Northeast COVID-19 and Pregnancy Study Group
Northeast COVID-19 and Pregnancy Study Group
A prospective and retrospective cohort study. The objective will to determine the frequency
 of COVID-19 in pregnant and postpartum women hospitalized with flu syndrome, to evaluate
 clinical and laboratory predictors of COVID-19 progression and to determine the factors
 associated with adverse maternal and perinatal outcomes in healthcare centers in two states
 of Northeast Brazil.The study will be conducted including pregnant and postpartum women with
 clinical or laboratorial diagnosis of COVID-19, admitted in six healthcare centers in the
 Northeast of Brazil. All pregnant and postpartum women with clinical and/or diagnosis of
 COVID-19, attended in prenatal care, in emergency (maternity triage), high-risk pregnancy
 ward, obstetric intensive care unit and rooming-in ward will be included. The data will be
 collected in specific forms. The exams will be carried out by trained professionals within
 each institution.
General Objective: To determine the frequency of COVID-19 in pregnant and postpartum women
 admitted with flu syndrome, to evaluate the clinical and laboratory predictors of COVID-19
 progression and to identify the factors associated with adverse maternal and perinatal /
 neonatal outcomes in six reference centers in the Northeast of Brazil.

 Specific objectives

 In pregnant and postpartum women admitted to the four institutions involved with flu-like
 symptoms or SARS:

 1. To describe the biological characteristics (maternal age and pre-pregnancy maternal
 weight, maternal height, pre-gestational body mass index - BMI and pre-gestational
 nutritional classification), sociodemographic characteristics (color, number of people
 living in the household, per capita family income, education, occupation, occupation,
 marital status, origin and religion), habits (smoking, drinking and use of illicit
 drugs), obstetric characteristics (number of pregnancies, parity, previous vaginal
 delivery and previous cesarean, previous abortions, number live children, entry into the
 study and number of prenatal consultations) and the service of origin (IMIP, HDM, ISEA
 or MFD);

 2. To describe the clinical characteristics (gestational age or postpartum days at the
 beginning of signs and symptoms, duration of symptoms, isolation, social distance and
 quarantine before signs and symptoms, need for hospitalization due to infection and / or
 complications, day of hospitalization due to flu-like syndrome and / or complications,
 length of hospital stay due to flu-like syndrome and / or complications and the main
 related signs and symptoms and days of onset - dry or productive cough, runny nose, sore
 throat, body pain, abdominal pain , chest pain, headache, smell and taste changes,
 dyspnoea, subfebrile state and fever, diarrhea, asthenia, saturation level, axillary
 temperature and mild / moderate signs and symptoms);

 3. To determine the frequency of COVID-19 infection according to the results of diagnostic
 tests (rapid test, RT-PCR and serology) applied during hospitalization;

 4. To describe the maternal laboratory parameters at the time of the diagnosis of influenza
 syndrome and the worst laboratory tests (result of RT-PCR for COVID-19, result of viral
 panel and type of virus, serology for COVID-19 - IgM, IgA and serial IgG, inflammatory
 cytokines - interleukins - IL-1ra, IL-6, IL-2, IL-5, IL-10, IL-12, IL-13, IL17A, IL-4,
 IL-1β, IL-9, IL-15, Interferon - IFN-γ, tumor necrosis factor - TNF-α, blood count,
 coagulogram, urea, creatinine, transaminases - ALT, AST, erythrocyte sedimentation rate
 - VSH, C reactive protein - CRP), D-dimer, lactic dehydrogenase - LDH, alkaline
 phosphatase, bilirubins, ferritin, troponin, blood culture, urine culture, blood gas
 analysis and day of all tests);

 5. To describe the radiological findings (chest X-rays, computed tomography), the pulmonal
 ultrasonography and day of exam alteration and normalization;

 6. To describe the therapeutic modalities performed (oxygen therapy - nasal catheter or
 Venturi with its maximum flows, use of prone in spontaneous ventilation and / or
 mechanical ventilation, use of mechanical ventilation, use of neuromuscular blocker, use
 of extracorporeal membrane oxygenation - ECMO, use of: antibiotics, azithromycin,
 hydroxychloroquine / chloroquine, antiparasitic drugs such as ivermectin, anticoagulant
 and / or antiretroviral, pulse therapy, convalescent plasma, need for renal replacement
 therapy, blood products and others, start day and duration of all therapeutic modalities
 performed);

 7. To describe the characteristics of obstetric ultrasound (tachycardia, frequency of
 diagnosis of fetal growth restriction, fetus small for gestational age - SGA, changes in
 amniotic fluid and fetal morphological changes) performed during the course of infection
 and post-infection follow-up;

 8. To describe the doppler velocimetric parameters of the uterine and fetal circulation
 (pulsatility index of the middle uterine arteries, the middle fetal cerebral artery -
 MCA, the umbilical artery, the venous duct, the frequency of changes in the doppler
 velocimetry of all the vessels studied and the speed of the systolic peak in MCA) during
 infection and in the post-infection follow-up;

 9. To describe invasive intrauterine diagnostic procedures (amniocentesis), gestational age
 at which amniocentesis was performed, indications, results of the RT-PCR test for
 COVID-19, results of the TORCHS survey, results of the karyotype and results of the
 inflammatory cytokines - interleukins - IL-1ra, IL-6, IL-2, IL-5, IL-10, IL-12, IL-13,
 IL17A, IL-4, IL-1β, IL-9, IL-15, Interferon - IFN- γ, tumor necrosis factor - TNF-α;

 10. To determine comorbidities / complications associated with pregnancy or the puerperium
 (need for hospitalization due to obstetric causes, length of hospital stay, obesity,
 multiple pregnancy, hypertensive syndromes, diabetes - clinical or gestational, heart
 disease, chronic obstructive pulmonary disease, bronchial asthma, cerebrovascular
 disease, renal failure, immunosuppression, severe acute respiratory syndrome - SARS,
 premature rupture of membranes, premature labor, placenta praevia, urinary tract
 infection, pneumonia, sepsis, septic shock, abortion, abruptio placenta, postpartum
 hemorrhage, infection of surgical site, endometritis, peritonitis, thromboembolic
 events, need for postpartum hysterectomy, need for other surgeries after delivery and
 tubal ligation, maternal near miss criteria);

 11. To describe the delivery outcomes (type of delivery - vaginal, spontaneous or operative,
 or cesarean section, indication for cesarean section, indication for labor induction,
 method of labor induction, duration of induction, gestational age at delivery, use of
 labor analgesia, type of anesthesia for cesarean section);

 12. To describe prenatal interventions (antenatal corticosteroid therapy - number of doses,
 use of magnesium sulfate and prophylactic antibiotic therapy);

 13. To describe the final maternal outcome (discharge of the pregnant woman, discharge of
 the postpartum woman, death of the pregnant woman and death of the postpartum woman);

 14. To describe perinatal and neonatal outcomes (fetal death, perinatal death, birth weight,
 birth weight adequacy - SGA, AGA, LGA, Apgar scores in the first and fifth minutes, need
 for neonatal resuscitation, ICU admission, need for assisted mechanical ventilation,
 oxygen therapy, oxygen therapy modalities, hypothermia, hypoglycemia, polycythemia,
 anemia, neonatal infection, chorioamnionitis, type of respiratory distress,
 breastfeeding, neonatal congenital infections (TORCHS), congenital malformation, other
 neonatal morbidities, neonatal near miss, neonatal death, days of life of neonatal death
 and length of hospital stay and in neonatal ICU);

 15. To determine the procedures in neonatal care in the delivery room (cord clamping - early
 or opportune, skin-to-skin contact, breastfeeding in the delivery room) and,
 subsequently, rooming-in or admission to a neonatal ICU / nursing unit;

 16. To describe the neonatal laboratory parameters of the suspected diagnosis or
 confirmation of COVID-19 and the worst test results (days of life of the newborn's
 suspected diagnosis, result of rapid neonate test, RT-PCR for COVID-19 in nasopharyngeal
 swab , result of viral panel and virus type, serology for COVID-19 - IgM, IgA and IgG
 serial, inflammatory cytokines - interleukins - IL-1ra, IL-6, IL-2, IL-5, IL-10, IL -12,
 IL-13, IL17A, IL-4, IL-1β, IL-9, IL-15, Interferon - IFN-γ, tumor necrosis factor -
 TNF-α, blood count, coagulogram, urea, creatinine, transaminases - ALT, AST, erythrocyte
 sedimentation rate - VSH, C-reactive protein - CRP), D-dimer, lactic dehydrogenase -
 LDH, alkaline phosphatase, bilirubins, ferritin, troponin, blood culture, urine culture,
 blood gas analysis and day of all tests);

 17. To describe the laboratory parameters in the placenta (result of RT-PCR / viral panel by
 swab and anatomopathological study) and in cord blood (RT-PCR);

 18. To determine the frequency of vertical transmission and the factors associated with a
 higher risk of its occurrence (gestational age at infection, severity of infection,
 laboratory markers, type of delivery, labor, cord clamping practice, placental findings,
 maternal interleukins);

 19. To describe the laboratory parameters in breast milk (result of RT-PCR / viral panel);

 20. To describe the neonatal imaging exams (chest X-rays, computed tomography and day of
 exam changes and normalization);

 21. To determine the association of biological, sociodemographic, obstetric variables,
 habits, clinical, maternal laboratory parameters in the diagnosis and the worst result,
 radiological findings, therapeutic modalities, ultrasound and doppler velocimetric
 characteristics, invasive procedures, comorbidities / complications and characteristics
 of childbirth with adverse maternal outcome (maternal near miss and maternal death).

 22. To determine the association of biological, sociodemographic, obstetric variables,
 habits, clinical, maternal laboratory parameters in the diagnosis and the worst result,
 radiological findings, therapeutic modalities, ultrasound and doppler velocimetric
 characteristics, invasive procedures, comorbidities / complications, delivery results,
 prenatal interventions, final pregnancy outcome, delivery room procedures, neonatal care
 and neonatal laboratory parameters, placenta, amniotic fluid and breast milk with
 adverse perinatal / neonatal outcome (neonatal near miss and fetal / neonatal death);

 23. To analyze maternal and perinatal mortality according to gestational age at the onset of
 symptoms (Kaplan-Meier survival curve);

 24. To compare data from two states in Northeast Brazil with official general data in the
 country according to the Ministry of Health for the pregnancy-puerperal cycle.

 25. In a subset of women routinely assessed on admission through the rapid test (ISEA and
 Unimed-João Pessoa), to determine the frequency of positive rapid test, positive RT-PCR,
 associated symptoms, asymptomatic carriers and to compare maternal and perinatal
 outcomes according to test results.

 26. To carry out long-term monitoring of women and babies included in the cohort in 2020, to
 detect recurrence of symptoms, frequency of reinfection, evolution of laboratory
 parameters (repetition of RT-PCR and serology) and monitoring of growth and development
 in the cohort of children aged six months, 12 and 24 months.

 Methods: A prospective and retrospective cohort study will be conducted including pregnant
 and postpartum women with clinical or laboratorial diagnosis of COVID-19, admitted in six
 healthcare centers in the Northeast of Brazil. All pregnant and postpartum women with
 clinical and/or diagnosis of COVID-19, attended in prenatal care, in emergency (maternity
 triage), high-risk pregnancy ward, obstetric intensive care unit and rooming-in ward will be
 included. The data will be collected in specific forms. The exams will be carried out by
 trained professionals within each institution. A database will be created on the RedCap
 platform. For the association of dependent variables (maternal mortality / near miss and
 unfavorable perinatal outcomes) with independent variables (biological, sociodemographic
 characteristics, history, clinical characteristics, ultrasound modifications, doppler
 velocimetric and laboratory tests, chi-square tests will be used and Fisher's exact, when
 pertinent, with a significance level of 5%. The relative risk and its 95% confidence interval
 will also be calculated to determine the strength of association between the variables.
 outcomes, Student t or Mann-Whitney tests will be adopted. A multivariate analysis will be
 performed to determine the variables that will actually remain associated, in addition, a
 Kaplan-Meier survival curve will be constructed.
Inclusion Criteria:

 -  Pregnant or puerperal women;

 -  Diagnosis of flu syndrome on admission;

 -  Testing for COVID-19 performed.

 Exclusion Criteria:

 -  Clinical impossibility of signing the Informed Consent Form (ICF), either by the
 patient or guardian (in the prospective arm);

 -  Incomplete or not located medical records (retrospective arm).