COVID-19 in third trimester of pregnancy

ABSTRACT

The COVID-19 pandemic disease, which affects the respiratory system and produces flu-like symptoms, is caused by the SARS-CoV-2 virus. It is transmitted by close contact, oronasal secretions, or droplets. In general, pregnant individuals are at increased risk than nonpregnant individuals for developing serious SARS-CoV-2 virus-related illnesses, particularly during the third trimester. Despite the lack of research on COVID-19-infected pregnant mothers, this review article has discussed the clinical and laboratory characteristics and impact of COVID-19 on delivery, management, and vaccination of pregnant individuals with COVID-19 infection.

INTRODUCTION

The original COVID-19 outbreak in December 2019 in the city of Wuhan, China, has evolved into an unprecedented catastrophe in public health and has become pandemic.[1]

Common cold, Middle East respiratory syndrome (MERS), and severe acute respiratory syndrome (SARS) are different illnesses brought on by the coronavirus family. Pregnant women generally have a higher chance of developing a severe illness from COVID-19 than nonpregnant women due to compromised immunity.[2]

According to the Centers for Disease Control and Prevention (CDC), people with COVID-19 during pregnancy are at higher risk for complications. Several studies demonstrated that influenza, SARS, and MERS pose a substantial risk of morbidity and mortality for expectant women compared to nonpregnant individuals.[3] A coronavirus called SARS-CoV spreads through personal contact, aerosol droplets, and contaminated environment. In 2012, MERS was discovered for the first time in Saudi Arabia.[4] Similar to SARS-CoV, abdominal pain, anorexia, nausea, vomiting, and diarrhea may also be the symptoms present in individuals with MERS-CoV infection.[5]

The current SARS-CoV-2 is a coronavirus, a nonsegmented enclosed positive-sense RNA virus.[6] Aerosolized droplets, direct contact, and respiratory secretions are the common modes of transmission for COVID-19 through the respiratory system.[7]

Recent data showed that increased hospitalization, intensive care (ICU) admission, and intubation were mostly required for almost all pregnant women infected with COVID-19. There is no published evidence indicating that COVID-19 infection during organogenesis could raise the risk of fetal loss or teratogenicity.[8] A case report showed that intrauterine vertical transmission was feasible, especially during the third trimester.[9,10] Cases of newborn infections brought on by horizontal spread have been documented.

Despite having few studies on pregnant women infected with COVID-19, this review article aims to discuss the clinical characteristics, investigations, laboratory, imaging findings, and management of pregnant women with COVID-19 infection. The impact of COVID-19 on delivery, effect on pregnancy outcomes, and vaccination during pregnancy is also covered in this article.

COVID-19 IN THE THIRD TRIMESTER OF PREGNANCY

As the COVID-19 pandemic disease continues, viral variants have become the latest concern globally.

The COVID-19 delta variant spread quickly globally and caused more hospitalizations, severe pregnancy problems, and stillbirths.[11] Omicron, another COVID-19 variant of concern, was discovered for the first time in South Africa and Botswana in November 2021 and considered a highly contagious virus.[12] It is a highly transmissible variant which attacks the upper respiratory tract and is harder to detect in polymerase chain reaction (PCR) tests. Another subvariant, Deltacron, first began to emerge in January 2022 and is made up of both delta and omicron strains.

Pregnant individuals are at higher risk for viral respiratory infections because of certain changes such as increased oxygen requirement, increased heart rate lower lung capacity, immunosuppression, and a greater risk of blood clots.

Variables causing seriously ill during or shortly after pregnancy includes: being over 35, and preexisting medical conditions such as diabetes, chronic hypertension, asthma, gestational diabetes, smoking, and preeclampsia. Residing or working in an area where there are more COVID-19 instances and where fewer people have received COVID-19 vaccinations.

Clinical characteristics, investigations, and imaging findings

In pregnant women, fever, exhaustion, myalgia, a sore tongue, nasal congestion, a dry cough, and breathlessness are the most typical manifestations clinically. Few pregnant women may experience chest discomfort, hemoptysis, coughing up expectorant, nausea, vomiting, and abdominal pain. Some patients, although, initially showed no symptoms of fever.[1]

The most typical pneumonia-onset symptoms were fever and cough.[13] Immunocompromised or comorbid patients may require ventilation for hypoxia. According to the clinical signs, the WHO categorizes the disease’s severity.[14] Pregnant individuals with COVID-19 were 76% more prone to suffer from preeclampsia/eclampsia.[15] Pregnant COVID-19 patients exhibited comparable clinical traits to COVID-19-infected nonpregnant patients.[16,17,18]

Nasopharyngeal swabs are the routinely used specimens for PCR testing. If a prior PCR test was negative but there is strong evidence of infection, a lower respiratory tract sample is retested.

Hematological values, particularly severity markers such as ferritin, D-dimer, procalcitonin, and troponin-I, which typically rise by two to three times in the third trimester, are evaluated using the blood sample for the COVID-19 profile. HIV, hepatitis B virus serology, and QuantiFERON tests may be recommended.[10]

Lymphocytopenia has been regarded as the most common abnormal result found in a study by Liu et al.[13] which is contrary to other findings.[16] Increased concentrations of aminotransferase and hypertensive C-reactive protein were observed.[17]

Lung ultrasound can be used alternative to X-ray imaging. Basal electrocardiogram and chest tomography can be used but individualized. Thoracic computed tomography (CT) is highly recommended for clinical diagnosis.[17] Ground-glass opacity has been observed to be the most frequent early finding in chest CT images whereas mixed or complete consolidations were observed compared to nonpregnant group.[13] Antenatal ultrasonography to monitor fetal growth should not be performed until actually necessary and should be delayed for 14 days after recovery from an acute sickness.[16]

Management of COVID-19 affected pregnant individuals

To facilitate access to expert management, COVID testing of symptomatic pregnant women should be prioritized. Regular prenatal appointments should be delayed until 7 days after the onset of symptoms unless they get worse. Asymptomatic or mild-to-moderate illness necessitates isolation precautions and follow-up, depending on the severity. Nonsteroidal anti-inflammatory drugs, including paracetamol, are safe and favored for treating symptoms.[19]

Patients with severe or urgent illnesses need additional oxygen, a high-flow nasal cannula, admittance to an ICU, or mechanical ventilation.[20] Hypoxemic respiratory failure requires the use of high-flow nasal oxygen and noninvasive ventilation. Dexamethasone administration can be used to address severe or critical sickness according to National Institutes of Health.[21] Pregnant women with COVID-19 are three times more commonly to have severe infection that requires antibiotic therapy and five times more commonly to get hospitalized to the critical care unit.[15]

Although remdesivir and chloroquine are two antiviral medications that have demonstrated encouraging inhibitory effects on SARS-CoV-2 multiplication in cell culture, chloroquine has reportedly showed negative effects on fetal development.[22,23] In comparison to chloroquine, hydroxychloroquine is a superior potential treatment drug due to its safety profile and remdesivir for hospitalized individuals with severe COVID-19.[23,24]

The safest medication regimen consists of nebulizing interferon (5 million IU in 2 mL of sterile water) twice daily combined with oral capsules of antiproteases lopinavir/ritonavir (200 mg/50 mg each capsule).[25] It is doubtful whether the medications molnupiravir, convalescent plasma, and ivermectin are appropriate for pregnant women.[26] To relieve pressure on the inferior vena cava, pregnant with sepsis need to be changed in the lateral decubitus position.[27] Prophylactic low-molecular-weight heparin should be given while in the hospital and for 2 weeks postpartum (independent of D-dimer levels).[10]

Pregnant individuals with COVID-19 are managed on a case-by-case basis and may require early diagnosis, investigations, preventive measures, routine fetal monitoring, and the right postnatal interventions.[28] Sufficient rest, diet, and electrolyte balance are required.[19] Since the COVID-19 infection can spread till 14 days after the onset of clinical symptoms, the symptoms are same for everybody who contracts the infection during postpartum discharge (or 1 month after the starting of symptoms or after showing negative PCR test).[10]

Whether or not they or their children have COVID-19, pregnant women and mothers should be counseled about care, nursing, and basic psychological support. The decision regarding pregnancy termination and delivery on emergency basis is challenging and depends on many factors, such as maternal health, gestational age, viability, and well-being of fetus.[14] It is highly recommended for pregnant women to keep check on their fetal movement counts daily.[29]

EFFECT ON PREGNANCY OUTCOMES

Infected pregnant women with concomitant conditions such as diabetes, hypertension, obesity, chronic lung disease, advanced age, or a combination of increased interleukin-6 and D-dimer levels may experience COVID-19 infection’s severe effects compared to the general population.[30]

No evidence has been reported on transmission from mother to child when there is infection in the third trimester except few patients with premature rupture of membranes, fetal distress, and preterm birth. Following a cesarean section delivery, new born’s cord blood and throat swabs were tested negatively, although amniotic fluid from six mothers tested positive.[17]

Chen et al. demonstrated that the babies were safe after the cesarean delivery with epidural or general anesthesia. Intraoperative hypotension was noticed in some individuals who underwent epidural anesthesia.[18] The previous studies reported that the risk of preterm birth was 59% more and among the babies born to COVID-19-infected mothers, 13% tested positive, especially with cesarean delivery.[31]

Fetal and neonatal problems, as well as vertical transmission, were more common in the first and second trimesters than later.[32] The infant in a case report showed no signs of SARS-CoV-2, which indicates that the virus could not induce perinatal problems or vertical transmission in the third trimester, particularly after 34 weeks of pregnancy.[33]

The diagnosis of COVID-19 was higher in women during their third trimester. Complications are more than doubled in pregnant women catching COVID, especially when they are not vaccinated and pregnancy can also increase the risk of complications in newborn babies.

The risk of death is more for pregnant individuals having COVID-19 than nonpregnant individuals.[15]

According to the CDC’s Surveillance for Emerging Threats to Mothers and Babies Network, there were 13,269 positive cases during the first trimester, 20,916 positive cases during the second trimester, and a maximum of 35,147 positive cases were reported during the third trimester, which suggests that susceptibility for COVID-19 infection is high in the third trimester.[34]

Maternal mortality, severe maternal morbidities, and poor infant outcomes are all increased by SARS-CoV-2 infection at any point during pregnancy, according to a review of 12 trials involving 13,136 pregnant women from 12 countries.[35]

VACCINATION AND PREGNANCY

The importance of immunization in pregnant women is a vital aspect of prenatal care, which benefits maternal and fetal health.

Despite having limited information regarding the safety of COVID-19 vaccines during pregnancy, the WHO declared that the advantages of vaccination would outweigh the harm. Vaccinating pregnant and breastfeeding women are safe and effective and it may help immunize both mothers and their babies, who receive antibodies through the placenta. The side effects from the vaccination are mild and similar for both pregnant and nonpregnant women.

The risk of getting infectious diseases is highest for newborn babies. Getting immunized during pregnancy can protect both mother and baby from infections till the baby gets their first vaccination. More than half of the pregnant women have remained unvaccinated due to the misinformation spread about the COVID-19 vaccine, such as miscarriage and infertility. It is highly recommended for pregnant and breastfeeding women to get vaccinated.

CONCLUSIONS AND FUTURE PERSPECTIVES

COVID-19 infection might have the worst impact on pregnant women than normal people due to immunocompromised conditions, especially true in the third trimester of pregnancy. There are few studies conducted on pregnant individuals having COVID-19 infection. This article has discussed different variants of COVID-19, risk factors in the pregnancy period, clinical characteristics, investigations, laboratory characteristics, imaging findings, and management of pregnant individuals having COVID-19 infection. The impact of COVID-19 on the delivery or birth of the fetus and the effect on pregnancy outcomes are also covered in this article. Vaccination during pregnancy can benefit individuals and society by preventing the spread of infectious diseases. However, further studies are required to revise and update the methods for COVID-19 prevention and treatment in pregnant women.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.