Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04558996 |
| Other study ID # |
55/20 |
| Secondary ID |
COV20/0021 |
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 1, 2020 |
| Est. completion date |
March 31, 2021 |
Study information
| Verified date |
September 2020 |
| Source |
Puerta de Hierro University Hospital |
| Contact |
Oscar M Martinez Perez, MD |
| Phone |
600417307 |
| Email |
oscarmartinezgine[@]gmail.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
Study title Spanish Registry of Pregnant Women with COVID-19 Protocol number and version
Number 55/20. 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 hospital's Biomedical Research Foundation to receive
donations: COV20/00021 - 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.
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 (e.g., miscarriage, stillbirth, growth
restriction) and neonatal outcomes (e.g., NICU, prematurity, death, birth defects).
7. Identify additional risk factors and risk modifiers (e.g., 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 and/or oropharyngeal swab was considered synonymous with
exposure/non-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 and/or 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 172,000 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, he/she
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 (i.e., 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 patient's 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 and/or 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.
Objective/s
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 (e.g., 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 and/or oropharyngeal swab was
considered synonymous with exposure/non-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 and/or 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
Fatigue/malaise Altered consciousness Headache Nausea/vomiting Diarrhoea Mild-moderate
pneumonia Severe pneumonia Septic shock/maternal mortality
The rest of the variables are defined in appendix 5 Statistics For the statistical analysis,
the SAS v9.4 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 Pearson's Chi-square
test or Fisher's 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 <0.05.
Substudy 2: Prospective observational study on maternal and neonatal morbidity in pregnant
women with COVID-19 Objective/s
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 (e.g., 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 and/or oropharyngeal swab was
considered synonymous with exposure/non-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 and/or 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 Fatigue/malaise Altered consciousness Headache
Nausea/vomiting Diarrhoea Mild-moderate pneumonia Severe pneumonia Septic shock/maternal
mortality
The rest of the variables are defined in appendix 5 Statistics For the statistical
analysis, the SAS v9.4 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 Pearson's
Chi-square test or Fisher's 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 <0.05. All
statistical analyses were carried out with SAS 9.4 software.
Substudy 3. Cohort study on obstetric pathology. Objective/s 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 (e.g., miscarriage, stillbirth,
growth restriction) and neonatal outcomes (e.g., 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 patient's 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: mean/range) 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 kg/m2)
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 Fatigue/malaise Altered consciousness Headache
Nausea/vomiting Diarrhoea Mild-moderate pneumonia Severe pneumonia Septic shock/maternal
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 Fisher's 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 <0.05. All statistical
analyses were carried out with SAS 9.4 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 Objective/s Determine the prevalence of
SARS_COV2 infection in Spanish pregnant women Design Cross-sectional study. The nQuery
Advisor Release 7.0 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 and/or oropharyngeal swab was
considered synonymous with exposure/non-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 and/or 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 v9.4 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 Fisher's 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 0.05. 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
SAS/3470/2009 and Royal Decree 577/2013 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 (e.g.: 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 14/2007.
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
3/2018, 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.
