Differences in attentional functioning between preterm and full-term children underline the importance of new neuropsychological detection techniques.

AIM: The aim of this study was to investigate specific attentional components in preterm born children who had not yet started school. METHODS: Between January and December 2011, we assessed 52 preterm and 52 full-term children aged between five years five months and six years two months, of comparable age and gender, at the Medical University of Vienna. Different attentional components were evaluated through selected subtests of the Test of Attentional Performance and the German version of the Wechsler Intelligence Scale for Children. Each child's behaviour was also evaluated using parental ratings and descriptive item-based evaluation during neuropsychological assessment. RESULTS: Children born preterm showed poor attentional performance in sustained attention, focused attention and distractibility, as well as reductions in processing speed in divided attention and flexibility tasks. Children born preterm also showed decreased volitional attention compared with automatic attention. No problems were detected in alertness or inhibition. In addition, a higher rate of aborted tests, decreased motivation and poorer parental ratings were detected among the preterm population compared with full-term born children. CONCLUSION: Our results highlighted differences in attentional functioning between preterm and full-term children, indicating the importance of new neuropsychological techniques for the detection of specific attentional disorders.

Amniocentesis for the detection of congenital toxoplasmosis: results from the nationwide Austrian prenatal screening program.

Prenatal diagnosis of congenital toxoplasmosis (CT) influences therapeutical management in pregnant women and their offspring. In Austria, a nationwide serological healthcare program to identify potential maternal toxoplasma infections during pregnancy exists. We assessed the clinical use of amniocentesis for toxoplasma-specific polymerase chain reaction (PCR) on amniotic fluid to detect CT. Data on serology, amniocentesis, PCR, complications, treatment, and paediatric clinical outcome were collected retrospectively among the birth cohort 1992-2008. There were 1386 women with amniocentesis, but only in 707 cases (51%) was acute maternal infection confirmed serologically. A high proportion (49%) of amniocenteses with negative PCR results in women with chronic infection or seronegativity were performed without clinical justification for the women or their foetuses. The positive and negative predictive values of PCR were 94.4% and 99.3%, respectively. Thirty-nine foetuses with CT, including four deaths, were reported. The five PCR-negative but infected infants were identified by the serological and clinical follow-up program. Thirty percent of amniocenteses were performed in the third trimester, and gestational age or treatment did not influence PCR sensitivity. Amniocentesis is indicated in women with acute maternal infection, and facilitated targeted therapies in pregnant women and their offspring. In women with late toxoplasma infection, negative amniotic fluid PCR made treatment of infants unnecessary. Serological and clinical follow-up of infants is important to confirm the infection status of the infant. Recommendations, based on our 17-year experience, to improve the current diagnostic strategies and to reduce unnecessary amniocentesis, are given.

Prenatal magnetic resonance imaging as a useful adjunctive to ultrasound-enhanced diagnosis in case of a giant foetal tumour of the neck.

Large cervical masses in the prenatal period are rare and can cause life threatening situations after birth. All available diagnostic techniques should therefore be used to determine the best mode of delivery in the case of such malformation. A large cervical mass was detected by ultrasound in a 41-year-old women, gravida 4, para 3, at 29 + 5 weeks of gestation. US imaging was most consistent with the diagnosis of a large cervical teratoma, but it was not possible to sufficiently evaluate the cervical anatomy of the oropharynx and trachea. An MRI scan demonstrated a distorted oropharynx and a trachea displaced to the right and posteriorly, but not detectable from the middle of the neck up to the larynx. Based on these facts, an EXIT procedure was planned and performed at 30 + 5 weeks of gestation. Foetal MRI provided valuable anatomical information for all specialists deciding on the indication and the pre-therapeutic planning of the EXIT procedure.

Knowledge-based interpretation of toxoplasmosis serology test results including fuzzy temporal concepts--the ToxoNet system.

Transplacental transmission of Toxoplasma gondii from an infected, pregnant woman to the unborn that occurs with a probability of about 60 percent [1] results in fetal damage to a degree depending on the gestational age. The computer system ToxoNet processes the results of serological antibody tests having been performed during pregnancy by means of a knowledge base containing medical knowledge on the interpretation of Toxoplasmosis serology tests. By applying this knowledge ToxoNet generates interpretive reports consisting of a diagnostic interpretation and recommendations for therapy and further testing. For that purpose it matches the results of all serological investigations of maternal blood with the content of the knowledge base returning complete textual interpretations for all given findings. The interpretation algorithm derives the stage of maternal infection from these that is used to infer the degree of fetal threat. To consider varying immune responses of particular patients, certain time intervals have to be kept between two subsequent tests in order to guarantee a correct interpretation of the test results. These time intervals are modelled as fuzzy sets, since they allow the formal description of the temporal uncertainties. ToxoNet comprises the knowledge base, an interpretation system, and a program for the creation and modification of the knowledge base. It is available from the World Wide Web by starting a standard browser like the Internet Explorer or the Netscape Navigator. Thus ToxoNet supports the physician in Toxoplasmosis diagnostics and in addition allows to adopt the way of making decisions to the characteristics of the particular laboratory by modifying the underlying knowledge base.

Multicenter evaluation of strategies for serodiagnosis of primary infection with Toxoplasma gondii.

The diagnostic performance of single-serum assays for toxoplasma-specific immunoglobulin (Ig)M. IgA. IgG, and IgE antibodies and of different combinations of such antibody assays in 20 European reference centers was assessed. A panel of 276 sera, of which 73 came from patients who seroconverted within 3 months (acute infection), 49 from patients who had seroconverted 3-12 months earlier (convalescence), and 154 from subjects who had two IgG-positive samples obtained 12 months apart (past infection), was tested with 20 toxoplasma-antibody assays and 195 combinations. In general, every assay with high diagnostic sensitivity showed low diagnostic specificity, i.e. no assay performed alone could reliably distinguish acute from past infection. Furthermore, no single assay (or combination) could separate convalescence from the other stages of toxoplasma infection. However, excellent diagnostic performances were reached by sequential use of highly sensitive IgM assays and methods examining IgG avidity or stage specificity. IgA or IgM assays were less suitable for confirmation of toxoplasma-IgM positivity. This study documents the strength of test combinations in assessing the stage of toxoplasma infection.

Ecological comparison of the risks of mother-to-child transmission and clinical manifestations of congenital toxoplasmosis according to prenatal treatment protocol.

We compared the relative risks of mother-to-child transmission of Toxoplasma gondii and clinical manifestations due to congenital toxoplasmosis associated with intensive prenatal treatment in Lyon and Austria, short term treatment in 51% of Dutch women, and no treatment in Danish women. For each cohort, relative risks were standardized for gestation at seroconversion. In total, 856 mother-child pairs were studied: 549 in Lyon, 133 in Austria, 123 in Denmark and 51 in The Netherlands. The relative risk for mother-to-child transmission compared to Lyon was 1.24 (95% CI: 0.88, 1.59) in Austria; 0.59 (0.41, 0.81) in Denmark; and 0.65 (0.37, 1.01) in The Netherlands. Relative risks for clinical manifestations compared with Lyon (adjusted for follow-up to age 3 years) were: Austria 0.19 (0.04, 0.51); Denmark 0.60 (0.13, 1.08); and The Netherlands 1.46 (0.51, 2.72). There was no clear evidence that the risk of transmission or of clinical manifestations was lowest in centres with the most intensive prenatal treatment.

Effect of intravenous iron supplementation on erythropoiesis in erythropoietin-treated premature infants.

OBJECTIVE: To test the efficacy and safety of combining intravenous iron in amounts approximating the in utero iron accretion rate and the postnatal iron loss with erythropoietin (EPO) in very low birth weight (VLBW) infants. METHODS: A prospective, controlled, randomized, unmasked trial lasting 21 days was performed in 29 clinically stable VLBW infants <31 weeks' gestation and <1300 g birth weight not treated with red blood cell transfusions during the study period. Mean (+/- standard error of the mean) age at study entry was 23 +/- 2.9 days. After a 3-day run-in baseline period in which all participants received oral supplements of 9 mg/kg/day of iron polymaltose complex (IPC), participants were randomized to receive 18 days of treatment with: 1) oral IPC alone (oral iron group); 2) 300 U of recombinant human EPO (r-HuEPO) kg/day and daily oral IPC (EPO + oral iron group); 3) 2 mg/kg/day of intravenous iron sucrose, r-HuEPO, and oral iron (intravenous iron + EPO group). To assess efficacy of the 3 treatments, serial blood samples were analyzed for hemoglobin (Hb), hematocrit (Hct), reticulocyte count, red blood cell indices and plasma levels of transferrin, transferrin receptor (TfR), ferritin, and iron. Oxidant injury was assessed before and after treatment by plasma and urine levels of malondialdehyde (MDA) and o-tyrosine. RESULTS: At the end of treatment, Hb, Hct, reticulocyte count, and plasma TfR were markedly higher in both of the EPO-treated groups, compared with the oral iron group. At study exit a trend toward increasing Hb and Hct levels and significantly higher reticulocyte counts were observed in the intravenous iron + EPO group, compared with the EPO + oral iron group. During treatment, plasma ferritin levels increased significantly in the intravenous iron + EPO group and decreased significantly in the other 2 groups. By the end of treatment, ferritin levels were significantly higher in the intravenous iron + EPO group compared with the other 2 groups. Although plasma and urine MDA or o-tyrosine did not differ among the 3 groups, plasma MDA was significantly greater in the subgroup of intravenous iron + EPO participants sampled at the end of the 2-hour parenteral iron infusion, compared with values observed immediately before and after parenteral iron-dosing. CONCLUSIONS: In stable VLBW infants receiving EPO treatment, parenteral supplementation with 2 mg/kg/day of iron sucrose results in a small, but significant, augmentation of erythropoiesis beyond that of r-HuEPO and enteral iron alone. However, to reduce the potential adverse effects of parenteral iron/kg/day on increasing plasma ferritin levels and on causing oxidative injury, we suggest that the parenteral iron dose used should be reduced and/or the time of infusion extended to maintain a serum iron concentration below the total iron-binding capacity.

Association of fetal and maternal carboxyhemoglobin levels in normal and Rh-alloimmune pregnancies.

OBJECTIVE: To compare paired antepartum fetal/maternal COHb ratios in whole blood from control and alloimmunized pregnancies and to examine the relationships between fetal and maternal COHb. METHODS: COHb levels were measured in paired fetal and maternal blood samples obtained at cordocentesis in 47 control and 16 Rh-alloimmunized pregnancies. COHb was determined by gas chromatography. Results were analyzed by t-test, regression and analysis of covariance. RESULTS: Although fetal/maternal COHb ratios for control and alloimmunized pregnancies were not statistically significantly different, i.e. 1. 11+/-0.04 and 1.26+/-0.09, respectively (P=0.09), fetal COHb levels were higher in Rh-alloimmunized fetuses (P=0.0002). Fetal COHb levels were also higher than paired maternal levels among the alloimmunized group (P=0.011), but not among the control group (1. 04+/-0.04, P=ns). In univariate regression analysis, fetal and maternal COHb levels were significantly correlated with one another in both control (r=0.52, P=0.0002) and alloimmunized pregnancy groups (r=0.52, P=0.05). Comparison of the slopes of the fetal versus maternal COHb plots for the two groups showed a significant difference (P=0.02), with the alloimmunized group having the steeper slope. CONCLUSION: Differences in the antepartum fetal-maternal COHb relationships in control and alloimmunized groups likely reflect increased endogenous CO production among alloimmunized fetuses as a result of pathologic hemolysis.

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.

The past and present role of the Sabin-Feldman dye test in the serodiagnosis of toxoplasmosis.

The dye test for the detection of Toxoplasma-specific antibodies was first described by Sabin and Feldman 50 years ago. The test is highly specific and sensitive and considerable information is available on the development and persistence of dye test antibodies after primary Toxoplasma infection. However, the test uses live Toxoplasma gondii and is now only employed in a few laboratories. It is still the reference method for the serodiagnosis of toxoplasmosis, and a multicentre study comparing dye test results between different laboratories was much needed. We report in this article the results of a multicentre evaluation of the test involving nineteen laboratories in eight countries. The study revealed overall satisfactory standardization between the laboratories, but there were differences in the test protocols, the use of reference/standard preparations and the interpretation of results. There is still no agreement on the level of dye test values which reflect infection with the parasite, and conversion from titres to international units (IUs) did not improve standardization. However, the results indicated that a value of > 4 IU or a titre of 1:16 met the definition of positivity of most participants. We recommend that the dye test be retained as a reference method and that interlaboratory standardization be improved by the use of a common protocol and the expression of results in titres.

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.

Antepartum fetal and maternal carboxyhemoglobin and cotinine levels among cigarette smokers.

The objective of this study was to examine the association of carboxyhemoglobin (COHb) and plasma cotinine levels among pregnant women who smoke cigarettes and their fetuses. Fifteen pregnant women who smoked and their fetuses undergoing cordocentesis had blood samples analysed simultaneously for COHb and cotinine. Linear regression was used to test for associations among study variables. Significant maternal-fetal associations were observed both with COHb (r = 0.72, p = 0.003) and with cotinine (r = 0.96, p = 0.003). Maternal cotinine levels were correlated with maternal and fetal COHb levels (r = 0.96, p = 0.003; r = 0.99, p = 0.0003, respectively). Fetal cotinine levels were correlated with COHb in maternal and in fetal blood (r = 0.81, p = 0.0003; r = 0.88, p<0.0001, respectively). The strong direct associations of maternal and fetal levels of COHb and cotinine indicate that maternal COHb and cotinine measurements may be interpreted as surrogates of fetal COHb levels. However, the specificity, ex vivo stability and ease of measurement of cotinine offer advantages over using COHb in quantifying fetal CO exposure following maternal cigarette smoking.

Follow-up of infants with congenital toxoplasmosis detected by polymerase chain reaction analysis of amniotic fluid.

This study was conducted to assess the validity of performing the polymerase chain reaction (PCR) on amniotic fluid for detecting fetal Toxoplasma infection. The primary endpoint was the outcome of the infant at 1 year of age. A prospective, consecutive study was performed in 49 infants born to mothers with primary Toxoplasma infection during pregnancy. PCR determinations of Toxoplasma gondii DNA in amniotic fluid were carried out as part of their prenatal management. Infants were examined at birth, and at 1, 3, 6, 9, and 12 months of age. Nine of 11 infants from pregnancies with positive PCR results proved to be infected based on follow-up serological investigations conducted during the first year of life. Two fetal deaths occurred. All 38 infants with negative PCR results remained uninfected at 1 year of age, irrespective of whether their mothers had received treatment with sulfadiazine/pyrimethamine or spiramycin alone. Psychomotor development was normal in all infants. This follow-up study confirms that PCR performed on amniotic fluid is a useful method for identification or exclusion of fetal Toxoplasma infection. Treatment of infected pregnant women and - in the event of a positive PCR result subsequent treatment of their infants is associated with a favorable outcome.

[Toxoplasmosis diagnosis in pregnancy: computer assisted follow-up interpretation of serologic tests]. / Toxoplasmose-Diagnostik in der Schwangerschaft: Computerunterstützte Verlaufsinterpretation von serologischen Tests.

Primary infection with Toxoplasma gondii during pregnancy can result in fetal infection with serious sequelae for the unborn if not treated properly. Early diagnosis enables drug therapy and significantly reduces the risk of fetal disease. A systematic serological screening procedure was established in Austria in 1975 to detect primary toxoplasma infection as early as possible during pregnancy. Since the screening program is based solely on observation and interpretation of serological data, the question arises whether a knowledge-based system for automatic interpretation can achieve a sufficient interpretative accuracy for introduction to routine work. For this reason the system Toxopert-I was developed. The system is aimed at facilitating routine laboratory work, as well as assuring quality by setting standards for therapy. The required knowledge base was designed as a knowledge graph, each state representing a certain interpretation. One or more available serological test results cause the knowledge graph to change its current state. If all available test results are processed, the final state reached corresponds to the respective current interpretation for the patient. A retrospective analysis of 1000 pregnant women yielded a total diagnostic sensitivity and specificity of over 99% in comparison with the clinician's diagnosis which was used as the Gold Standard.

Hydroxyl radical generation in oxygen-treated infants.

OBJECTIVE: Because the hydroxyl radical is capable of oxidizing phenylalanine to O-tyrosine, we sought to determine whether increased levels of O-tyrosine are found in urine of infants treated with supplemental oxygen. METHODS: A total of 39 consecutively admitted neonates to an intensive care unit were included. Twenty-seven received supplemental oxygen therapy for respiratory disease, and 12 did not. Urinary O-tyrosine levels were determined on two or more occasions using high-performance liquid chromatography with results expressed as a percentage of the urinary phenylalanine concentration. Using simple and stepwise multiple linear regression analyses, urinary O-tyrosine was examined for associations with relevant clinical conditions and laboratory measurements. RESULTS: Infants supplemented with oxygen showed significantly higher mean +/- SEM urinary O-tyrosine levels (0.40% +/- 0.028) compared with those remaining in room air (0.18% +/- 0.012). Mean daily FIO2 was the clinical and laboratory variable most highly correlated with urinary O-tyrosine (r = 0.66). In the stepwise regression, significant associations were also found for renal fractional sodium excretion and Apgar score at 5 minutes. CONCLUSIONS: Hydroxylation at the O position of phenylalanine, a specific direct marker for the hydroxyl radical attack, was strongly associated with oxygen treatment in neonates. This finding increases our understanding of the pathogenesis of oxygen injury and suggests a basis for developing therapeutic approaches.

Toxopert-I: knowledge-based automatic interpretation of serological tests for toxoplasmosis.

Primary infection with Toxoplasma gondii, a parasite found in most regions of the world, is asymptomatic in more than 80% of cases. However, primary infection with Toxoplasma gondii in a pregnant woman might cause fetal infection and severe damage. Most cases do not require treatment. This applies to women without any infection (denoted as seronegative) and women who have acquired the infection before conception (denoted as latent). In contrast, women with postconceptual infection require immediate treatment to prevent or ameliorate fetal infection. We have developed an expert system, called Toxoport-I, designed for routine laboratory work, which automatically interprets serological test results of toxoplasma infection. By using the system the clinician can also examine questionable cases by interactively exploring possible results. We used a popular method of designing expert systems applied to medical interpretation and therapy advice, the rule-based one. In order to meet the requirements of automatic interpretation in toxoplasma serology the following characteristics were introduced: the interpretation of sequences of test results, the possibility of excluding inconsistent test results and the adaptability of the knowledge base. A decision graph that covers the different kinds of infections as well as therapy and recommendations for further tests was designed, implemented and was clinically tested by carrying out a retrospective study including 1000 pregnant women. A comparison of Toxoport-I and the clinician's interpretations yielded sensitivity and specificity rates of over 99% each.

Rhesus isoimmunization: increased hemolysis during early infancy.

The objective of the present study was to determine whether whole blood carboxyhemoglobin (COHb) and plasma bilirubin, two indicators of hemolysis, are elevated in infants with severe Rh isoimmune hemolytic disease during the first months of life. Beginning at 2 wk of age and continuing monthly for 3 mo, serial blood samples were obtained for COHb, plasma bilirubin, Hb, reticulocyte count, plasma erythropoietin, plasma enzymes, and plasma iron. Because control infants (n = 13) and infants with ABO hemolytic disease (n = 5) did not differ from one another in any of the study parameters, these two groups were combined and compared with infants with the Rh isoimmunization. Infants with severe Rh isoimmune hemolytic disease (n = 13) were found to have significantly lower Hb and significantly higher bilirubin, the COHb fraction divided by the Hb concentration (COHb/Hb), and plasma erythropoietin levels at 2 and 6 wk of age, and reticulocyte counts at 6 wk. The remaining parameters were not different between the control-ABO group and Rh-isoimmune group at any of the study intervals. The study's two primary indicators of hemolysis, plasma bilirubin and COHb/Hb, were significantly correlated with one another in the Rh-immunized group (r = 0.66, p < 0.0001), but not in the combined control-ABO group. Serial Rh antibody concentrations measured in the serum of four neonates with Rh isoimmunization demonstrated a mean half-life of 14.3 d. We speculate that, among infants with severe Rh isoimmune hemolytic disease, elevated total bilirubin levels and COHb/Hb ratios identified in the early weeks of life indicate continuing hemolysis due to persistence of maternal Rh antibodies.