Anne Naessens

Treatment of toxoplasmosis during pregnancy: A multicenter study of impact on fetal transmission and children’s sequelae at age 1 year ☆ ☆☆ ★

OBJECTIVE Toxoplasmosis during pregnancy can cause fetal infection, with unpredictable sequelae in later life. We measured the effects of prenatal antibiotic therapy on the fetomaternal transmission of Toxoplasma gondii and on the appearance of sequelae in the congenitally infected child at age 1 year. STUDY DESIGN In a multicenter study we investigated consecutive women with Toxoplasma seroconversion during pregnancy. Data were obtained from 144 women recruited in 5 different Toxoplasma reference centers. Through multivariate analysis we assessed the association between transmission and appearance of sequelae as a function of the following parameters: estimated gestational age at infection, administration of antibiotic therapy, duration of antibiotic therapy, and time lapse between infection and the start of antibiotic therapy. RESULTS Sixty-four of the 144 women (44%) gave birth to a congenitally infected infant. Multivariate analysis showed that transmission was predicted neither by whether antibiotics had been administered nor by the time lapse between infection and the start of antibiotic therapy, but only by the gestational age at which maternal infection occurred (P <.0001). Sequelae were found in 19 children (13%), 9 of whom (6%) had severe sequelae. Administration of antibiotics was predictive of the absence of sequelae (P =.026, odds ratio 0.30, 95% confidence interval 0.104-0.863), in particular the absence of severe sequelae (P =.007, odds ratio 0.14, 95% confidence interval 0.036-0.584). The sooner antibiotics were given after the infection, the less frequently sequelae were seen (P =. 021). CONCLUSION Prenatal antibiotic therapy after toxoplasmosis during pregnancy had no impact on the fetomaternal transmission rate but reduced the rate of sequelae among the infected infants. The early start of treatment resulted in a significant reduction in the number of severely affected infants.

A 10-Year Prospective Study of Sensorineural Hearing Loss in Children with Congenital Cytomegalovirus Infection

OBJECTIVE To determine the incidence, characteristics, and evolution of sensorineural hearing loss (SNHL) in infants with a congenital cytomegalovirus infection (cCMV). STUDY DESIGN In a prospective 10-year study, 14 021 unselected live-born infants were screened for cCMV by virus isolation in urine. Congenitally infected newborns were evaluated for SNHL during the first 5 years of life. RESULTS A total of 74 of the 14 021 infants (0.53%) were congenitally infected; of these, 4 (5.4%) were symptomatic at birth. Hearing testing could be performed in 60 of the infants. SNHL was found in 21% of the asymptomatic and in 33% of symptomatic congenitally infected infants. Late-onset hearing loss was detected in 5%, progression in 11%, fluctuation in 16%, and improved hearing threshold in 18% of the infants with cCMV. SNHL was observed in 15% of infected infants born after a maternal primary infection, in 7% born after a maternal recurrent infection, and in 40% after a maternal infection of indeterminate timing. CONCLUSIONS In our study population, 0.53% of the infants had cCMV infection, 22% of whom developed SNHL. Long-term follow up and repeated audiologic testing is needed, because progression, fluctuation, improvement, and late-onset hearing loss are important features of cCMV infection. The search for a neonatal screening program to detect all cCMV is worthwhile.

Prenatal diagnosis of congenital toxoplasmosis: A multicenter evaluation of different diagnostic parameters☆☆☆★

OBJECTIVE Our purpose was to evaluate different methods of diagnosing congenital toxoplasmosis prenatally by amniocentesis and cordocentesis. STUDY DESIGN In a retrospective multicenter study, we investigated consecutive women who had seroconversion for Toxoplasma gondii during pregnancy and who underwent either amniocentesis or cordocentesis or both to obtain a prenatal diagnosis of fetal toxoplasmosis. Data were obtained from 122 patients recruited in 6 different European Toxoplasma reference centers. Infants born to these mothers were followed up until 1 year of age to confirm or exclude congenital toxoplasmosis. Sensitivity, specificity, positive predictive value, and negative predictive value were measured for the following parameters: (1) detection of the parasite in amniotic fluid by mouse inoculation, (2) detection of the parasite in amniotic fluid by in vitro cell culture, (3) detection of Toxoplasma deoxyribonucleic acid in amniotic fluid by a polymerase chain reaction assay, (4) detection of the parasite in fetal blood by mouse inoculation, (5) detection of specific immunoglobulin M antibodies in fetal blood, and (6) detection of specific immunoglobulin A antibodies in fetal blood. RESULTS The polymerase chain reaction test performed on amniotic fluid had the highest level of sensitivity (81%) and also a high level of specificity (96%). The combination of the polymerase chain reaction test and mouse inoculation of amniotic fluid increased sensitivity to 91%. The sensitivity of immunoglobulins M and A in fetal blood was 47% and 38%, respectively. In congenitally infected fetuses a negative correlation was observed between positive serologic parameters and gestational age at the time of maternal infection and at prenatal diagnosis. CONCLUSION Congenital toxoplasmosis is best predicted by prenatal examination with the combination of T gondii polymerase chain reaction and mouse inoculation of amniotic fluid. The role of cordocentesis in the diagnosis of congenital toxoplasmosis is limited.

Evaluation of Different Cytomegalovirus (CMV) DNA PCR Protocols for Analysis of Dried Blood Spots from Consecutive Cases of Neonates with Congenital CMV Infections

ABSTRACT Two protocols for the extraction of cytomegalovirus (CMV) DNA and two methods for the amplification of CMV DNA in dried blood spots were evaluated for the retrospective diagnosis of congenital CMV infection. During the period from 1996 to 2006, a urine screening program detected 76 congenitally infected neonates. Stored Guthrie cards with blood from 55 cases and 12 controls were tested. Two spots of dried blood were cut from each card and evaluated in two centers. CMV DNA was extracted from a whole single spot. Center 1 used phenol-chloroform extraction and ethanol precipitation followed by a conventional PCR. Center 2 used the NucliSens easyMAG automated DNA/RNA extraction platform (bioMérieux) followed by a real-time PCR. For evaluation of the extraction method, DNA extracted from each blood spot was evaluated by the amplification method used by the collaborating center. The sensitivities were 66% for center 1 and 73% for center 2. None of the controls were positive. A sensitivity as high as 82% could be obtained by combining the most sensitive extraction method (the phenol-chloroform procedure) with the most sensitive PCR method (real-time PCR). The detection rate was not influenced by the duration of storage of the spots. The sensitivity was higher with blood from congenitally infected cases due to a primary maternal CMV infection, regardless of the protocol used. However, the difference reached significance only for the least-sensitive protocol (P = 0.036).

Diagnosis of congenital toxoplasmosis in the neonatal period: A multicenter evaluation.

OBJECTIVE To evaluate different laboratory tests used to diagnose congenital toxoplasmosis in the neonatal period. STUDY DESIGN A retrospective multicenter study of 294 pregnant women who experienced seroconversion for Toxoplasma gondii and subsequently delivered live-born infants. Fetal infection was assessed via specific IgM and IgA antibodies (cord and neonatal blood) and detection of T gondii in placenta and cord blood by mouse inoculation. RESULTS Ninety-three (32%) of the 294 infants were congenitally infected. The sensitivity of IgA in cord blood and in neonatal blood was 64% and 66%; the sensitivity of IgM was 41% and 42%, respectively. Mouse inoculation of the placenta and cord blood had sensitivities of 45% and 16%. Positive results of the serologic tests in congenitally infected children correlated significantly with the gestational age at the time of maternal infection but was not significantly influenced by the administration of specific antiparasitic treatment during pregnancy. CONCLUSION Specific T gondii IgA antibody is a more sensitive test than IgM for detecting congenital toxoplasmosis in the neonatal period. The overall specificity is better for serologic tests performed on neonatal blood than for those on cord blood. Neonatal screening with IgM or IgA antibodies will not detect the majority of children with congenital toxoplasmosis when the maternal infection occurred before the 20th week of pregnancy.

Prevention of toxoplasmosis during pregnancy – an epidemiologic survey over 22 consecutive years

Abstract Background: Prevention of congenital toxoplasmosis is most often based on the results of a serological screening program in pregnant women followed by prenatal and postnatal treatment of women and their newborns when infection is already established during pregnancy or on cord blood (secondary prevention). Little effort has been made to study primary prevention of toxoplasmosis during pregnancy. Objective: To assess the possibilities of two different programs aimed at preventing the acquisition of toxoplasmosis during pregnancy. Methods: During the first study period (1979–1982) the natural incidence of toxoplasmosis in pregnancy was studied in 2986 pregnant women. In the second study period (1983–1990) the incidence of toxoplasmosis was studied in 8300 women. During this period, seronegative women received a written list of recommendations on how to avoid a toxoplasma infection during pregnancy. In the third study period (1991–2001) the incidence of toxoplasmosis was studied in 16541 women. During this period, the prevention campaign consisted of a leaflet explaining a) toxoplasmosis as a disease and b) what measures should be taken to avoid toxoplasmosis during pregnancy. The third part of the campaign involved a reiteration of these recommendations during antenatal classes held around mid-gestation. The impact of the two prevention programs was studied by measuring the seroconversion rate in seronegative women. Results: Twenty of 1403 seronegative women in the first period (1.43%), 19 of 3605 women in the second period (0.53%) and 8 of 8492 in the third period (0.09%) seroconverted during pregnancy. The first prevention campaign reduced the seroconversion rate by 63% (p<0.05 OR 2.729 95% CI 1.452–5.084). The second prevention program resulted in a reduction rate of 92% compared to the seroconversion rate in the first period (p<0.0001 OR 15.34 95% CI 6.741–34.89). Conclusion: Promotion of simple measures is very effective in the prevention of toxoplasmosis during pregnancy. Primary prevention should not only be based on education about preventive measures given by physicians, but these guidelines should be reiterated during antenatal classes and leaflets distributed containing written recommendations on the nature of the disease and its avoidance.

Neonatal screening for congenital cytomegalovirus infections.

Abstract We evaluated a screening program for the detection of congenital cytomegalovirus in 3075 unselected pregnant women. From each live-born child urine for CMV culture was collected within 7 days after birth. Each fetus expelled after a spontaneous second trimester abortion and each stillborn infant were also evaluated for a possible congenital CMV infection. For each congenital infection stored maternal sera were analysed to determine whether maternal infection was primary or recurrent. Fifteen out of the 3075 pregnancies studied resulted in a congenitally infected infant (0.49 %). Nine maternal CMV infections were primary infections; five were recurrent infections, and in one case the type of infection could not be determined. Three congenital infections resulted in severe sequelae, leading to the termination of pregnancy in two instances and to neonatal death in one case. One of these severe fetal infections was due to a recurrent maternal infection. Follow-up of the other 12 neonates demonstrated hearing disorders in two children. One was born after a primary maternal infection and one after a recurrent maternal infection. We conclude that congenital CMV infections occurs in 0.49% of all pregnancies in the population studied. Twenty percent of the congenitally infected infants present severe sequelae at birth or during pregnancy, and an additional 17% have audiological deficits at 1 year of age. Severe sequelae may occur after both primary and recurrent maternal CMV infection.

Prevention of congenital toxoplasmosis.

Abstract In utero infection with Toxoplasma gondii may result in congenital defects such as hydrocephalus, chorioretinitis and mental retardation; these defects may be present at birth or may develop later in life. Prevention of this disease can be achieved in different ways. The most effective measure is to prevent the acquisition of the disease during pregnancy by avoiding risk factors for Toxoplasma gondii infection. Health education may decrease the incidence of toxoplasmosis during pregnancy by 60%. A second preventive measure is based on serologic screening during pregnancy to identify infected women. Treatment during pregnancy results in a significant reduction in the incidence of sequelae including severe handicaps. A third possible intervention is treating infected neonates. Antibiotic treatment of infected children has a beneficial effect on the development of sequelae and the sooner therapy is started after birth, the better the outcome. This overview presents the potential benefits and harms of these different options available for the prevention of congenital toxoplasmosis.

Recovery of microorganisms in semen and relationship to semen evaluation

Semen samples from 120 consecutive unselected men attending our fertility clinic were studied to determine the bacterial isolation rate of semen and its influence on semen quality. Each sample was cultured aerobically, anaerobically, and for Ureaplasma urealyticum and Mycoplasma hominis. The following were analyzed for each semen specimen: motility, morphologic features, and number of sperm cells and viscosity of the ejaculate. Four of the 120 samples had negative results; 101 cultures yielded one or more aerobic organisms (the majority with less than 20,000 microorganisms/ml); 26 yielded anaerobic organisms; and 40 yielded U. urealyticum. No single aerobic or anaerobic organism could be related to abnormal semen samples. Only the presence of U. urealyticum correlated significantly with abnormal semen samples (P less than 0.005). The most affected parameters were the number of spermatozoa (P less than 0.005) and motility (P less than 0.05). We conclude that routine aerobic and anaerobic bacterial cultures of semen are not useful in the clinical evaluation of male infertility. The usefulness of routine screenings for U. urealyticum must be investigated further.

Epidemiology and Pathogenesis of Ureaplasma Urealyticum in Spontaneous Abortion and Early Preterm Labor

The role of U. urealyticum in spontaneous and recurrent spontaneous abortion was studied in 633 women. Cervical colonization with U. urealyticum was found in 42.6% of 310 normal pregnant women, in 41.6% of 84 patients who underwent induced abortion, in 41.5% of 41 normal fertile patients, in 53.3% of 122 patients with spontaneous abortion and in 64.5% of 76 patients with recurrent spontaneous abortion. The cervical isolation rate was significantly higher in patients with spontaneous abortion (p<0.05) and recurrent spontaneous abortion (p<0.005) than in normal pregnant women. Endometrial colonization was more frequent in patients with recurrent spontaneous abortion (27.6%) than in normal fertile women (9.7%) (p<0.05). Moreover, in 6 patients with intact membranes and uncontrollable preterm labor resulting in fetal loss (all between the 20th and 28th week of gestation) U. urealyticum was isolated in 5 of them from the cervix, in 4 patients from the placenta and in 2 out of 4 from the amniotic fluid. Histological examination of the placenta showed signs of chorioamnionitis in 5 patients. From this study we conclude that although U. urealyticum is a common inhabitant of the lower genital tract, it may play a role in the etiology of spontaneous abortion and uncontrollable preterm labor.