Vaginal microbiome as a tool for prediction of chorioamnionitis in preterm labor: a pilot study.

Intra-amniotic infection (IAI) is a major cause of preterm birth with a poor perinatal prognosis. We aimed to determine whether analyzing vaginal microbiota can evaluate the risk of chorioamnionitis (CAM) in preterm labor cases. Vaginal discharge samples were collected from 83 pregnant women admitted for preterm labor. Based on Blanc's classification, the participants were divided into CAM (stage ≥ II; n = 46) and non-CAM (stage ≤ I; n = 37) groups. The 16S rDNA amplicons (V1-V2) from vaginal samples were sequenced and analyzed. Using a random forest algorithm, the bacterial species associated with CAM were identified, and a predictive CAM (PCAM) scoring method was developed. The α diversity was significantly higher in the CAM than in the non-CAM group (P < 0.001). The area under the curve was 0.849 (95% confidence interval 0.765-0.934) using the PCAM score. Among patients at < 35 weeks of gestation, the PCAM group (n = 22) had a significantly shorter extended gestational period than the non-PCAM group (n = 25; P = 0.022). Multivariate analysis revealed a significant difference in the frequency of developmental disorders in 3-year-old infants (PCAM, 28%, non-PCAM, 4%; P = 0.022). Analyzing vaginal microbiota can evaluate the risk of IAI. Future studies should establish appropriate interventions for IAI high-risk patients to improve perinatal prognosis.

Recurrent neonatal sepsis and progressive white matter injury in a premature newborn culture-positive for group B Streptococcus: A case report.

RATIONALE: Group B Streptococcus (GBS) remains a principal pathogen causing neonatal sepsis and meningitis, particularly in premature infants with relatively insufficient immunity. Recurrence may occur uncommonly, largely associated with subclinical mucosal persistence or repetitive exposure to exogenous sources. White matter injury (WMI) including cystic periventricular leukomalacia (PVL) has been associated with intrauterine infection/inflammation, and neonatal infection as a more significant predictor including postnatal sepsis and recurrent infection, even without microbial neuroinvasion. Furthermore, clinical and experimental evidence of WMI by some bacteria other than GBS without central nervous system invasion has been reported. However, there is little evidence of WMI associated with neonatal GBS sepsis in the absence of meningitis in the literature. PATIENT CONCERNS: A newborn at 30+4 weeks' gestation with low birthweight presented with 2 episodes (with a 13-day interval with no antibiotic therapy) of neonatal sepsis culture-proven for GBS with early-onset presentation after clinical chorioamnionitis via vertical GBS transmission and the associated conditions including prematurity-related neonatal immunodeficiency and persistent mucosal GBS carriage after the first antibiotic treatment. The perinatal GBS infection was complicated by progressive WMI presenting with ventriculomegaly and cystic PVL without a definite evidence of meningitis, intraventricular hemorrhage, and documented cerebral hypoxia or hypoperfusion conditions including septic shock. DIAGNOSES: Recurrent group B streptococcal sepsis and cystic PVL with ventriculomegaly. INTERVENTIONS: Two episodes of GBS sepsis were treated with 15-day parenteral antibiotic therapy, respectively. OUTCOMES: Resolution of the recurrent GBS sepsis without further relapses, however, complicated by WMI and subsequent about 6 months delay in motor development at 12 months' corrected age. LESSONS: This case suggests WMI associated with GBS bacteremia without central nervous system entry by viable GBS and also shows that in premature infants, intrauterine GBS infection with no interventions may lead to extensive and persistent GBS colonization, early-onset and recurrent GBS disease, and WMI. Postnatal as well as intrauterine infection/inflammation controls with maternal prophylaxis may be pivotal for prevention and limiting the magnitude of neurologic injury.

Psychiatric Disabilities and Other Long-term Consequences of Childhood Bacterial Meningitis.

BACKGROUND: Bacterial meningitis is known to cause hearing impairments and neurologic deficits; however, less is known regarding psychiatric disabilities. In this study, we assessed psychiatric disabilities and other long-term consequences of childhood bacterial meningitis. METHODS: From a previously validated dataset, we selected children having had bacterial meningitis. We then reviewed medical records and child health records from discharge onwards to identify disabilities. We calculated the occurrence of disabilities with a 95% confidence interval (CI), and we used a χ test to assess possible individual risk factors associated with occurrence of disabilities. RESULTS: Of the 80 children included in this study, permanent disabilities not attributed to preexisting diseases were noted in 56% (CI: 45-67) during the mean observation period of 19 years and 2 months. Psychiatric disease was diagnosed in 30% (CI: 21-41), and another 5% (CI: 2-13) were under ongoing investigations for symptoms of psychiatric disease. Hearing impairments affected at least 30% (CI: 20-40), and neurologic deficits affected at least 23% (CI: 15-34). While other disabilities were often detected within the first year, psychiatric disabilities were detected after a mean time period of 14 years (CI: 11:1-16:11). Although some associations were noted, no individual risk factor was able to predict the occurrence of disabilities. CONCLUSIONS: Psychiatric disabilities affect more than one-third of survivors and are among the most common long-term consequence of childhood bacterial meningitis. Late discovery and predictive difficulties call for a revision of current guidelines to include a specific long-term strategy for detecting psychiatric disabilities.

Difficulties in developmental follow-up of preterm neonates in a randomised-controlled trial of Bifidobacterium breve M16-V - Experience from Western Australia.

BACKGROUND: Probiotics may be neuroprotective for preterm neonates due to their anti-inflammatory effects and ability to facilitate nutrition. AIM: To assess long-term effects of early probiotic supplementation on neuropsychological development in preterm infants. STUDY DESIGN: Follow up study. SUBJECTS: Children at age 3 to 5 years who had participated as preterm infants (<33 week) in the randomised controlled trial. OUTCOMES: Primary: Continuous early learning composite measure derived from the Mullen's Scale of Early Learning (MSEL). Other outcomes were assessed by the Developmental, Dimensional and Diagnostic Interview, Developmental NEuroPSYchological assessment-2nd Edition, Parental questionnaires using children's communication checklist-2nd edition, social responsiveness scale, and Vineland Adaptive Behavioural Scales-2nd edition. MEASURES: Continuous scores derived from all the measures. RESULTS: 67 children of the 159 participants (42%) (Probiotic: 36/79, Placebo: 31/80) were followed-up for at least one neuropsychological assessment. All six assessments were completed in 18/31 (58.1%) of the control vs. 11/36 (30.6%) probiotic group children. Multivariable analysis of MSEL composite score showed no evidence of probiotic effect univariately, or after adjustment for gestation, intrauterine growth restriction, Apgar <7 at 5 min and age at assessment (adjusted mean effect in probiotic group: -2.7, 95% CI -8.5-3.0, p = 0.349). CONCLUSION: There was no significant effect on neurodevelopment of children assessed at the age of 3 to 5 years who participated as preterm neonates in the RCT of B. breve M-16V. The validity of these results is limited by the reduced sample size due to high rate of loss to follow up.

The infant microbiome and implications for central nervous system development.

Neurodevelopmental impairment remains a significant morbidity in former very low birth weight premature infants. There is increasing evidence the microbiome affects neurodevelopment but mechanistic causes are largely unknown. There are many factors which affect the developing microbiome in infants including mode of delivery, feeding, medications, and environmental exposures. The overall impact of these factors may differ between premature and term infants. The microbiome and brain have well recognized bidirectional communication pathways via neural, hormonal, and immunologic mechanisms. Understanding the interplay between these different pathways has been possible with the use of animal models, particularly germ-free mice. The intricate relationship between the microbiome and the brain remains a research priority not only to improve the care, but to also improve the long-term neurodevelopmental outcomes in this vulnerable population.

Enteric Infections in Young Children are Associated with Environmental Enteropathy and Impaired Growth.

OBJECTIVE: To investigate the relationship between faecal contamination in child play spaces, enteric infections, environmental enteropathy (EE) and impaired growth among young children. METHODS: A prospective cohort study was conducted of 203 children 6-30 months of age in rural Bangladesh. Stool samples were analysed by quantitative PCR for Shigella, Enterotoxigenic Escherichia coli (ETEC), Campylobacter jejuni, Giardia intestinalis and Cryptosporidium spp. Four faecal markers of intestinal inflammation were also measured: alpha-1-antitrypsin, myeloperoxidase, neopterin and calprotectin. Child growth was measured at baseline and 9 months after enrolment. E. coli was measured in soil in child play spaces. RESULTS: Forty-seven percent of study children had three or more enteric pathogens in their stool. Thirty five percent (71/203) of children had Shigella, 30% (61/203) had ETEC, 73% (148/203) had C. jejuni, 79% (160/203) had Giardia intestinalis and none had Cryptosporidium. Children with ETEC had significantly higher calprotectin concentrations (Coefficient: 1.35, 95% Confidence Interval [CI]: 1.005, 1.82). Children with Shigella had a significantly higher odds of being stunted at our 9-month follow-up (OR: 2.01, 95% CI: 1.02, 3.93). Children with Giardia intestinalis had significantly higher E.coli counts in the soil collected from their play spaces (OR: 1.23, 95% CI: 1.02, 1.48). CONCLUSION: Enteric infections were significantly associated with EE and impaired growth in rural Bangladesh. These findings provide further evidence to support the hypothesis that contaminated soil in child play spaces can lead to enteric infections, many of which are likely subclinical, resulting in EE and impaired growth in young children.

Neurodevelopmental Impairment in Children After Group B Streptococcal Disease Worldwide: Systematic Review and Meta-analyses.

BACKGROUND: Survivors of infant group B streptococcal (GBS) disease are at risk of neurodevelopmental impairment (NDI), a burden not previously systematically quantified. This is the 10th of 11 articles estimating the burden of GBS disease. Here we aimed to estimate NDI in survivors of infant GBS disease. METHODS: We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data on the risk of NDI after invasive GBS disease in infants <90 days of age. We did meta-analyses to derive pooled estimates of the percentage of infants with NDI following GBS meningitis. RESULTS: We identified 6127 studies, of which 18 met eligibility criteria, all from middle- or high-income contexts. All 18 studies followed up survivors of GBS meningitis; only 5 of these studies also followed up survivors of GBS sepsis and were too few to pool in a meta-analysis. Of meningitis survivors, 32% (95% CI, 25%-38%) had NDI at 18 months of follow-up, including 18% (95% CI, 13%-22%) with moderate to severe NDI. CONCLUSIONS: GBS meningitis is an important risk factor for moderate to severe NDI, affecting around 1 in 5 survivors. However, data are limited, and we were unable to estimate NDI after GBS sepsis. Comparability of studies is difficult due to methodological differences including variability in timing of clinical reviews and assessment tools. Follow-up of clinical cases and standardization of methods are essential to fully quantify the total burden of NDI associated with GBS disease, and inform program priorities.

Neurodevelopment of Preterm Infants at 24 Months After Neonatal Supplementation of a Prebiotic Mix: A Randomized Trial.

OBJECTIVES: Fetal brain maturation is disrupted by preterm birth. Inflammation during the neonatal period may further harm neurodevelopmental outcomes. The present study aimed to determine the effect of short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides/pectin-derived acidic oligosaccharides (scGOS/lcFOS/pAOS) on neurodevelopmental outcomes measured by Bayley Scales of Infant and Toddler Development in preterm infants at 24 months. METHODS: In this randomized controlled trial, scGOS/lcFOS/pAOS or placebo was supplemented between days 3 and 30 of life. Serum samples at day 1, 7, and 14 were analyzed for cytokine levels. Stool samples at day 1, 7, 14, and 30 were measured for bacterial count and bifidobacteria percentage. At 24 months corrected age infants were followed up by a blinded pediatric psychologist for the Bayley Scales of Infant and Toddler Development II or III. RESULTS: Seventy-seven of one hundred one (76%) eligible infants participated in the follow-up study. Neurodevelopmental outcomes were not different in the scGOS/lcFOS/pAOS and placebo group. Infections during the neonatal period, lower percentages of bifidobacteria at day 7 (F = 3.8, P = 0.05) and day 14 (F = 5.0, P = 0.02) and higher levels of Interleukine (IL)-1ß (F = 4.0, P = 0.04) and IL-8 (F = 8.0, P = 0.01) at day 7 are associated with lower mental developmental index. Lower psychomotor outcomes are associated with IL-2 (F = 4.0, P = 0.05), IL-4 (F = 6.0, P = 0.02) at birth, and interferon gamma at day 7 (F = 4.4, P = 0.04). CONCLUSIONS: scGOS/lcFOS/pAOS showed no significant improvement of neurodevelopmental outcomes at 24 months in preterm infants. Infections, lower bifidobacteria counts, and higher serum cytokine levels during the neonatal period were associated with lower neurodevelopmental outcomes at 24 months of age indicating the relevance of microbiome and immune responses in neurodevelopmental processes.

Helicobacter pylori Infection in Pediatrics.

This review includes the main pediatric studies published from April 2014 to March 2015. The host response of Treg cells with increases in FOXP3 and TGF-ß1 combined with a reduction in IFN-γ by Teff cells may contribute to Helicobacter pylori susceptibility in children. Genotypic variability in H. pylori strains influences the clinical manifestation of the infection. Helicobacter pylori infection is associated with variables indicative of a crowded environment and poor living conditions, while breast-feeding has a protective effect. Intrafamilial infection, especially from mother to children and from sibling to sibling, is the dominant transmission route. Studies showed conflicting results regarding the association between H. pylori infection and iron deficiency anemia. One study suggests that H. pylori eradication plays a role in the management of chronic immune thrombocytopenic purpura in H. pylori-infected children and adolescents. The prevalence of H. pylori was higher in chronic urticaria patients than in controls and, following H. pylori eradication, urticarial symptoms disappeared. An inverse relationship between H. pylori infection and allergic disease was reported. Antibiotic resistance and insufficient compliance to treatment limit the efficacy of eradication therapy. Sequential therapy had no advantage over standard triple therapy. In countries where H. pylori infection is prevalent, studies focusing on virulence factors and antibiotic susceptibility may provide anticipation of the prognosis and may be helpful to reduce morbidity and mortality.

Association of late-onset neonatal sepsis with late neurodevelopment in the first two years of life of preterm infants with very low birth weight / Associação de sepse neonatal tardia com atraso do neurodesenvolvimento nos primeiros dois anos de vida de recém-nascidos pré-termos de muito baixo peso

OBJECTIVE: To establish the influence of late-onset sepsis on neurodevelopment of preterm infants with very low birth weight (VLBW), according to the etiologic agent METHOD: This was a cohort of newborns with birth weight < 1,500 g and gestational age less than 32 weeks, admitted to the institutional intensive care unit (ICU) with up to 48 hours of life, and followed-up at the outpatient follow-up clinic for preterm infants with VLBW until 2 years of corrected age. Exclusion criteria: death within the first 72 hours of life, congenital malformations and genetic syndromes, children with congenital infection by the human immunodeficiency virus (HIV), congenital infection (STORCH), presence of early-onset spesis and cases with more than one pathogen growth in blood cultures. Septic and non-septic infants were compared regarding neonatal outcomes and mortality. Neurodevelopment was assessed using the Bayley Scale (BSDI-II) at 18 to 24 months of corrected age. RESULTS: 411 preterm infants with VLBW were eligible; the mean gestational age was 29 ± 2.2 weeks and mean birth weight was 1,041 ± 281grams. Late-onset sepsis occurred in 94 preterm infants with VLBW (22.8%). VLBW infants with Gram-positive infection showed motor deficit when compared to the non-septic group, 68.8% vs. 29.3%, respectively (OR 6; 1.6-21.8, p = 0.006); the cognitive development was similar between the groups. The overall mortality rate from infection was 26.7%; considering the pathogens, the rates were 18.7% for coagulase-negative Staphylococcus, 21.8% for Gram-positive bacteria, and 50% for Gram-negative bacteria and fungi. CONCLUSION: Neonatal sepsis has a significant influence on late neurodevelopment at 2 years of corrected age in preterm infants with VLBW, and Gram-positive infections are associated with motor deficit. .

OBJETIVO: Estabelecer a influência da sepse tardia no neurodesenvolvimento de prematuros de muito baixo peso (MBP) recém-nascidos (RNs) de acordo com o agente etiológico. MÉTODOS: Coorte de RN com peso de nascimento < 1.500 g e idade gestacional < 32 semanas,internados na UTI da instituição dentro de 48 horas de vida, e atendidos no ambulatório de MBP para até dois anos de idade corrigida. Foram excluídos: a morte nas primeiras 72 h de vida, malformações congênitas e síndromes genéticas, filhos de mães HIV-positivas e infecção congênita, presença de sepse precoce, e os casos com mais de um microorganismo identificado em hemoculturas. RNs sépticos e não sépticos foram comparados quanto resultados neonatais, mortalidade e neurodesenvolvimento avaliados através das escalas Bayley (BSDI-II) aos 18-24 meses de idade corrigida. RESULTADOS: Um total de 411 RNs prematuros de muito baixo peso eram elegíveis, com idade gestacional = 29 ± 2,2 semanas e peso de nascimento = 1.041 ± 281 g. Sepse tardia ocorreu em 94 casos (22,8%). MBP RN com infecção causada por microrganismos Gram-positivos apresentaram atraso motor, quando comparado com o grupo sem sépsis - 68,8% vs 29,3% (OR 6; 1,6-21,8,p = 0,006), e atraso cognitivo, foi semelhante. Taxa de mortalidade global de infecção foi de 26,7%, e as taxas de mortalidade por grupo microorganismo foram: Staphylococcus coagulase negativa, 18,7%; Gram-positivos, 21,8%; Gram-negativas e fungos, 50%. CONCLUSÃO: A sepse neonatal tem uma influência significativa no atraso no desenvolvi mento neuropsicomotor aos dois anos de idade corrigida em prematuros de muito baixo peso RN e as infecções por germes gram-positivos estão associadas com atraso motor. .

Association of late-onset neonatal sepsis with late neurodevelopment in the first two years of life of preterm infants with very low birth weight.

OBJECTIVE: To establish the influence of late-onset sepsis on neurodevelopment of preterm infants with very low birth weight (VLBW), according to the etiologic agent. METHOD: This was a cohort of newborns with birth weight<1,500 g and gestational age less than 32 weeks, admitted to the institutional intensive care unit (ICU) with up to 48 hours of life, and followed-up at the outpatient follow-up clinic for preterm infants with VLBW until 2 years of corrected age. EXCLUSION CRITERIA: death within the first 72 hours of life, congenital malformations and genetic syndromes, children with congenital infection by the human immunodeficiency virus (HIV), congenital infection (STORCH), presence of early-onset sepsis and cases with more than one pathogen growth in blood cultures. Septic and non-septic infants were compared regarding neonatal outcomes and mortality. Neurodevelopment was assessed using the Bayley Scale (BSDI-II) at 18 to 24 months of corrected age. RESULTS: 411 preterm infants with VLBW were eligible; the mean gestational age was 29 ± 2.2 weeks and mean birth weight was 1,041 ± 281 grams. Late-onset sepsis occurred in 94 preterm infants with VLBW (22.8%). VLBW infants with Gram-positive infection showed motor deficit when compared to the non-septic group, 68.8% vs. 29.3%, respectively (OR 6; 1.6-21.8, p=0.006); the cognitive development was similar between the groups. The overall mortality rate from infection was 26.7%; considering the pathogens, the rates were 18.7% for coagulase-negative Staphylococcus, 21.8% for Gram-positive bacteria, and 50% for Gram-negative bacteria and fungi. CONCLUSION: Neonatal sepsis has a significant influence on late neurodevelopment at 2 years of corrected age in preterm infants with VLBW, and Gram-positive infections are associated with motor deficit.

Impact of sepsis on neurodevelopmental outcome in a Swiss National Cohort of extremely premature infants.

OBJECTIVE: Neonatal sepsis causes high mortality and morbidity in preterm infants, but less is known regarding the long-term outcome after sepsis. This study aimed to determine the impact of sepsis on neurodevelopment at 2 years' corrected age in extremely preterm infants. PATIENTS AND METHODS: This was a multicenter Swiss cohort study on infants born between 2000 and 2007 at 24(0/7) to 27(6/7) weeks' gestational age. Neurodevelopmental outcome was assessed with the Bayley Scales of Infant Development-II. Neurodevelopmental impairment (NDI) was defined as a Mental or Psychomotor Developmental Index lower than 70, cerebral palsy (CP), or visual or auditory impairment. RESULTS: Of 541 infants, 136 (25%) had proven sepsis, 169 (31%) had suspected sepsis, and 236 (44%) had no signs of infection. CP occurred in 14 of 136 (10%) infants with proven sepsis compared with 10 of 236 (4%) uninfected infants (odds ratio [OR]: 2.90 [95% confidence interval (CI): 1.22-6.89]; P = .016). NDI occurred in 46 of 134 (34%) infants with proven sepsis compared with 55 of 235 (23%) uninfected infants (OR: 1.85 [95% CI: 1.12-3.05]; P = .016). Multivariable analysis confirmed that proven sepsis independently increased the risk of CP (OR: 3.23 [95% CI: 1.23-8.48]; P = .017) and NDI (OR: 1.69 [95% CI: 0.96-2.98]; P = .067). In contrast, suspected sepsis was not associated with neurodevelopmental outcome (P > .05). The presence of bronchopulmonary dysplasia, pathologic brain ultrasonography, retinopathy, and sepsis predicted the risk of NDI (P < .0001). CONCLUSIONS: Proven sepsis significantly contributes to NDI in extremely preterm infants, independent of other risk factors. Better strategies aimed at reducing the incidence of sepsis in this highly vulnerable population are needed.

Pediatric autoimmune neuropsychiatric disorders associated with Streptococcus in identical siblings.

Termed pediatric autoimmune neuropsychiatric disorders associated with Streptococcus (PANDAS), these cases of childhood-onset obsessive compulsive disorder and tic disorders resemble the presentation of Sydenham chorea, in that they have an acute onset following a group A beta-hemolytic streptococcal infection (group A Streptococcus), with accompanying neurological signs, and an episodic or sawtooth course. Familial associations of this subgroup of patients remain understudied. This report provides phenotypic descriptions of three youth with PANDAS as well as their genetically identical siblings (in two cases of twins and one case of triplets). These cases highlight the potential for environmental influences for discordant presentations in genetically identical siblings. Despite identical genetics, presentations showed marked variation across siblings (from a full PANDAS presentation to asymptomatic). Further research into environmentally driven influences such as postinfectious molecular mimicry and epigenetic factors that may influence the manifestation of these pediatric neuropsychiatric disorders will promote our understanding of their prevention and treatment.

Early influences and childhood development. Does helicobacter play a role?

In the late 1960s, Rene Dubos showed that a variety of nutritional stress in utero or in early infancy could have dramatic impact on childhood development that was irreversible. This included detectable changes in the brain. Since that time, iron deficiency anemia (IDA) has been identified as one of the major nutritional stresses that leads to permanent behavioral changes in both experimental animals and humans resulting in poorer cognitive, motor, and social-emotional function. It has been proposed that these changes play an important part in the inter-generational transmission of poverty. More recently, it is becoming clear that Helicobacter pylori causes IDA in populations on an iron-limiting diet. The main thesis of this article is that H. pylori infection may indeed have an impact on childhood development and that much more research is needed in this area as intervention via immunization or antimicrobial therapy in populations in the developing world may have major positive benefits via cure of IDA and prevention of brain damage in the young.

Group A streptococcal meningitis as a complication of an infected capillary haemangioma.

UNLABELLED: We report a case of group A streptococcal meningitis in an infant resulting from an infected capillary haemangioma. The child suffered significant morbidity including cerebral infarction, epilepsy, and developmental delay. Treatment of infected capillary haemangiomas remains controversial and inconsistent. CONCLUSION: Our experience of this infant, resulting in profound neurological morbidity suggests that group A Streptococcus can be a virulent organism in the young child and that capillary haemangiomas must be treated aggressively at the first sign of infection.

[Obsessive-compulsive disorders in children. Subtypes of OCD and their relation to infection with group A streptococci]. / Obsessiv-kompulsiv tilstand hos børn. Undertyper af OCD og deres relation til infektion med gruppe-A-beta-haemolytiske streptokokker.

The present review describes the theory of a spectrum of obsessive-compulsive disorders (OCD). This spectrum includes such disorders as trichotillomania, eating disorders, body dysmorphic disorder, and possibly pervasive developmental disorders. OCD with an onset in childhood is presented as a specific subtype, with more boys affected and frequently co-morbid with tics and Tourette's syndrome. Furthermore, it seems to be more genetically determined and have more significant deviations, as measured by neuro-imaging studies, than has OCD with an adult onset. The PANDAS theory (paediatric autoimmune neuropsychiatric disorder associated with streptococcal infections) is described. This subtype of OCD is, still on a speculative basis, connected to infections with beta-haemolytic streptococci. The obsessive-compulsive symptoms are characterised by a sudden onset, "sawtoothed" course with relapses and remissions, and are associated with neurological abnormalities. There are still no clinical consequences in terms of penicillin treatment of this PANDAS subtype of OCD.

Long-term outcomes of childhood meningitis.

Meningitis and meningococcal disease remain a major source of anxiety to paediatricians and parents alike. Survival rates have improved with rapid diagnosis and appropriate management. However, survivors remain at risk of long-term neurodevelopmental sequelae.

Perinatal infections and brain injury: current treatment options.

Antimicrobial therapy can ameliorate infection and prevent long-term morbidity caused by several pathogens that infect the fetus and neonate. Ultimately, however, preventive strategies need to be developed and incorporated into routine preconceptional care. The future of prevention lies in immunizations, and if past and current successes with smallpox, polio, rubella, and measles vaccination programs are any indication, the future is bright for the developing fetus.

Neurological soft signs in mainstream pupils.

AIMS: (1) To examine the relation between neurological soft signs and measures of cognition, coordination, and behaviour in mainstream schoolchildren. (2) To determine whether high soft sign scores may predict children with significant problems in other areas. METHODS: A total of 169 children aged between 8 and 13 years from mainstream schools were assessed. They form part of a larger study into the outcome of meningococcal disease in childhood. Half had previous meningococcal disease and half were controls. Assessment involved measurement of six soft signs followed by assessment of motor skills (movement ABC), cognitive function (WISC-III), and behaviour (Conners' Rating Scales). RESULTS: Children having an age corrected soft sign score above the 90th centile were considered to have an excess of soft signs. When compared to the other children they had significantly worse scores on the other three measures. Median movement ABC score was 15.3 v 7. Mean total IQ scores were lower by 10.3 points. Median behaviour scores were significantly higher on both parental and teacher questionnaires. A soft sign score above the 90th centile had a sensitivity of 38% for detecting cognitive impairment, 42% for detecting coordination problems, and 25% for detecting possible attention deficit hyperactivity disorder. CONCLUSION: In this group of children higher scores on the soft sign battery were related to significantly worse performance on measures of cognition, coordination, and behaviour. However, although soft sign assessment may be of interest it cannot accurately predict which children are likely to have impairment in other areas.