Obstetric, Neonatal Outcomes and Histopathological Changes in COVID-positive Pregnancies in a South Indian Population

INTRODUCTION

In 2019, it was officially declared by the World Health Organization of the global pandemic of COVID-19.¹ At the time, there were few cases of pregnant women infected with the highly infectious novel corona virus 2019, and most of them had a mild illness course.^2,3 There is limited evidence about the in utero infectivity of the virus and early positive neonatal testing.^2,3 COVID-19 might be transmitted vertically from mother to fetus and causes clinically significant infection.⁴

Varied symptoms that present in pregnant mothers are dyspnea, myalgia, anorexia, nausea, nonproductive cough, and fever during the fourth day before the pandemic.⁵ Viral pneumonia is an important cause of morbidity and mortality among pregnant women.⁶ Maternal pneumonia is associated with several adverse obstetrical outcomes, including premature rupture of membranes (PROM) and preterm labor (PTL), intrauterine fetal demise (IUFD), intrauterine growth restriction (IUGR), and neonatal death.⁶

Literature review states that neonates infected with COVID-19 are usually asymptomatic.⁷ Detection rates of real-time polymerase chain reaction (RT-PCR) and the interpretation of immunoglobulin-M and immunoglobulin-G antibodies levels in cord and neonatal blood were discussed concerning the immaturity of the fetal and neonatal immune systems.⁷

Complications of preeclampsia and need for cesarean section compared with non-COVID pregnancies are also found to be on the rise.⁸

As the pandemic was catastrophic with difficulties faced in the management of pregnant mothers in India and with the minimal literature regarding the incidence and risk factors, concerning vertical transmission, this study was being conducted to bridge the knowledge gap and evolve treatment strategies to reduce maternal and neonatal morbidity and mortality.

AIMS AND OBJECTIVE(S) OF THE STUDY

The primary objective—to determine the incidence of vertical transmission in COVID-positive pregnancies.

The secondary objectives were as follows:

• To correlate the maternal demographic details.

• Neonatal outcomes to maternal COVID-19 infection in mother.

• Maternal morbidities related to COVID-19 infection and their outcome.

• To correlate maternal lab parameters with COVID-19 infection.

• To correlate the histopathological findings of placenta with COVID-19 infection.

MATERIALS AND METHODS

This study was done in a tertiary care center, in South India. It was a cross-sectional study, which was done during the COVID-19 pandemic. The duration of the study was from August 2020 to January 2021. Universal testing for COVID-19 was started in the 1st wave of the pandemic in June 2020 at St. John’s Medical College and Hospital. All COVID-19-positive pregnant women who got admitted to the delivery unit were included in the study, and those pregnant women who were COVID-19-suspected but tested negative for COVID-19 were excluded from the study.

The study was approved by the Institutional Ethics Committee (IEC no.: 212/2020). The clinical conditions of the patients were studied after taking informed consent. COVID-19 diagnosis was confirmed by the use of qualitative RT-PCR on the maternal nasopharyngeal swab or rapid antigen testing. The study participant’s demographic details, data related to COVID-19 disease, and obstetrical complications, if any, were recorded. BG Prasad’s classification was used based on per capita income to stratify the population’s socioeconomic status.⁹ Patient’s inpatient charts were studied on the treatment received and the mode of delivery. The neonates were tested with nasopharyngeal RT-PCR after 24 hours of birth.

Symptoms and signs of COVID-19 like temperature >100.4°F, respiratory rate, etc. (as per hospital guidelines) and treatment of the same like oxygen and antibiotics were recorded. The disease was classified as asymptomatic, mild, moderate, or severe COVID-19 as per the hospital protocol.

Mild cases were defined as symptomatic patients with the respiratory rate (RR) ≤ 24 cycles per minute (CPM) and SpO2 >94% at room air. Moderate cases were defined as symptomatic patients with pneumonia, RR 24–30 per minute, and SpO2 90–94% at room air. Severe cases were defined as those with pneumonia, RR >30 CPM, and SpO2 less than 90% as per the hospital (St. John’s Medical College) protocol.

RESULTS

A total of 825 pregnant mothers delivered during the study period, out of which 82 pregnant women were diagnosed to be COVID-19-positive. The mean gestational age of the study population was 37.91 ± 2.08 weeks and 52 (63.4%) women belonged to the age group of 20–30 years. In total, 58 (70.7%) of the women were detected to be COVID-19-positive by the RT-PCR test. In total, 45 (54.9%) women were primigravidae. In total, 75 (91.5%) women had mild COVID infection as classified by the institutional protocol. Common presentation to the hospital for admission was safe confinement 32 (39%), followed by pain in the abdomen 20 (24.4%), leaking per vagina 11 (13.4%), presence of COVID-19 symptoms 6 (7.3%), increased BP reading 6 (7.3%), decreased fetal movements 4 (4.9%), and bleeding per vagina 3 (3.7%).

The obstetric complications encountered during the pregnancy associated with COVID-19 infection were preeclampsia 10 (12.2%), gestational diabetes 8 (9.8%), premature rupture of membranes 5 (6.1%), oligohydramnios 4 (4.9%), previous lower segment cesarean section (LSCS) 4 (4.9%), and fetal growth restriction 1 (1.2%). Also, medical complications such as hypothyroidism 11 (13.4%) and anemia 7 (8.5%).

In total, 27 (32.9%) mothers underwent emergency LSCS 27 (32.9%). The most common indication being nonprogression of labor 18 (22%) followed by previous LSCS in labor 10 (12.2%), cephalopelvic disproportion 8 (9.8%), nonreactive NST 6 (7.3%), worsening maternal condition 5 (6.1%), and COVID-positive pregnancy 1 (1.2%), as seen in Table 1. Three COVID-positive mothers had ICU admissions.

Out of 983 mothers, 112 (11.3%) were tested positive for COVID-19 infection. There were 39 (47.6%) boys and 43 (52.4%) girl babies. In total, 20 (24.4%) babies needed NICU admission. The placenta weight at the time of delivery was 500–1000 gm 50 (61%), as seen in Table 2.

During the initial period, 15.3% of the total enrolled neonates were separated from the mother, 68% were roomed in with the mother. In total, 94 (80%) were born at term gestation and 29 (24.7%) were low birth weight. Out of 82 COVID-19-exposed neonates, 4 (4.8%) neonates were COVID-19-positive. All these infected neonates were roomed in with their mother. One out of 4 babies, who was positive for COVID-19, had respiratory distress (RDS). About 89% of the neonates were exclusively breastfed at discharge and at 92% at 3 months of follow-up. About 20 neonates (16.5%) were admitted to the NICU, the main reasons for admission were—transient tachypnea of newborn and problems related to prematurity None of the other babies had any COVID-19 symptoms.

There was a significant increase in the level of D-dimer in multigravida when compared with primigravidae, as seen in Table 3.

DISCUSSION

The total number of pregnant women admitted during the study period was 825 women of which 82 pregnant women were diagnosed to be COVID-19-positive. The mean gestational age of the study population was 37.91 ± 2.08 weeks. In a study based in the United States by Gulersen et al., it was seen that out of 25 patients who delivered during hospitalization with COVID-19 infection, the majority were indicated deliveries and no deliveries were less than 33 weeks of gestation.¹ Most patients of our study presented in the third trimester. Similar results were seen in China, Henan, and France.^2,7,10

In a study based in China, seven patients presented with a fever and cough (in four of nine patients), myalgia (in three), sore throat (in two), and malaise (in two).² In our study, the presence of COVID symptoms was present in only 6 (7.3%) patients. The most common presentation to the hospital for admission was mainly for safe confinement 32 (39%), pain in the abdomen 20 (24.4%), leaking per vagina 11 (13.4%), increased BP reading 6 (7.3%), decreased fetal movements 4 (4.9%), and bleeding per vagina 3 (3.7%).

The most common mode of delivery was by LSCS in our study, which was similarly noticed in various studies across the world during the time in China, Henan, and Birmingham.^2,8,10

In a study-based in Peru, the mode of testing was by RT-PCR of neonatal nasopharyngeal swab as soon as 16 hours after delivery.³ In our institution, the RT-PCR sampling of the neonate was done at 24 hours after birth. In our institution, we performed RT-PCR for eligible babies in view of the low sensitivity of RAT.¹¹ The Peru study concluded that every COVID-19-positive mother presented during the third trimester of pregnancy and had mechanical ventilation and preterm deliveries with RT-PCR-positive neonates were concluded in the study.³ In our study, the majority of the women were detected to be COVID-positive by the RT-PCR test 58 (70.7%) and were primigravidae 45 (54.9%). Most women had mild COVID 75 (91.5%). Additional RT-PCR tests on amniotic fluid, placenta, and cord blood were suggested to ascertain the possibility of intrauterine vertical transmission in a Chinese study.¹²

Another Wuhan-based study noticed two COVID-19 cases with infection during the third trimester of pregnancy and found good outcomes.⁴ This report provided evidence of low risk of intrauterine infection by vertical transmission of the infection, wherein 2 women were studied with COVID, although the products of conception had no evidence of the virus.⁴ A study based in Tanzania stated similar views of the low possibility of vertical transmission of the virus.¹³ In our study, it was also found that the frequencies of mother and neonate being positive for COVID-19 were seen in 2 (2.4%) cases. Mother being COVID-19-negative and neonate being COVID-19-positive was 2 (2.4%). A China and Peru study stated that there was low evidence of vertical transmission of COVID-19 infection.^2,3 In a study conducted by Yale University, it was seen that of 936 neonates from mothers with coronavirus disease-2019, 27 neonates had a positive result for COVID-19 viral RNA test using nasopharyngeal swab.¹⁴ Zamaniyan et al.,⁵ Amouroux A et al.,⁷ Antoun L et al.,⁸ and He Z et al.¹⁵ had contrary findings wherein descriptions and vertical transmission have been demonstrated in their respective study populations.

Effective implementation of protection measures during delivery, including a negative-pressure delivery room, was suggested to prevent the infant from acquiring COVID-19infection in a Hangzhou study.¹⁶ Strict delivery protocols and management of COVID-19-positive deliveries were followed in our institution which helped achieve a good maternal and neonatal outcome in our study. We followed strict hand hygiene, donning, and doffing of personal protective equipment before the conduct of every delivery. Similar protocols were seen by Hu X et al.¹⁷ Measures at the time of admission till discharge were taken to reduce the chance of transmission of infection such as strict monitoring of hand hygiene practices, rooming-in, a distance of two meters after direct breastfeeding, masking, hand hygiene, and cough etiquette.

In yet another Iran-based study, a total of 31 infected pregnant mothers with COVID-19 were reported.⁶ No COVID-19 infection was detected in their neonates or placentas.⁶ Two mothers died from COVID-19-related respiratory complications after delivery.⁶ In our study, there was no case reported of maternal death probably due to the intense monitoring and timed management of the mothers who were reported to be COVID-19-positive.

In our study, neonatal outcomes in babies born of COVID-19-positive mothers showed that the number of girl babies 43 (52.4%) born was higher than the number of boy babies 39 (47.6%).

APGAR 1 minute for 6–7 was 31 (37.8%) and APGAR 5 minutes > 8 was 76 (92.7%).

NICU admissions were seen in 20 neonates out of the 82 deliveries for fetal hypoxia and tachypnea, similar results were seen in a study done in China and Henan.^2,12 It was evident to notice that the reason for NICU admission was not related to COVID infection.

A study on the histopathology of 16 placentas from patients with COVID-19 showed maternal vascular malperfusion (MVM), particularly abnormal or injured maternal vessels, and intervillous thrombi.¹⁹ The study concluded that COVID-19 placentas showed an increased prevalence of decidual arteriopathy and other features of MVM, which was a pattern of placental injury.¹⁸ Another study described 3 out of a series of 19 placentas demonstrated chronic mild inflammation.¹⁹ The study concluded that the placenta is capable of being infected but was rare.¹⁹ The most common findings were infarcts, diffuse hypercapillarization of the villi, extravillous trophoblastic proliferation, and decidual vasculopathy seen in 8 placentas. The other common finding was villitis of unknown etiology (VUE), which was lymphohistiocytic type seen in 6 cases and most of them were low grade and multifocal in distribution. The possibility of low oxygenation combined with a low rate of vertical transmission could be a possible explanation for the findings of our study.

An Italian study concluded that the presence of SARS-CoV-2 RNA on the fetal side of the placenta in 2 cases of mothers who were COVID-19-positive suggested the possibility of vertical transmission of COVID-19.²⁰ The placental examination was available in only a few cases in the study. Among those, we found a higher number of cases showing lesions of uterine hypoxia, which is an indicator of maternal vascular malperfusion. We also found inflammatory lesions like villitis to be higher in placentas from COVID-positive mothers. Similar findings were observed in a study by Menter T et al. and Garg R et al. from Agra, India, where lesions of maternal vascular malperfusion and villitis were higher in placentas,^21,22 but they did not find vertical transmission in their study.^23–27

CONCLUSION

The incidence of vertical transmission in COVID-19-positive pregnancies is 2.4% in a South Indian population, which appears to be low. Lower segment cesarean section seems to benefit both mother and neonate, with a lesser number of babies requiring NICU care. Placental histopathology seems to have a good possible confirmatory laboratory test in COVID-19 pregnancies. Timed testing of the mother and neonate is beneficial in a tertiary care setup and could be the dictum of recommendation in high-resource settings. Total bilirubin and D-dimer may help in the prognostication of the infection concerning multigravidae and primigravidae.

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