An Observational Study on Impact of COVID-19 in Pregnancy: Clinical Profiles and Foetomaternal Outcomes in Caesarean Section Cases at a Tertiary Care Centre, Gujarat, India

1. Assistant Professor, Department of Obstetrics and Gynaecology, Government Medical College and New Civil Hospital, Surat, Gujarat, India. 2. Professor and Head, Department of Obstetrics and Gynaecology, Government Medical College and New Civil Hospital, Surat, Gujarat, India.

Abstract

Introduction: The Coronavirus Disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, has resulted in a crippled healthcare system worldwide. In this unprecedented situation, it is important to analyse the impact on the vulnerable population of pregnant women, especially those with high-risk pregnancies and those undergoing a Caesarean section (CS).

Aim: To analyse the clinical profile, foetomaternal outcomes, and co-morbidities in COVID-19-affected pregnancy cases undergoing a CS.

Materials and Methods: This was a retrospective observational study conducted at the Department of Obstetrics and Gynaecology, Government Medical College, and New Civil Hospital in Surat, Gujarat, India during the first wave of the COVID-19 pandemic from April 2020 to December 2020. The study included a total of 65 cases of COVID-19-positive mothers undergoing a C-section. Demographic parameters such as age, obstetric history, details of the C-section (like gestational age at the time of the procedure, indication, and category of the C-section), associated co-morbidities, severity of COVID-19-related symptoms and treatment, neonatal parameters {such as birth weight, Appearance, Pulse, Grimace, Activity and Respiration (APGAR) score, and COVID-19 status of the baby at birth} were analysed. Additionally, a comparison of the C-section rate and complications such as the development of severe anaemia requiring blood transfusion, postoperative development of urinary tract infections, surgical site infections, and the association of hypertensive disorders of pregnancy was conducted between COVID-19-affected and unaffected pregnancies undergoing a C-section during the study period. Data on COVID-19 negative cases were obtained from the monthly labour room statistics submitted to the department. The Chi-square test and Fisher’s-exact test were used to compare parameters of the COVID-19 positive and negative groups and a p-value of less than 0.05 was considered statistically significant.

Results: Out of a total of 6246 deliveries conducted at the institute during the study period, the CS rate among affected and non affected women was 44.5% (65 out of 146) vs. 32.8% (2006 out of 6100) {p=0.003, Relative Risk (RR) 1.3, 95% Confidence Interval (CI) 1.12-1.62}. The mean age of women with COVID-19 undergoing a CS was 25.3 years. The difference in the rate of blood transfusion requirement in COVID-19-affected cases was 9 out of 65 (13.8%) vs. 120 out of 2006 (6%) in COVID-19 negative pregnancies (RR 2.3, 95% CI: 1.2-4.3). The difference in the rate of urinary tract infections in the postoperative period was statistically significant in COVID-19-infected patients, 5 out of 65 (7.7%) vs. 58 out of 2006 (2.9%) in non infected patients (p=0.0451, RR 2.6, 95% CI 1.1-6.4). The prevalence of hypertensive disorders among COVID-19 positive and negative mothers undergoing CS was very high in the present study (16 out of 65, 24.6% vs. 160 out of 2006, 8.1%, RR 3.08, 95% CI 1.9-4.8). Neonatal parameters like low APGAR score at birth were seen in 5 cases (8%), low birth weight in 20 cases (30%), and 3 babies (4.5%) were COVID-19 positive at birth.

Conclusion: Higher rates of caesarean sections, increased prevalence of hypertensive disorders of pregnancy, anaemia requiring blood transfusion, and postoperative development of urinary tract infections among COVID-19-affected mothers undergoing a caesarean section.

Coronavirus disease 2019, High risk pregnancy, Surgical outcome

It all started with a cluster of cases of pneumonia from Wuhan, Hubei Province in China in December 2019. Since then, the novel Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV-2 has engulfed the entire world with preternatural speed. On the 11th of March 2020, the World Health Organisation declared COVID-19 a pandemic as it had already affected 114 countries (1). Physiological changes during pregnancy create an immune-compromised state to protect the allogenic foetus at the cost of increased susceptibility to infections. Previous pandemics like the Spanish flu from 1918-1920, the H1N1/Swine flu pandemic of 2009, the Severe Acute Respiratory Syndrome (SARS) outbreak of 2002-2004, and the Middle East Respiratory Syndrome (MERS) of 2012 have all shown increased morbidity in the obstetric population, with 50% requiring critical care and more than 25% mortality rates (2),(3). Though preliminary data related to the obstetric population was reassuring, soon the landscape changed, showing compromised outcomes. We reported our index obstetric case on the 11th of April 2020, and since then, the numbers have been staggering. Data related to mode of delivery and foetomaternal outcomes were limited. However, the development of SARS-CoV-2 pneumonia and associated co-morbidities posed a greater risk for undergoing a CS (4). Spike proteins S1 and S2 of SARS-CoV-2 have 10-20 times higher affinity for Angiotensin-converting Enzyme-2 (ACE2) receptors in alveolar epithelial cells of the lungs, kidneys, heart, and intestines compared to previous SARS viruses (5). Increased expression of ACE2 receptors, imbalance of the Renin-Angiotensin system, and imbalance of angiogenic and antiangiogenic factors show overlapping mechanisms between the cytokine storm of SARS-CoV-2 infection and the development of pneumonia, hypertension, coagulopathy, haemorrhage, and other infections (6),(7),(8). Adverse pregnancy outcomes are associated with COVID-19-affected mothers, especially if they undergo a CS (9),(10). Hence, the present study was conducted with the aim of analysing the clinical profile, foetomaternal outcomes, associated co-morbidities, and complications of COVID-19-affected high-risk pregnancy cases undergoing a CS at the study centre.

Material and Methods

The present retrospective observational study was conducted at the Department of Obstetrics and Gynaecology, Government Medical College and New Civil Hospital in Surat, Gujarat, India, during the first wave of the COVID-19 pandemic, i.e., from April 2020 to December 2020. Before the study, institutional ethical board clearance was obtained from GMCS with EC ID: 325/2020.

During the pandemic, the present study centre was the highest designated referral hospital for COVID-19 patients in South Gujarat, India. Obstetric patients were triaged on admission based on clinical parameters and confirmation of COVID-19 status either by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) assay or by rapid antigen testing as per prevailing guidelines provided by the Indian Council of Medical Research (ICMR). Management protocols followed were in accordance with the guidelines provided by the All India Institute of Medical Sciences/ICMR-COVID-19 National Task Force and the Joint Monitoring Group, as well as literature published by the Royal College of Obstetricians and Gynaecologists (RCOG) (11).

Inclusion criteria: Patients admitted to the labour room with COVID-19 positive or negative status undergoing a CS were included.

Exclusion criteria: Patients admitted to the labour room with COVID-19 positive or negative status undergoing vaginal delivery were excluded from the study.

Study Procedure

During the study period, a total of 65 patients with COVID-19 infection underwent a CS. Data required for the study were retrieved from the case papers and record forms of the labour room for each patient. Detailed clinical history and maternal parameters such as age, obstetric history, travel history, details of CS including gestational age, category, and indication of CS, type of anaesthesia, duration of surgery and hospital stay, clinical severity of COVID-19 symptoms, mode of oxygen therapy, and associated co-morbidities were studied and analysed. Clinical severity of symptoms was assigned according to the clinical management protocol for COVID-19 in adults provided by the Government of India and the Ministry of Health and Family Welfare (12).

Neonatal parameters such as APGAR score at birth, birth weight, COVID-19 status of the baby, and outcomes such as being alive and discharged from the nursery or early neonatal death were analysed. Additionally, a comparison of complications such as severe anaemia requiring a blood transfusion, hypertensive disorders of pregnancy, and the development of postoperative urinary tract infections and surgical site infections was conducted between COVID-19 infected and non-infected mothers undergoing a C-section during the study period. Data from 2006 COVID-19-negative patients were collected from the monthly labour/maternity services data of the department.

Statistical Analysis

For the analysis, International Business Machines (IBM) Statistical Package for the Social Sciences (SPSS) for Windows, Version 23.0 (IBM Corp., Released 2015, Armonk, New York) was used. The data were expressed in the form of frequency with percentages n (%). The Chi-square test was used to compare parameters of COVID-19 positive and negative groups, and a p-value of less than 0.05 was considered statistically significant.

Results

During the study period, a total of 6246 deliveries were conducted at the study institute. Out of these, 146 were COVID-19 positive mothers, and 65 of them underwent Lower Segment Caesarean Section (LSCS). LSCS in COVID-19 mothers was done only when obstetrically indicated or when it was necessary for the resuscitation of critically-ill mothers. A total of 65 COVID-19-positive mothers underwent CS, and 81 had vaginal delivery (CS rate of 44.52%). Among COVID-19 negative mothers, 2006 underwent CS, and 4094 had vaginal delivery during the same time (CS rate of 32.88%). This difference was statistically significant with a p-value of 0.003 (RR 1.3, 95% CI 1.12-1.62).

Out of 65 mothers, the majority of them were young, belonging to the age group of 20-25 years, and 30 of them resided in hotspot areas identified by the Municipal Corporation for increased prevalence of COVID-19. A total of 28 (43%) patients were referred to the study centre, and 8 (12%) patients had a positive travel or contact history (Table/Fig 1) (13).

The clinical profile of COVID-19 mothers requiring LSCS has been delineated in [Table/Fig-2a,b]. A total of 10 (15%) of pregnancies undergoing LSCS amongst COVID-19 positive mothers were pre-term; around 53 (83%) were term, and the rest were late-term. Approximately 33 (51%) of the C-sections were done on an urgent basis, belonging to the Royal College of Obstetricians and Gynaecologists (RCOG) categories one and two (11). According to Robson’s classification, 14 (21%) belonged to group two, and another 14 (21%) belonged to 5C (14). About 36 (55%) were done for maternal indications, and the rest 45% (n=29) were for foetal indications. Around 92% (n=60) of them were under spinal anaesthesia. Five patients required general anaesthesia due to indications like antepartum eclampsia, severe preeclampsia with multiorgan failure, acute kidney injury, and one of them had dilated cardiomyopathy with interstitial lung disease in a known case of tuberous sclerosis.

A total of 26 (40%) of them were confirmed positive cases at the time of the C-section, and the rest of the reports were received later on. A total of 15 (23%) of them had moderate to severe symptoms of COVID-19 and required oxygen therapy. A total of 15 (23%) of them were admitted to the high dependency unit or intensive care unit. Hospital stay was prolonged in 28% (n=18) of the cases, and it was beyond 10 days (Table/Fig 3). A total of 62 (92%) babies were alive and discharged from the nursery eventually. Five babies had a very low birth weight of less than 1.5 kilograms. There were five cases of early neonatal deaths, of which there were two pairs of very low birth weight twins; they also required exchange transfusion and later succumbed to complications due to hyperbilirubinemia and sepsis. One of the five cases had a very poor APGAR at birth due to severe birth asphyxia. Three babies tested positive for COVID-19 (Table/Fig 4). The prevalence of severe anaemia and the requirement of blood transfusion, the incidence of developing urinary tract infection postoperatively, and cases complicated by hypertensive disorders of pregnancy were higher among COVID-19 positive patients compared to COVID-19 negative patients (Table/Fig 5).

Out of 65 patients, 11 (17%) required higher antibiotics other than Departmental routine protocol of injectable Ceftriaxone, Metronidazole, and Gentamicin for caesarean section patients. One of the patients developed severe postpartum depression. Out of 65 COVID-19 positive caesarean section cases, there was one maternal mortality due to COVID-19 pneumonia.

Discussion

The COVID-19 pandemic opened up many new research avenues across the globe. Uncertainty regarding clinical outcomes due to the interaction of this novel virus with human systems was a matter of concern for all, and apprehension increased by multiple folds in the case of vulnerable populations like pregnant women.

At the institute, COVID-19 and non COVID-19 work were running simultaneously with strict adherence to standard operational protocols for triaging and managing patients, with separate designated wards, labour rooms, and operating theatres. Based on the annual audit of maternity services from previous years, our CS rate was between 28-34%. As a tertiary care centre, nearly 45-50% of the total obstetrics patients were referrals.

During the study period, the CS rate among the COVID-19 affected group and the non affected group was 44.5% vs. 33.8% (RR 1.3, 95% CI 1.12-1.62). During the initial phase of the pandemic, some studies have shown a lower threshold with a CS rate of up to 70% in affected mothers in order to prevent vertical transmission and adverse outcomes (15),(16).

According to a study by Smith LH et al., pregnant women who were symptomatic for COVID-19 in early pregnancy, mildly symptomatic in later pregnancy, or were COVID-19 negative had a comparable adjusted risk of preterm birth of around 10%. However, those experiencing moderate to severe disease in later weeks of gestation had an increased risk ratio of 3.7 for indicated preterm delivery (17). In the present study, there were preterm caesarean sections in 15% of cases.

Based on studies, spinal anaesthesia was the preferred modality for obstetric patients with COVID-19, and if general anaesthesia was necessary, it should be administered after preoxygenation with 100% oxygen and Rapid Sequence Induction and Intubation (RSII) (18),(19). Approximately 8% of the patients underwent general anaesthesia, and pre-oxygenation and RSII were performed to avoid manual ventilation and the generation of viral aerosols from the airways.

The rate of vertical transmission of COVID-19 in the present study was 4.4%, comparable to 3.2% (95% CI 2.2-4.3) as given in the meta-analysis published by Kotlyar AM et al., (20). However, teratogenicity and morbidity in neonates are still being explored.

The difference in the rate of surgical site infection in caesarean sections among COVID-19 positive and negative patients was not statistically significant (p=0.811, >0.05, RR<1 -0.8). This could be attributed to measures like the correct use of personal protective equipment, hand sanitisation, and an increase in safer practices for waste disposal and disinfection. Antonello VS et al., described a 49% decrease in surgical site infections in caesarean sections during the pandemic in their study (21).

In the present study, the difference in the rate of postoperative urinary tract infections was statistically significant in COVID-19 infected patients. Marand AJB et al., found a 50% increase in White Blood Cells (WBC) in urine and damage to uroepithelium, as well as acute kidney injury due to cytopathic effects of the virus, damage due to immune complexes, hypoxic injury, and cytokine storm (22).

The requirement for blood transfusion postoperatively was higher in COVID-19 positive mothers, and the difference was statistically significant. Studies have shown a possible link between COVID-19 patients developing anaemia due to inflammation, altered iron metabolism, reduced bioavailability, cytokine-mediated inhibition of erythropoiesis, and a decreased half-life of Red Blood Cells (RBC) (23),(24).

The prevalence of hypertension among COVID-19 positive and negative mothers undergoing caesarean sections was very high in the present study (24.6% vs. 8.1%, RR 3.08, 95% CI 1.9-4.8). A meta-analysis by Conde-Agudelo A and Romero R showed higher rates of hypertensive disorders of pregnancy in women, around 24% in mild or moderate disease (adjusted RR, 1.24; 95% CI, 0.98-1.58) and 40% in severe or critical disease (adjusted RR, 1.61; 95% CI, 1.18-2.20), as compared to 18% in asymptomatic infection (25). In a cohort study published by Metz TD et al., severe-critical COVID-19 was associated with an increased risk of caesarean sections (59.6% vs. 34.0%, adjusted relative risk 1.57, 95% CI 1.30-1.90) and hypertensive disorders of pregnancy (40.4% vs. 18.8%, adjusted relative risk 1.61, 95% CI 1.18-2.20) (26). The pathophysiology of preeclampsia and SARS-CoV-2 infection overlap in aspects of endothelial dysfunction, vasculopathy, and thrombosis (27).

The SARS-CoV-2 binds to ACE2 receptors, down-regulating the Renin-Angiotensin System. It is also an important regulator of placental function. The balance between vasodilatory and vasoconstrictive mechanisms is disrupted. Trophoblastic invasion and uteroplacental blood flow are hampered. Increased circulating blood levels of sFlt-1 and angiotensin II type 1-receptor autoantibodies are found in COVID-19 infected mothers. These two are also markers of preeclampsia (6),(28),(29).

The present study treatment protocol included oxygen therapy, antibiotics like Ceftriaxone, Metronidazole, and Gentamycin. Labetalol was the antihypertensive of choice. Azithromycin and Hydroxychloroquine were administered, along with low molecular weight Heparin after the first 24 hours postsurgery. Furosemide was used for pulmonary oedema, and steroids were given if advised by the intensivist. Remdesivir was not available at that time. A total of 11 patients required higher antibiotics such as Clindamycin, Piperacillin, and Tazobactum, as per culture sensitivity reports. One of the patients developed postpartum depression and was started on clonazepam and escitalopram after a psychiatry consultation. Unfortunately, one out of the 65 patients succumbed to COVID-19 pneumonitis.

Compared to COVID-19 negative mothers, COVID-19 positive pregnancies definitely had a compromised clinical outcome. The odds of exaggerated co-morbidities and chances of mortality are high (30),(31). From the limited data available so far, it seems that any surgical intervention like a C-section can worsen the clinical outcome of a COVID-19 positive patient (32),(33).

In the present study, clinical characteristics, management interventions, complications, and outcomes of COVID-19 infected obstetric population undergoing a C-section were described in detail. Overall, these findings highlight the associated co-morbidities in COVID-19 infected patients undergoing a C-section and add to the growing evidence related to the better management of SARS-CoV-2 infected obstetric patients.

Limitation(s)

The main limitations of the present study are its retrospective observational study design and the small sample size, as it is a single-centre study.

Conclusion

Higher caesarean section rates, increased prevalence of hypertensive disorders of pregnancy, anaemia requiring blood transfusion, and postoperative development of urinary tract infections were observed among COVID-19-affected mothers undergoing a caesarean section. Neonatal outcomes such as low APGAR scores at birth and low birth weight were associated with early neonatal deaths. The complexity of the impact of the pandemic on pregnancy and the exacerbation of co-morbidities have emphasised the need for a robust healthcare system, an individualised approach to high-risk pregnancies, and larger scientific studies to deepen existing knowledge.

DOI and Others

DOI: 10.7860/JCDR/2024/71410.19803

Date of Submission: Apr 22, 2024
Date of Peer Review: Jun 03, 2024
Date of Acceptance: Jul 01, 2024
Date of Publishing: Aug 01, 2024

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? No
• For any images presented appropriate consent has been obtained from the subjects. NA

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EMENDATIONS: 6