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Primary infection with Toxoplasma gondii in pregnant women occurs all over the world with frequencies between 0.1-1%. In approximately 40% of the cases, the unborn child is infected. The risk of fetal infection increases during pregnancy, while at the same time the risk of severe disease decreases. As a result, infants with congenital toxoplasmosis are mostly asymptomatic at birth, but long-term studies indicate that up to 85% of them will develop sequelae including chorioretinitis (leading to severe impairment of vision), hearing loss or mental retardation. Early recognition of maternal infection and treatment with spiramycin or pyrimethamine-sulphadiazine will reduce the parasitic colonization of the placenta by more than 60% and prevent infection in the fetus. If fetal infection has already occurred, maternal treatment modifies the fetal disease. Therapy during the first year of life improves the prognosis. It is possible today to identify infected fetuses by prenatal diagnosis based on detection of the parasite in cord blood, amniotic fluid and placental tissue. Specific antibodies and non-specific signs of infection in fetal blood give additional information. Advances in laboratory techniques have made it feasible to consider serological surveillance of pregnant women. The present recommendation is that each country should provide data on the incidence of toxoplasma infection in pregnancy and thereby decide whether it represents a problem and what measures should be adopted. This paper summarizes the present knowledge of the parasite and its implication for the mother and unborn child. The effect and problems of primary and secondary prevention in pregnancy are discussed as well as the efficacy of treatment. The need for future research including long-term follow-up studies are emphasized.
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PMID:Toxoplasmosis in pregnancy. 851 40

In most instances Cytomegalic virus causes a sub-clinical infection, rendering the pregnant mother unaware of being infected. However, primary CMV is the most common infection during pregnancy that may have long-term neuro-developmental sequelae in 10%-20% of children born to these mothers. The clinical findings in these children include intrauterine growth restriction (IUGR), microcephaly, hearing and visual impairment, developmental delay, mental retardation and various neurological deficits. Serological diagnosis of primary CMV in the mother is difficult because IgM antibodies persist for long periods of time and both IgG and IgM antibodies may rise during secondary infection that is generally less dangerous to the human embryo in comparison to primary infection. A more reliable diagnostic procedure is to assess fetal infection by polymerase chain reaction (PCR) and CMV culture performed in amniotic fluid at least 6 weeks following presumed maternal infection and past the 21st week of pregnancy. Due to the difficulties in serological diagnosis and the common lack of typical clinical findings, there seems to be no reason to perform routine serological studies for CMV in pregnant mothers or in women prior to planning pregnancy. The best preventive measure is appropriate immunization against CMV, but no effective immunization seems to exist as of today.
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PMID:[The effects of Cytomegalic virus (CMV) infection during pregnancy on the developing human fetus]. 1211 75

Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection and mental retardation. HCMV infection, while causing asymptomatic infections in most immunocompetent subjects, can be transmitted during pregnancy from the mother with primary (and also recurrent) infection to the fetus. Hence, careful diagnosis of primary infection is required in the pregnant woman based on the most sensitive serologic assays (immunoglobulin M [IgM] and IgG avidity assays) and conventional virologic and molecular procedures for virus detection in blood. Maternal prognostic markers of fetal infection are still under investigation. If primary infection is diagnosed in a timely manner, prenatal diagnosis can be offered, including the search for virus and virus components in fetal blood and amniotic fluid, with fetal prognostic markers of HCMV disease still to be defined. However, the final step for definite diagnosis of congenital HCMV infection is detection of virus in the blood or urine in the first 1 to 2 weeks of life. To date, treatment of congenital infection with antiviral drugs is only palliative both prior to and after birth, whereas the only efficacious preventive measure seems to be the development of a safe and immunogenic vaccine, including recombinant, subunit, DNA, and peptide-based vaccines now under investigation. The following controversial issues are discussed in the light of the most recent advances in the field: the actual perception of the problem; universal serologic screening before pregnancy; the impact of correct counseling on decision making by the couple involved; the role of prenatal diagnosis in ascertaining transmission of virus to the fetus; the impact of preconceptional and periconceptional infections on the prevalence of congenital infection; and the prevalence of congenitally infected babies born to mothers who were immune prior to pregnancy compared to the number born to mothers undergoing primary infection during pregnancy.
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PMID:Diagnosis and management of human cytomegalovirus infection in the mother, fetus, and newborn infant. 1236 75

Congenital toxoplasmosis may develop after maternal primary infection during pregnancy. The infection is usually asymptomatic in pregnant women but poses a risk of severe effects on the fetus. In Italy the incidence is about 6 per thousand. The infection is transmitted to the fetus in approximately 50 percent of such cases. The risk of transmission rises with growing gestational age at the time of primary infection; on the contrary, the seriousness of the effect on the fetuses becomes less active with more advanced pregnancies. Infants with congenital toxoplasmosis are mostly asymptomatic at birth but long-term studies have indicated that up to 85% of them will develop serious sequelae as severe impairment of vision, mental retardation and deafness during the months or the years after the birth. Preventing congenital toxoplasmosis is fundamental. All seronegative women should be encouraged to observe good dietary and general health regulations until delivery. Today the diagnosis in the mother is more reliable because of the improvements in serological techniques. Moreover, it is possible to identify infected fetuses by prenatal procedures such as ultrasonography, amniocentesis and cordocentesis, of which the last two consent to detect the parasite and/or specific antibodies. Recently a polymerase chain reaction (PCR) assay has been developed for the detection of Toxoplasma in the amniotic fluid. Adequate serological screening of pregnant and prenatal diagnosis can be helpful in reducing the incidence of congenital toxoplasmosis; furthermore abortion should be reserved only to cases with severe toxoplasmosis revealed by ultrasonography. Early recognition of pregnant infection and a specific treatment could reduce the parasitic colonization in the placenta by more than 60% and prevent infection in the fetus. If the fetal infection has already occurred, maternal treatment may modify the fetal disease. Spiramycin as immediate treatment of maternal primary infection is essential in preventing Toxoplasma transmission to the fetus. If the fetus results non-infected, spiramycin should be prolonged until delivery. If the fetus is infected, pyrimethamine-sulphadiazine combination should be given in repeated courses alternated with courses of spiramycin. However, there is an urgent need for more active and safer compounds; it would be useful to evaluate in the pregnant woman other potential therapeutic agents as atovaquone and azithromycin.
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PMID:[Toxoplasmosis in pregnancy: recent acquisitions and new prospects]. 1496 66

Seroconversion to cytomegalovirus (CMV) occurs in 1-4% of pregnant women. The majority of these women are seropositive prior to pregnancy. In 0.2-2.5% of the newborn infants, there is evidence of intrauterine infection, most of them are born without any clinical findings. The typical clinical symptoms of congenital CMV (symptomatic congenital CMV) that are found in 10-20% of infected neonates include intrauterine growth restriction (IUGR), microcephaly, hepatosplenomegaly, petechiae, jaundice, chorioretinitis, thrombocytopenia, anemia and/or other atypical findings. Of special problem are the different neurodevelopmental sequelae such as mental retardation, motor impairment, sensorineural hearing loss or visual impairment, which may occur even in infants who are free of symptoms at birth. Most infants born with severe neonatal symptoms of congenital CMV are born to mothers with primary infection in pregnancy. However, since over 60% of the infants infected in utero with CMV are born to mothers with preconceptional immunity who have secondary infection in pregnancy, and more and more studies show severe sequelae in these infants, we have to conclude that congenital CMV may be a significant problem even in children born to mothers with pre-pregnancy immunization. This may justify the use of invasive methods for the detection of possible fetal infection even in cases of secondary CMV infection. This also brings in an additional problem, when considering the need for proper immunization against CMV, as immunization is primarily aimed for women without immunity.
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PMID:Fetal effects of primary and secondary cytomegalovirus infection in pregnancy. 1658 Sep 41

Seroconversion to cytomegalovirus occurs in 1-4% of pregnant women, most of whom are seropositive prior to pregnancy. In 0.2-2.5% of their newborn infants there is evidence of intrauterine infection; most are born without any clinical findings The typical clinical symptoms of symptomatic congenital CMV are observed in 10-20% of infected neonates. They include intrauterine growth restriction, microcephaly, hepatosplenomegaly, petechiae, jaundice, thrombocytopenia, anemia, chorioretinitis, hearing loss and/or other findings. Long-term neurodevelopmental sequelae include mental retardation, motor impairment, sensorineural hearing loss and/or visual impairment. These may occur even in infants who are free of symptoms at birth. Most infants born with severe neonatal symptoms of congenital CMV are born to mothers with primary infection during pregnancy. However, since about half of the infants infected with CMV in utero, including those with severe neonatal symptoms, are born to mothers with preconceptional immunity, we have to conclude that congenital CMV may be a significant problem even in children born to mothers with pre-pregnancy immunization. This may justify the use of invasive methods for the detection of possible fetal infection even in cases of non-primary CMV infection. This should also be a consideration when deciding upon population screening or immunization for CMV.
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PMID:Fetal effects of primary and non-primary cytomegalovirus infection in pregnancy: are we close to prevention? 1759 85

Toxoplasmosis is caused by an intracellular protozoan, Toxoplasma gondii, which has a wide geographical distribution. The main infection routes are ingestion of cysts from raw or badly-cooked meat, ingestion of oocysts from substrates contaminated with the feces of infected felines and congenital transmission by tachyzoites. The congenital form results in a severe systemic disease, because if the mother is infected for the first time during gestation, she can present a temporary parasitemia that will infect the fetus. Many of the clinical symptoms are seen in congenitally-infected children, from a mild disease to serious signs, such as mental retardation. Early diagnosis during the pregnancy is highly desirable, allowing prompt intervention in cases of infection, through treatment of pregnant women, reducing the probability of fetal infection and consequent substantial damage to the fetus. Conventional tests for establishment of a fetal diagnosis of toxoplasmosis include options from serology to PCR. Prevention of human toxoplasmosis is based on care to avoid infection, understanding the disease and serological exams during gestation. Pregnant women should be tested serologically from three months gestation, until one month after childbirth. Inclusion of serology for congenital toxoplasmosis along with the basic Guthrie test for PKU is of fundamental importance for early diagnosis of infection and so that treatment is initiated, in order to avoid possible sequels in the infant.
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PMID:Toxoplasma gondii infection in pregnancy. 1796 77

Human Cytomegalovirus (CMV) is the main cause of mental retardation and sensorineural hearing loss related to congenital infections. Justification of systematic screening for fetal CMV infection is still controversial and is not recommended in most developed countries. This is mainly justified by the paucity of antenatal prognostic factors and the lack of established intrauterine treatment when fetal infection has been diagnosed. Our aim was to review the current state of the knowledge about the CMV congenital infection and to highlight recent advances in the diagnosis as well as in the identification of prognostic factors.
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PMID:[Cytomegalovirus (CMV) congenital infection]. 1833 44

Primary cytomegalovirus (CMV) infection occurs during pregnancy in 1% to 4% of seronegative women and may be transmitted to the fetus in up to 40% of cases. Up to 10% of intrauterine CMV infections result in symptomatic congenital disease at birth. Half of these children and 13% of those born with asymptomatic infection will develop significant clinical sequelae in infancy, especially sensorineural hearing loss. Routine CMV screening during pregnancy is not recommended in Spain owing to the absence of an effective CMV vaccine, the lack of preventive measures or therapy during pregnancy, the difficulty in diagnosing a reactivated infection, and the possibility of symptomatic congenital infections in children of immune women. However, sensitive and specific methods to diagnose primary maternal and fetal infection now exist, and new preventive and therapeutic measures have been developed. Currently, these procedures are not universally available and need to be tested in larger trials. Furthermore, the prevalence of seropositive status in pregnant women, the frequency of congenital infection, and the percentage of infants born with hearing impairment and mental retardation in our country are not known. Therefore, it would not be appropriate to introduce routine screening for CMV in pregnancy at the present time. However, increased efforts should be made to inform women about congenital CMV disease, to develop the diagnosis of fetal infection and methods to determine the extent of involvement in the case of suggestive ultrasound findings, and to treat symptomatic infected newborns with antivirals to reduce hearing impairment.
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PMID:[Congenital cytomegalovirus infection: is serological screening during pregnancy necessary?]. 1940 63

Cytomegalovirus (CMV) is the leading cause of congenital infection in developed countries, affecting 0.3 to 0.6% of all live births in Europe. Primary CMV infection occurs in 1 to 4% of seronegative women during pregnancy and may be transmitted to the fetus in 40% of cases. Up to 10% of intrauterine CMV infections result in symptomatic congenital disease at birth. Half of these children and 13% of those born with asymptomatic infection will develop long-term sequelae, especially neurosensory hearing loss and mental retardation. Accurate diagnosis of primary maternal and fetal infection is now possible using the avidity index of anti-CMV IgG and virological testing to detect the virus in amniotic fluid. Symptomatic congenital infection may be preventable using CMV hyperimmune globulin during pregnancy. The gold standard for diagnosis of congenital CMV infection is the detection of the virus in urine within the first 2 weeks of life by rapid cell culture techniques (shell vial) or nucleic acid amplification of viral DNA (PCR). Retrospective diagnosis can be achieved by detection of viral DNA by PCR in dried blood spots (Guthrie card) collected on filter paper in the first days of life. Currently available drugs for the treatment of congenital CMV include ganciclovir and its oral prodrug valganciclovir. Treatment with intravenous ganciclovir for six weeks may prevent hearing deterioration in children with symptomatic congenital CMV infection and central nervous system involvement. Valganciclovir may be an excellent alternative because of its good bio-availability, providing plasma concentrations similar to those achieved with intravenous ganciclovir.
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PMID:[Consensus document from the Spanish Society of Paediatric Infectious Diseases (SEIP) on the diagnosis and treatment of congenital cytomegalovirus infection]. 1981 69


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