The COVID-19 pandemic in Brazilian pregnant and postpartum women: results from the REBRACO prospective cohort study | Scientific Reports – Nature.com

The REBRACO study was a comprehensive prospective epidemiological approach studying COVID-19 in pregnancy in Brazil. The initiative has established a multicentre network that performed evaluation and monitoring of maternal conditions related to COVID-19 in symptomatic pregnant and postpartum women, and also collected relevant information on healthcare to better plan actions related to confronting the pandemic in the participating centers.

Maternal and pregnancy outcomes from women who had COVID-19 seem to vary according to the context; women from low-income settings are more vulnerable to adverse outcomes due to COVID-1917 and underlying conditions such as asthma, non-white ethnicity, older age (>34 years) and having over 35weeks of gestation were factors independently associated to severe COVID-1918. According to our study, approximately one in six women with confirmed COVID-19 infection had SARS (16.3%) and required admission to the intensive care unit (16.7%). The lethality rate of COVID-19 was 4.7% in the obstetric population. Also, around a fifth of women had any severe maternal outcome which included SARS, admission to ICU or maternal death.

A secondary analysis of a multicentre international study involving 73 centers in 22 different countries showed that the incidence of composite adverse fetal outcome (abortion, stillbirth, neonatal death and perinatal death) was significantly higher when the infection occurred in the first trimester19. In our study, we found that postpartum women had six-fold increased risk for SARS compared to first trimester pregnant woman. Also, trimester of infection was not identified as a significant risk factor. However, we acknowledge that this is still a relevant subject of investigation, considering the possible impact on maternalfetal interface and long-term consequences of the disease. A single center prospective cohort study conducted in Turkey including more than 1400 pregnant women showed that the infections course and obstetric consequences may change between pregnant trimesters. Deterioration or need for advanced support can be observed even in pregnant women with no other health issues20.

Furtheremore, special attention should be given to postpartum women, once they might be at risk for the first and second types of delays. The need for taking care of the baby, stress, new onset or exacerbation of mental health disorders and constraints of physiological needs may result in fatigue and sleep disruption may play a role on postponing their own care21. The INTERCOVID Multinational Cohort Study comprised of 43 centers in 18 countries showed that COVID-19 was associated with higher risk for preterm birth (1.59-fold), especially provider-initiated PTB (1.97-fold), low birth weight (1.5-fold) and severe neonatal morbidity (2.6-fold)22. Also, there are systematic reviews on the topic showing that severe outcomes are associated with the moment of pregnancy, presence of some coexisting morbidities and availability of local resources to early identify signs of severity in order to provide health support23.

A systematic review published in April, 2021, evaluated the differences of clinical presentation, management and prognosis of laboratory-confirmed COVID-19 between around 29,000 pregnant women and 560,000 non-pregnant women24. The risk of ICU admission (RR 2.26 [1.683.05]) and need of invasive mechanical ventilation (RR 2.68 [2.073.47]) were significantly higher amongst pregnant women. Although the controls (non-pregnant women) differed in age, obesity and smoking status, and ethnicity characteristics, the higher risk for adverse outcomes highlights the importance of adequate surveillance of cases involving pregnant women24. During pregnancy there are physiological changes involving the immunological systems (altered cell-and-antibody-mediated immune response), cardiovascular system (increase of maternal blood volume, heart rate, cardiac output by 3050%, and vascular resistance decreases) and respiratory system (decrease in functional residual capacity, end-expiratory volumes, and residual volumes)25. These changes may explain why the risk of severe COVID-19 may be higher during pregnancy than in the general population.

In Brazil, data on maternal outcomes related to the COVID-19 pandemic suggest that the access and quality of health care for pregnant and postpartum women may have been neglected5. Our data has shown that vulnerable women (non-white, low schooling, attending ANC service only at public system) were more likely to present SARS. In another Brazilian study including 669 maternal COVID-19 SARS cases with similar age and morbidity, black women (n=134) were more likely to be admitted with poorer health condition (higher prevalence of dyspnea and low O2 saturation at admission) and to have ICU admission (27.6% vs 19.4%, p<0.001), mechanical ventilation (14.9% vs 7.3%, p<0.001), and death (17.0% vs 8.9%, p<0.001) than white women5. The involved underlying factors might include gender inequalities, racial disparities and defective policies involving general education and reproductive health5,26. A Brazilian study addressing the Acute Respiratory Distress Syndrome Surveillance System for COVID-19 cases among pregnant or postpartum women in early 2020 showed that black women were more likely to present severe COVID-19 infection and to die when compared to white women5. In addition, ICU or respiratory supports were not available for approximately 27% and 14%, respectively, of the women who had died due COVID-196.

A cross-section study conducted in Jordan held telephone interviews with 1300 participants (men and women) to address gender-based disparities during COVID-19 including health indices, mental well-being and economic burden27. The study showed that women in Jordan are experiencing worse outcomes in terms of mental well-being and economic burden, which may widen the gender gap issue. Also, the access to antenatal care was available for only half of the Jordanian pregnant women interviewed. Not only the direct effect of the SARS-CoV-2 infection may be responsible for maternal and pregnancy outcomes, but the substantial effect of the pandemic on the health care services. A comprehensive systematic review assessed the impact of the COVID-19 pandemic on maternal and pregnancy outcomes. They included 40 studies from Jan, 2020 to Jan, 2021 and demonstrated that maternal and perinatal outcomes have worsened globally, especially in low-resource settings, which reinforced the need for policies to strengthen health care systems28.

Testing capacity can be considered an indirect indicator of the local policies favouring COVID-19 spread control. A study conducted in four regions of Italy in the early outbreak of the pandemic (FebMar 2020) assessed the association between testing policies and COVID-19 mortality29. The study showed that regions that applied a broader testing policy had significant less COVID-19 mortality. Ideally, tests should have been offered for all women. According to the guidelines of the Brazilians Ministry of Health, RT-qPCR for universal screening at delivery or for symptomatic women should be offered for all pregnant and postpartum women30. Although the guideline has followed international recommendation as those given by the WHO generals director (saying: test, test, test)31, it has never been actually implemented by the government. The testing provision and its use for promoting individual and collective counselling have been very heterogeneous and scarce across the country32. Also, Brazil for a long time lacked solid programmes in favour of pandemic-containment strategies. The country, which has about 3,000,000 deliveries/ year, faced conflicting outrageous policies against vaccines, massive testing and use of personal protective equipment by politicians33. Recently, an ecological study assessing country-level determinants associated with severity of COVID-19 in 37 countries excluded Brazil from the analysis of testing capacity due to lack of representative and reliable data34. According to our data, some few maternal characteristics were associated with the higher provision of SARS-CoV-2 tests, including being at third trimester pregnant or postpartum periods and history of chronic hypertension. Also, women who were tested were more likely to have tachypnea or desaturation at admission, SARS, ICU admission or any severe maternal outcome. Although it suggests that, due lack of resources, women at higher risk were more likely to have access to tests, the efforts should be taken to promote universal testing coverage among pregnant and postpartum women, not only for preventing morbidity but to corroborate recommendation related to the combat of the spread of the virus and to better follow-up the women. Our high positivity among suspected cases suggest that testing was mostly available for more severe cases, notably, in some institutions where testing was only performed if there was the need for hospital admission.

There are some risk-stratification and prediction models developed for non-pregnant population35,36,37, but it may not be applicable for the obstetric population due to the pregnancy physiological modifications. Our findings may be useful to inform the development of risk stratification coupled with specific strategies for managing healthcare. The calculation of risk ratios for confirmed COVID-19 and for SARS related to COVID-19 may be useful for developing models containing these symptoms, which can help in the identification and management of cases of COVID-19 in pregnant women, especially in contexts with low availability of diagnostic tests or provision of limited resources such as ICU beds. In our study, symptomatic women who were admitted to the ICU were more likely to have chronic conditions such as asthma (16.2% vs 7.0%, p-value=0.007; data not shown), overweight or obesity (85.8% vs 64.2%, p-value=0.017; data not shown), chronic hypertension (16.2% vs 8.8%, p-value=0.049; data not shown) and confirmed COVID-19 (73.8% vs 48.6%, p-value<0.001; data not shown) when compared to women who were not admitted to ICU.

Our definition for confirmed COVID-19 cases did not include only positive RT-PCR tested cases; it included both laboratory specific tests (RT-PCR, serology or antigen tests) and/or radiological findings. The nasopharyngeal RT-PCR is considered the gold-standard test for confirming SARS-CoV-2 exposure. However, an alternative definition based on other findings may be considered, especially in low-resourced settings. Considering that general laboratory findings and clinical presentation (symptoms and signs) are very unspecific in the COVID-19 infection24,38, the use of radiological findings (usually ground-glass opacities) may be a reasonable alternative for managing and treating patients with COVID-19 cases39,40. Despite the difficult access to CT scans, its findings have high positive predictive value and can be used as an alternative method to confirm the diagnosis. The Centers for Disease Control and Prevention (CDC/USA) and the Brazilian Health Regulatory Agency (ANVISA) have recommended the use of suggestive radiological findings in the definition of confirmed COVID-19 cases41,42.

In late 2020, there was raised awareness towards the possibility of worse outcomes associated to new SARS-CoV-2 variants of concern (VOCs) with reported increased transmissibility, risk of hospitalization and virulence20,43. The dissemination of VOCs in Brazil was reported since December 2020, mostly the Gamma lineage (PANGO: P.1). The Alpha lineage of SARS-CoV-2 (PANGO: B.1.1.7) was also introduced in Brazil early during 202144.

The higher frequency of congenital anomaly in confirmed COVID-19 pregnant women rises concern, however, this might reflect the enhanced surveillance employed to positive COVID-19 cases and not the virus itself. From the 19 cases of congenital anomaly, only 6 were tested for SARS-CoV-2 neonatal infection; all were negative The Brazilian Teratology Information Service has proposed some strategies to investigate, detect and prevent possible embryonic damaging effects of the new coronavirus, including multidisciplinary approach to report the events43. Nevertheless, data from this national system has not been published yet; multicenter well-designed studies are crucial for addressing this topic.

This was a multicentre prospective study comprising 15 maternities in four regions of Brazil, including maternities with public, private and mixed maternities with deliveries per year ranging from 2000 to 6000 in the period. The study had a significant loss of follow-up, especially for pregnancy outcomes (19.3%). The majority of the participating centers were local/regional referral units for COVID-19 cases, but in most cases, they were not able to closely follow the women who had mild-infection and who did not require hospitalization. This should be taken into account during the interpretation of our findings, as it may have overestimated the rate of poorer outcomes for those who were followed until the end of pregnancy.

Our results suggest structural problems of access and quality of health services. Although COVID-19 is present in all social contexts, the pandemic highlighted the social discrepancies that worsening results of the disease in Brazil. COVID-19 infection in pregnancy results in increased maternal morbidity and mortality and need for management resources such as admission to the ICU. Proper surveillance, testing and follow-up of suspected cases and an appropriate structuring of obstetric units widely implemented are crucial for fighting the pandemic and reducing the burden to maternal health. The findings from this study may help to promote awareness about the situation and to increment policies for decreasing disparities among vulnerable populations.

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The COVID-19 pandemic in Brazilian pregnant and postpartum women: results from the REBRACO prospective cohort study | Scientific Reports - Nature.com