Heather Scott

Genetic susceptibility to viral exposure may increase the risk of cerebral palsy.

Aim: Cytokine polymorphisms may alter the fetal inflammatory response, increasing susceptibility to cerebral palsy (CP). This study investigates associations between selected inflammatory mediator and cytokine gene polymorphisms (Toll‐like receptor‐4 (TLR‐4) Asp299Gly, interleukin‐6 G‐174C and interleukin‐4 C‐589T) and CP from 443 CP infants and 883 control infants. Results were correlated with viral nucleic acids in the same samples.

The prevalence of inherited thrombophilias in a Caucasian Australian population.

Aims: To describe the prevalence of four inherited thrombophilias and their combinations for the first time in a large Caucasian Australian population. Methods: Newborn screening cards of 883 Caucasian babies born in South Australia in 1986–1999 were de‐identified and tested for the following inherited thrombophilic polymorphisms: factor V Leiden (G1691A), prothrombin gene mutation (G20210A), methylenetetrahydrofolate reductase gene (MTHFR) C677T and A1298C, as well as compound heterozygosity for the MTHFR polymorphisms. Results: The birth prevalences of heterozygosity and homozygosity for the four thrombophilic polymorphisms were: factor V Leiden 9.5% and 0.7%, prothrombin gene 4.1% and 0.2%, MTHFR C677T 37.3% and 12.4%, and MTHFR A1298C 38.3% and 11.8%, respectively. Compound heterozygosity for MTHFR C677T and A1298C was seen in 16.6% of the population. Overall, 64.2% and 24.5% of the population studied were homozygous and heterozygous, respectively, for at least one of the four polymorphisms studied. Conclusion: Inherited thrombophilic polymorphisms are common in the Caucasian Australian population. Knowledge of the background prevalence of these polymorphisms will allow further study of their associations in future disease research.

A special supplement: findings from the Australian Cerebral Palsy Register, birth years 1993 to 2006

To briefly outline the strengths and limitations of cerebral palsy (CP) registers, and to report on findings of the Australian Cerebral Palsy Register (ACPR) pertaining to a population cohort of children with CP.

Proposed new definition of cerebral palsy does not solve any of the problems of existing definitions.

‘Proposed new definition of cerebral palsy does not solve any of the problems of existing definitions’ SIR–The proposed new definition1 set out in the first sentence (32 words), is no shorter than that of Mutch et al.2 (31 words) and does not solve any of the problems of existing definitions. The second sentence does not add to the definition, as the comorbidities it describes may or may not be present. While brevity is a virtue, clarity is far more important, but we do not consider that the terms used in the new definition improve clarity. For example, ‘lesions or anomalies’ are replaced by ‘disturbances’ which suggests an active agent – does that exclude genetic anomalies? Furthermore, the new definition states that the disturbances which occurred in the past were non-progressive. What constitutes a non-progressive disturbance? For example, it might be argued that asphyxia is a progressive condition in that, after the initial hypoxic insult there is a biochemical cascade that creates much of the resulting damage. Surely, what the authors meant is that the lesion or anomaly in the brain, once recognized in early childhood, is no longer progressive. Knowledge of this fact, however protracted the development of the lesion or anomaly might have been in the past, is very important to the child, their family and caregivers, and has long been a criterion for belonging to the cerebral palsy (CP) group. With or without the long annotation, the phrase ‘developing fetal or infant brain’, adds no further clarity to the age range at which CP may be acquired than ‘in the early stages of development’ and we agree with Blair and Love that ‘activity limitation’ is too imprecise a term to define the lower limit of severity required to be included in the group, and may, therefore, be incorrect. In short, none of the aspects of previous definitions that could benefit from clarification appears to have been clarified by this new definition. The Australian Cerebral Palsy Register (ACPR) is a collaboration between CP registers in each of the States and Territories of Australia. We are committed to pooling the information on people with CP from the whole of our vast continent and are acutely aware both of the need for a valid and reproducible definition of CP and the difficulties in creating one. We are disappointed in this proposed new definition which seems to offer only new wording without additional clarity, and request that more thought be given to its further clarification.

Biological sex and the risk of cerebral palsy in Victoria, Australia

Males typically outnumber females in cerebral palsy (CP) cohorts. To better understand this ‘male disadvantage’ and provide insight into causal pathways to CP, this study used 1983 to 2009 Australian CP and population birth cohorts to identify associations and trends with respect to biological sex and CP.

Increase in late diagnosed developmental dysplasia of the hip in South Australia: risk factors, proposed solutions

Objectives: To review evidence for the increased incidence of late diagnosed developmental dysplasia of the hip (DDH) in South Australia; to identify perinatal risk factors associated with late DDH in babies born between 2003 and 2009 in SA.

Congenital anomalies in cerebral palsy: where to from here?

Proportions of cases of cerebral palsy (CP) with congenital anomalies recorded in Australian CP registers range from 15% to 40%. The anomalies seen in CP are extremely variable. We have identified that CP registers often do not have quality data on congenital anomalies, necessitating linkage with congenital anomaly registers. However, a lack of unified processes and definitions in congenital anomaly registers and data collections means that linkages are complex, need to be carefully planned, and limitations acknowledged. Historically in CP research, congenital anomalies have been classified by International Classification of Disease codes, then combined into brain and other major and minor anomalies. Systems have been developed to classify congenital anomalies into aetiologically related groups, but such a classification has yet to be trialled in CP. It is anticipated that primary prevention of a small proportion of cases of CP is possible through the primary prevention of congenital anomalies, especially those due to teratogens. Owing to the anticipated low prevalence of each subgroup, global collaboration will be required to further these lines of enquiry.

Reproductive Technologies and the Risk of Birth Defects

From the Robinson Institute (M.J.D., V.M.M., K.J.W.), Research Centre in the Early Origins of Health and Disease (M.J.D., V.M.M., K.J.W.), Discipline of Public Health (V.M.M., K.J.W.), and Discipline of Paediatrics and Reproductive Health (M.J.D., E.A.H.), University of Adelaide, the South Australian Birth Defects Register, Women’s and Children’s Hospital (P.V.E., H.S., E.A.H., A.C.), the Epidemiology Branch, South Australian Department of Health (K.P., A.C.), and the South Australian Clinical Genetics Service, SA Pathology (E.A.H.) — all in Adelaide, SA, Australia. Address reprint requests to Dr. Davies at the Robinson Institute, Medical School South, Frome Rd., Adelaide, SA 5005, Australia, or at michael.davies@adelaide.edu.au.

Age range for inclusion affects ascertainment by birth defects registers.

BACKGROUND The South Australian Birth Defects Register (SABDR) has collected the date of diagnosis of notified birth defects since the 2005 birth year cohort. This study aims to document the age at diagnosis for each of the main diagnostic categories of birth defects, to produce a profile of when defects are diagnosed. METHODS Deidentified data were extracted from the SABDR for birth years 2005 to 2007. Each birth defect was assigned to a mutually exclusive date of diagnosis category (termination/stillbirth; neonatal [birth-28 days]; 1 month-1 year; 1-2 years; 2-3 years; 3-4 years; 4-5 years; unspecified). Each defect was also grouped according to the International Classification of Diseases Ninth edition-British Paediatric Association major diagnostic categories (nervous, cardiovascular, respiratory, gastrointestinal, urogenital, musculoskeletal, chromosomal, metabolic, hematological/immune, other). RESULTS There were 6419 defects identified in 3676 individuals, and 98.6% of defects had a diagnosis date recorded. Terminations of pregnancy/stillbirths accounted for 20.3% of defects notified, and a further 46.7% of defects were diagnosed within the neonatal period. A total of 81.5% of defects were diagnosed by 1 year of age. An additional 17.2% of defects were diagnosed between the ages of 1 and 5 years. There were wide differences in age at diagnosis between the major diagnostic categories. CONCLUSION This study highlights the value of birth defect registers collecting information about birth defects from terminations of pregnancy, stillbirths, and live births up to a childs fifth birthday. Reviewing diagnosis date provides insight into the pattern of diagnosis of different birth defects. This provides valuable information to medical specialists and researchers regarding the interpretation of information from birth defect data collections. Birth Defects Research (Part A) 106:761-766, 2016.

Comprehensive investigation of congenital anomalies in cerebral palsy: protocol for a European-Australian population-based data linkage study (The Comprehensive CA-CP Study)

Introduction Cerebral palsy (CP), an umbrella term for non-progressive conditions of cerebral origin resulting in motor impairments, is collectively the most common cause of physical disability in childhood. Cerebral and/or non-cerebral congenital anomalies are present in 15%–40% of children with CP. In order to identify effective prevention strategies for this substantial proportion of CP, a comprehensive understanding of the epidemiology of these congenital anomalies is required. International collaboration is needed, as previous attempts have fallen short due to a lack of power, since the anomalies are individually rare and CP comprises many clinical descriptions. The aim of this study is to generate new knowledge about the aetiologies of CP through a focused investigation into the role of congenital anomalies. Methods and analysis This collaborative, population-based data linkage study includes nine geographic regions (six in Europe, three in Australia) served by both congenital anomaly and CP registers. Register data for children with CP (both with and without congenital anomalies) and children with specific congenital anomalies (without CP) born between 1991 and 2009 will be linked and de-identified within each region. The resulting linked data sets will be quality assured, recoded, harmonised and then pooled into one data set. Analysis of the combined data set will include: frequencies/proportions of congenital anomalies and outcomes (type of CP, severity, impairments); descriptive analyses comparing timing of congenital anomaly development and brain injury/abnormality responsible for CP; ORs to calculate the odds of CP following a specific congenital anomaly; and identification of anomalies on causal pathways to CP. Ethics and dissemination Ethics approval for this collaborative study, The Comprehensive CA-CP Study, has been obtained from the Cerebral Palsy Alliance Human Research Ethics Committee (EC00402). Study findings will be disseminated at conferences and published in peer-reviewed journals, and recommendations will be made regarding the collection and classification of congenital anomaly data by CP registers.