Maternal and Fetal Outcomes in Critically Ill Patients Infected with COVID‐19: A Case Series Open Access

The first case of COVID-19 in the UAE was identified on January 29, 2020, almost a month after the outbreak in Wuhan, China. At the time of writing this article, approximately 1,051,241 people in the UAE were affected by COVID-19 with 2,349 deaths due to COVID-19 pneumonia [1]. Before December 2019, the all-cause maternal mortality ratio in the UAE was extremely low at three for every 100,000 live births [2]. The exact number of maternal deaths due to COVID-19 or associated with COVID-19 is still being calculated.

At our tertiary care hospital, which also has high-risk maternity services, 12,997 were admitted for COVID-19. A total of 769 pregnant patients with positive COVID-19 swabs were admitted from March 2020 to December 2022. Out of these, 8 had severe-to-critical COVID-19 pneumonia. Three of the mothers died after a prolonged stay in the intensive care unit (ICU). All 3 patients were delivered by emergency cesarean (two for maternal reasons). Most patients who presented with severe or critical COVID-19 infection were in the late second trimester. There was no neonatal mortality due to COVID-19 in our study.

Pregnant women are immunosuppressed and at a high risk of viral respiratory infections. A systematic review and meta-analysis indicated that approximately less than one-third (i.e., 31.1%) of pregnant women who were admitted to the hospital for COVID-19 infection were admitted to the ICU and 2.7% of those admitted to the hospital for COVID-19 infection have died, while about 11.3% of newborn infants were admitted to the ICU and 2.2% of them experienced perinatal death [3]. Severe COVID-19 pneumonia is defined when respiratory rate is above 30/min, oxygen saturation (SpO₂) is below or equal to 93%, PaO2/FiO2 < 300, and/or pneumonic infiltrates involving more than 50% of the lungs are seen. Critical COVID-19 is when patients suffer respiratory failure, septic shock, and/or multiple organ dysfunction, probably due to cytokine storm [4].

A patient in her mid-30s, gravida 2, para 1, previous cesarean section, was referred from another hospital to our ICU. She was 31 weeks pregnant and presented to the Obstetrics and Gynecology emergency department with breathing difficulty and a history of fever. She had no previous medical history. Her body mass index was 31.1 kg/m². At the time of admission to the hospital, she was fatigued, tachypneic (respiratory rate of 36 breaths/min), had a temperature of 36.9°C, SpO₂ of 85%, a heart rate of 152 beats/min, and her blood pressure was 126/68 mm Hg. She tested positive for COVID-19 with a polymerase chain reaction test, arterial blood gas indicated moderate acute respiratory distress syndrome (ARDS) and required double O₂ flow given (15 L/min by nonrebreathing mask and 4 L/min by nasal), fluid bolus was also started (Table 1).

As her condition did not improve, the multidisciplinary team, consisting of an obstetrician, intensivist, anesthetist, and neonatologist, advised intubation and emergency cesarean section. She delivered a male newborn, weighing 1,885 g, with Apgar 7 at 1 min and 8 at 5 min. She was intubated and started on low-molecular-weight heparin 60 mg subcutaneous, hydrocortisone 100 mg intravenous, 2 doses of tocilizumab, pegylated interferon alfa-2a, 80 μg subcutaneous weekly, and piperacillin-tazobactam. She was on nasogastric feeding. In spite of maximum ventilation support, her condition worsened, and she showed signs of upper gastrointestinal bleeding (coffee ground aspirate from a nasogastric tube) and a drop in hemoglobin, for which she received 2 units of packed red blood cells.

Her condition further deteriorated, so veno-venous extracorporeal membrane oxygenation (ECMO) was placed by a cardiologist after 8 days of her admission. Her chest X-ray showed diffuse opacification in both lungs, left more than right. The patient became hypertensive on day 12 and needed glyceryl trinitrate to target systolic less than 140 mm Hg. Despite high ionotropic support, the patient remained in critical condition, and her Glasgow Coma Score was 3 or less. She developed pleural effusion, pneumothorax, and acute kidney injury. Her condition was further complicated by septic shock, and she ultimately went into disseminated intravascular coagulation. Unfortunately, despite all resuscitative measures, the patient expired after 38 days of admission to the ICU. Figure 1 shows the timeline of the patient in comparison with investigations and chest X-ray findings for all 3 patients.

A patient in her mid-30s, gravida 4, para 3, previous 1 cesarean section, presented to the emergency at 29 weeks 4 days of gestation with a history of generalized body pain, fever, fatigue, and difficulty breathing for 2 days. She was a known case of systemic lupus erythematosus with positive anti-Ro antibodies. She also had lupus nephritis, beta thalassemia trait, and gestational diabetes mellitus well controlled on the glucophage. Her COVID-19 test on admission was positive. She was diagnosed with COVID-19 pneumonia and was on 2 L of nasal oxygen.

Five days later, she developed preeclampsia and hemolysis elevated liver and low platelet syndrome, had an unsatisfactory cardiotocography, and decided for delivery by emergency cesarean section. She delivered a live baby boy of weight 1,630 g with Apgar score of 7 and 9 (at 1 and 5 min, respectively). Postoperatively, she remained critical, intubated, and on a mechanical ventilator with high parameters. Her chest X-ray showed worsening pneumonia. She was noticed to have abdominal distension, and her urgent abdomen and pelvis computerized tomography scan reported significant pneumomediastinum and pneumoperitoneum. She had more than 5 sessions of prone positioning. Daily trial of reducing the fraction of inspired oxygen failed due to desaturation and progressive lung fibrosis.

The patient remained on mechanical ventilation, fully anticoagulated, and treated with methylprednisolone. She further developed hypotension and fever and was treated with ertapenem for positive blood culture along with vasopressors. The patient continued to desaturate despite being in the prone position and on maximum ventilator support due to COVID-19 lung fibrosis and severe ARDS. She developed refractory shock along with desaturation and was on maximum vasopressor and ventilator support. She went into bradycardia and asystole, and cardiopulmonary resuscitation started as per advanced cardiac life support (ACLS) guidelines, but she did not recover and passed away (Fig. 2).

A patient in mid-20s, gravida 3, para 2, with previous uncomplicated normal vaginal deliveries at 27 weeks 5 days, with no high-risk factors or history of contact with COVID-19, presented to the hospital with a history of fever, cough, nausea, vomiting, and diarrhea. She had not taken COVID-19 vaccine due to pregnancy. She developed breathing difficulty and chest pain 1 day before attending the hospital. She was admitted to the medical isolation ward with confirmed moderate-to-severe COVID-19 pneumonia and chest X-ray, demonstrating multifocal infiltrates in both lungs. At the time of admission, her pulse was tachycardic (138 bpm), her respiratory rate was 36 bpm, she had high-grade fever (39.1°C), and her SpO₂ was at 90%. An obstetrical exam confirmed a live pregnancy, consistent with her gestational age, and her cardiotocography was reactive.

She was started on nasal O₂, dexamethasone 6 mg BD, ceftriaxone IV, then meropenem and vancomycin, enoxaparin SC 80 mg BD, remdesivir, and tocilizumab. The results of 2 initial SARS-CoV-2 tests repeated after 1 week were negative, and although she remained critically ill and required vasopressor support and high-flow nasal cannula (>60 L/min), her saturation on O₂ continued to worsen, dropping to 88%. On day 20 of admission, the patient was shifted to the ICU, and 2 days later, emergency cesarean section was performed at 30 weeks 6 days for fetal distress under general anesthesia. Her cesarean was uncomplicated, but post-cesarean, she decompensated and could not be extubated. Due to ARDS, long-term ventilation, and inotrope infusion without signs of improvement, ECMO was decided on day 47 of admission. She continued on ECMO for 50 days, but her condition did not improve. In spite of intensive resuscitation, the patient developed acute renal failure, septic shock, and disseminated intravascular coagulation. She expired after 97 days of her admission. Neonate was discharged in good condition after 57 days of birth. The maternal and neonatal data are shown in Tables 1 and 2 (Fig. 3).

During the influenza pandemic of 1919, maternal mortality in cases complicated by pneumonia was more than 50% [5]. Seasonal influenzas during the 20th century, as well as pandemic of H1N1 influenza, were more serious in pregnant women, needed intensive treatments, but did not have high mortality rates. Maternal mortality rates have increased significantly during the COVID-19 pandemic. After adjusting for demographic factors such as age, ethnicity, and other medical problems, pregnant women with COVID-19 were 3 times more likely to be admitted to an ICU than were nonpregnant women (confidence interval [CI] = 2.6–3.4). Pregnant women were also 3 times more likely to receive invasive ventilation (95% CI = 2.2–3.8) and 2.4 times more likely to receive ECMO (95% CI = 1.5–4.0) [6].

The risk of death from severe bacterial or viral pneumonia in pregnancy is nearly 17% [7]. The presence of COVID-19 complicates the treatment of pneumonia. The cytokine storm causes extensive lung damage, which is exacerbated by the immunosuppressive state of pregnancy. The fear of COVID-19 diagnosis during pregnancy in women and their families, as well as reluctance to seek medical help due to fear of adverse effects of medications and procedures such as X-ray and computerized tomography scans on the fetus, are barriers to early diagnosis and treatment. Certain treatments may be avoided because of concerns about the effects on pregnancy. To avoid developing ARDS and causing irreversible lung damage, pneumonia, particularly COVID-19 pneumonia, must be aggressively managed. Prior to 2019, the most common cause of maternal mortality was obstetric hemorrhage, followed by infection or sepsis [8], but COVID-19 is the most significantly associated diagnosis with maternal mortality since the pandemic.

Pregnancy is a risk factor for severe and life-threatening COVID-19, and vaccination is the most effective way to reduce the risk of COVID-2 infection and reduce morbidity and mortality. The current recommendations from health organizations such as the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) are to encourage antenatal, postnatal, and breast-feeding women to get vaccinated against COVID-19. Pregnancy makes vaccination difficult because patients, families, and healthcare workers are concerned about the potential negative effects of vaccination on fetal growth and development, antibody transfer through the placenta to the fetus, and the safety of maternal vaccination. Pregnancy was an exclusion criterion in initial trials to assess the safety of COVID-19 vaccines, but subsequent studies have explicitly demonstrated that the benefits of vaccination outweigh the potential risks [9]. Overall, no pregnancy-specific concern has been identified with COVID-19 vaccination.

Guidelines for managing COVID-19 in pregnancy are still being developed. Obstetricians, anesthetists, and intensivists face a unique set of challenges during pregnancy. Certain procedures, such as anticoagulation, can result in excessive bleeding, which can harm both the mother and the fetus because pregnancy and delivery are prone to hemorrhage. Many pregnant patients are unable to perform prone positioning, which is known to be beneficial. The safety of antivirals and other novel anticorona therapies on the fetus is unknown, and there is a risk that they will not be used in a timely manner. Maternal benefit and maternal survival must be prioritized so that mothers can receive appropriate and timely healthcare. As more data becomes available, standardized global guidelines must be developed and implemented to ensure maternal safety.

Goal 3 of the Sustainable Development Goals aims to “ensure healthy lives and promote well-being for all at all ages.” The primary goal of SDG-3 is to reduce global maternal mortality to less than 70 per 100,000 live births by 2030 [10]. The global maternal mortality ratio was 211 (uncertainty interval 199–243) deaths per 100,000 live births, and an annual reduction of 6.4% is required to achieve the SDG of 70 maternal deaths per 100,000 live births, with no country having a maternal mortality rate that is more than twice the global average.” [11, 12]. However, this was before the pandemic.

Maternal mortality from any cause has increased significantly since the beginning of the COVID-19 pandemic. According to a large systematic review and meta-analysis, which analyzed 422,488 women compared to pregnant women who did not have COVID-19, those pregnant women who did have COVID-19 had a higher risk of maternal death (odds ratio 6.09, 95% CI: 1.82–20.38) [13]. This has had a negative impact on the maternal mortality ratio. Blood loss, infection, and pregnancy-induced hypertension were traditionally the leading causes of maternal mortality, particularly in low-income countries. With COVID-19, even developed countries such as the USA have seen a 33% increase in maternal mortality and a 41% increase in late maternal deaths after March 2020 [14, 15].

The reason for maternal deaths is COVID-19, although the associated high-risk factors may have attributed to it. Our facility is a tertiary care center that caters to high-risk women, and we did not report a single maternal death in the last 10 years, but we had 3 in a short gap from March 2020 to December 2022 due to COVID-19. The exact impact of the COVID-19 pandemic on the maternal mortality ratio is still being assessed. Certainly, the pandemic had a significant impact on healthcare, and the mortality ratio has been pushed back many years as a result of the increased mortality of pregnant women in the last 3 years. To ensure that target mortality ratios are met, the COVID-19 recovery framework must include the maternal cause.

There was a significant increase in maternal deaths due to COVID-19 at our center. Neonates born to COVID-19-affected mothers were not affected. Pregnancy with COVID-19 is a unique challenge as the life of the fetus is also at risk. Timing of delivery is a difficult decision to make as extreme preterm and maternal resuscitation need to be balanced. On the other hand, certain treatment options such as prone positioning, ECMO, and high-dose anticoagulation are difficult to provide in an antenatal patient. Proper global healthcare policies pertaining to maternal health are needed to ensure maternal safety prior to another unpredictable viral pandemic.

We would like to thank all physicians, nursing, and support staff for taking care of patients during the COVID-19 pandemic.

This study complies with the guidelines for human studies and conducted ethically in accordance with the World Medical Association Declaration of Helsinki and approved by the Dubai Scientific Research Ethics Committee (DSREC) under decision number DSREC-12/2021_08 dated December 21, 2021, focused on 3 pregnant patients who, despite receiving extensive multidisciplinary care, unfortunately did not survive and passed away. In Case 3, written (signed electronically) patient informed consent was obtained from the patient’s spouse, while in Case 2, consent was acquired from the patient’s sister. However, in Case 1, despite diligent efforts to contact the patient’s relative, none could be reached. We tried reaching the dead patients’ contacts by all possible means but did not find anyone. In addition, the Dubai Scientific Research Ethics Committee (DSREC) under decision number DSREC-GL06-2023 agreed to waive the consent requirement for all mothers and neonates involved.

The authors have no conflicts of interest to declare.

The study did not receive any funding sources.

Zenab Yusuf Tambawala: manuscript drafting, data consolidation, revision, and correspondence. Fatima Cherifi and Wafa Mohsen: data collection and manuscript drafting. Tazeen Makhdoom: data collection, revision, and ethical approval. Lama Khalid Hamza: manuscript drafting and revision.

The data that support the findings of this study are not publicly available due to privacy and security reasons but are available from the corresponding author upon reasonable request.