Introduction

One of the fascinating things about viruses is their ability to decipher sophisticated strategies to survive and cause damage in the body when the conditions are favourable, like when the immune system is compromised, causing the virus to exit its latent stage. Pregnancy is one of those factors that can reactivate some of these viruses, which might lead to complications. 

Viral infections in pregnancy can increase the risk of maternal and foetal morbidity and mortality. Additionally, these infections can result in diverse pregnancy outcomes such as miscarriage, premature labour, congenital abnormalities, etc. Some viral infections have increased susceptibility during pregnancy, while for other viruses, a greater severity is recognised in pregnant women.

One of the viruses that can be reactivated in pregnancy is Epstein-Barr Virus. This article elucidates some basic information about this virus and the associated concerns during pregnancy.

What is epstein-barr virus?

Epstein-Barr Virus (EBV) or human herpesvirus 4 is one of the most common viruses that can infect up to 95% of the world’s adult population.¹ It is a double-stranded DNA virus that is the causative factor of various diseases. These diseases include infectious mononucleosis, oral diseases, autoimmune diseases, multiple sclerosis, etc.^{1, 2} However, the primary infection caused by EBV is infectious mononucleosis, especially in children.² EBV infection is also implicated in haematological malignancies and lymphomas.³

The seroprevalence of EBV increases with age and has been seen to be higher in people assigned female at birth (AFAB), especially among non-caucasians with large households, low parental education, and low household income.⁴ EBV can effectively switch between a latent and a lytic life cycle. Consequently, this virus can cause relapsing or reactivating infections, which is more prevalent if you have a weakened immune system.⁵ Severe EBV infection has been associated with immunodeficiency and can also predispose people to other viral infections, including bacterial and fungal infections.⁶

How EBV establishes an infection

The stages in the life cycle of EBV include;

• Primary infection
• Establishment of latency
• Reactivation to produce new virions¹

The primary infection caused by EBV is usually asymptomatic and occurs in children and young adults. The major transmission route to a host occurs orally through an exchange of salivary fluid by kissing.¹ Transmission can also occur via semen during sexual contact, blood transfusion, and organ transplantation.⁷

The glycoproteins in the viral envelope of EBV play a vital role in viral attachment and entry into the host B-lymphocytes and epithelial cells, respectively. Infection of B-lymphocytes induces their replication and differentiation into memory B-lymphocytes.¹ The circulating B-lymphocytes can spread the infection throughout the reticuloendothelial system, resulting in an aggressive immune response that stimulates the lymphocytes to replicate excessively. This results in the enlargement of lymphoid tissue in the lymph nodes, liver, and spleen.¹

After primary infection, EBV establishes a latent infection in the circulating pool of B cells and epithelial cells of the oropharynx.⁸ This minimises viral replication to evade the immune system and resides undetected in your body. Most people stay in the latent phase of EBV infection and don’t display clinical manifestations. However, when your immune system is compromised, EBV can be reactivated and cause different diseases. The newly produced virions (after EBV has been reactivated) then infect the co-localised B cells in the lympho–epithelial structures of Waldeyer’s ring.⁹

EBV initiates a unique dual-life cycle: either latent (nonproductive) infection or lytic (productive) replication. The virus undergoes lytic replication in epithelial cells in vitro and subsequently establishes lifelong latency in the memory B lymphocytes. As a result, EBV can alternate between cell types (i.e. B cells and epithelial cells). During latent infection, only a few genes are usually expressed. These genes are required for maintenance of the viral genome, evasion of surveillance by your immune system, cell growth, and proliferation.¹

Understanding EBV infection in pregnancy

Pregnant women have a higher incidence of EBV reactivation due to cellular immune response to EBV is suppressed in pregnancy.¹⁰ Pregnant mothers can shed the virus in saliva, which can likely affect their infants early in life. This reactivation also induces protective antibody responses to EBV-specific antigens and boosts antibody-dependent cellular cytotoxicity (ADCC).¹⁰  

The maturity and immunocompetence of the immune system at the time of the primary infection with EBV and the number of offspring determine whether infectious mononucleosis will occur and its severity.¹⁰  Women with significant EBV reactivation after serological testing have shorter pregnancies, birth defects, and lower birth weight. However, EBV latency is restored in the mother after childbirth.¹⁰ 

EBV reactivation in pregnancy increases the risk of developing the following conditions; 

• Acute lymphoblastic leukaemia 
• Testicular cancer¹¹
• Congenital abnormalities
• Renal disease
• Liver issues 

Furthermore, pregnancy has a suppressive effect on the EBV antigen-specific T-lymphocyte cytotoxic activity. This suppressive effect is magnified in HTLV-I carriers, which implies that specific infections or chronic diseases in pregnancy can intensify EBV reactivation.¹²

Management and treatment of EBV in pregnancy

The main aim in the management of EBV in pregnancy is to alleviate the symptoms. These include providing adequate supportive care, proper hydration, use of NSAIDs, and acetaminophen for relieving fever and myalgias.¹³ However, the use of ibuprofen should be avoided for pregnant women. The use of corticosteroids can be beneficial in patients with airway infections or autoimmune complications caused by EBV infection.¹³

Adequate rest and hydration are essential, especially during pregnancy, because foetal development depends on a hydrated mother. The main focus is to minimise organ infection or damage and to ensure the mother’s temperature is stable. The developing foetus is more sensitive to temperature changes, which can cause pregnancy complications. High temperature increases the risk of miscarriage during the first trimester of pregnancy, birth defects, and premature delivery.¹³

How to prevent EBV infection in pregnancy

As immune dysregulation is the main trigger for EBV reactivation in pregnant women, efforts to fortify cell-mediated immunity must be considered. This includes reducing chronic stress levels and avoiding the exchange of salivary fluid if you are diagnosed with EBV infection in pregnancy. As EBV is an opportunistic latent virus, reactivated EBV in pregnant women should be monitored.¹⁴ This is because EBV virus capsid antigen (VCA) IgG antibody titers provide an indirect measure of cell-mediated immune function. In other words, decreases in antibody titers are indicative of improved cell-mediated immunity and reduced risk of development of congenital abnormalities after childbirth.¹⁴

Diagnosis of EBV infection

It has already been stated that EBV infection in pregnancy can cause foetal anomalies and increased risk of developing other health issues.¹¹ Thus, to identify primary EBV infection during pregnancy, testing for EBV antibodies in the serum of pregnant women is the most accurate method of diagnosis.¹³

Besides, in pregnant women with symptoms of an illness caused by a virus, one or more EBV antibody tests can be done along with tests for cytomegalovirus (CMV), toxoplasmosis, and other infections. This will help in the differential diagnosis of EBV and rule out other conditions that may have similar symptoms. 

FAQs

Q1: What are the symptoms of EBV infection?

Answer - In adolescents and young adults, symptoms of EBV are fever, sore throat, pharyngitis, hepatomegaly, lymphadenopathy, and splenomegaly. 

Q2: Can I breastfeed my baby if I have EBV?

Answer - Although EBV can be present in breast milk, there is a lack of evidence that supports EBV transmission via breastfeeding. However, other conditions can increase the risk of transmission to infants. These include having malaria at birth. Hence, malaria plays a pivotal role in enhancing the transmission of EBV and can result in EBV infection before 6 months of age of an infant. 

Q3: Are there any other complications associated with EBV?

Answer - EBV is associated with several complications. These include splenic rupture, airway obstruction from tonsillar edema, myocarditis, encephalitis, cholecystitis, pancreatitis, and autoimmune hemolytic anaemia. Early diagnosis and management are therefore recommended to avoid EBV infection progression.

Summary

• Epstein-Barr Virus (EBV) is a widely distributed oncogenic (cancer-causing) virus capable of invading the B lymphocytes and causing different diseases. However, EBV primary infection is infectious mononucleosis
• EBV exhibits 3 major life cycles in a living host: primary infection, latency phase and reactivation under favourable conditions. The virus is transmitted through salivary fluid via kissing, sexual contact or blood transfusion
• EBV reactivation can occur in pregnancy due to a suppressed immune response, stress and other factors. This can increase the risk of transmission to infants and the development of congenital abnormalities
• EBV infection can be managed with mild analgesics, providing adequate supportive care, and proper hydration are some ways to manage in pregnancy
• Differential diagnosis to rule out other conditions should be included while a diagnosis of EBV is made in pregnant women. Appropriate monitoring is required throughout the pregnancy