Discussion:
The COVID-19 pandemic has created an unprecedented global health crisis, with the rapid spread of the infection and the uncertainty surrounding its impact on pregnancy due to the lack of scientific data. Obstetricians have had to adapt their practices based on pragmatic approaches in response to this challenging situation (1).
Pregnancy triggers physiological changes that primarily affect the cardiorespiratory and immune systems. These changes include Th2 immunotolerance and alterations in the major histocompatibility complex expression at the maternal-fetal interface, making pregnant women more vulnerable to viral infections such as influenza or SARS-CoV-2 (2).
Pregnant women are at a heightened risk of developing respiratory pathologies and severe pneumonia due to their immunosuppressed state and adaptive physiological changes during pregnancy. These changes can make them more intolerant to hypoxia, putting them at higher risk during pandemics and other respiratory outbreaks.
Historical evidence, such as the influenza pandemic of 1918, highlights the increased vulnerability of pregnant women during pandemics. During that pandemic, pregnant women had a mortality rate of 2-6%, compared to the general population. Similarly, during the H1N1 2009 pandemic influenza virus outbreak, pregnant women faced a relative risk of 3-4 for complications from infection and were more than four times as likely as the general population to be admitted to the hospital.
A multicenter study conducted in France since the start of the COVID-19 pandemic examined data from 33 maternity clinics and found that 617 pregnant women tested positive for SARS-CoV-2, with the most commonly reported symptoms being cough (62.2%), fever (46.2%), anosmia (27.2%), dyspnea (26.7%), and diarrhea (8.8%). Of the pregnant women, 20.7% required respiratory assistance, with 4.7% requiring mechanical ventilation, 1% needing extracorporeal membrane oxygenation (ECMO), and 0.2% died. Risk factors for needing respiratory assistance included age over 35, high pre-pregnancy body mass index (>30 kg/m²), pre-existing diabetes or a history of pre-eclampsia, and a current diagnosis of gestational hypertension or pre-eclampsia. These risk factors are similar to those found in the general population.
A meta-analysis published in September 2020 that included 77 studies found that pregnant women with COVID-19 had a 40% incidence of fever and a 39% incidence of cough. They were more likely to require intensive care unit admission and invasive ventilation. The analysis found 73 deaths (0.1%). Risk factors for severe disease included age, high body mass index, chronic hypertension, and diabetes. Women with pre-existing comorbidities had a higher risk of ICU admission (OR = 4.21) (5).
In a case-control study comparing data from 8,207 pregnant women and 83,205 non-pregnant women with confirmed SARS-CoV-2 infection, it was found that pregnant women had a higher risk of intensive care hospitalization (RR 1.2) and mechanical ventilation (RR 1.9) compared to their non-pregnant counterparts. However, there was no significant difference in mortality risk between pregnant and non-pregnant women with the virus.
Various biological abnormalities have been observed in individuals with COVID-19, as per existing literature. One such abnormality is lymphopenia, which can be identified in patients as early as the viral disease phase. During the first week of illness, elevated levels of transaminases may also be observed. In the second week, which is considered the inflammatory response phase, markers such as CRP, procalcitonin, and ferritin may increase (7).
Special attention is required in managing pregnant women with COVID-19, considering the potential impact of pregnancy on the respiratory and cardiovascular systems. Close monitoring is particularly crucial during the first two weeks of the disease’s evolution, as rapid deterioration can occur during this period.
Hospitalization of pregnant women with confirmed or suspected COVID-19 is not always required, except in cases where there is a need for oxygen support. In situations where symptoms are not severe, ambulatory management with symptomatic treatment is generally advised. However, it is crucial to educate the woman about the symptoms that require medical reassessment, such as fever, cough, and dyspnea. Self-medication should be avoided.
Hospitalization is necessary in cases where severe symptoms develop rapidly, such as a respiratory rate of 25 cycles per minute or higher and oxygen saturation levels of less than 95% in ambient air. Management in the hospital may involve a thoracic CT scan, oxygen therapy, invasive ventilation, and corticosteroid therapy to reduce inflammation when C-reactive protein (CRP) levels are greater than 50(2).
Oxygen therapy is initiated based on respiratory rate and saturation levels. The threshold for initiating oxygen therapy is when SpO2 falls below 95%.
According to the latest recommendations, antibiotic therapy is not recommended for COVID-19 unless there is a documented co-infection (7).
SARS-CoV-2 infection increases the risk of thrombosis in patients, and therefore, it is crucial to systematically assess the thrombotic risk in all patients with confirmed infection. The completion of ongoing studies, including the FREEDOM COVID-19 trial, is necessary to determine if therapeutic-dose anticoagulation provides additional efficacy in reducing thrombotic events, preventing intubation, or improving survival compared to prophylactic-dose anticoagulation in hospitalized patients (9).
Vitamin D supplementation may be beneficial for COVID-19 patients with vitamin D deficiency or insufficiency, but there is no evidence to support its use in the prevention or reduction of disease severity in individuals with normal blood vitamin D levels (10). Beigmohammadi et al. found that vitamin supplementation led to significant changes in serum levels of various vitamins and inflammatory markers, and reduced the rate of hospitalization lasting more than 7 days, but did not have a significant effect on mortality (11).
According to the PAN-COVID study, which is an international multicenter study conducted in 43 centers across 18 different countries to evaluate the pregnancy and neonatal outcomes of women with COVID-19. The study found that infection during pregnancy is associated with preterm birth, primarily due to fetal distress. Although the incidence of small for gestational age and fetal growth restriction was not higher than expected, there was a significant difference in the proportion of participants affected by stillbirth and FGR, depending on whether they delivered within two weeks or after. To address this, clinicians should have a low threshold for delivery if they detect concerns with fetal movements or heart rate monitoring during this period.
The study also found that SARS-CoV-2 infection during pregnancy does not seem to affect birth weight or increase the risk of congenital malformations. However, the effect of infection on miscarriage was not determined. The rate of pre-eclampsia among the study participants was not higher than expected, and neonatal infection was uncommon(12).