Maternal and Congenital Toxoplasmosis: Diagnosis and Treatment Recommendations of a French Multidisciplinary Working Group.

Women infected with toxoplasmosis during pregnancy do not present symptoms in most cases, but the consequences of the congenital infection may be severe for the unborn child. Fetal damage can range from asymptomatic to severe neurological alterations to retinal lesions prone to potential flare up and relapses lifelong. Despite the possible severity of outcome, congenital toxoplasmosis (CT) is a neglected disease. There is no consensus regarding screening during pregnancy, prenatal/postnatal treatment or short or medium term follow-up. Since 1992, France has offered systematic serological testing to non-immune pregnant women, monthly until delivery. Any maternal infection is thus detected; moreover, diagnosis of congenital infection can be made at birth and follow-up can be provided. "Guidelines" drawn up by a multidisciplinary group are presented here, concerning treatment, before and after birth. The recommendations are based on the regular analysis of the literature and the results of the working group. The evaluation of the recommendations takes into account the robustness of the recommendation and the quality of the evidence.

Tobacco smoke in infants with bronchopulmonary dysplasia.

UNLABELLED: Exposure to tobacco smoke has been not evaluated in children with bronchopulmonary dysplasia (BPD). We evaluate the association of in utero smoking (IUS) and environmental tobacco smoke (ETS) with the respiratory events of BPD and non-BPD children. Two hundred sixty-two children born before 35 weeks of gestational age (GA) and regularly followed up in our regional network for preterms were enrolled. They were paired according to their BPD status, their gestational age and birth weight (131 children with BPD and 131 without BPD, 28 mean weeks GA; mean weight 1000 g). Respiratory data were obtained prospectively during their first 2 years of life. A complementary questionnaire was completed by the parents about their child's respiratory health at the age of 2, their home environment, and tobacco status. IUS concerned 12.6 %; ETS, 48.8 % (67 % in BPD children treated with oxygen at home). No further influence on respiratory outcome could be found by exposure to intrauterine smoke or extrauterine tobacco smoke in this patient sample. CONCLUSION: IUS and ETS exposures are as high in preterm children as in a general pediatric population. The highest exposure occurs among BPD infants treated with oxygen at home. WHAT IS KNOWN: • Environmental tobacco smoke (ETS) and in utero smoking (IUS) are responsible for many morphological, functional, and clinical changes in children. • Children with bronchopulmonary dysplasia (BPD) have more respiratory events in their first years of life than preterm children without BPB, maybe triggered by ETS and IUS. What is New: • The exposition to ETS and IUS is high in preterm children with and without BDP, as high as in a general. • Pedaitric population, particularly in children with BPD and treated with oxygen at home. • No further influence on respiratory outcome could be found by exposure to ETS or IUS in our studied population.

[Congenital toxoplasmosis: randomised comparison of strategies for retinochoroiditis prevention]. / Toxoplasmose congénitale : comparaison randomisée de stratégies de prévention des rétinochoroïdites.

In France, children with confirmed congenital toxoplasmosis receive a treatment for a period of 12 to 24 months. Such prolonged treatment may generate potentially severe risks, in particular hematologic and cutaneous. Our objective is to compare the effectiveness of two therapeutic strategies on the prevention of retinochoroiditis by a randomized, non-inferiority, open-label, parallel study including 486 children, 3 to 6 months of age with a non-severe form of congenital toxoplasmosis. Following randomization, pyrimethamine-sulphonamide treatment is initiated for a period of three months, followed by a treatment with Fansidar(®) for 9 months, or therapeutic abstention. Follow-up visits during a two-year period will include an examination of the eye, a blood test, and questionnaires to evaluate the children's quality of life and their parents' anxiety. Confirming the non-inferiority of the effectiveness of a short-term treatment will improve the quality of life of parents and children.

Accuracy of real-time polymerase chain reaction for Toxoplasma gondii in amniotic fluid.

OBJECTIVE: To provide clinicians with information about the accuracy of real-time polymerase chain reaction (PCR) analysis of amniotic fluid for the prenatal diagnosis of congenital Toxoplasma infection. METHODS: This was a prospective cohort study of women with Toxoplasma infection identified by prenatal screening in three centers routinely carrying out real-time PCR for the detection of Toxoplasma gondii in amniotic fluid. The data available were gestational age at maternal infection, types and dates of maternal treatment, results of amniocentesis and neonatal work-up and definitive infectious status of the child. We estimated sensitivity, specificity and positive and negative predictive values both overall and per trimester of pregnancy at the time of maternal infection. RESULTS: Polymerase chain reaction analysis was carried out on amniotic fluid for 261 of the 377 patients included (69%). It was accurate with the exception of four negative results in children who were infected. Overall sensitivity and negative predictive value were 92.2% (95% confidence interval [CI] 81-98%) and 98.1% (95% CI 95-99.5%), respectively. There was no significant association with the trimester of pregnancy during which maternal infection occurred. Specificity and positive predictive values of 100% were obtained for all trimesters. CONCLUSION: Real-time PCR analysis significantly improves the detection of T. gondii on amniotic fluid. It provides an accurate tool to predict fetal infection and to decide on appropriate treatment and surveillance. However, postnatal follow-up remains necessary in the first year of life to fully exclude infection in children for whom PCR results were negative. LEVEL OF EVIDENCE: III.

[Management of congenital toxoplasmosis in France: current data]. / Prise en charge de la toxoplasmose congénitale en France : données actuelles.

Congenital toxoplasmosis is caused by transplacental contamination of the fetus withToxoplasma gondiifollowing maternal primary infection. The risk of mother-to-child transmission depends on the term of pregnancy at the time of maternal infection. The risk is lower than 5% in the first trimester but can reach 90% in the last days of pregnancy. Inversely, however, fetal disease is more severe when contamination occurs early in pregnancy. The French prevention program officially recommends monthly serological screening of susceptible women during pregnancy and information about hygiene and dietary rules. Prenatal diagnosis of congenital toxoplasmosis is based on a combination of examinations: PCR testing for the parasite in amniotic fluid, mouse inoculation, fetal ultrasonography, and magnetic resonance imaging. Neonatal screening consists of PCR of the placenta, mouse inoculation, detection of specific IgM and IgA in the newborn, ocular fundus examinations by indirect ophthalmoscopy, and transfontanellar ultrasonography. As soon as maternal infection is suspected, preventive treatment with spiramycin begins; the treatment is changed to a combination of pyrimethamine-sulfonamide if fetal infection is proved. Some teams are using this combination as first-line treatment after 30 weeks of gestation, without performing amniocentesis. Recent European multicenter studies raise questions about the effectiveness of prenatal treatment on mother-to-child transmission and on the reduction in the number and severity of fetal sequelae. A randomized controlled trial is required to prove the efficacy of prenatal treatment in general and of specific drugs, in particular. As soon as infection is confirmed, infected children are treated with the pyrimethamine-sulfonamide combination for 12 to 24 months. Recent multicenter studies show that postnatal treatment does not prevent ocular lesions: 5% of treated children had choroiditis lesions at birth, 20% at 5 years, and 30% at 8 years of age. Furthermore no consensus exists about the duration of postnatal treatment (3 months in Denmark versus 12 months in France). A multicenter randomized controlled trial is necessary to assess the efficacy of postnatal treatment and determine its duration. A surveillance system was set up in 2007 by the National Reference Center for Toxoplasmosis to determine the perinatal burden of this infection and to assess the national policy.

Effects of maternally administered drugs on the fetal and neonatal kidney.

The number of pregnant women and women of childbearing age who are receiving drugs is increasing. A variety of drugs are prescribed for either complications of pregnancy or maternal diseases that existed prior to the pregnancy. Such drugs cross the placental barrier, enter the fetal circulation and potentially alter fetal development, particularly the development of the kidneys. Increased incidences of intrauterine growth retardation and adverse renal effects have been reported. The fetus and the newborn infant may thus experience renal failure, varying from transient oligohydramnios to severe neonatal renal insufficiency leading to death. Such adverse effects may particularly occur when fetuses are exposed to NSAIDs, ACE inhibitors and specific angiotensin II receptor type 1 antagonists. In addition to functional adverse effects, in utero exposure to drugs may affect renal structure itself and produce renal congenital abnormalities, including cystic dysplasia, tubular dysgenesis, ischaemic damage and a reduced nephron number. Experimental studies raise the question of potential long-term adverse effects, including renal dysfunction and arterial hypertension in adulthood. Although neonatal data for many drugs are reassuring, such findings stress the importance of long-term follow-up of infants exposed in utero to certain drugs that have been administered to the mother.

Fetal and neonatal consequences of antenatal exposure to type 1 angiotensin II receptor-antagonists.

Sartans are selective type 1 angiotensin II receptor-antagonists that are used in the treatment of arterial hypertension. Few reports are available concerning the use of sartans during pregnancy. We report two cases of adverse fetal outcome in hypertensive pregnancies exposed to sartans. In the first case, anamnios and fetal renal failure due to severe tubular dysgenesia led to termination of pregnancy in the 27th week. The second patient presented with hypocalvaria and developed fetal renal failure. The use of sartans during the two last trimesters of pregnancy should be strictly avoided.