Causation in cerebral palsy: Parental beliefs and associated emotions.

AIM: To better understand parents' beliefs about causation in cerebral palsy (CP) and the emotions related to those beliefs. METHOD: We surveyed 226 parents of children with CP aged 1 to 18 years, recruited from the Victorian Cerebral Palsy Register, to evaluate their beliefs about the causes of CP, including genetic causes, causes specific to their own child, and their attitudes and emotions in relation to these. RESULTS: Although 92% of participants reported that understanding the causes of their child's CP was important, uncertainty about the cause was expressed by 13%. The most frequently endorsed causal factors, in general and in their own child respectively, were intrapartum hypoxia (81%, 36%) or brain damage (69%, 22%), brain damage during pregnancy (73%, 28%), and preterm birth (66%, 28%). Genetic causes were deemed relevant by 13% of participants and hospital or professional error by 16%. Parents shared related feelings of anger (59%), sadness (80%), guilt (61%), and confusion (53%); parental anger was more likely when their child's CP was attributed to intrapartum events. INTERPRETATION: Substantial parental interest in understanding the causes of CP, together with uncertainty about the causes, parents' causal attributions, and significant emotional sequelae, highlight a strong need for provision of information and support for families of children recently diagnosed with CP. WHAT THIS PAPER ADDS: Understanding the causes of their child's cerebral palsy (CP) was important to parents. Parents most often endorsed intrapartum factors as a cause of CP. Parents reported experiencing strong emotions about the causes of their child's CP.

Neonatal well-being and timing of brain injury in persons with cerebral palsy born at term or late preterm.

AIM: To describe the distribution of neuroimaging patterns in a term/late preterm population-based cohort with cerebral palsy (CP), ascertain associations between neuroimaging patterns and neonatal well-being, estimate the proportion with antenatal or perinatal timing of neuropathology, and apply this information to the understanding of common mechanisms of brain injury and causal pathways. METHOD: The cohort for this observational study comprised 1348 persons born between 1999 and 2017 in Victoria, Australia. Using algorithms designed for the study, neonatal well-being and timing of brain injury were tabulated for the whole cohort and across neuroimaging patterns and birth epochs. RESULTS: Clinical and demographic profiles, neonatal well-being, and timing of brain injury differed across neuroimaging patterns. An estimated 57% of the cohort had a complicated neonatal period. Timing of brain injury was antenatal in 57% and perinatal in 41%. A decrease in the relative proportions of perinatal timing of brain injury was observed over a period when the rates of CP in live births at term decreased. INTERPRETATION: This study begins to bridge the knowledge gap about causation in CP, moving towards better description of the main mechanisms of brain injury and their contribution within CP cohorts, and facilitating the ability to monitor changes over time and the success of preventive measures. WHAT THIS PAPER ADDS: In a population-based, term/late preterm cohort with cerebral palsy, 57% had a complicated neonatal period. In the same cohort, 57% had presumed antenatal timing of brain injury. The relative proportion with perinatal injury decreased over time.

Survival of individuals with cerebral palsy in Victoria, Australia: A longitudinal cohort study spanning four decades.

AIM: To provide an updated description of the rates, trends, and predictors of mortality of individuals with cerebral palsy (CP), born in the Australian state of Victoria between 1970 and 2012. METHOD: Data were extracted for 4807 individuals (2091 females; 2716 males). The probability of survival to 30th June 2017 was calculated using the Kaplan-Meier method. Mortality rates were calculated per 1000 person-years using age strata and compared with population mortality rates to produce mortality ratios. Cox proportional hazards regression was used to calculate hazard ratios for selected demographic and clinical characteristics and to estimate the effect of birth epoch on 15-year survival. RESULTS: There were 666 recorded deaths. Compared to the general population, mortality was higher for all persons with CP and highest for children aged 1 to 15 years (45-62 times). We observed 35% improvement in the probability of survival to 15 years for births in the 2000s relative to the 1970s (hazard ratio 0.65, 95% confidence interval [CI] 0.49, 0.86), but only 4% improvement for the subgroup with complex CP (hazard ratio 0.96, 95% CI 0.69, 1.33). INTERPRETATION: The observed improvements in survival for those born in the 2000s is likely related predominantly to a proportional reduction in complex CP within the cohort. WHAT THIS PAPER ADDS: Length of survival improved for Australians with cerebral palsy (CP) born this millennium. Improved survival was mainly because of a proportional reduction in complex CP. A small improvement in length of survival was seen for children with complex CP.

Developmental outcomes for survivors of placental laser photocoagulation for the management of twin-to-twin transfusion syndrome.

BACKGROUND: Fetoscopic laser coagulation of placental anastomoses reverses the pathological process in twin-to-twin transfusion syndrome, thereby increasing survival, but there are a paucity of studies addressing long-term neurodevelopmental outcome of survivors. This study aimed to ascertain the presence of neurodevelopmental disabilities in child survivors of monochorionic pregnancies managed by placental laser photocoagulation in the Australian state of Victoria. METHODS: All pregnancies undergoing placental laser photocoagulation with the Victorian Fetal Therapy Service between 2006-2017 were included. Information on each surviving child, including demographics, perinatal course, and developmental progress was collected from parents, and consent was sought to complete the Child Behaviour Checklist. Interviewers evaluated whether this information was consistent with a diagnosis of any of 14 neurodevelopmental conditions. A three-tiered outcome measure was allocated for each child: (1) unimpaired or developmentally normal, (2) mild or moderate neurological impairment, or (3) severe neurological impairment. Clinical predictors for adverse outcome were identified. RESULTS: Of 116 pregnancies (113 twin, 3 triplet), 96 (83%) resulted in 1 + surviving fetuses. 57/113 (50%) twin pregnancies resulted in 2 survivors, 36 (32%) in 1 survivor, and 20 (18%) in no survivors. Of the 235 fetuses, 154 (65.5%) survived to follow-up. Survival increased from 59% in 2006-2008 to 73% in 2015-2017. 90/154 (58%) survivors were followed up at a mean age of 7.5 [SD 3.0] years. Based on parental interview and Child Behaviour Checklist data, 28/90 (31%) participants were assessed as having neurodevelopmental impairment, 27 of mild-moderate severity and 1 severe. Speech/language disorders, attention deficit (hyperactivity) disorders, and fine motor impairment were most common. Neonatal length of stay conferred the highest risk of impairment. CONCLUSION: Substantial variation exists between fetal therapy services in the type and length of neonatal follow-up following fetoscopic laser coagulation, contributing to a lack of data on long-term outcomes. The findings from this study support increasingly urgent calls to undertake systematic and sustained follow-up of fetoscopic laser coagulation survivors until school age. Information from this study may assist parents in their decision-making when offered fetal surgery. Importantly, it highlights a group for targeted surveillance and early intervention.

Anticholinergic medications for reducing drooling in children with developmental disability.

AIM: To determine: the effectiveness of three anticholinergic medications in reducing drooling in children with developmental disabilities (such as cerebral palsy, intellectual disability, and autism spectrum disorder), the frequency and nature of side effects, and their impact on treatment discontinuation. METHOD: After prescription of benzhexol hydrochloride, glycopyrrolate, or scopolamine patches at a tertiary saliva control clinic, all carers of 110 consecutive, eligible patients were recruited over a 5-year period. They provided data for 52 weeks, or until drug discontinuation, on compliance, drooling, adverse effects, and reasons for cessation. We evaluated and compared best drooling response, side effects, and drug cessation rates using survival analysis, and the effect of baseline variables on the discontinuation rate using proportional hazards regression. RESULTS: Among 110 participants (71 males, 39 females; mean age 8y 5mo [SD 4y 3mo], range 1y 11mo-18y 11mo), benzhexol, glycopyrrolate, and scopolamine were prescribed 81, 62, and 17 times respectively, with respective response rates of 85%, 75%, and 65%. Poor head control and poor oromotor function were predictive of poor response. Side effects frequently prompted drug cessation in males more than females (hazard ratio 1.8 [95% confidence interval 1.0-3.2], p=0.048). Glycopyrrolate had the fewest side effects. INTERPRETATION: Benzhexol, glycopyrrolate, and scopolamine reduce drooling, but improvement is offset by adverse side effects. Overall, glycopyrrolate performs best. WHAT THIS PAPER ADDS: In drooling, glycopyrrolate produced the greatest improvement with fewer side effects compared with benzhexol and scopolamine. Poor head control and poor oromotor function were associated with poor response. Medication side effects were common and often led to treatment discontinuation. Behavioural issues instigated cessation of benzhexol more often in males than females.

MEDICAMENTOS ANTICOLINÉRGICOS PARA REDUCIR EL BABEO EN NIÑOS CON TRASTORNOS DEL DESARROLLO: OBJETIVO: Determinar: la eficacia de tres medicamentos anticolinérgicos en la reducción del babeo en niños con trastornos del desarrollo (como parálisis cerebral, discapacidad intelectual y el trastorno del espectro autista), la frecuencia y la naturaleza de los efectos secundarios y su impacto en la interrupción del tratamiento. MÉTODO: Después de la prescripción de trihexifenidilo, glicopirrolato o parches de escopolamina en una clínica terciaria de control de saliva, fueron reclutados los cuidadores de 110 pacientes elegibles durante un período de 5 años. Estos proporcionaron datos sobre el cumplimiento, babeo, efectos adversos y razones para el cese, durante 52 semanas o hasta la interrupción del medicamento. Se evaluó y comparó la mejor respuesta al babeo, efectos secundarios y tasas de cese de drogas, utilizando el análisis de supervivencia y el efecto de las variables basales en la tasa de interrupción utilizando el modelo de riesgos proporcionales. RESULTADOS: Entre 110 participantes (71 varones y 39 mujeres; edad promedio de 8 años 5 meses [DE 4 años 3 meses], con rango de 1 año 11 meses - 18 años 11 meses), se prescribió trihexifenidilo, glicopirrolato y escopolamina, 81, 62, y 17 veces respectivamente, con tasas de respuesta respectivas de 85%, 75% y 65%. El pobre control cefálico y la mala función oromotora eran predictores de una respuesta deficiente. Los efectos secundarios provocaron el cese de las drogas con más frecuencia en los varones que en las mujeres (relación de riesgo 1,8 [intervalo de confianza del 95% 1,0-3,2], p 0,048). Glicopirrolato tuvo el menor número de efectos adversos INTERPRETACIÓN: El trihexifenidilo, el glicopirrolato y la escopolamina reducen el babeo, sin embargo, la mejora se contrarresta por los efectos secundarios. En general, el glicopirrolato tiene mejores resultados.

MEDICAÇÕES ANTICOLINÉRGICAS PARA REDUZIR SIALORRÉIA EM CRIANÇAS COM DEFICIÊNCIAS DESENVOLVIMENTAIS: OBJETIVO: Determinar: a efetividade de três medicações anticolinérgicas na redução da sialorréia em crianças com deficiências desenvolvimentais (como paralisia cerebral, deficiência intelectual, e transtorno do espectro autista), a frequência e natureza dos efeitos colaterais, e seu impacto na descontinuação do tratamento. MÉTODO: Após prescrição de hidroclorido benzexol, glicopirrolato, ou faixas de escopolamina em uma clínica terciária de controle da salivação, todos os cuidadores de 110 pacientes elegíveis consecutivos foram recrutados em um período de 5 anos. Eles forneceram dados de 52 semanas, ou até a descontinuação da medicação, sobre adesão, sialorréia, efeitos adversos, e razões para interrupção. Avaliamos e comparamos a melhor resposta para salivação, efeitos colaterais e interrupção da medicação usando análise de sobrevivência, e o efeito das variáveis na linha de base na taxa de descontinuação usando regressão de riscos proporcionais. RESULTADOS: Entre 110 participantes (71 do sexo masculino, 39 do sexo feminino; média de idade 8a 5m [DP 4a 3m], variação 1a 11m-18a 11m), benzexol, glicopirrolato, e escopolamina foram prescritos 81, 62, e 17 vezes respectivamente, com as respectivas taxas de resposta de 85%, 75%, and 65%. Pouco controle de cabeça e função oromotora foram preditivos de pior resposta. Efeitos colaterais mais frequentemente causaram interrupção da medicação em meninos do que em meninas (taxa de risco 1,8 [intervalo de confiança a 95% 1,0-3,2], p=0,048). Glicopirrolato teve menos efeitos colaterais. INTERPRETAÇÃO: Benzexol, glicopirrolato, ou escopolamina reduzem a sialorréia, mas as melhoras são atenuadas pelos efeitos colaterais. Em geral, glicopirrolato teve o melhor desempenho.

Twin-to-twin transfusion syndrome neurodevelopmental follow-up study (neurodevelopmental outcomes for children whose twin-to-twin transfusion syndrome was treated with placental laser photocoagulation).

BACKGROUND: Twin-to-twin transfusion syndrome (TTTS) is a serious complication of 10-15% of twin or triplet pregnancies in which multiple fetuses share a single placenta. Communicating placental vessels allow one fetus (the donor) to pump blood to the other (the recipient). Mortality rates without intervention are high, approaching 100% in some series, with fetal deaths usually due to cardiac failure. Surgical correction using laser photocoagulation of communicating placental vessels was developed in the 1980s and refined in the 1990s. Since it was introduced in Victoria in 2006, laser surgery has been performed in approximately 120 pregnancies. Survival of one or more fetuses following laser surgery is currently > 90%, however the neurodevelopmental outcomes for survivors remain incompletely understood. Prior to laser therapy, at least one in five survivors of TTTS had serious adverse neurodevelopmental outcomes (usually cerebral palsy). Current estimates of neurological impairment among survivors following laser surgery vary from 4 to 31% and long-term follow-up data are limited. METHODS: This paper describes the methodology for a retrospective cohort study in which children aged 24 months and over (corrected for prematurity), who were treated with laser placental photocoagulation for TTTS at Monash Health in Victoria, Australia, will undergo comprehensive neurodevelopmental assessment by a multidisciplinary team. Evaluation will include parental completion of pre-assessment questionnaires of social and behavioural development, a standardised medical assessment by a developmental paediatrician or paediatric neurologist, and age-appropriate cognitive and academic, speech and fine and gross motor assessments by psychologists, speech and occupational therapists or physiotherapists. Assessments will be undertaken at the Murdoch Children's Research Institute/Royal Children's Hospital, at Monash Health or at another mutually agreed location. Results will be recorded in a secure online database which will facilitate future related research. DISCUSSION: This will be the first study to report and evaluate neurodevelopmental outcomes following laser surgery for twin-to-twin transfusion syndrome in Victoria, and will inform clinical practice regarding follow-up of children at risk of adverse outcomes.

Growth Trajectories in Genetic Subtypes of Prader-Willi Syndrome.

Prader-Willi syndrome (PWS) is a rare disorder caused by the loss of expression of genes on the paternal copy of chromosome 15q11-13. The main molecular subtypes of PWS are the deletion of 15q11-13 and non-deletion, and differences in neurobehavioral phenotype are recognized between the subtypes. This study aimed to investigate growth trajectories in PWS and associations between PWS subtype (deletion vs. non-deletion) and height, weight and body mass index (BMI). Growth data were available for 125 individuals with PWS (63 males, 62 females), of which 72 (57.6%) had the deletion subtype. There was a median of 28 observations per individual (range 2-85), producing 3565 data points distributed from birth to 18 years of age. Linear mixed models with cubic splines, subject-specific random effects and an autoregressive correlation structure were used to model the longitudinal growth data whilst accounting for the nature of repeated measures. Height was similar for males in both PWS subtypes, with non-deletion females being shorter than deletion females for older ages. Weight and BMI were estimated to be higher in the deletion subtype compared to the non-deletion subtype, with the size of difference increasing with advancing age for weight. These results suggest that individuals with deletion PWS are more prone to obesity.

Long-term impact of saliva control surgery in children with disability.

Sialorrhea is a common problem in children with disability, often negatively affecting socialization, self-esteem, and burden of care. Saliva control surgery is an available option to manage this problem, particularly when other conservative methods have failed. As little is known about the long-term impact of surgery, we followed up 62 patients who had combined bilateral submandibular duct translocation and bilateral sublingual gland excision at our pediatric hospital between 1994 and 2014. Eligible individuals were identified through a search of ICD procedure codes. When families of patients were contacted successfully, they were invited to complete a 14-item questionnaire designed specifically for this study. The results indicated that long-term outcomes of surgery were very good; 13/62 (21%) individuals no longer had a drooling problem and another 30 (48%) experienced only mild to moderate drooling. Although 84% families reported some or major improvement in drooling, 9 families reported that they would not go through the experience again because of a difficult recovery period, lack of effectiveness of the intervention, changes in saliva consistency that caused coughing and gagging, and dental decay. None of the collected variables were predictive of good or poor outcome. The study indicated that surgical intervention is effective in the long term in the majority of cases and can be recommended to other families who attend our saliva control clinic.