I. Cytomegalovirus (CMV)
1. General Introduction
CMV is a prevalent double-stranded DNA virus, transmitted by contact with infected blood, urine or saliva, sexual transmission, incubation period 28-60 days, average 40 days, viraemia can be detected 2-3 weeks after primary infection, after primary infection, CMV is still latent in the host cells, re-infection can occur, i.e. secondary infection. In China, IgG-positive pregnant women are >90% and IgM-positive pregnant women are 1-2%. In the United States, the incidence of primary infection in pregnant women who were previously serologically negative for CMV is 0.7%-4%, and the incidence of secondary infection is as high as 13.5%. CMV is the most common congenital infection, occurring in 0.2%-2.2% of newborns. The risk of sequelae is most pronounced with vertical mother-to-child transmission via the placenta; transmission by contact with secretions or breastfeeding is often asymptomatic and does not cause serious sequelae. The risk of fetal infection in primary infection is about 30%-40%, and the risk of fetal infection in early and middle pregnancy is 30%, 34%-38%, and 40%-72%, respectively, with serious sequelae of infection in early pregnancy. At birth, 12%-18% of infected fetuses have signs and symptoms, 25% of these children have sequelae, 30% die, and 65%-80% of survivors have severe neurological disease. The incidence of fetal infection is low in secondary infections, with vertical transmission rates of about 0.15%-2%. Congenital hearing loss is the most serious sequela.
2. Diagnostic methods and criteria for maternal CMV infection
Most adult CMV infections are asymptomatic, making identification of the primary infection difficult. The diagnosis of adult CMV infection is usually determined by serologic testing. CMV-IgG testing, performed on serum specimens collected at 3-4 week intervals, is the basic test for the diagnosis of primary infection. Serologic conversion or a 4-fold or greater increase in titer is evidence of infection. Measurement of IgG antibody affinity, combined with IgM titers improves the identification of primary infection (sensitivity 92%) and is better than serial serologic testing.
3. Diagnostic methods and criteria for fetal CMV infection
Fetal congenital CMV infection should be considered after the determination of maternal primary infection. Since comprehensive screening is not recommended, it is more commonly indicated by ultrasound, but the positive predictive value of a single ultrasound indicator of CMV infection is weak, predicting only 3% of CMV infections. Amniotic fluid CMV culture is 70%-80% sensitive and PCR is 78%-98% sensitive (92%-98% specificity). Fetal blood is less sensitive than amniotic fluid and has additional risks to the fetus that are unnecessary. After 21 weeks of amniotic fluid CMV-DNA testing, although positive culture or PCR is highly predictive of congenital infection, CMV testing in amniotic fluid does not predict congenital CMV infection severity.
4. Management of maternal-fetal CMV infection
There is no treatment for maternal or fetal CMV infection, and antiviral drugs are not recommended in routine clinical workup, only for the treatment of AIDS patients and organ transplant recipients. passive immunization with CMV-specific immunoglobulins to prevent fetal CMV infection is under investigation and is not recommended for use outside of experimental studies. In cases of known maternal CMV infection, referral to a maternal-fetal medicine center or infectious disease specialist is indicated. Usually, continuous ultrasound monitoring, including assessment of fetal anatomy (e.g., ventricles) and growth and development.
5. How to prevent CMV
High-risk groups seronegative pediatricians practicing for 10 months, 11% seroconverted; 53% of families with young children had one or more of their family members seroconverted. Pregnant women should practice personal hygiene and use gloves or hand sanitization. Avoid sharing utensils or kissing children with young children, but this is difficult to achieve. There is no vaccine yet, but research has begun.
6. Whether to screen for CMV before or during pregnancy
Screening for maternal IgM has limitations in identifying primary or secondary infection, and the results make it difficult to counsel on fetal risk, so routine screening for CMV in pregnant women is not recommended.
II. Microvirus B19 (PVB19)
1. General introduction
PVB19 is a single-stranded DNA virus that causes an infectious erythematous rash in children, also known as fifth disease. Transmission is by respiratory secretions and hand-to-mouth contact. Infected individuals are generally infectious for 5-10 days after exposure and before the appearance of the rash, and are no longer infectious after the rash appears. IgM and IgG are produced after infection, with IgM lasting from one to several months for recent infection; IgG antibody duration is uncertain, and if IgG-positive IgM-negative, this indicates previous infection and lifelong immunity. seropositivity for PVB19 increases with age, with 50%-65% of women of childbearing age being positive. The risk of infection correlates with the level of exposure, with the risk of serologic conversion being 50% for exposed infected family members and approximately 20%-50% for childcare workers or teachers. The rate of maternal-fetal transmission following acute PVB19 infection during pregnancy is 17-33%. Fetal infection can occur without adverse outcome in most cases, but is associated with spontaneous abortion, fetal edema, and stillbirth. The rate of fetal loss in serologically confirmed infected pregnant women ranges from 8%-17% before 20 weeks of gestation and 2%-6% after 20 weeks of gestation. An estimated 8-10% (possibly up to 18-27%) of non-immune fetal edema is associated with PVB19. The virus is cytotoxic to erythrocyte precursors, often causing aplastic anemia, and myocarditis or fetal chronic hepatitis can also lead to edema. Before 20 weeks of gestation, PVB19 infection has a serious effect on the fetus: stillbirths tend to occur 1-11 weeks after maternal infection, and if edema does not occur 8 weeks after infection, it will not occur later.
2. Diagnostic methods and criteria for maternal PVB19 infection
As soon as possible after maternal exposure to PVB19, antibody screening should be performed to monitor serologic conversion, IgM (-)
IgG (+): previous infection and immunity, no risk of mother-to-child transmission. IgM (+).
IgG regardless of negative: monitor the fetus for potential infection. IgM (-) IgG (-) in suspected PVB19 infection: recheck within 4 weeks and recheck IgM or IgG positive to monitor the fetus for potential infection.
3. Diagnostic methods and criteria for fetal PVB19 infection
PCR for PVB19 DNA in amniotic fluid is used to diagnose fetal infection. It can quantify the viral load in serum and tissues, but is not widely used. Quantitative PCR is sensitive up to 100%. Detection of fetal PVB19 infection should be considered when fetal edema is detected on ultrasonography.
4. Management of maternal-fetal PVB19 infection
Serologically diagnosed pregnant women with acute PVB19 infection should be monitored for fetal anemia by serial ultrasound to assess ascites, placenta enlargement, cardiomegaly, edema, and fetal growth restriction; MCA-PSV can accurately predict fetal anemia. Ultrasound is performed every 1-2 weeks at 8-12 weeks post-exposure, with no fetal abnormalities on ultrasound and minimal adverse outcomes associated with PVB19 infection. Intrauterine blood transfusion should be considered for severe fetal anemia. Stillbirth can occur in a fetus without hydrops.
5. How to prevent PVB19
There are limited ways to prevent transmission during outbreaks of PVB19 infection in places of prolonged close contact (schools, homes, nurseries), and exposure cannot be reduced by identifying and excluding persons with acute PVB19 virus infection. It is not recommended that pregnant women be removed from their workplace during an epidemic and should go to inform their physician if they are exposed to a suspected PVB19 infected person.
6. Whether to screen before or during pregnancy
Routine screening of pregnant women for PVB19 is not recommended.
Varicella-zoster (VZV)
1. General information
VZV is a highly contagious DNA herpesvirus with a 60%-90% infection rate in susceptible individuals after exposure. The disease is benign and self-limiting in children, with severe disease in adults, such as encephalitis and pneumonia, and approximately 10%-20% of pregnant women infected with varicella develop pneumonia, with an estimated mortality rate of up to 40%. Transmission is by respiratory droplets and close contact. The incubation period is 10-20 days after exposure, with an average of 14 days, and contagion begins 48 hours before rash onset and continues until blisters crust over. The primary infection is called chickenpox, and then the virus is latent in the sensory ganglia and can be reactivated, causing blisters and erythema, called herpes zoster. Antibodies may develop after infection, and later lifelong immunity to primary VZV. Because of the high natural immunity, varicella infection during pregnancy is uncommon, estimated at 0.4‰-0.7‰, even before routine vaccination, and is even lower after application of the vaccine. Approximately 10-20% of pregnant women infected with chickenpox develop pneumonia, with a mortality rate of up to 40%. Varicella can cross the placenta leading to congenital or neonatal varicella. The risk of congenital varicella syndrome is low, about 0.4%-2%, and is characterized by skin scarring, limb hypoplasia, chorioretinitis, and microcephaly. Neonatal VZV infection and mortality rates are high in those with maternal morbidity from 5 days prenatally to 2 days postnatally.
2. Diagnostic methods and criteria for maternal VZV infection
Diagnosis is usually based on the clinical presentation of typical pruritus and blistering rash, without laboratory tests. If laboratory diagnosis is required, uncovered skin breaks or vesicular fluid sampling for varicella DNA by PCR. pregnant women with a history of prior infection or varicella vaccination should be immune to varicella in early pregnancy.
3. Diagnostic methods and criteria for fetal VZV infection
The incidence of fetal varicella secondary to VZV infection is only 1%-2%, but the consequences are severe. Fetal varicella can be suggested by ultrasound after acute maternal varicella infection. Ultrasound manifestations of congenital varicella: edema, strong echogenicity of liver and intestine, cardiac malformation, limb malformation, microcephaly and fetal growth restriction.
4. Management of maternal-fetal VZV infection
If oral acyclovir is administered within 24 hours of the appearance of the rash, the duration and number of new lesion formations can be reduced, and systemic symptoms can be improved. Given that oral acyclovir is safe during pregnancy, it should be considered prior to the onset of the disease in pregnant women with the potential for severe VZV infection. Intravenous acyclovir reduces morbidity and mortality in maternal varicella-associated pneumonia. Acyclovir treatment of pregnant women has not been shown to improve or prevent the fetal effects of congenital varicella syndrome. Varicella zoster immunoglobulin should be given to pregnant women with varicella for 2-5 days after birth to their newborns, although this treatment does not universally prevent neonatal varicella. Newborns with varicella within 2 weeks of birth should be treated with intravenous acyclovir
5. How to prevent VZV
Women of childbearing age should be immunized if they have no history of varicella infection, an unknown immunization history, or are serologically negative. Conception should be delayed for 3 months after the last vaccination. Termination of pregnancy is not required after varicella vaccination in early pregnancy. Pregnant women with no history of varicella infection or immunization record should wait until the herpes of a VZV-infected person has crusted over and is no longer infected before being exposed, and if unintentional exposure should be followed by VZIG as soon as possible, ideally within 96 hours of exposure. Pregnant women with no history of varicella infection or immunization should receive the first dose of varicella vaccine immediately after completion or termination of pregnancy, with a second dose given 4-8 weeks later.
6. Whether to screen for VZV before or during pregnancy
Those with a history of varicella infection are 97%-99% immunized for life. Know the VZV immune status of women of childbearing age before conception and get vaccinated before conception if necessary. Postpartum vaccination is recommended for pregnant women with confirmed varicella non-immune status. Given the high lifelong immunity of VZV, screening is not required and only questions about their immune status are needed.
IV. Toxoplasma gondii (TOX)
1. General Introduction
Toxoplasmosis is caused by intracellular parasitic Toxoplasma gondii and is benign and self-limiting in immunocompetent adults. Toxoplasma gondii exists in two forms: trophozoites, which are invasive, and encysts, pseudocapsules or cysts, which are latent forms. Cats are the only final host of Toxoplasma gondii. Transmission routes: consumption of undercooked infected meat, encapsulation in insect-contaminated food; contact with oocysts in cat feces; contact with insects in contaminated clothing or soil. The incubation period is 5-18 days and is usually asymptomatic. Untreated infected pregnant women have a 20%-50% incidence of congenital toxoplasmosis, with mother-to-child transmission more likely to occur in late gestation. Manifestations of congenital toxoplasmosis include rash, fever, hepatosplenomegaly, ascites, peripheral calcification, ventricular enlargement, and seizures. Most infected children are born without clinical signs of infection, but 90% will develop sequelae.
2. Diagnostic methods and criteria for maternal TOX infection
Serological detection of TOX-specific antibodies is the main method of clinical diagnosis, but false positives and false negatives are high. The test can be used for primary screening of pregnant women with suspected TOX infection with IgM (-).
IgG (+) indicates previous infection and there is no need to worry about maternal-fetal transmission in immunocompetent women. IgM (-) IgG (-) indicates no infection or recent infection that has not yet had sufficient time to turn positive; IgM (+).
IgG (+) indicates recent history of infection or false positive.
3. Diagnostic methods and criteria for fetal TOX infection
Toxoplasma gondii infection should be suspected when ultrasound findings are abnormal including but not limited to ventricular dilatation, intracranial calcification, microcephaly, hepatosplenomegaly, ascites, and fetal growth restriction. When toxoplasmosis is suspected, amniotic fluid PCR is the preferred diagnostic method and amniocentesis should be performed after 18 weeks.
4. Management of maternal-fetal TOX infection
The diagnosis should be confirmed in the reference laboratory when maternal toxoplasmosis infection is suspected. Treatment of pregnant women with acute toxoplasmosis with spiramycin cannot reduce or prevent fetal infection, but can reduce the severity of fetal disease. In case of combined fetal infection, treatment should be switched to a combination of etanercept, sulfadiazine, and folic acid.
5. How to prevent TOX
Enhance health education, learn proper hand washing methods, pet care measures, and dietary advice.
6. Whether to screen for TOX before or during pregnancy
Routine screening for TOX in pregnant women is not recommended, and in the United States, prenatal screening for toxoplasmosis is limited to immunocompetent or HIV-positive women.