Northeast COVID-19 and Pregnancy Study Group

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.