Many viral and parasitic infections during pregnancy are strongly associated with serious adverse maternal and fetal outcomes. In the United States, the most common infections affecting pregnancy include cytomegalovirus (CMV), microvirus B19, varicella zoster virus (VZV), and Toxoplasma gondii. The main purpose of this guideline is to describe the characteristics of these infections, their transmission routes and effects on the mother and child, and to present guidelines for treatment during pregnancy. Liu Zongyin, Department of Obstetrics, Baoji Maternal and Child Health Hospital
Background.
Generally speaking, perinatal infections have a more serious impact on the fetus if they occur in early pregnancy, because infections in early pregnancy interfere with the differentiation of fetal organs. Infections in middle and late pregnancy can lead to fetal neurological damage or developmental disorders. Although congenital infections can also be completely asymptomatic, intrauterine infections are likely to reveal associated abnormal ultrasound findings, including intrauterine growth restriction, enhanced intestinal echogenicity, intracranial or intrahepatic calcifications, hydrocephalus, microcephaly, isolated ascites, pericardial or pleural effusions, or non-immune edema.
Cytomegalovirus (CMV)
Cytomegalovirus is a double-stranded DNA herpesvirus that is transmitted through contact with infected blood, saliva, urine, or sexual contact. The incubation period of cytomegalovirus is 28-60 days, with an average of 40 days. The infection produces immune antibodies IgM that disappear within 30-60 days. Viraemia can be detected 2-3 weeks after the initial infection. Adults with initial cytomegalovirus infection usually have no clinical symptoms. Only a few patients present with manifestations of mononucleosis syndrome, including leukocytosis, lymphocytosis, abnormal liver function, fever, malaise, muscle pain, and chills (1). After initial infection, cytomegalovirus becomes latent in the host cells and recurrent infection occurs when the latent virus is activated. In only a very few cases, recurrent cytomegalovirus infections are caused by infection with a new virus.
The prevalence of cytomegalovirus infection in pregnant women varies geographically for both primary and recurrent infections, with the incidence of primary infection ranging from 0.7% to 4%, while the incidence of recurrent infection rises to 13.5% (2). vertical transmission of CMV may occur as a result of transplacental infection due to primary or recurrent CMV infection, exposure to contaminated genital tract secretions during delivery, or breastfeeding. Most infants with congenital cytomegalovirus infection are born asymptomatic. Clinical manifestations of congenital CMV infection include jaundice, skin petechiae, thrombocytopenia, hepatosplenomegaly, developmental delay, and nonimmune edema (3, 4). The annual cost of treating complications due to CMV infection in the United States is estimated to be approximately $2 billion (2), and these costs cover the treatment of 50-80% of CMV seropositive pregnant women.
CMV infection is the most common congenital infection, occurring in 0.2%-2.2% of all newborns, and is the leading cause of congenital deafness. Vertical transmission can occur at any stage of pregnancy, and the risk of vertical transmission is greatest when the infection occurs late in pregnancy. However, CMV infection in early maternal pregnancy can lead to more severe fetal sequelae. The risk of vertical transmission to the fetus in pregnant women with initial CMV infection is 30-40% (6), and of fetuses with intrauterine infection due to initial infection, 10% are born with symptoms of CMV infection and develop sequelae (7). Close to 30% of severely infected infants die and 80% of survivors have severe neurological disorders (5, 8). The incidence of severe fetal infection is significantly lower in pregnant women with recurrent infection than in those with initial infection. The incidence of vertical transmission in pregnant women with recurrent CMV infection is 0.15-2% (8, 9), and fetuses infected with maternal reactivated CMV virus are usually born asymptomatic. Congenital deafness is the most typical and severe sequelae due to recurrent infection, and congenital infection due to recurrent infection does not necessarily result in multiple sequelae (9). CMV infection due to exposure to infected cervical secretions or breast milk is not clinically symptomatic and does not have severe neonatal sequelae.
Microvirus B19
Minuscule virus B19 is a single-stranded DNA virus that causes infectious erythema in childhood, also known as fifth disease. In immunocompetent adults, the most common symptoms of B19 infection are a somato reticular rash and peripheral arthropathy, however nearly 33% of infected individuals are asymptomatic (10). Another clinical manifestation is transient aplastic crisis, which is more common in those with underlying hemoglobinopathies. Most infections are mild and most people are able to recover completely with only supportive treatment after a B19 infection.
Most transmission of B19 is through respiratory and hand-to-mouth contact. Infected individuals are infectious from 5-10 days after infection until the appearance of the rash, after which the rash is no longer infectious (11). IgM antibodies persist for 1 to several months, indicating recent infection, and IgG antibodies persist for a long time, indicating previous infection and immunity if combined with IgM negativity. The incidence of serologic positivity for B19 increases with age and is higher than 60% in adolescents and adults (11). The risk of B19 infection in pregnant women is related to the level of exposure to the infected population. The risk of serological positivity in people with infected family members approaches 50% (12-15). The risk of transmission in the nursery or classroom is relatively low, approximately 20-50% (15-17).
Although B19 infection can adversely affect the fetus, the pathogenic risk to the fetus from recent infection in pregnant women is relatively low (18). Placental transmission has been reported in about 33% of cases (19), and fetal infection with B19 is associated with spontaneous abortion, fetal edema, and stillbirth. The incidence of pregnancy loss among pregnant women serologically positive for B19 is 2- 9% (20-22). Some reports suggest that up to 18% of non-immune edema is due to intrauterine microvirus B19 infection (23-24). Fetal edema is usually caused by aplastic anemia, myocarditis and chronic fetal hepatitis. Severe fetal effects of B19 infection occur mostly in pregnant women infected before 20 weeks of gestation (20). Embryonic abortion often occurs 1-11 weeks after maternal infection with the virus. However, if fetal edema does not occur within 8 weeks after maternal infection, edema does not recur (23). Long-term follow-up of surviving fetuses with congenital microvirus B19 infection is usually normal (25, 26).
Varicella zoster virus (VZV)
Varicella zoster virus is a DNA herpesvirus that is highly contagious and is transmitted by respiratory or close contact. The morbidity rate after exposure in susceptible individuals is 60-90%. The incubation period after infection is 10-20 days, with an average of 14 days (27). Patients are infectious from 48 hours prior to the appearance of herpes until the scabs of the blistering epidermis fall off. Primary infection leads to chickenpox with clinical signs of fever, depression, itching of macules and formation of small blisters. After primary infection, VZV is latent in the sensory ganglia and, if activated, can cause a blister-like rash called herpes zoster. Antibodies to VZV are produced in the patient within a few days of infection, and lifelong immunity is acquired from previous VZV infections.
Because of the widespread natural immunity in the population, varicella infection in pregnant women is uncommon (incidence 0.4-0.7/1000 pregnant women) (28). Complicated varicella infection during pregnancy can have unintended adverse effects on the pregnant woman, fetus and newborn. The resulting disease is usually benign and self-limiting in childhood; however, national data on chickenpox deaths indicate that although the incidence of chickenpox in adults aged 20 years and older is less than 5%, this population accounts for 55% of chickenpox-related deaths (29). Serious complications, such as encephalitis and pneumonia, are more common in adults than in children. Varicella pneumonia during pregnancy is a high risk factor for maternal mortality (30, 31).
Varicella during pregnancy may be transmitted through the placenta, leading to congenital or neonatal varicella. The risk of congenital varicella syndrome, which occurs at a low incidence of approximately 2%, is only associated with infection in the first 20 weeks of pregnancy and manifests as skin scar formation, limb hypoplasia, chorioretinitis, and microcephaly (32-34). When varicella occurs in pregnant women between 5 days before and 48 hours after delivery, there is a high mortality rate in neonates infected with VZV because of the relative immaturity of the neonatal immune system and the lack of maternal antibody protection after birth (35, 36).
Toxoplasma gondii
Toxoplasmosis is caused by intracellular parasites of Toxoplasma gondii. Toxoplasma gondii exists in several forms: either as invasive schizonts, or as vesicles or ova with invasive potential. Humans are usually infected by eating undercooked meat from a Toxoplasma-infected animal, by bites from infected insects, and by close contact with a cat infected with Toxoplasma (the only identified host). Toxoplasma infection is usually asymptomatic, although after an incubation period of 5-18 days, some nonspecific symptoms may develop. The most common is asymptomatic cervical lymphadenopathy, which is symptomatic in only 10-20% of adult patients. Other symptoms include fever, malaise, night sweats, muscle pain, and hepatosplenomegaly. Infection with Toxoplasma gondii results in parasitemia, which occurs in pregnant women where Toxoplasma gondii can be implanted in the placenta and subsequently lead to fetal infection. Transmission of Toxoplasma gondii from an infected pregnant woman is now recognized as the most important mode of transmission of congenital Toxoplasma gondii. The chance of transmission depends on the timing of maternal infection, and the later in the gestational cycle the infection occurs, the greater the chance of transmission. The chance of vertical transmission of infection is 10-15% in early pregnancy, up to 25% in mid-trimester, and over 60 in late pregnancy (37, 38). The severity of the infection also depends on the week of gestation when vertical transmission occurs. The earlier the fetus is infected, the more severe the disease. Most infected infants are born without manifestations of infection, but 55-85% develop sequelae, including chorioretinitis (which can cause severe damage to vision), deafness, or mental deficits (39-41). Other clinical manifestations of congenital Toxoplasma infection include rash, hepatosplenomegaly, ascites, fever, ventricular calcification, giant ventricles, and epilepsy (42-44).
IgM antibodies appear early and peak within 1 month after acute Toxoplasma infection. IgG antibodies appear after IgM antibodies, are detectable for several weeks after infection, and provide immunity. High titers of IgG and IgM antibodies may persist for years, and in immunocompetent adults, the clinical course is benign and self-limiting.
Clinical considerations and guidelines
Cytomegalovirus
◆ How is maternal CMV infection diagnosed?
The vast majority of adult CMV infections are asymptomatic, making the diagnosis of initial infection difficult. Adult CMV infection is usually diagnosed by serologic testing, but the virus can also be detected by culture or PCR testing of infected blood, urine, saliva, cervical secretions, or breast milk. A serum sample collected every 3-4 weeks for CMVIgG testing as a parallel control is the primary method for diagnosing initial CMV infection. A positive serum IgG antibody titer from negative to positive or a single significant increase (more than 4-fold, e.g., from 1:4 to 1:16) is diagnostic of infection. a positive CMV-specific IgM antibody is helpful in diagnosing initial infection, but cannot be relied upon exclusively. IgM antibody titers may not be positive during acute infection or may persist only for a few months after the initial infection (45). A small percentage of women with recurrent infections produce IgM antibodies (7). The sensitivity of serum IgM antibodies for diagnosis has been reported to be 50-90% (45).
◆How to diagnose fetal CMV infection?
Congenital CMV infection in the fetus is suspected when a pregnant woman is diagnosed with initial CMV infection or when there are specific findings on fetal ultrasound (46). Positive ultrasound findings include abdominal and hepatic calcifications, calcified edema at the lateral ventricular rim, echogenic bowel, ascites, hepatosplenomegaly, and giant ventricles (46-53). The definitive diagnosis of fetuses with developmental abnormalities, especially those involving the central nervous system, is currently low (46, 54).
CMV infection can be diagnosed prenatally by detecting CMV IgM antibodies in fetal blood (55-57), but this test has a high rate of false positives (58). In addition to this, IgM antibodies cannot be detected in the first half of pregnancy due to the immature fetal immune system and limited fetal serological testing. Tests for fetal thrombocytopenia or abnormal liver function have been proposed as a method to diagnose congenital CMV. However, these tests are not specific for CMV and normal results do not rule out severe infection.
CMV can be detected by culture or PCR testing of the amniotic fluid of infected fetuses. the sensitivity of CMV culture is 50-69% and the sensitivity of PCR testing is 77-100%. The negative and positive predictive values of amniotic fluid culture and PCR testing are comparable (55-57, 59-64). The sensitivity of prenatal diagnosis of CMV infection by amniotic fluid testing is relatively low if done before 21 weeks of gestation (65). The time interval between maternal infection and testing can affect the reliability of the test (62). Although amniotic fluid culture or PCR tests are valid, neither can detect all congenital CMV infections. In addition to this, CMV testing in amniotic fluid does not predict the severity of congenital infections. The combination of the two methods can confirm intrauterine infection with a sensitivity of 80-100 (56). Fetal blood testing is less sensitive than amniotic fluid testing (64), and specific positive ultrasound findings can help improve the diagnosis of congenital CMV infection.
◆How is CMV infection in pregnant women, fetuses, and congenital newborns treated?
Currently, there is no effective treatment for CMV infection in pregnant women or fetuses. Antiviral therapy with drugs such as ganciclovir or phosphonucleic acid is used only for the treatment of CMV retinitis in acquired immunodeficiency disease (AIDS). In vitro trials have shown that ganciclovir passes through the placenta by simple diffusion (66), and the use of this drug for postnatal treatment of congenital CMV infection has been reported in the literature (67-69). Ganciclovir and superimmune gammaglobulin have given hope for the treatment of newborns with congenital CMV infection (70-72). No studies have yet confirmed the effectiveness of these drugs in preventing long-term neurological sequelae.
A live attenuated vaccine applying the Towne125 gene family has been developed that is relatively safe and efficacious (73-76) and relatively inexpensive (77). Acceptance of vaccination has been reluctant due to concerns about reactivation of the vaccine and infection of the host, possible transmission of the virus through cervical secretions or breast milk, and its carcinogenicity (78). However, scientific research in this area is advancing rapidly and it is believed that more new treatment options will be available in the future.
◆How to educate women at high risk for CMV prevention?
Risk factors for CMV infection include a history of abnormal cervical cytology, low socioeconomic status, non-native North American birth, conception before age 15, and coexistence with other sexually transmitted diseases. The most effective step an OB/GYN can take to reduce CMV infection is to educate patients about prevention. This should include careful handling of potentially infectious items, such as diapers; hand washing all supplies for pediatric or immunocompromised adults; and explaining that proper hygiene is very effective in preventing disease transmission (3, 12, 79). In addition, women should be advised to avoid high-risk behaviors such as intravenous drug use and needle sharing. Encourage the use of condoms for contraception.
Should high-risk women be routinely screened for CMV before or during pregnancy?
Routine testing for CMV virus (4, 7, 80, 81) during pregnancy is not currently recommended. Because maternal IgM antibody screening is of very limited use to identify initial infection or reinfection, it is difficult to interpret fetal risk to pregnant women with these results. In addition, maternal immunity does not completely eliminate the possibility of fetal infection.
Although CMV viruses are not highly infectious, certain groups of women are at higher risk of CMV infection. It was confirmed that 11% of seronegative caregivers turned positive within 10 months of employment, and 53% of families with young children had 1 or more family members who tested seropositive within a year (83, 84).2 Cross-sectional studies have shown that an increased number of deliveries is an independent factor in increasing CMV seroprevalence, suggesting the presence of child-mother potential for transmission (85). Therefore, women with children or those working with children can significantly reduce the risk of infection by safe practices, such as the use of latex gloves and strict hand washing after contact with diapers or respiratory secretions.
Minute virus B19
◆Which method is effective in diagnosing microvirus B19 infection in pregnant women?
Maternal serological testing is the most commonly used method to diagnose acute microvirus B19 infection. Enzyme-linked immunosorbent assay (Elisa), radioimmunoassay and protein immunoblotting can detect antibodies to B19 virus (20). the sensitivity of IgM and IgG assays is generally 79% (10, 87). Positive maternal serum IgM antibodies specific for B19 are diagnostic of initial infection, and because of the potential for false positives, experienced laboratories should test for titers. a positive IgG and negative IgM suggests previous exposure or infection with B19, but no adverse perinatal outcome.
Microscopic observation of microviral B19 or nucleated erythrocyte-specific intranuclear inclusion bodies in infected tissue or blood confirms the diagnosis of microvirus infection.
Which method can effectively diagnose fetal microvirus B19 infection?
Diagnosis of fetal microvirus B19 can be achieved by isolating viral particles from aborted infants or placental tissue (89-90). PCR can also be used to detect microvirus B19 in fetal tissues, including autopsied tissue, serum, amniotic fluid, and placenta (91-95). Data from a limited number of small sample studies suggest that PCR may have reached 100% sensitivity for the detection of the microviruses (94-96). There is no reliable serologic method for detecting specific IgM antibodies in the fetus. Because, as in other intrauterine infections, IgM antibodies do not appear in the fetal circulation until after 22 weeks of gestation, limiting the use of this test.
Ultrasound remains the mainstay for the diagnosis of fetal microvirus B19 infection. Severe fetal infections can manifest with atopic edema. Serial ultrasounds are performed on the fetus until 10 weeks after the infection is confirmed in the pregnant woman. If no signs of fetal edema are found, no other tests are necessary.
◆How to manage a pregnant woman, fetus, or congenital neonate with microvirus B19 infection?
After maternal exposure to B19, serologic testing should be performed to determine if immune antibodies to IgG have been developed, and if no IgG antibodies are detected, the test should be repeated in 3-4 weeks and a paired sample should be used to confirm serologic positivity. If the test does not turn positive, the fetus is not at risk of intrauterine infection. If serology is positive, serial ultrasound examinations of the fetus should be performed over the next 10 weeks to assess for fetal edema, placenta enlargement, and growth restriction.
A data set included 618 pregnant women who had been exposed to B19 of the microvirus, only 311 (50.3%) were suspected of having the infection, and of these suspected cases, only 52 were confirmed to be infected with the microvirus. None of these cases was found to have fetal edema (14). However, in those presenting with fetal edema, cord blood aspiration should be performed to detect erythrocyte pressure, white blood cells, and platelet count, viral DNA, and to prepare for blood transfusion therapy (97, 98). Intrauterine blood transfusion therapy should be considered if anemia is present (21, 99).
◆ Should a serologically negative woman with occupational exposure quit her job?
When there is an epidemic outbreak of microvirus B19 infection, there are currently very limited measures to prevent its transmission in schools, homes, or kindergartens due to occupational exposure from ongoing close contact (20). Exposure to infection cannot be eliminated by confirming the diagnosis and isolating the infected population; up to 20% of the infected population is asymptomatic, and the infected population is infectious before symptoms appear. Whether to isolate pregnant women from work settings where the virus is endemic is controversial, and measures to routinely isolate high-risk populations during outbreaks of microvirus B19 infection are not currently recommended (14, 20).
Varicella zoster virus (VZV)
◆ How is VZV infection diagnosed in pregnant women?
The diagnosis usually relies on clinical manifestations and does not require laboratory tests, especially if herpes develops after exposure to the virus. If laboratory tests are needed, VZV antigens can be detected by immunofluorescence techniques in broken skin tissue or blister fluid. Varicella infection can also be confirmed by fluorescent antibody testing for membrane antigens or Elisa testing for VZV antibodies (28).
◆How to diagnose fetal VZV infection?
Two small sample studies estimated the incidence of congenital varicella syndrome following infection in pregnant women to be 1-2% (32, 34), but these studies were subject to error, so the incidence may have been overestimated. Although the incidence of congenital varicella syndrome is small, once infected, the effects on the fetus are so severe that reliable prenatal diagnostic methods are of great interest.
The possibility of VZV infection should be suspected in the presence of abnormal fetal ultrasound findings. Abnormal ultrasound findings in congenital varicella include fetal edema, strong echogenicity of the liver and intestines, heart defects, limb malformations, microcephaly, and intrauterine growth restriction. In one study, congenital varicella infection was found in five fetuses with ultrasound abnormalities, all of whom died within 4 months of birth (100). However, not all fetuses with abnormal ultrasound had a poor outcome (101). Although the sensitivity of ultrasound diagnosis is uncertain, it remains the method of choice for the diagnosis of congenital varicella.
Invasive prenatal diagnosis may provide confirmation of the diagnosis in women infected with VZV in the first half of pregnancy if the laboratory test is negative (102). However, if the virus is present, neither culture nor PCR methods to detect viral DNA in the chorion, amniotic fluid or fetal blood, nor virus-specific antibodies can accurately predict the severity of fetal infection (101, 103).
◆What are effective treatments for congenital VZV infection in pregnant women, fetuses, and newborns?
Oral acyclovir, if given within 24 hours of the appearance of herpes, can reduce the formation and duration of new skin lesions and also help reduce systemic symptoms in children, adolescents, and adults (104-106). Oral acyclovir is safe and can be used in pregnant women if skin breakdown worsens (107). Acyclovir should be administered intravenously to pregnant women with VZV infection and combined pneumonia, which reduces maternal morbidity and mortality due to pneumonia (31, 108).
Treatment with acyclovir in pregnant women does not reduce or block the adverse effects of congenital varicella syndrome on the fetus (109). Infants of mothers with varicella 5 days before or 2 days after delivery are administered varicella herpes immunoglobulin (VZIG) (110), although it does not universally block neonatal varicella. Acyclovir should be applied intravenously to newborns with varicella in the first 2 weeks of life (107, 111).
◆What measures are effective in preventing chickenpox?
Non-pregnant women of childbearing age should be asked if they have ever been infected with chickenpox, and if they have not been infected, vaccination is recommended. Varicella vaccine has been available since March 1995 and has been shown to be used in healthy susceptible individuals aged 12 months and older (112). Conception is possible after 1 month of the 2nd vaccination.
Antibodies are detectable in 70-90% of people without a significant history of varicella infection (112). A part of the population believes that the economic benefit ratio of prenatal VZV screening for all pregnant women with no or uncertain history of varicella infection is not high (113). Yet another part believes that the management of the above-mentioned pregnant women exposed to VZV based on immune testing results is more recommendable than universal administration of varicella herpes immunoglobulin in terms of economic effect ratio (114). Patients who are not immune to VZV should be advised to avoid contact with varicella patients. If exposure has occurred, prophylactic administration of varicella immunoglobulin during the incubation period can block or reduce clinical signs of VZV and reduce the risk of infection (106). Rapid determination of VZV membrane antigen or anti-VZV antibody levels in pregnant women who have been exposed to VZV is a rapid and effective way to decide whether to apply immunoglobulin for passive immunization (115). Although varicella immunoglobulin injection within 72 hours of varicella virus exposure in pregnant women is very effective in reducing the severity of maternal varicella, the sooner the injection should be given, the better (116, 117). and immunoglobulin injections in pregnant women do not reduce or block fetal infection.
Toxoplasma gondii
◆How to diagnose Toxoplasma gondii infection in pregnant women?
Acute infection is confirmed if Toxoplasma gondii is isolated from blood or body fluids; however, serological testing for Toxoplasma-specific antibodies is the main method of diagnosis. There are many antibody kits available, and the Sabin-Feldman stain test is one method for detecting IgG, and all other methods must be compared to it. However, this test can only be done by some reference laboratories. Indirect fluorescent antibodies, indirect erythrocyte agglutination and agglutination tests, and enzyme-linked immunosorbent assays can be used to detect antibodies to Toxoplasma gondii. However, Toxoplasma serological tests have not been well standardized and have a high rate of false positives. IgM antibody titers can persist at high levels for many years in healthy populations (e.g., R1:512) (118). Both IgG and IgM antibodies can be used for the initial evaluation of people suspected of having Toxoplasma gondii infection. If initial test results are inconclusive, retesting pre and post controls with samples taken every 3 weeks will provide the most accurate assessment. In cases of high clinical suspicion, blood samples should be retained for repeat testing, as results vary widely between laboratories. If evidence of initial infection is found, retesting should be done at a recognized reference laboratory.
◆What methods are effective in diagnosing and monitoring Toxoplasma gondii infection in the fetus?
Ultrasonography can detect severe congenital Toxoplasma gondii infection. Suggestive positive findings include: giant ventricles, cranial calcification, microcephaly, ascites, hepatosplenomegaly, and intrauterine growth restriction. Testing fetal blood after 20 weeks of gestation to detect specific IgM is the most sensitive diagnostic method for the diagnosis of congenital Toxoplasma gondii infection (119). Although no single test is very sensitive (43, 120), in combination with fetal blood testing for antibodies or performing mouse inoculation, amniotic fluid PCR testing, or ultrasonography of the giant ventricle, 77-93% of infant infections can be diagnosed prenatally. The successful diagnosis of Toxoplasma gondii intrauterine infection with amniotic fluid PCR testing can be done earlier than checking fetal blood and has a high sensitivity despite the fact that false positives and false negatives do exist (125) (37, 121-124).
◆How is Toxoplasma gondii infection in pregnant women, fetuses, and congenital newborns treated?
Treating pregnant women with acute Toxoplasma infection reduces but does not eliminate the risk of congenital infection in the fetus (42, 43). Pregnant women with a confirmed acute infection need to be treated medically as soon as possible until the results of the fetal test are known. Spiramycin aggregates in the placenta and is able to reduce vertical fetal transmission by 60% (126), but it cannot be used as the only drug to treat a fetus with a confirmed infection. Spiramycin is available from the U.S. Food and Drug Administration (FDA) only after serologic confirmation from a reference laboratory has been obtained. It is recommended for pregnant women at risk of infection if the fetal infection is not clear. If the fetus is definitively infected, add treatment with etanercept, sulfonamides, and folinic acid, as these drugs are more effective than spiramycin alone in eliminating parasites from the placenta and in the fetus (127). With treatment, even fetuses with very early Toxoplasma infection have a successful pregnancy outcome (128).
Pharmacological treatment of infants with symptomatic congenital Toxoplasma gondii infection consists of etanercept and sulfadiazine, alternating monthly with spiramycin, for 1 year (127). Treatment can eliminate or reduce the presence of intracranial calcified foci, thus promoting the recovery of neurological function (129).
◆ Should I be routinely screened for Toxoplasma gondii during pregnancy?
A multicenter study in the United States showed that approximately 38% of pregnant women had previous Toxoplasma gondii infection (130). Pregnant women with previous Toxoplasma infection have been shown to be at no risk of delivering a congenitally infected newborn. Serologic screening as a method of preventing congenital Toxoplasma infection has the greatest value in countries with high seropositivity rates, with routine prenatal screening for Toxoplasma required in France and Australia (39). However, in the United States routine screening during pregnancy is now not recommended unless the woman is already infected with human immunodeficiency virus (HIV). Because IgM antibodies can persist for long periods of time, there may be uncertainty in the results of serologic testing during pregnancy (131). Pregnant women living in special environments, such as cat owners, should be screened for Toxoplasma gondii titers. A study from Belgium showed that the implementation of a counseling and education program for pregnant women, such as advice to avoid undercooked or raw meat, to wear gloves when touching soil, and to avoid owning a cat unless the cat owned was a real domestic cat with a strictly controlled diet, resulted in a 63% reduction in Toxoplasma gondii infection in pregnant women (131).
Summary
The following recommendations are derived from limited and differently viewed scientific data (Level B in evidence-based medicine).
▲ Pregnant women with negative VZV serology who were exposed to varicella should be given varicella immunoglobulin.
▲ Pregnant women with varicella should receive oral acyclovir to eliminate maternal symptoms and intravenous acyclovir if pneumonia develops.
▲Pregnant women with acute microvirus B19 infection during pregnancy should be monitored with continuous ultrasound for at least 10 weeks after infection to rule out fetal edema.
▲Fetal blood should be obtained for fetal edema manifestations and treated with blood transfusion if necessary.
▲ Pregnant women with Toxoplasma gondii infection should be treated with oral spiramycin. In case of definite diagnosis of fetal infection, multiple drugs (etanercept, sulfonamides, folinic acid) should be combined with alternate application of spiramycin.
The following recommendations are from the preliminary consensus and expert opinion (Level C of evidence-based medicine)
▲ Routine serologic screening for CMV and Toxoplasma gondii is not recommended for all pregnant women.
▲ Non-pregnant women of childbearing age who do not have a history of varicella infection should be vaccinated against varicella.
▲ Diagnosis of Toxoplasma gondii infection should be corroborated by a reliable reference laboratory.
▲Pregnant women exposed to Toxoplasma B19 should be screened serologically to determine if they are at risk of switching positive.
▲ Pregnant women should be educated on methods to prevent CMV or Toxoplasma gondii infection during pregnancy.