Viral infections during pregnancy can lead to three different perinatal outcomes-no effect, spontaneous abortion, and congenital viral syndrome.
Currently, prenatal care lacks definitive criteria for the prenatal treatment of viral infections other than those known to be TORCH infections (including Toxoplasma gondii, other microorganisms, rubella virus, cytomegalovirus, and herpes simplex virus). Although these guidelines all refer to the diagnosis of infection, there is no effective prevention strategy or treatment to prevent adverse pregnancy outcomes.
With the increasing risk of epidemics and the serious impact on maternal and infant safety, it has become particularly important to understand the mechanisms of viral infections during pregnancy and preventive and curative measures. Below, we will focus on the common viral infections.
Herpes simplex virus
HSV-1 and HSV-2 are among the eight DNA viruses known to infect humans. HSV-1 and HSV-2 enter the body through epithelial mucosal cells and broken skin, and then migrate and reside in neural tissue. HSV-2 is often found in the lumbosacral nerve. Both can cause genital damage and dermoid.
NHANES states that the incidence of HSV-2 is significantly higher in women than in men. Factors affecting a woman’s risk of infection prior to pregnancy include race, poverty, cocaine abuse, early onset of sexual activity, number of sexual partners, sexual behavior, and having bacterial vaginitis.
The rate of HSV seropositivity in pregnant women was 72%. This suggests that any exposure to HSV-1 or HSV-2 can lead to viral infection and antibody production. During pregnancy, HSV infection is associated with spontaneous abortion, intrauterine growth restriction, preterm delivery, and congenital and neonatal herpesvirus infections. However, clinical treatment focuses on reducing mother-to-child transmission and thus reducing the risk of neonatal herpesvirus infection.
The risk of perinatal transmission is lowest when HSV-1 and HSV-2 antibodies are present early in pregnancy. In contrast, the risk of neonatal infection is 30%-50% for primary or initial genital HSV infection in late pregnancy and <1% in early pregnancy. If primary HSV infection occurs late in pregnancy, antibodies will not inhibit replication and transmission in time for delivery. Trans-placental or episodic transmembrane transmission between mother and child is uncommon; 80-90% of perinatal transmission occurs at delivery. However, recurrent herpes may also occur in neonates with HSV infection.
Neonatal herpes infections are divided into three categories.
Localized skin, eye and mouth (SEM); central nervous system (CNS) with or without SEM; and diffuse disease (untreated, with mortality exceeding 80%). Infected neonates exhibit significant mental retardation, blindness, seizures, and learning disabilities.
The use of antiviral suppressive therapy in the last month of pregnancy reduces the likelihood of asymptomatic viral infection, recurrent clinical HSV virus, and recurrent disease leading to cesarean delivery. If foci or prodromal symptoms develop before delivery, cesarean delivery is recommended to reduce the risk of fetal exposure to the virus, even if ART is used.
Invasive treatments such as manual rupture of membranes, fetal scalp electrodes, and surgical vaginal delivery should be avoided during delivery in asymptomatic HSV-infected women. Minimize fetal exposure to vaginal secretions that may contain the virus. In the case of premature rupture of membranes at term (PPROM), the risk of preterm delivery must be weighed against the risk of HSV infection. This generally depends on gestational age and clinical presentation. There is no consensus on the optimal time of delivery for preterm premature rupture of membranes in pregnant women with a history of HSV.
Varicella-zoster virus
Varicella is an acute primary disease caused by varicella-zoster virus and is a common, highly contagious, self-limiting disease most often seen in children. It is spread by respiratory secretions or close contact, with maculopapular, blistering rashes on the skin all over the body, starting on the face and trunk and then spreading to the extremities. The incubation period of the virus is 15 days and is contagious from two days before the appearance of the rash until all lesions have crusted over and disappeared. After the first episode of varicella-zoster, the virus resides in the posterior spinal root ganglion. Recurrence can cause herpes zoster and is commonly seen in adults.
Primary varicella infection during pregnancy results in significantly higher maternal-fetal morbidity and mortality. In children, the onset is often self-limiting and mild, but if varicella pneumonia occurs during pregnancy, the course is often fulminant. About 10-20% of pregnant women with varicella develop pneumonia, with a mortality rate of up to 40%.
Fetal morbidity and mortality are associated with the development of congenital varicella syndrome. This syndrome is characterized by limb hypoplasia, microcephaly, hydrocephalus, cataracts, intrauterine growth restriction, and mental deficits. The risk of congenital varicella syndrome is 0.4-2% when the mother is infected with varicella before 20 weeks of gestation. This syndrome is thought to occur as a result of reactivation of varicella virus in utero and fetal resistance to the primary infection.
Herpes zoster during pregnancy is less common, with an incidence of approximately 0.1%. The risk of congenital varicella syndrome is negligible because antibodies in the maternal blood prevent the virus from infecting the fetus through the placenta. Acute infection of the mother with the virus before 5 days of delivery or within 2 days after delivery results in a 10-20% incidence of infection in the newborn. This is due to the absence of antibodies to the virus in the mother’s blood at the time the virus is disseminated through the placenta. The infant begins to show symptoms 5-10 days after delivery. The clinical picture varies, from cutaneous lesions to systemic disease, with a mortality rate of about 30%.
Since there is no treatment available to reduce viral transmission, the primary goal of treatment for pregnant women is to reduce maternal morbidity.
Cytomegalovirus
Cytomegalovirus (CMV) is a widespread virus with a variety of clinical manifestations. The prevalence of CMV infection in women of childbearing age is 60% in developed countries and 90% in developing countries. Seropositive results are the most important factor in the fight against congenital CMV infection. The remaining 40% of women in developed countries are vulnerable to infection; if infection occurs during pregnancy, it can have deleterious effects on pregnancy.
Person-to-person transmission occurs through contact with closed eye secretions, urine, saliva, semen, cervical and vaginal secretions, breast milk, tissue or blood of an infected person. Primary maternal infection accounts for approximately 1-4% of the susceptible population, with a recurrence rate of approximately 10% in seropositive women. Most maternal CMV infections are unrecognizable before delivery, but mild fever and nonspecific clinical symptoms such as fatigue, myalgia, rhinitis, pharyngitis, and headache may occur. In addition, it appears that pregnancy does not affect the clinical severity of the infection.
Vertical transmission commonly follows primary maternal infection, often through mechanisms such as transplacental transmission following viral infection, trans-secretory transmission during delivery through the utero-vagina, postpartum transmission through breastfeeding and maternal genital tract transmission (rare).
According to the effect of maternal infection on the fetus, CMV is the most common congenital viral infection with a birth prevalence of about 0.5%. CMV mainly affects the ventricles, the organ of Corti and the eighth cerebral nerve, which explains why CMV infection causes congenital deafness. In addition, human neuronal cells can be infected by CMV in vitro, which would explain why the central nervous system is affected by the virus during fetal development.
The rate of fetal infection seems to increase with gestational weeks. However, the severity of the disease seems to be the opposite of the gestational week. Most mothers with primary infection and almost all mothers with non-primary infection deliver newborns that are initially asymptomatic. 10-15% of initially asymptomatic newborns show signs of impaired neurodevelopment by age three. Approximately 5-20% of newborns born to mothers with primary CMV infection are symptomatic at birth. The mortality rate for these newborns is approximately 5%. 5-15% of asymptomatic newborns will have future sequelae.
Prenatal diagnosis of CMV fetuses requires amniocentesis, which is performed at 6 weeks of presumed infection and after 21 weeks of gestation. Ultrasound findings often indicate a poor prognosis, and a normal ultrasound does not guarantee a normal outcome. Quantitative DNA measurements of CMV in amniotic fluid and the efficacy of prenatal treatment have not been proven. Given this factor and the prevalence of the virus in nature, general screening of pregnant women is not currently recommended.
Rubella virus
Rubella viruses are RNA viruses that are transmitted by respiratory secretions and are most commonly seen in children. In adults, rubella is a self-limiting disease characterized by a rash. The rash is initially seen on the face and neck and rapidly spreads to the trunk and extremities. The incubation period is 12-23 days. The infection period is seven days before and seven days after the onset of the rash. 25-50% of patients are asymptomatic. Maternal rubella infection in early pregnancy results in a 50% fetal infection rate, which decreases to 1% after 12 weeks of gestation. The diagnosis of primary maternal infection should be made by serological tests. The diagnosis of fetal infection includes fetal serum IgM testing or amniotic fluid virus culture.
The risk of CRS depends on gestational age. Therefore, counseling regarding fetal risk and treatment should be individualized. Two mechanisms have been proposed for rubella cytopathology – virus-induced inhibition of cell division and direct cytopathic effects.
Rubella vaccine became available in 1960, and the implementation of general screening and preconception vaccination led to a significant reduction in the risk of congenital rubella infection.
Human immunodeficiency virus
According to the Centers for Disease Control and Prevention (CDC), approximately 50,000 people are infected with HIV each year in the U.S. Eighty percent of these infections are transmitted sexually, 20% through contaminated needles, and the remainder through blood transmission and mother-to-child transmission.
The majority of people infected with HIV eventually develop AIDS and eventually die from opportunistic infections or malignancies. Without treatment, 90% of people living with HIV develop AIDS after 5-10 years. treatment with ARVs extends life expectancy, with an average survival time of more than 15 years even after developing AIDS.
The most common clinical manifestations of acute retroviral syndrome are fever, lymphadenopathy, sore throat, rash, myalgia/arthralgia, and headache. Diagnosis is confirmed by HIV immunoassay (ELISE or Western blot) and HIV viral RNA testing. Without treatment, CD4 T-cell levels decline and opportunistic infections may lead to death. However, as mentioned above, treatment with antiretroviral drugs results in significantly longer life expectancy.
Reducing mother-to-child transmission of HIV is considered to be the most effective initiative. Pregnancy does not affect the course of the disease, and HIV infection during pregnancy includes the risk of vertical transmission. the exact mechanism of mother-to-child transmission of HIV is not known. Transmission may occur intrauterine, during delivery, or while breastfeeding. The greatest risk of transmission comes from maternal disease progression, which may be due to a high maternal HIV viral load. Without treatment, the risk of vertical transmission is as high as 25%. The rate of mother-to-child transmission has been reduced to 1% due to the promotion of prenatal HIV testing, counseling, maternal use of anti-retroviral drugs, post-exposure prophylaxis for newborns, use of cesarean section at delivery, and non-use of breastfeeding.
Hormonal status in the body, environmental regulation of the female reproductive system mucosa, and morphological changes in the female reproductive tract are associated with susceptibility to HIV during pregnancy.
Hepatitis B virus
Hepatitis B virus (HBV) is the most common form of chronic hepatitis. Chronic carriers can transmit the disease for many years before developing symptoms. Infection often occurs in early childhood, often without clinical manifestations, and becomes a chronic carrier. Chronic HBV infection leads to an increased risk of chronic liver insufficiency, cirrhosis, and hepatocellular liver cancer.
The population most likely to be affected is newborns, especially in areas with high disease prevalence and lack of diagnosis for infected females, and infants are vulnerable to becoming chronic carriers. On the other hand, in areas where prenatal screening and adequate neonatal prophylaxis are available, the main cause of transmission in young populations is exposure to contaminated blood products and body fluids or sexual contact transmission.
Acute HBV infection during pregnancy is usually less symptomatic and is not associated with teratogenicity or mortality. Treatment is primarily supportive therapy and monitoring of biochemical liver function tests and prothrombin time. Antiviral therapy is not required unless the patient has acute liver failure or persistent severe hepatitis. Patients who have not progressed to advanced liver disease tolerate chronic hepatitis B infection well, but require liver function tests during all trimesters and postpartum because of occasional hepatitis episodes.
Reducing the risk of perinatal transmission is of paramount importance. General maternal screening screens women who are positive for hepatitis B surface antigen. Biochemical testing of liver function and viral load can guide treatment regimens. Infants of mothers with hepatitis B should receive active and passive immunization with hepatitis B vaccination within 12 hours of birth.
Influenza virus
Common symptoms of influenza include cough, fever, rhinitis, myalgia, headache, chills, and sore throat. Symptoms such as nausea and vomiting and ear infections are less common. Common signs include fever, tachycardia, facial flushing, runny nose and trans-lymphadenopathy.
Influenza viruses that infect humans are divided into three major groups (A, B and C). Types A and B are the major causes of human illness and are both closely associated with seasonal epidemics; type A can cause pandemics. On the basis of nucleoprotein antigenicity, influenza A viruses are further divided into different subtypes based on hemagglutinin (H) and neuraminidase (N). h1n1 is a specific subtype of influenza A virus. Micro-mutations result in a constant antigenic drift that makes the antigenicity of the virus completely different from that of the previous one, so the influenza vaccine must be renewed annually.
Pregnancy is a high risk factor for illness and death from pandemic and seasonal influenza. During seasonal influenza, pregnant women are at a much higher risk of complications from influenza. Therefore, influenza vaccination is recommended for pregnant women during seasonal influenza. Although it is extremely rare for the virus to affect the fetus through the placenta, the inflammatory response produced by the mother may indirectly affect the fetus.
Many cases leading to adverse pregnancy outcomes have occurred in previous influenza pandemics. the 1918 influenza pandemic was associated with a very high incidence of spontaneous abortion and preterm delivery, especially in pregnant women with pneumonia. the 1957 Asian influenza pandemic was associated with an increase in central nervous system defects and several other adverse pregnancy outcomes (e.g., birth defects, spontaneous abortion, stillbirth, and preterm delivery).
Maternal viral infection was strongly associated with the development of leukemia, schizophrenia and Parkinson’s disease during the same period. Although influenza viruses do not directly affect the fetus, fever, a concomitant symptom of influenza, may have adverse effects. High fever can lead to adverse pregnancy outcomes, especially fetal neural tube defects. Therefore, reducing the duration of fever with fever-reducing medications and folic acid supplementation may reduce the risk.
The CDC recommends that all pregnant women of any gestation should be vaccinated against influenza during the flu season. In addition, pregnant women who develop flu symptoms should be screened and treated immediately.
Viruses are not scary; what is scary is that humans know nothing about them. If we figure out the pathogenesis of the virus and solve the problem at the source, then all the difficulties will be solved. This article lists several common viruses and describes the possible potential pathogenesis and preventive measures, hoping to provide new ideas for future treatment and prevention.