Introduction

It is not the first time that Zoonotic virus have led to worrisome situations all over the world. At two separate occasions, the Severe Acute Respiratory Syndrome (SARS) in 2003 followed by Middle East respiratory syndrome (MERS) in 2012 resulted in case fatality rate (CFR) of 10.5% and 34.4% respectively.1, 2 At the time of writing, COVID-19 with the global cumulative incidence of 185, 786, 411 reported cases and 4, 019, 859 associated deaths with a CFR of 2.2% has already caused more deaths than MERS and SARS combined.3 An insight from the past has taught us to evolve continuously on every front to prevent mortality in highly vulnerable community from these infections. This brings us to the cohort scrutinized thoroughly in this study i.e. pregnant women who are regarded as one of the highly vulnerable groups to this respiratory syndrome. As the physiological changes in pregnant subjects go hand-in-hand over different trimesters, it makes them more prone to respiratory infections that ultimately progress to respiratory failure.

Since the beginning of this pandemic, several studies have shed light on the genetic, virologic, epidemiologic and clinical aspects of this emerging infection. Leaving aside the significant heterogeneity in reported studies, contradictory observations have been reported in terms of adverse effects on mother as well as on newborns, causing fetal distress, premature labor, respiratory distress, thrombocytopenia accompanied by abnormal liver function, and even death.4, 5, 6, 7 Moreover, lack of clarity on the route of infection in SARS-Cov-2-positive neonates as well as conflicting evidence from nucleic acid-based testing and antibody testing,8, 9 in neonates born to mothers with COVID-19 has raised further eyebrows among treating obstetricians. But, due to variation in demographics, treatment protocol and logistical resources, realization on neonatal outcomes following maternal COVID-19 in pregnancy is still based on case series and centre experiences. Hence, we too as a part of medical fraternity felt the need to study the effect of SARS-CoV-2 infection on maternal, fetal and neonatal outcomes in order to formulate better management plans for the future. Our study is not a typical case control analysis as it studies the retrospectively collected data of antenatal patients diagnosed with SARS-CoV-2. Ultimately, every individual must co-ordinate, co-operate, collaborate and innovate to reduce the morbidity and mortality in this pandemic.

Materials and Methods

Study design

A retrospective cohort study was undertaken among the pregnant women with confirmed or suspected SARS‐CoV‐2 infection who were admitted/referred to a tertiary Covid Care Centre (CCC), Ahmedabad, Gujarat over a span of three months starting from 1st April 2021 to 30th June 2021.

Patients with following inclusion criteria were enrolled in the study:

1. All symptomatic antenatal patients diagnosed with SARS-CoV-2 by RT-PCR method.

2. Patient with written informed consent signed by patient/guardian.

Following mothers were excluded from study:

1. Any pregnant patient diagnosed with SARS-CoV-2 and delivered outside the study centre.

2. Any asymptomatic pregnant patient diagnosed with SARS-CoV-2.

RT-PCR test being highly specific is the current gold standard diagnostic method for the diagnosis of COVID-19. Only Indian Council of Medical Research (ICMR) approved kits were used for the detection of the SARS-CoV2. On admission, the nasopharyngeal and oropharyngeal swabs of patients were taken and sent for RT-PCR. Detection was based on RT‐PCR method targeting the RNA‐dependent RNA polymerase (RdRp) gene. HRCT thorax scan examination was carried out in selective patients (only mothers). Chest X-ray of selective neonates (case specific) were take. Clinical manifestations such as fever, coughing, myalgia, fatigue, headache, diarrhoea or dyspnea were recorded.

Diagram 1

Flowchart of the study

Results

We studied 22 COVID-positive (RT-PCR) mothers over a span of 3 months who were admitted in the dedicated COVID ward/ICU in accordance with the inclusion−exclusion criteria.

Table 1 depicts the demographic details as well as baseline characteristics of the pregnant patients at presentation. The mean age of the mothers was 30.2 ± 4.0 years (range 23–37 years) and the mean gestational age was 29.7 ± 9.1 weeks. 15 (68.2%) patients had none of the comorbidities while 3 (13.6%) had obesity, 2 (9.1%) patients each with hypothyroidism and diabetes mellitus were also recorded. One patient each with Juvenile Myoclonic Jerks, Epilepsy, pregnancy induced DM and Pregnancy induced HTN respectively. On admission, the main complaint was malaise in 17 (77.3%), followed by fever in 16 (72.7%), dry cough in 5 (22.7%), headache in 4 (18.2%), diarrhoea in 3 (13.6%) and sore throat in 2 (9.1%) patients. 77.3% of the women enrolled were in the third trimester followed by first (13.6%) & second trimester (9.1%). 8 (36.4%) patients had mild while 9 (40.9%) and 5 (22.7%) had moderate and severe severity of the disease respectively.

Table 2 demonstrates the radiological investigation. Pulmonary CT scan on admission was carried out for all 22 cases. Following CT signs were evaluated for each patient: Location: a) Peripheral, b) Intermediate, c) Subpleural; Density: a) Ground-glass opacity; Lung Lobe involvement: a) Single lobe, b) Bilateral / Multiple lobes. Among them 14 (63.6%) patients were normal, while remaining 36.4% cases were found abnormal in different degrees including ground-glass opacity (GGO), patch-like shadows mostly affecting the multiple lobes.

Table 3 demonstrates the need of respiratory support. 63.6% of the subjects required respiratory support in one way or other i.e. 40.9% with nasal oxygen therapy and remaining 22.7% with invasive ventilation. 8 (36.4%) patients required no respiratory support.

Table 4, Table 5 depicts the mode of delivery in pregnant patients presenting in third trimester and the indications of delivery respectively. More than half of the patients (64%) required a cesarean section (CS) for obstetrics indications (seven for maternal distress, one each for obstructed labor and severe oligohydramnios respectively), and the rest of the patients (36%) delivered vaginally. Out of five patients who delivered normally, none required instrumental delivery.

Table 6 shows the incidence of anaesthesia used in C-section. All the nine patients who got delivered through CS were administered spinal anaesthesia.

Table 7, Table 8 demonstrates the type of intervention and details about the medical management used during the course of the treatment respectively. 12 (54.5%) patients required only medical intervention while remaining 10 (45.5%) required both medical & surgical intervention.

Table 9, Table 10 depicts the obstetric & medical complications and final maternal outcome respectively. The current study had the maternal mortality rate of 13.6% (3/22) owing to various medical complications with two of them succumbing to multiple organ failure with Disseminated intravascular coagulation (DIC) & one patient to sepsis with DIC. The patient with Postpartum Haemorrhage (PPH) responded to the treatment and got discharged.

Table 11 depicts the neonatal outcome. The Apgar score (measured at two separate time intervals i.e., at 1^st minute and at 5^th minute) was normal in 8 (80%) babies. The mean Apgar score at 1^st minute and at 5^th minute was 7.1 ± 1.9 and 8.6 ± 2.1 respectively. Both the babies bearing low Apgar scores required NICU admission. Among them, one neonate was discharged well with a good outcome. Only one neonatal death was recorded because of the diffuse exudative lesions & lung whiteout. Six Intrauterine fetal death were also recorded in this study.

Table 12 shows the other characteristics of the patients which were recorded during the course of the treatment. The baseline patient characteristics are presented as mean and standard deviation for continuous variables.

Discussion

Evaluating the implications of COVID-19 on maternal and neonatal outcome becomes more relevant when we look back in the time of the outbreak caused by coronaviruses at two separate instances. In the year 2003, high maternal mortality during the first trimester and intrauterine growth restriction in the second and third trimesters was recorded at the time of SARS-CoV-1 outbreak.17 This was followed by an another similar viral outbreak in the year 2012, termed as MERS-CoV infection in which a case series of 11 patients reported the CFR of 35% for pregnant women and 27% for infants.18 A study by WHO comprising of 25 national and international experts travelled to the affected parts of China in 2020 and investigated 147 pregnant women (64 confirmed, 82 suspected, and 1 asymptomatic with COVID-19) concluded that pregnant women were not at higher risk for developing severe disease due to COVID-19.19 However, preliminary data of several studies from different countries had demonstrated fluctuating course of the disease from asymptomatic or mild symptoms to maternal death. Moreover, insights from the past pertaining to human coronavirus outbreaks suggests that pregnant women and their fetuses are particularly susceptible to poor outcomes. Hence, our study on 22 pregnant women with confirmed COVID-19 diagnosis was undertaken in order to draw conclusion about any maternal and neonatal consequences that needs our immediate attention and we tried to compare our results with the similar kind of published studies on national as well as on international front. The mean age of the mothers was 30.2 ± 4.0 years and the mean gestational age was 29.7 ± 9.1 weeks. Average body mass index (BMI) was 25.8 ± 2.6 kg/m². Fever, dry cough, sore throat, malaise, sore throat, and occasional diarrhoea were the common presenting symptoms. Studies by Yang et al and Guan et al in 2020 reported that individuals with co‐morbid diseases are more susceptible to COVID‐19.20, 21 Approximately one‐ third of confirmed cases in the present study had co‐morbid diseases (31.8%) and is consistent with the literature. Comparison of maternal baseline characteristics between several published studies has been depicted in Table 13.10, 11, 12, 13, 14

COVID-19 pneumonia in pregnant patients warrants special consideration as CT radiation is a factor in fetal teratogenicity. Chest CT was performed in approximately one‐quarter (27.3%) of the confirmed cases in the present study and more than half of them had findings consistent with COVID‐19 infection indicating radiologic imaging might be useful in appropriately selected cases. Also, lymphocytopenia and neutrophilia were the other findings in the present study. The timing and choice of delivery is also the dilemma among pregnant women with COVID infection but the real onus is on the health professionals to formulate an individualised delivery plan depending on the weeks of gestation and maternal and fetal conditions. Generally, vaginal delivery is the first choice to avoid any risks of major surgery. Septic shock or fetal distress should prompt emergency cesarean delivery. In the present study, 64% required a cesarean section (CS) under spinal anesthesia for obstetrics indications while the rest of the five patients (36%) delivered vaginally. We found a higher operative delivery rate in this study group owing to obstetrics indications (seven for maternal distress, one each for obstructed labor and severe oligohydramnios respectively) and not because of COVID-19. A poorer neonatal outcome in pregnancy and higher rate of the CS with COVID-19 was reported in a systematic review and meta-analysis published by Mascio et al.22

A total of 10 neonates (including one set of twins) were born with median gestational age at birth being 37 weeks. As COVID-19 presents as an acute infection, if developed close to delivery it is unlikely to have an impact on birth weight and mean birth weight in the current study was 2,638 grams. Most of the neonates were asymptomatic and had no signs of SARS-CoV-2 infection confirmed by nasopharyngeal swab testing on day 1 and repeated on day 3. Isolation is the key to prevent infection transmission to neonates and thus majority of neonates are isolated in NICU to closely monitor their condition. Only two neonates (born at 37 and 38 weeks of gestation, respectively) both with low Apgar scores at 1^st minute & 5^th minute experienced respiratory distress and required neonatal ICU (NICU) admission. One neonate from NICU was discharged with a good outcome. Only one neonatal death was recorded throughout the study because of the diffuse exudative lesions & lung whiteout (Figure 2). Six intrauterine fetal deaths were also recorded owing to obstetrics reasons. In terms of maternal mortality; hypertensive disorders of pregnancy, obstructed labor, complications of induced abortion, haemorrhage and sepsis are the leading severe obstetric complications in developing countries. The current study had the maternal mortality rate of 13.6% (3/22) owing to various medical complications with two of them succumbing to multiple organ failure & one woman to sepsis. In lieu of these findings, maternal mortality cannot be ruled out with COVID-19 infection during pregnancy. Table 14 compares the pregnancy outcomes of women with COVID-19 in different studies.15, 16

As with the majority of case series, the design of the current study is also subject to limitations, and findings of this study have to be seen in light of some of the factors. The nature of the study is retrospective, single-institution study with limited time frame and with small sample size. So caution must be employed while extrapolating this data to cohorts of other countries. However, single-centre studies with homogeneous populations and standard care processes, offers the advantage over multicentre studies that differs in the availability of their logistical resources and lack of uniformity in patient management. The another limitation of the study was the lack of statistics pertaining to the final outcome data of the pregnant women who had not delivered by the end of the study period.

Figure 1

26-year-old pregnant woman with gestational age of 38 weeks presented with fever, dry cough and malaise underwent CT scan examination. (a) Coronal chest CT image of mother obtained just before delivery shows bilateral extensive ground-glass opacities (GGOs) with crazy wave pattern in both lungs. (b) Chest X-ray image at birth of the vaginally delivered baby girl (APGAR score of 3 & 4 at 1st min and 5th min respectively.) shows white-out lung, a complication due to maternal respiratory distress during labor

Conclusion

The world is battling with SARS Cov-2 infection for the past 1.5 years only. This relatively new virus with its ever-emerging mutations has baffled the medical fraternity. Even though multiple studies have been published on COVID-19 in pregnancy, there are still many unanswered questions. The clinical course of COVID‐19 during pregnancy appears to be unique to each patient, with a higher incidence of DIC and multiorgan failure leading to maternal mortality. Hence, it isn't easy to generalize a treatment algorithm as coronavirus affects almost all the body organs. A multidisciplinary team approach is vital in individualizing the timing, mode for delivery, and course of management in these patients.

Source of Funding

None.

Conflict of Interest

None.