological study without a drug under study the provisions on Pharmacovigilance in Ministerial Order SAS34702009 and Royal Decree 5772013 in relation to reporting adverse reactions to approved drugs will be followed Investigators who are aware of possible adverse reactions during the study should notify them as quickly as possible to the Autonomous Center for Pharmacovigilance corresponding to their healthcare area through any of the channels that the institution makes available through the yellow card system or via online through the SINAEM website It is also recommended that the Investigator or reporting doctor reports all adverse reactions to the marketing authorization holder of the drugs involved Additionally the conditions of use outside the marketing authorization of the drug must be reported eg off-label use overdose misuse abuse and medication errors or occupational exposure as well as cases of suspected drug interactions pregnancy exposure during breastfeeding and lack of efficacy
Ethical aspects This study will be carried out under conditions of respect for the fundamental rights of the person and the ethical principles that affect biomedical research with human beings following the international recommendations contained in the Declaration of Helsinki and its subsequent revisions Likewise national recommendations will be followed in accordance with the Biomedical Research Law 142007
During the completion of this study the investigators will strictly adhere to the provisions of this protocol fully completing the Case Report Form
Informed consent In accordance with the criteria of good clinical practice the subjects will be duly informed of all those details concerning their participation in the study and will freely give their consent in writing or orally recording this fact in their medical records
Preferably written or oral consent will be sought for cases and controls chosen at random from among pregnant women who have given birth in each centre and who have COVID-19 The patient may sign the consent electronically See appendix 7
Safety Measures and Confidentiality Protection of human subjects Pregnant women and newborns participate in the registry as mentioned above No biological samples are collected for specific analysis in this study
The laboratory tests collected in the registry will be those carried out in each site according to its protocol No extra lab tests will be carried out for this study and there is no handling of biological tests The data collected through the national registry for SARS-CoV-2 in pregnancy does not contain personally identifiable information
The data of the subjects included in it will be treated in accordance with Organic Law 32018 of 5th December on the Protection of Personal Data and guarantee of digital rights
Use of the data contained in the registry
The use of the data contained in this registry within any scientific research project will previously require
Approval by the local Clinical Research Ethics Committee CREC of the study site
Approval by the Scientific Committee a body that will be constituted to give scientific output to the database
Signing of the data protection law contract A citation policy will be established for the registry as well as for the authorship order of the different sites providing patients to each research project
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| COV200021 | OTHER_GRANT | CARLOS III INSTITUTE | None |