Catherine Peckham

Mother-to-child transmission of toxoplasmosis: risk estimates for clinical counselling

BACKGROUNDnWomen who acquire toxoplasmosis infection during pregnancy (in most cases detected through serological screening) require counselling about the risk of congenital infection and its clinical sequelae. Reliable estimates of risk are not currently available. We undertook an analysis of data from women referred to the toxoplasmosis reference laboratory, Lyon, France, between 1987 and 1995.nnnMETHODSnInformation was collected from clinical notes kept at the laboratory and, where necessary, from the relevant obstetrician or paediatrician via telephone. Methods were developed to derive estimates of the risk of congenital toxoplasmosis by exact duration of gestation at maternal seroconversion.nnnFINDINGSnWe analysed obstetric and paediatric data on 603 confirmed maternal toxoplasmosis infections. At least 564 women received antiparasitic drugs according to a standard protocol. Congenital infection status was ascertained in 554 cases, and infected children were followed-up for a median of 54 months. The overall maternal-fetal transmission rate was 29% (95% CI 25-33), which masked a sharp increase in risk with duration of gestation from 6% at 13 weeks to 72% at 36 weeks. However, fetuses infected in early pregnancy were much more likely to show clinical signs of infection. These effects counterbalance, and women who seroconverted at 24-30 weeks of gestation carried the highest risk (10%) of having a congenitally infected child with early clinical signs who was thus at risk of long-term complications.nnnINTERPRETATIONnThis information will assist the clinical counselling of pregnant women diagnosed with acute toxoplasmosis and may guide individual decisions on investigative and therapeutic options. Further studies are required to determine the long-term risks of clinical symptoms and disability due to congenital toxoplasmosis.

Incidence, cause, and short-term outcome of convulsive status epilepticus in childhood: prospective population-based study

BACKGROUNDnConvulsive status epilepticus is the most common childhood medical neurological emergency, and is associated with significant morbidity and mortality. Most data for this disorder are from mainly adult populations and might not be relevant to childhood. Thus we undertook the North London Status Epilepticus in Childhood Surveillance Study (NLSTEPSS): a prospective, population-based study of convulsive status epilepticus in childhood, to obtain a uniquely paediatric perspective.nnnMETHODSnClinical and demographic data for episodes of childhood convulsive status epilepticus that took place in north London were obtained through a clinical network that covered the target population. We obtained these data from anonymised copies of a standardised admission proforma; accident and emergency, nursing, ambulance, and intensive-care unit notes; and interviews with parents, medical, nursing, and paramedic staff. We investigated ascertainment using capture-recapture modelling.nnnFINDINGSnOf 226 children enrolled, 176 had a first ever episode of convulsive status epilepticus. We estimated that ascertainment was between 62% and 84%. The ascertainment-adjusted incidence was between 17 and 23 episodes per 100,000 per year. 98 (56%, 95% CI 48-63) children were neurologically healthy before their first ever episode and 56 (57%, 47-66) of those children had a prolonged febrile seizure. 11 (12%, 6-18) of children with first ever febrile convulsive status epilepticus had acute bacterial meningitis. Conservative estimation of 1-year recurrence of convulsive status epilepticus was 16% (10-24%). Case fatality was 3% (2-7%).nnnINTERPRETATIONnConvulsive status epilepticus in childhood is more common, has a different range of causes, and a lower risk of death than that in adults. These paediatric data will help inform management of convulsive status epilepticus and appropriate allocation of resources to reduce the effects of this disorder in childhood.

Treatment of community-onset, childhood convulsive status epilepticus: a prospective, population-based study

Summary Background Episodes of childhood convulsive status epilepticus (CSE) commonly start in the community. Treatment of CSE aims to minimise the length of seizures, treat the causes, and reduce adverse outcomes; however, there is a paucity of data on the treatment of childhood CSE. We report the findings from a systematic, population-based study on the treatment of community-onset childhood CSE. Methods We collected data prospectively on children in north London, UK, who had episodes of CSE (ascertainment 62–84%). The factors associated with seizure termination after first-line and second-line therapies, episodes of CSE lasting for longer than 60 min, and respiratory depression were analysed with logistic regression. Analysis was per protocol, and adjustment was made for repeat episodes in individuals. Results 182 children of median age 3·24 years (range 0·16–15·98 years) were included in the North London Convulsive Status Epilepticus in Childhood Surveillance Study (NLSTEPSS) between May, 2002, and April, 2004. 61% (147) of 240 episodes were treated prehospital, of which 32 (22%) episodes were terminated. Analysis with multivariable models showed that treatment with intravenous lorazepam (n=107) in the accident and emergency department was associated with a 3·7 times (95% CI 1·7–7·9) greater likelihood of seizure termination than was treatment with rectal diazepam (n=80). Treatment with intravenous phenytoin (n=32) as a second-line therapy was associated with a 9 times (95% CI 3–27) greater likelihood of seizure termination than was treatment with rectal paraldehyde (n=42). No treatment prehospital (odds ratio [OR] 2·4, 95% CI 1·2–4·5) and more than two doses of benzodiazepines (OR 3·6, 1·9–6·7) were associated with episodes that lasted for more than 60 min. Treatment with more than two doses of benzodiazepines was associated with respiratory depression (OR 2·9, 1·4–6·1). Children with intermittent CSE arrived at the accident and emergency department later after seizure onset than children with continuous CSE did (median 45 min [range 11–514 min] vs 30 min [5–90 min]; p<0·0001, Mann-Whitney U test); for each minute delay from onset of CSE to arrival at the accident and emergency department there was a 5% cumulative increase in the risk of the episode lasting more than 60 min. Interpretation These data add to the debate on optimum emergency treatment of childhood CSE and suggest that the current guidelines could be updated. Funding An anonymous donor to UCL Institute of Child Health; the Wellcome Trust; UK Department of Health National Institute for Health Research Biomedical Research Centres Funding Scheme; Medical Research Council.

Detection of virus in vertically exposed HIV-antibody-negative children

BACKGROUNDnHIV-infected mothers can transmit their infection to their children in utero or at delivery (vertical transmission). There have been cases of children who were reported as acquiring infection vertically and later clearing the infection. We report the frequency of this phenomenon in a European cohort study.nnnMETHODSnIn four centres of the European Collaborative Study of children born to HIV-infected mothers, 299 children became HIV-antibody-negative and 264 of these had been followed up with virus culture and PCR for viral DNA at least once.nnnFINDINGSnNine of the 264 children were positive by virus culture or PCR, and subsequently seroreverted. Two of the nine tested virus-positive after they became antibody-negative. Six cases were virus-positive early in life and became negative thereafter, which is consistent with clearance of infection. The pattern was less clear in the other three. The nine cases had had their last virus test at age 16-101 months. All nine children had been bottlefed only. Eight had been delivered vaginally. The children had no HIV-related symptoms and received no anti-HIV treatments. Based on only those children who had two or more positive virological tests, we estimate that 2.7% (6/219) cleared or tolerated the virus.nnnINTERPRETATIONnThe detection of virus or viral DNA in uninfected children born to HIV-infected mothers was rare and was not associated with clinical disease or immunological abnormalities. The timing of samples will affect the documentation of clearance since, in uninfected children of HIV-positive mothers who cleared the virus, viraemia was intermittent. Current paediatric opinion is to inform parents of children who serorevert that the child is not HIV-infected.

Outcomes of childhood epilepsy at age 33 years: A population-based birth-cohort study

Purpose:u2002 There is uncertainty about health and socioeconomic outcomes of children with epilepsy, knowledge of adult outcomes, and factors associated with adverse outcomes are essential to guide prognosis, improve management, and determine appropriate allocation of resources.

Low incidence of congenital toxoplasmosis in children born to women infected with human immunodeficiency virus

In children born to immunocompetent women, congenital toxoplasmosis almost always results from primary infection during pregnancy. However, reactivation of latent toxoplasmosis during pregnancy could occur in HIV-infected pregnant women, particularly in those who are severely immunocompromised, and result in maternal-fetal transmission of the parasite. This mode of infection has been described in case reports but the risk of transmission is unknown. Findings on toxoplasmosis are presented from the European Collaborative Study, a prospective study of children born to women known to be HIV-infected at the time of delivery. In 1058 children followed for a mean duration of 35 months, only one child developed clinical toxoplasmosis. This child was HIV-infected, severely immunocompromised, and acquired toxoplasmosis postnatally. Congenital infection was excluded serologically in a subgroup of 167 children, of whom an estimated 71 had been at risk of infection. These clinical and serological findings indicate a low general risk of maternal-fetal transmission of Toxoplasma infection in HIV-infected women. It is not possible to draw conclusions about the risk of transmission for severely immunocompromised HIV-infected women because most women in the study were asymptomatic.

Socioeconomic deprivation independent of ethnicity increases status epilepticus risk

Background:u2002 A higher incidence of convulsive status epilepticus (CSE) has been reported in nonwhite compared to white populations. Socioeconomic factors can be intricately involved in observed ethnic “effects,” and the importance of socioeconomic status on health conditions is widely recognized. Understanding the effect of socioeconomic factors on CSE would provide insights into etiology and management, leading to the development of novel prevention strategies.

Vertical transmission of HIV infection.

Transmission of HIV infection from mother to child may occur before, during or after delivery. Estimates of the rate of vertical transmission range from 15–20% in Europe to 25–35% in Africa. Mother‐to‐child transmission is associated with progression of disease in the mother, severe prematurity and breastfeeding. The association with mode of delivery needs further investigation. Attention is now being given to intervention to reduce mother‐to‐child transmission of HIV infection.

In utero exposure to antiretroviral therapy: feasibility of long-term follow-up

Abstract Most uninfected children born to diagnosed HIV-infected women in the United Kingdom (UK) are exposed to antiretroviral therapy (ART) in utero and neonatally, and concerns exist about potential adverse effects of such exposure. We explored the feasibility of using national clinic-based follow-up to investigate the association between ART exposure and adverse health events occurring after the neonatal period. Active surveillance of obstetric and paediatric HIV infection is conducted through the National Study of HIV in Pregnancy and Childhood (NSHPC). Between 2002 and 2005, health professionals enrolled previously notified uninfected children in a consented follow-up study (the CHildren exposed to AntiRetroviral Therapy (CHART) study). Follow-up information was collected opportunistically using a standard questionnaire. Of 2104 eligible uninfected children born in the UK between 1996 and 2004, 704 (33.5%) were enrolled in CHART; parents of 4.8% (100/2104) declined, 2.8% (59/2104) had gone abroad, 21.6% (455/2104) were not contactable, and the remaining 37.3% (786/2104) were not enrolled mainly because of lack of clinic resources or unwillingness of health professionals to approach the families. Demographic characteristics and type of ART exposure for enrolled and non-enrolled children were similar. Latest information on enrolled children was available at a median age of 24 months. Minor childhood ailments were reported in the majority of children, febrile seizures in 1.6% (11/704), and major health problems in 3.8% (27/704). It was reassuring that prevalence of these outcomes was within UK norms, but numbers were small and duration of follow-up was limited. The difficulties encountered in enrolling and retaining children in this study indicate that comprehensive clinic-based follow-up of ART-exposed uninfected children is not practical. Alternative approaches are required; a robust, secure data linkage protocol would provide a more feasible and sustainable system for long-term monitoring of in utero ART exposure.