Hippokratia 2022, 26(1): 32-37
Mihajlovic S1,2, Savic P3,4, Potparevic N1, Lackovic M1
1Department of Obstetrics and Gynecology, University hospital “Dr. Dragisa Misovic” , 2Department of Obstetrics and Gynecology, Faculty of Medicine, University of Belgrade, 3Department of General Surgery, University hospital “Dr. Dragisa Misovic”, 4Department of Surgery and Anesthesiology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
Background: Pregnancy poses a risk factor for respiratory infections due to hormonal changes, reduced tolerance to hypoxia, immunodeficiency, and increased susceptibility towards viral infections. Pregnant women might develop a broad spectrum of clinical conditions associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, from asymptomatic to potentially life-threatening complications. Critical respiratory failure associated with the progression of viral pneumonia is the most severe complication of the coronavirus disease (COVID-19). In some cases, it may require intubation and invasive mechanical ventilation.
Case series: In this case series, we evaluated the outcomes and clinical features of eight critically ill pregnant patients requiring invasive mechanical ventilation during treatment. The most commonly observed symptoms were fever at admission to the hospital, cough, difficulty breathing, and fatigue. Less frequently observed were sore throat and loss of smell and taste. All patients had anemia, and hypertension was the second most common comorbidity in pregnancy. Pregnant patients with lethal outcomes were older than those who recovered. They had higher body mass index values, more symptoms at admission, and higher C-reactive protein values and ferritin levels. Acute Respiratory Distress Syndrome (ARDS) was diagnosed in five cases, and none of these patients survived.
Conclusion: Obesity, maternal age, and diagnosis of ARDS were most commonly observed in our group of patients with lethal outcomes. Preventive measurements, counseling, and enlightenment of potential risk factors, such as obesity, advanced maternal age, and pregnancy-related comorbidities, should be the cornerstones in crises such as COVID-19 when medical care and resources are limited or restricted. HIPPOKRATIA 2022, 26 (1):32-37.
Keywords: Coronavirus disease, COVID-19, pregnancy, respiratory failure, mechanical ventilation, critical care, outcomes
Corresponding author: Milan Lackovic, MD, PhD, Milana Tepica 1, 11000, Belgrade, Serbia, tel: +381113630700, fax: +381113672025, e-mail: firstname.lastname@example.org
In this dynamic world of needs, hopes, and dreams, where new boundaries and limits are constantly set and pushed forward, and everything has become relative, human life and even our existence have suddenly become seriously threatened by the presence of a new, unknown enemy, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Suddenly, fear of the unknown shaped the efforts to protect fundamental human needs and rights. This fear unsettles human nature, especially for pregnant women who are bringing new life to this world, a life that might have been endangered even before it was brought to this world, and a world where nothing is the same.
During the last three years, maternal morbidity and mortality data regarding the coronavirus disease (COVID-19) pandemic has dramatically changed. From the initial point of view that pregnancy poses some protective features, it is now known that pregnant women might develop a wide spectrum of clinical features, from asymptomatic to life-threatening complications associated with the SARS-CoV-2 infection1. Critical respiratory failure associated with viral pneumonia progression might lead to acute respiratory distress syndrome (ARDS), which is one of the most severe COVID-19 infection complications. In order to preserve vital functions, invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) is often required2.
Due to hormonal changes, reduced tolerance to hypoxia, immunodeficiency, and increased susceptibility towards viral infection, pregnancy poses a risk factor for the progression of respiratory infection3. Compared to non-pregnant women of reproductive age, pregnant COVID-19 patients are more likely to be hospitalized, be transferred to intensive care units (ICU), and ultimately require intubation and mechanical ventilation management4. Several risk factors have been identified and are considered relevant to distinguish low from high-risk patients to provide better triage and timely treatment. Advanced maternal age, preexisting medical conditions, pregnancy-related comorbidities, obesity, race, and ethnicity are among the most common ones5.
Since devastating consequences are closely related to COVID-19 infection and the vulnerable state of pregnancy3,4, it is imperative to provide a timely, efficient, and safe therapeutic approach for all pregnant women. Experiences with antiviral and immune-modulating therapy have proven reassuring profiles regarding their safety, but an individualized approach and possible adverse events must be addressed6. mRNA vaccines have proven safe and effective in preventing severe infections. Therefore, advocacy for COVID-19 vaccination as the primary infection prevention among pregnant and reproductive-age women should be a high priority7.
Reports regarding maternal outcomes among critically ill COVID-19-infected pregnant patients remain scarce, and it is essential to present and describe experiences from different centers. More knowledge benefits medical professionals caring for critically ill patients and might improve decision-making strategies. Therefore, our study aims to present experiences from one of Serbia’s referral centers for COVID-19-positive patients during the SARS-CoV-2 pandemic.
In this series of cases, we have presented maternal outcomes and clinical features of eight consecutive critically ill pregnant patients requiring invasive mechanical ventilation as a measure of life support. Before their hospitalization, all patients were tested and had positive throat swabs for COVID-19 on quantitative real-time polymerase chain reaction. None of these patients was vaccinated.
Patients were treated in Serbia’s referral center for COVID-19-positive patients, a tertiary health care center, the University Hospital “Dr. Dragisa Misovic” in Belgrade. The retrospective observational case series included patients hospitalized in ICU from March 2020 until November 2021, and it was retrospectively approved by the Institutional Review Board in August 2020 (No: 01-8816). We have included in the series all pregnant patients who required and received invasive mechanical ventilation during their course of treatment in our center. Patients were transferred to ICU, and eventually, invasive mechanical ventilation was initiated based on peripheral blood oxygen saturation, blood gas analysis, respiratory and heart rate, and systolic and diastolic blood pressure. In all eight cases, non-invasive mechanical ventilation was initially administered. Table 1 presents the general characteristics of admitted pregnant women and mechanical ventilation outcomes.
Table 2 presents the symptoms on admission to the hospital of pregnant women who tested positive on SARS- CoV-2, were transferred to ICU, and supported with invasive mechanical ventilation. Three out of eight patients had more than 50 % of tested symptoms on admission (52.6 %). Fever (body temperature >38 °C) on admission, cough, and systemic inflammatory response syndrome were present in all those patients (100 %). Difficulty breathing and fatigue were present in six out of eight patients (75 %). Less frequent were sore throat, loss of smell and taste (every fourth patient). The least frequent was abnormal uterine bleeding (12.5 %). Headache and diarrhea were absent in any admitted patient (0 %) (Table 2).
Table 3 presents the risk factors, and laboratory findings of the positive pregnant women transferred to ICU and supported with invasive mechanical ventilation. Regarding risk factors, it is shown that all pregnant women were diagnosed with anemia, while the second most frequent risk factor was hypertension (37.5 %). None of them had diabetes mellitus (0 %) (Table 3).
Pregnant patients with lethal outcomes were older (35.20 ± 6.26 years), had higher body mass index (BMI) (32.27 ± 9.43), had more symptoms (9.40 ± 0.89), had more risk factors (1.80 ± 0.84), higher C-reactive protein (CRP) values (218.94 ± 83.85) and higher ferritin levels (388.20 ± 322.11) than those pregnant ICU patients who recovered. On the contrary, in pregnant ICU patients with lethal outcomes, lesser days to hospitalization from symptoms’ onset (4.80 ± 1.30 days), lesser days to mechanical ventilation from symptoms’ onset (7.00 ± 1.58 days), and lower gestational age on admission (200.8 ± 56.37 days) were noticed (Table 4).
All patients in this case series were in critical condition due to progressive respiratory failure and pneumonia resulting from SARS-CoV-2 infection. Invasive mechanical ventilation was initiated after the various modes of non-invasive mechanical ventilation support failed to provide adequate oxygen supply.
Out of the eight pregnant women in this case series, lethal outcomes were registered in five cases. Initial reports from the beginning of the pandemic revealed that more than 90 % of patients in the general population who received invasive mechanical ventilation eventually died8. Outcomes among pregnant patients were more encouraging9. ARDS was diagnosed in five cases, and none of these patients survived. The oldest patient in this case series was 42 years of age, while the youngest was 26 years old. The average age of our patients was 33.5 years. Comparisons between the two groups, those recovered and decedent, suggest that women in the decedent group were nearly five years older.
Advanced maternal age is an individual risk factor for the progression of COVID-19 infection in pregnancy5. However, it often goes hand in hand with other comorbidities and chronic diseases, such as hypertension-related conditions and glucose intolerance10. Acquired cardiovascular diseases are often accompanied by diabetes, obesity, and advanced maternal age, and their management is often challenging10. Although COVID-19 infection does not increase the risk for hypertension-related conditions among pregnant women11, it imposes an additional challenge in managing these patients. It led to rising maternal mortality rates during the pandemic1. Cardiac insufficiency and heart failure led to the death of four patients in our case series. Three were previously diagnosed with a hypertensive disorder; one patient had gestational hypertension, and two suffered from chronic hypertension. None of our patients was diagnosed with pregestational or gestational diabetes. In Serbia, organized screening for gestational diabetes is performed between the 24th and 28th week of gestation, but due to the COVID-19 crisis, the screening procedure was not performed, which partially explains the lack of gestational diabetes diagnosis; more importantly, it emphasizes the importance of screening procedure and consequences that pandemic has had on perinatal care in Serbia. Other countries have experienced similar challenges regarding compromised perinatal care, and valuable experiences have taught us to prioritize childbearing people and strive for high-quality maternal care12.
Obesity remains a global health threat among modern-age men and women, and it is the denominator for metabolic and chronic diseases13. Seven patients had BMI values beyond recommended, and four of them were obese, including one patient with class III obesity. The BMI discrepancy was apparent between the two compared groups. Patients in the recovered group were averagely overweight (average BMI: 28.06 ± 4.04 kg/m2), and patients in the decedent group were mainly obese (average BMI: 32.27 ± 9.43 kg/m2), a difference that might pose a significant strategic approach in triage and treatment planning. Furthermore, the only patient who successfully recovered and continued her pregnancy is, at the same time, the only patents whose BMI value was below 25 kg/m2. Obesity leads to a chronic inflammatory state, interferes with cellular immune response, and might increase antiviral, anticoagulant, and antibacterial resistance14. Obesity is recognized among pregnant women as a key comorbidity and risk factor for disease severity and even with negative survival prognosis14,15.
The decedent patients group had twice as many symptoms on hospital admission and nearly the same percentage of risk factors. From the begging of the pandemic, pregnant patients with multiple COVID-19-related symptoms on admission were at higher risk of severe COVID-19 infection16. This group of patients also had a shorter time between the symptoms onset and hospitalization commencement, and this important fact should raise awareness that these patients must be closely monitored. Preventive hospitalization should be considered when providing adequate monitoring for outpatients is impossible.
All presented laboratory results mentioned above were collected on the day of the initiation of mechanical ventilation. More progressive lymphopenia and neutrophilia were observed in the group of decedent patients. These findings agree with data from existing literature regarding COVID-19 manifestations and the progression of COVID-19 infection17. All patients in our series were anemic, and anemia is a well-known risk factor for the severity of COVID-19 infection and poor pregnancy outcome1,4. Hyperferritinemia is associated with excessive inflammatory reactions and higher mortality rates18. Ferritin levels were more than 50 % higher in the decedent group compared to the recovered group of patients. Therefore, this marker of infection must be closely assessed along with the patient’s clinical condition to guide clinicians and ensure rapid patient assessment and management.
Susceptibility for COVID-19 infection is closely associated with the third trimester of pregnancy19. The mean gestational age at delivery was 33 weeks and four days. Emergency cesarean section was performed in six cases, one pregnancy was successfully continued, and a patient at 16th weeks of gestation died before the pregnancy was terminated. Six live preterm newborns were transferred to the neonatal ICU for further treatment, and they all had negative swabs for SARS-CoV-2 infection.
The main limitation of this case series is the small sample size. Due to the low number of enrolled pregnant women, it was impossible to draw statistical conclusions. Another limitation is that all patients in these case series belong to the Serbian population.
Patients in this case series were critically ill and of the same race and ethnicity belonging to the Serbian population. Obesity, maternal age, and diagnosis of ARDS were most commonly observed in patients with lethal outcomes. Preventive measurements, counseling, and enlightenment of potential risk factors, such as obesity, advanced maternal age, and pregnancy-related comorbidities, should be the cornerstones in crises such as COVID-19 when medical care and resources are limited or restricted.
Conflict of Interest
The authors certify that there is no conflict of interest.
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