Pål A. Jenum

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.

Maternal Serum Levels of 25-Hydroxy-Vitamin D During Pregnancy and Risk of Type 1 Diabetes in the Offspring

Previous studies indicate reduced risk of type 1 diabetes after intake of vitamin D supplements during pregnancy or early childhood. We aimed to test whether lower maternal serum concentrations of 25-hydroxy-vitamin D (25-OH D) during pregnancy were associated with an increased risk of childhood-onset type 1 diabetes. In this case-control study nested within a cohort of 29,072 women in Norway, 25-OH D levels were measured using a radioimmunoassay on samples from late pregnancy in 109 women delivering a child who developed type 1 diabetes before 15 years of age (case subjects) and from 219 control women. Dividing the levels of maternal 25-OH D into quartiles, there was a trend toward a higher risk of type 1 diabetes with lower levels of vitamin D during pregnancy. The odds of type 1 diabetes was more than twofold higher for the offspring of women with the lowest levels of 25-OH D compared with the offspring of those with levels above the upper quartile. Given future replication in independent cohorts, our findings provide support for the initiation of a randomized intervention trial to prevent type 1 diabetes in children by enhancing maternal 25-OH D status during pregnancy.

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.

Risk Factors for Community-Acquired Urinary Tract Infections Caused by ESBL-Producing Enterobacteriaceae -A Case-Control Study in a Low Prevalence Country

Community-acquired urinary tract infection (CA-UTI) is the most common infection caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, but the clinical epidemiology of these infections in low prevalence countries is largely unknown. A population based case-control study was conducted to assess risk factors for CA-UTI caused by ESBL-producing E. coli or K. pneumoniae. The study was carried out in a source population in Eastern Norway, a country with a low prevalence of infections caused by ESBL-producing Enterobacteriaceae. The study population comprised 100 cases and 190 controls with CA-UTI caused by ESBL-producing and non-ESBL-producing E. coli or K. pneumoniae, respectively. The following independent risk factors of ESBL-positive UTIs were identified: Travel to Asia, The Middle East or Africa either during the past six weeks (Odds ratio (OR) = 21; 95% confidence interval (CI): 4.5–97) or during the past 6 weeks to 24 months (OR = 2.3; 95% CI: 1.1–4.4), recent use of fluoroquinolones (OR = 16; 95% CI: 3.2–80) and β-lactams (except mecillinam) (OR = 5.0; 95% CI: 2.1–12), diabetes mellitus (OR = 3.2; 95% CI: 1.0–11) and recreational freshwater swimming the past year (OR = 2.1; 95% CI: 1.0–4.0). Factors associated with decreased risk were increasing number of fish meals per week (OR = 0.68 per fish meal; 95% CI: 0.51–0.90) and age (OR = 0.89 per 5 year increase; 95% CI: 0.82–0.97). In conclusion, we have identified risk factors that elucidate mechanisms and routes for dissemination of ESBL-producing Enterobacteriaceae in a low prevalence country, which can be used to guide appropriate treatment of CA-UTI and targeted infection control measures.

Prevalence of Toxoplasma gondii specific immunoglobulin G antibodies among pregnant women in Norway.

During one year from June 1992 serum IgG antibodies to Toxoplasma gondii among 35,940 pregnant women were measured in a cross-sectional study conducted in Norway. The overall prevalence was 10.9%. The lowest prevalences were detected in the north (6.7%) and in the inland counties (8.2%). A significantly higher prevalence was detected in the southern counties (13.4%) where a mild, coastal climate prevails. Women with foreign names had a higher prevalence (22.6%) than women with Norwegian names (10.0%). The high prevalence among women living in the capital city (Oslo) as compared to other cities and rural areas (13.2% vs. 10.1% and 10.2% respectively), was explained by the higher proportion of foreign women in Oslo. Prevalence significantly increased with age in women over 34 years old. This increase was only detected among women with Norwegian names. An increase in prevalence according to number of children was detected. Women without children had a prevalence of 8.8% while women with three children or more had a prevalence of 14.9%. Multivariate analyses showed that being seropositive was independently associated with county of residence, age, nationality and number of children.

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.

Angiogenic Factors in Maternal Circulation and the Risk of Severe Fetal Growth Restriction

Maternal angiogenic factors (placental growth factor, soluble fms-like tyrosine kinase 1 (Flt-1), and soluble endoglin) may be associated with fetal growth restriction, and the associations may differ according to stage of pregnancy. Among children born to pregnant women without preeclampsia in Norway between 1992 and 1994, 217 singletons with severe growth restriction (small for gestational age (SGA), <2.5th percentile) were compared with 378 singleton controls. For each angiogenic factor, SGA risk was related to concentrations in maternal serum collected in the first 2 trimesters, by using women with a serum concentration in the middle third at both samplings as reference. A low placental growth factor (lowest third) at both samplings was associated with high risk of SGA (odds ratio=3.8, 95% confidence interval: 1.6, 8.8). An increase from the lowest to the highest third of soluble Flt-1 was associated with high SGA risk (odds ratio=6.2, 95% confidence interval: 2.4, 16.1). Women with high soluble endoglin (highest third) at the second sampling had approximately a 3.5-fold increased risk of SGA. Low maternal soluble Flt-1 in early pregnancy followed by a strong subsequent increase in soluble Flt-1 and soluble endoglin was associated with a particularly high risk of severe fetal growth restriction.

Is preeclampsia an infectious disease

Background. Studies have suggested a strong paternal factor in the etiology of preeclampsia. If preeclampsia is caused by an infectious agent transmitted by the woman’s partner, seronegative women who may experience primary infection in pregnancy should be at increased risk of preeclampsia as compared to previously infected women. The aim of this study was to assess the impact of being seronegative for some viruses transmitted by close contact on the risk of developing preeclampsia.

Diagnosis of congenital Toxoplasma gondii infection by polymerase chain reaction (PCR) on amniotic fluid samples : The Norwegian experience

As part of a screening project for detection of Toxoplasma gondii infection among pregnant women in Norway, nested polymerase chain reaction (PCR) aimed at the detection of T. gondii in amniotic fluid samples was included in the diagnostic routine. The results were compared with the routine criteria for congenital infection: i) T. gondii detected in amniotic fluid or cord blood by mouse inoculation, ii) specific IgM or IgA in serum collected after birth, and/or iii) specific IgG persisting beyond one year of age. The PCR was based on the B1 gene with an internal control gene amplified together with the B1 gene. One hundred and two amniotic fluid samples collected during pregnancy and/or at delivery from 67 pregnant women with serological evidence of primary T. gondii infection were available for examination by both B1‐PCR and mouse inoculation. Six samples were positive and 86 samples were negative by both methods (90% concordance). One sample was mouse inoculation positive and B1‐PCR negative while nine samples were B1‐PCR positive and mouse inoculation negative, of which five were associated with four infants without proven infection. 59% and 41% of samples associated with infected infants were positive by B1‐PCR and mouse inoculation, respectively. The difference was mainly due to a lower detection rate by mouse inoculation after antiparasitic treatment. The specificity of B1‐PCR was 94%. Even though B1‐PCR performed on amniotic fluid samples did not detect all infected infants, it represented a valuable tool in addition to conventional methods in the diagnosis of congenital T. gondii infection.

Etiology of community-acquired pneumonia and diagnostic yields of microbiological methods: a 3-year prospective study in Norway

BackgroundDespite recent advances in microbiological techniques, the etiology of community-acquired pneumonia (CAP) is still not well described. We applied polymerase chain reaction (PCR) and conventional methods to describe etiology of CAP in hospitalized adults and evaluated their respective diagnostic yields.Methods267 CAP patients were enrolled consecutively over our 3-year prospective study. Conventional methods (i.e., bacterial cultures, urinary antigen assays, serology) were combined with nasopharyngeal (NP) and oropharyngeal (OP) swab samples analyzed by real-time quantitative PCR (qPCR) for Streptococcus pneumoniae, and by real-time PCR for Mycoplasma pneumoniae, Chlamydophila pneumoniae, Bordetella pertussis and 12 types of respiratory viruses.ResultsEtiology was established in 167 (63%) patients with 69 (26%) patients having ≥1 copathogen. There were 75 (28%) pure bacterial and 41 (15%) pure viral infections, and 51 (19%) viral–bacterial coinfections, resulting in 126 (47%) patients with bacterial and 92 (34%) patients with viral etiology. S. pneumoniae (30%), influenza (15%) and rhinovirus (12%) were most commonly identified, typically with ≥1 copathogen. During winter and spring, viruses were detected more frequently (45%, P=.01) and usually in combination with bacteria (39%). PCR improved diagnostic yield by 8% in 64 cases with complete sampling (and by 15% in all patients); 5% for detection of bacteria; 19% for viruses (P=.04); and 16% for detection of ≥1 copathogen. Etiology was established in 79% of 43 antibiotic-naive patients with complete sampling. S. pneumoniae qPCR positive rate was significantly higher for OP swab compared to NP swab (P<.001). Positive rates for serology were significantly higher than for real-time PCR in detecting B. pertussis (P=.001) and influenza viruses (P<.001).ConclusionsEtiology could be established in 4 out of 5 CAP patients with the aid of PCR, particularly in diagnosing viral infections. S. pneumoniae and viruses were most frequently identified, usually with copathogens. Viral–bacterial coinfections were more common than pure infections during winter and spring; a finding we consider important in the proper management of CAP. When swabbing for qPCR detection of S. pneumoniae in adult CAP, OP appeared superior to NP, but this finding needs further confirmation.Trial registrationClinicalTrials.gov Identifier: NCT01563315.