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This is a brief background paper for a supplementary issue of Developmental Medicine & Child Neurology by the Australian Cerebral Palsy Register Group. It provides context for the reader of the supplement including a description of the establishment and development of state and territory cerebral palsy registers in Australia. [ABSTRACT FROM AUTHOR]

The study of humpback whale song using passive acoustic monitoring devices requires bioacousticians to manually review hours of audio recordings to annotate the signals. To vastly reduce the time of manual annotation through automation, a machine learning model was developed. Convolutional neural networks have made major advances in the previous decade, leading to a wide range of applications, including the detection of frequency modulated vocalizations by cetaceans. A large dataset of over 60 000 audio segments of 4 s length is collected from the North Atlantic and used to fine-tune an existing model for humpback whale song detection in the North Pacific (see Allen, Harvey, Harrell, Jansen, Merkens, Wall, Cattiau, and Oleson (2021). Front. Mar. Sci. 8, 607321). Furthermore, different data augmentation techniques (time-shift, noise augmentation, and masking) are used to artificially increase the variability within the training set. Retraining and augmentation yield F-score values of 0.88 on context window basis and 0.89 on hourly basis with false positive rates of 0.05 on context window basis and 0.01 on hourly basis. If necessary, usage and retraining of the existing model is made convenient by a framework (AcoDet, acoustic detector) built during this project. Combining the tools provided by this framework could save researchers hours of manual annotation time and, thus, accelerate their research., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).)

Aims: The primary aim of this study was to report the radiological outcomes of patients with a dorsally displaced distal radius fracture who were randomized to a moulded cast or surgical fixation with wires following manipulation and closed reduction of their fracture. The secondary aim was to correlate radiological outcomes with patient-reported outcome measures (PROMs) in the year following injury., Methods: Participants were recruited as part of DRAFFT2, a UK multicentre clinical trial. Participants were aged 16 years or over with a dorsally displaced distal radius fracture, and were eligible for the trial if they needed a manipulation of their fracture, as recommended by their treating surgeon. Participants were randomly allocated on a 1:1 ratio to moulded cast or Kirschner wires after manipulation of the fracture in the operating theatre. Standard posteroanterior and lateral radiographs were performed in the radiology department of participating centres at the time of the patient's initial assessment in the emergency department and six weeks postoperatively. Intraoperative fluoroscopic images taken at the time of fracture reduction were also assessed., Results: Patients treated with surgical fixation with wires had less dorsal angulation of the radius versus those treated in a moulded cast at six weeks after manipulation of the fracture; the mean difference of -4.13° was statistically significant (95% confidence interval 5.82 to -2.45). There was no evidence of a difference in radial shortening. However, there was no correlation between these radiological measurements and PROMs at any timepoint in the 12 months post-injury., Conclusion: For patients with a dorsally displaced distal radius fracture treated with a closed manipulation, surgical fixation with wires leads to less dorsal angulation on radiographs at six weeks compared with patients treated in a moulded plaster cast alone. However, the difference in dorsal angulation was small and did not correlate with patient-reported pain and function., Competing Interests: The authors disclose that the UK National Institute for Health Research (NIHR) provided grant funding for the DRAFFT2 trial. The research was supported by the NIHR Oxford Biomedical Research Centre (BRC). In addition, M. L. Costa declares that the University of Oxford receives research grant funding from the NIHR and Wellcome for research into musculoskeletal trauma., (© 2024 Costa et al.)

Objective: To report the prevalence of cerebral palsy (CP) in children with severe congenital heart defects (sCHD) and the outcome/severity of the CP., Methods: Population-based, data linkage study between CP and congenital anomaly registers in Europe and Australia. The EUROCAT definition of severe CHD (sCHD) was used. Linked data from 4 regions in Europe and 2 in Australia were included. All children born in the regions from 1991 through 2009 diagnosed with CP and/or sCHD were included. Linkage was completed locally. Deidentified linked data were pooled for analyses., Results: The study sample included 4989 children with CP and 3684 children with sCHD. The total number of livebirths in the population was 1 734 612. The prevalence of CP was 2.9 per 1000 births (95% CI, 2.8-3.0) and the prevalence of sCHD was 2.1 per 1000 births (95% CI, 2.1-2.2). Of children with sCHD, 1.5% (n = 57) had a diagnosis of CP, of which 35 (61%) children had prenatally or perinatally acquired CP (resulting from a brain injury at ≤28 days of life) and 22 (39%) children had a postneonatal cause (a brain injury between 28 days and 2 years). Children with CP and sCHD more often had unilateral spastic CP and more intellectual impairments than children with CP without congenital anomalies., Conclusions: In high-income countries, the proportion of children with CP is much higher in children with sCHD than in the background population. The severity of disease in children with CP and sCHD is milder compared with children with CP without congenital anomalies., Competing Interests: Declaration of Competing Interest Funding support received for the overarching Comprehensive CA-CP Study: the Cerebral Palsy Alliance Research Foundation (The Comprehensive CA-CP Study PG1215 and PG2816 and salary support from Cerebral Palsy Alliance Research Foundation (S.G., S.M., H.S.S., N.B.). The study sponsors played no role in the study or the paper. The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Diagnostic needle arthroscopy offers an alternative imaging modality to magnetic resonance imaging (MRI) for the diagnosis of intra-articular pathology., Purpose: To compare the accuracy of a needle arthroscopy device (Mi-eye2) versus MRI in identifying intra-articular anatomic abnormalities in the glenohumeral joint, with formal arthroscopy as the gold standard., Study Design: Cohort study; Level of evidence, 2., Methods: A total of 22 patients underwent diagnostic needle arthroscopy of the shoulder, of whom 20 had preoperative MRI scans. A standardized 12-point noninstrumented diagnostic arthroscopy was performed on each patient using the 0° needle arthroscope, followed by a 30°, 4 mm-diameter conventional arthroscope. Intraoperative images were randomized and reviewed by 2 independent blinded fellowship-trained shoulder surgeons for identification of key pathology and anatomic structures. The MRI scans were reviewed by a single musculoskeletal radiologist to identify pathology in the same key areas., Results: For the identification of rotator cuff pathology, needle arthroscopy (sensitivity, 0.75; specificity, 1.00) was superior to MRI (sensitivity, 0.75; specificity, 0.75) with an interobserver reliability (κ) of 0.703. For long head of the biceps pathology, needle arthroscopy (sensitivity, 0.67; specificity, 0.95) was superior to MRI (sensitivity, 0.00; specificity, 0.83). It was less accurate for labral (sensitivity, 0.33; specificity, 0.50; κ = 0.522) and articular cartilage pathology (sensitivity, 0.00; specificity, 0.94; κ = 0.353). The number of anatomic structures that could be clearly identified was 8.35 of 12 (69.58%) for needle arthroscopy versus 10.35 of 12 (86.25%) for standard arthroscopy., Conclusion: Diagnostic needle arthroscopy was found to be more accurate than MRI for the diagnosis of rotator cuff and long head of the biceps pathology but was less accurate for diagnosing labral and cartilage pathology. Although the field of view of a 0° needle arthroscope is not equivalent to a 30° conventional arthroscope, it presents an alternative with potential for use in an outpatient setting., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: The Mi-eye2 devices used in the study were provided by Trice Medical. H.C. has received education support from Arthrex and consulting fees from Arthrex, Medartis, and Xiros. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2023.)

Aim: To investigate temporal trends in birth prevalence, disability severity, and motor type for singletons with prenatal or perinatally acquired cerebral palsy (CP)., Method: Numerator data, number of children with CP born a singleton between 1995 and 2014, confirmed at 5 years of age, were drawn from three state registers with population-level ascertainment. Birth prevalence estimates and 95% confidence intervals (CI) were calculated per 1000 singleton live births for the three states combined, overall, by gestational age group, by dichotomized disability severity, and spastic laterality. Poisson regression models were used to analyse trends. Using data from all eight registers, trends in the proportional distribution of CP subtypes overall and stratified by gestational age were examined., Results: Birth prevalence of CP declined from 1.8 (95% CI 1.6-2.0) in 1995 to 1996 to 1.2 (95% CI 1.1-1.4) in 2013 to 2014 (average 5% per 2-year epoch, p < 0.001). Declines in birth prevalence were observed across all gestational age groups with the largest decline in children born at <28 weeks (average 8% per epoch, p < 0.001). Prevalence of moderate-severe disability declined for children born at <28 and ≥37 weeks (average 11% and 7% per epoch respectively, p < 0.001). The proportions of bilateral spastic CP declined (p < 0.001) at <28 weeks (p = 0.014) and ≥37 weeks (p < 0.001). The proportion of children with dyskinesia increased (28-31 weeks: p = 0.021, 32-36 weeks: p = 0.001, and ≥37 weeks: p < 0.001)., Interpretation: Birth prevalence of CP and moderate-severe disability (<28 and ≥37 weeks) declined in Australian singletons between 1995 and 2014, reflecting changes in prenatal and perinatal care over time., What This Paper Adds: Declines in birth prevalence of prenatal or perinatally acquired cerebral palsy were observed for singletons born in Australia between 1995 and 2014. These declines were evident across all gestational age groups. Declines in birth prevalence of moderate-severe disability were observed for children born at <28 weeks and ≥37 weeks., (© 2022 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

ABSTRACTHip fracture rehabilitation has two streams: high tolerance short duration (HTSD) and low tolerance long duration (LTLD). This study examined patient characteristics and outcomes in HTSD and LTLD associated with length of stay (LOS) and discharge destination. We retrospectively examined patients' medical charts following hip fracture surgery and collected demographic, functional, and health characteristics. A statistical analysis was done to describe the differences between HTSD (n = 73) and LTLD (n = 57) patient characteristics and their relationship with LOS and discharge destination. Those in LTLD were significantly older, less independent with prefracture bathing and instrumental activities of daily living, had lower Functional Independence Measure (FIM) admission scores, and more co-morbidities. Higher FIM motor score on admission in HTSD and greater change in FIM total score in LTLD was significantly correlated with discharge home. Diabetes in LTLD and lower total admission FIM in HTSD was significantly associated with increased LOS.

Aim: 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., Method: Within birth gestation groups, sex ratios were calculated to evaluate any male excess in the CP cohort compared with livebirths, neonatal deaths, neonatal mortality and survival rates, neonatal survivors, and CP rates in survivors. Sex- and gestation-specific trends in neonatal mortality, CP rates, and CP sex ratios were assessed by plotting their annual frequencies and fitting quadratic curves., Results: Over-representation of males in preterm live births partly explained the male excess in the CP cohort after preterm birth, especially at 28 to 31 weeks. Higher CP rates in male neonatal survivors also contributed to the male excess in CP, particularly at <28 and 37+ weeks. Higher neonatal mortality rates in males at all gestations had little impact on the CP sex ratio. There was no clearly discernible change over time in the CP sex ratio., Interpretation: Gestation-specific associations between sex and CP provide insight into causal pathways to CP and suggest sex-specific differences in response to neuroprotective strategies., (© 2016 The Authors. Developmental Medicine & Child Neurology © 2016 Mac Keith Press.)

Aim: 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., Method: De-identified data were extracted from the ACPR for people with CP in birth years 1993 to 2006, from South Australia, Victoria, and Western Australia. Live birth prevalence of CP was estimated and risk factors described., Results: The overall birth prevalence of CP (including those whose CP was postneonatally acquired) for the 1993 to 2006 birth cohort was 2.1 per 1000 live births (95% confidence interval [CI] 2.0-2.2). Excluding cases with a known postneonatal cause, the birth prevalence for pre/perinatally acquired CP was 2.0 per 1000 live births (95% CI 1.9-2.1). A downward trend in rates of CP in those born extremely preterm was evident over at least three consecutive periods across all three regions. Most (58.6%) children were born at term (≥ 37 wks). Male sex, early gestational age, low birthweight, and multiple birth were risk factors for CP., Interpretation: Overall rates of CP did not change during this period. The proportion of those with CP born extremely preterm decreased. The ACPR Group will investigate whether this pattern continues when data pertaining to the next birth cohort for all three regions becomes available., (© 2016 The Authors. Developmental Medicine & Child Neurology © 2016 Mac Keith Press.)

Unlabelled: Congenital cytomegalovirus (cCMV) is a contributing cause of neurodevelopmental disabilities including cerebral palsy (CP). In this case series we reviewed the neuroimaging findings of children with CP and cCMV infection in the context of the children's clinical profile., Participants: Children with CP and laboratory confirmed cCMV (n=12) reported to the Australian CP Register, born in South Australia and Victoria, 1993-2006, with magnetic resonance imaging (MRI) and/or computerized tomography (CT) report available. Clinical details and neuroimaging findings were tabulated and compared to published literature. Children in this series were mostly born at term (n=8), with symptoms or signs of cCMV (n=10) and had spastic quadriplegia (n=9), epilepsy (n=8), intellectual deficit (n=12), communication (n=10) and hearing impairments (n=9). All but one had abnormal neuroimaging findings reported on MRI or CT (n=11): most commonly brain malformations including disorders of neuronal migration (n=10), such as lissencephaly, pachygyria and polymicrogyria, and cerebellar hypoplasia (n=5). Other findings included ventricular dilatation (n=8), calcifications (n=7) and white matter abnormalities (n=6). This study suggests that brain malformations, calcifications, ventricular dilatation and cerebellar hypoplasia are common neuroimaging patterns in children with CP and cCMV infection. The presence of these findings should prompt investigations for congenital cytomegalovirus.

Objective: Previous studies have suggested associations between certain genetic variants and susceptibility to cerebral palsy (CP). This study was designed to assess established and novel maternal and child genetic and epidemiologic risk factors for CP along with their interactions., Methods: DNA from 587 case and 1154 control mother-child pairs was analyzed. A panel of 35 candidate single nucleotide polymorphisms (SNPs) were examined and included SNPs in genes associated with (1) thrombophilia, (2) inflammation, and (3) risk factors for CP (eg, preterm birth). Comparisons were specified a priori and made by using a χ(2) test., Results: There were 40 fetal and 28 maternal associations with CP when analyzed by CP subtype, gestational age, genotypes of apolipoprotein E, and haplotypes of mannose-binding-lectin. After Bonferroni correction for multiple testing, no fetal or maternal candidate SNP was associated with CP or its subtypes. Only fetal carriage of prothrombin gene mutation remained marginally associated with hemiplegia in term infants born to mothers with a reported infection during pregnancy. Odds ratio directions of fetal SNP associations were compared with previously reported studies and confirmed no trend toward association., Conclusions: Except for the prothrombin gene mutation, individual maternal and fetal SNPs in our candidate panel were not found to be associated with CP outcome. Past reported SNP associations with CP were not confirmed, possibly reflecting type I error from small numbers and multiple testing in the original reports.

Objective: To investigate if carriage of interleukin 1 (IL-1) receptor antagonist gene variants are associated with sudden infant death syndrome (SIDS) in a large cohort of case-control demographically matched infants., Design: 118 SIDS and 233 control infants, who were matched to each SIDS infant by date of birth, sex, birth weight (±500 g), gestational age and ethnicity, were genotyped for an IL-1RN 89 bp tandem repeat polymorphism and analysed for significant associations., Results: No significant difference in genotype frequencies was observed between low and normal birthweight infants and year of birth (1987-1994, when the SIDS incidence was higher). In infants born between 1987 and 1994, an association was observed with SIDS and allele 2 where 18% of SIDS infants carried the 2/2 genotype compared with 9% of controls (χ(2) p=0.026, OR 2.46). Allele 3 was found at a low frequency, but was significantly more common in SIDS infants (3.1%) compared with controls (0.9%, Fisher's exact p=0.04, OR 3.76)., Conclusion: The higher prevalence of IL-1RN allele 2, which predisposes to poor outcomes from infection, in SIDS infants born between 1987 and 1994 (ie, prior to the dramatic decrease in SIDS incidence) suggests that the high incidence during this period could point to infection playing a role in aetiology. An association of IL-1RN allele 3 with SIDS was also found, but should be interpreted with caution due to the low frequency of this variant. The consequence of allele 3 carriage is currently unknown in the absence of functionality studies for this isoform.

We sought a convenient and reliable method for collection of genetic material that is inexpensive and noninvasive and suitable for self-collection and mailing and a compatible, commercial DNA extraction protocol to meet quantitative and qualitative requirements for high-throughput single nucleotide polymorphism (SNP) multiplex analysis on an automated platform. Buccal swabs were collected from 34 individuals as part of a pilot study to test commercially available buccal swabs and DNA extraction kits. DNA was quantified on a spectrofluorometer with Picogreen dsDNA prior to testing the DNA integrity with predesigned SNP multiplex assays. Based on the pilot study results, the Catch-All swabs and Isohelix buccal DNA isolation kit were selected for our high-throughput application and extended to a further 1140 samples as part of a large cohort study. The average DNA yield in the pilot study (n=34) was 1.94 microg +/- 0.54 with a 94% genotyping pass rate. For the high-throughput application (n=1140), the average DNA yield was 2.44 microg +/- 1.74 with a >or=93% genotyping pass rate. The Catch-All buccal swabs are a convenient and cost-effective alternative to blood sampling. Combined with the Isohelix buccal DNA isolation kit, they provided DNA of sufficient quantity and quality for high-throughput SNP multiplex analysis.

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., Results: At all gestational ages (GA), TLR-4 was associated with a decreased risk of developing CP (homozygous/heterozygous odds ratio (OR) 0.70, 95% confidence interval (CI) 0.50-0.98) and interleukin (IL)-6 was associated with an increased risk of developing hemiplegia (OR 1.38, 95% CI 1.05-1.83). For infants born 32-36 weeks GA, there was a tenfold increase in the risk of quadriplegic CP with homozygous/heterozygous IL-6 (OR 10.42, 95% CI 1.34-80.82). Viral exposure in combination with IL-4 in preterm infants was associated with a fourfold increased risk of quadriplegia (homozygous/heterozygous OR 4.25, 95% CI 1.21-14.95). In very preterm infants, the absence of detectable viral exposure in combination with IL-4 decreased the risk of developing CP (homozygous/heterozygous OR 0.31, 95% CI 0.13-0.76)., Conclusion: Polymorphisms in TLR-4 may be associated with a decreased risk of CP. Polymorphisms in IL-6 or IL-4 may act as susceptibility genes, in the presence of viral exposure, for the development of hemiplegic and quadriplegic CP. These associations require confirmation but they suggest a hypothesis for CP causation due to double jeopardy from neurotropic viral exposure and genetic susceptibility to infection.

Aim: To determine if conjoint analysis is a suitable tool to use with the adolescent population to determine what factors adolescents consider important in inpatient hospital facilities., Method: Conjoint analysis requires the sorting of options, in this instance cards describing service attributes, into most preferred to least preferred scenarios and the resulting information analysed. A purposive group of 29 young people was recruited to ascertain what factors they considered important in inpatient hospital facilities. They were also asked their views on the ease of using conjoint analysis and about their experience with hospitals. Analysis was undertaken using the SPSS (Statistical Package for the Social Sciences) conjoint programme., Results: These young people could use the conjoint analysis approach. Their main preference for inpatient facilities was to have dedicated adolescent space. An important part of the decision regarding the choice of type of facility was the ability to use their cell phone., Implications: Adolescents have firm views and should always be consulted. In today's health environment many management decisions have to be made within economic constrains. If characteristics of services which are important can be ascertained and if economic considerations are added, the results can show how an optimal service can be provided within a definable resource.

Objective: The objective of this study was to examine whether selected genetic polymorphisms in the infant are associated with later-diagnosed cerebral palsy., Methods: A population-based case-control study was conducted of 28 single-nucleotide polymorphisms measured in newborn screening blood spots. A total of 413 children with later-diagnosed cerebral palsy were born to white women in South Australia in 1986-1999, and there were 856 control children. Distributions of genotypic frequencies were examined in total cerebral palsy, in gestational age groups, and by types of cerebral palsy and gender. Genotyping was performed by using a TaqMan assay., Results: For inducible nitric-oxide synthase, possession of the T allele was more common in all children with cerebral palsy and for heterozygotes who were born at term. For lymphotoxin alpha, homozygous variant status was associated with risk for cerebral palsy and with spastic hemiplegic or quadriplegic cerebral palsy. Among term infants, heterozygosity for the endothelial protein C receptor single-nucleotide polymorphism was more frequent in children with cerebral palsy. In preterm infants, the variant A allele of interleukin 8 and heterozygosity for the beta-2 adrenergic receptor were associated with cerebral palsy risk. Interleukin 8 heterozygote status was associated with spastic diplegia. Variants of several genes were associated with cerebral palsy in girls but not in boys., Conclusions: Two of the 28 single-nucleotide polymorphisms examined were associated with all types of spastic cerebral palsy in both gestational age groups and others with cerebral palsy in gestational age or cerebral palsy subgroups. Some of these associations support previous findings. There may be a genetic contribution to cerebral palsy risk, and additional investigation is warranted of genes and gene-environment interactions in cerebral palsy.

Apolipoprotein E (APOE) plays a significant role in lipid metabolism and has been implicated in the growth and repair of injured neurons. Two small studies have suggested an association between APOE genotype and cerebral palsy. We investigated if APOE genotype is associated with an increased risk for cerebral palsy, influences the type of cerebral palsy or interacts with prenatal viral infection to influence risk of cerebral palsy. The population-based case-control study comprised newborn screening cards of 443 Caucasian patients with cerebral palsy and 883 Caucasian matched controls. APOE genotyping was performed on DNA extracted from dried blood spots. Allelic and genotypic frequencies did not differ between cases and controls and combined frequencies were 0.10 (epsilon2), 0.76 (epsilon3), 0.14 (epsilon4), 0.03 (epsilon2/epsilon2), 0.10 (epsilon2/epsilon3), 0.03 (epsilon2/epsilon4), 0.02 (epsilon4/epsilon4), 0.21 (epsilon3/epsilon4), 0.61 (epsilon3/epsilon3). APOE genotype was correlated with cerebral palsy, type of cerebral palsy, gestation at birth and the presence of viral nucleic acids detected in previous work. Analysis by gestational age (all gestational ages, >/=37, 32-36 and <32 weeks) and type of cerebral palsy (all types, diplegia, hemiplegia and quadriplegia) showed no association between APOE genotype and cerebral palsy in this Caucasian population. An association between prenatal viral infection, APOE genotype and cerebral palsy was not demonstrated. These results did not confirm an association between APOE genotype, cerebral palsy, type of cerebral palsy and prenatal infection in a Caucasian population. Given the low frequency of APOE epsilon2 and some of the heterozygote and homozygote combinations in this study, a larger study is assessing this further.

Objective: The objective of the study was to investigate the associations between infection, polymorphisms in the mannose-binding lectin gene (MBL), and cerebral palsy (CP)., Study Design: This was a case-control study using deoxyribonucleic acid from newborn screening cards of 443 Caucasian CP cases and 883 Caucasian controls to screen for 6 polymorphisms within the MBL gene. These polymorphisms combine to create haplotypes with high (HYPA), intermediate (LYQA, LYPA), low (LXPA), and defective (HYPD, LYQC, LYPB) circulating MBL levels., Results: chi(2) Analyses demonstrated significant differences between CP cases and controls (less than 37 weeks chi(2) 14.99, P = .02; less than 32 weeks chi(2) 13.62, P = .02). The MBL haplotype LYPA was associated with CP at all gestations (odds ratio [OR] 1.57, 95% confidence interval [CI], 1.00 to 2.46), less than 37 weeks (OR 2.43, 95% CI, 1.41 to 4.18), and less than 32 weeks (OR 2.54, 95% CI, 1.34 to 4.76). LYPA was also associated with hemiplegic CP for babies born at less than 37 weeks (OR 2.77, 95% CI, 1.02 to 7.26) and less than 32 weeks (OR 4.48, 95% CI, 1.55 to 12.65). HYPD was associated with quadriplegic CP at all gestations (OR 3.47, 95% CI, 1.41 to 8.31) as well as for babies born at less than 32 weeks (OR 7.86, 95% CI, 1.67 to 29.48). Subanalysis on samples previously testing positive for exposure to viral infection demonstrated similar patterns of significance as those presented above, whereas analysis on samples negative for exposure to viral infection showed no positive associations between any of the MBL haplotypes and CP. Potential type I error from multiple analyses is a caveat., Conclusion: MBL haplotypes LYPA or HYPD may be associated with an increased risk of CP in the presence of exposure to viral infection and may act as susceptibility factors for CP.

Objective: The purpose of this study was to investigate associations between fetal inherited thrombophilia and adverse pregnancy outcomes, including pregnancy-induced hypertensive disorders (PIHD), antepartum hemorrhage (APH), small-for-gestational age <10th percentile (SGA), and preterm birth (PTB)., Study Design: Seven hundred and seventeen cases and 609 controls were genotyped for Factor V Leiden (FVL, G1691A), Prothrombin gene mutation (PGM, G20210A), and Methylenetetrahydrofolate reductase (MTHFR) C677T and MTHFR A1298C using DNA from newborn screening cards., Results: For babies born <28 weeks' gestation, PGM was associated with an increased risk of SGA (OR 6.40, 95%CI 1.66-24.71) and APH with SGA (OR 6.35, 95%CI 1.63-24.75). Homozygous MTHFR A1298C was associated with an increased risk of SGA for babies born 28-31 weeks gestation (OR 4.00, 95%CI 1.04-15.37), and with APH and SGA for babies born <32 weeks' gestation (OR 3.57, 95%CI 1.09-11.66). Homozygous MTHFR C677T was associated with a reduced risk of PTB and SGA (OR 0.52, 95%CI 0.28-0.96) for babies born 32 to 36 weeks' gestation. Homozygous FVL decreased the risk of PTB <32 weeks' gestation (OR 0.55, 95%CI 0.31-0.98)., Conclusion: Fetal thrombophilic polymorphisms may be related to adverse pregnancy outcomes, in particular SGA.

Objective: The purpose of this study was to investigate associations between inherited cytokine polymorphisms and cerebral palsy., Study Design: This was a case-control study that used DNA from the newborn infant screening cards of 443 white infants with cerebral palsy and 883 white control infants to test for the following cytokine polymorphisms: tumor necrosis factor-alpha-308, mannose-binding lectin-221, and 3 polymorphisms in exon-1 of the mannose-binding lectin gene at codon-52, -54, and -57., Results: At all gestational ages mannose-binding lectin codon-54 increased the risk of the development of diplegia (homozygous or heterozygous odds ratio, 1.55; 95% CI, 1.03-2.32). For babies who were born at term, the risk of the development of quadriplegia was associated with heterozygous tumor necrosis factor-alpha (odds ratio, 1.82; 95% CI, 1.04-3.15), and mannose-binding lectin codon-54 was associated with diplegia (homozygous or heterozygous odds ratio, 2.12; 95% CI, 1.10-4.05). The presence of any polymorphism in mannose-binding lectin exon-1 at term approximately doubled the risk of the development of diplegia (odds ratio, 1.94; 95% CI, 1.05-3.62). Homozygous or heterozygous tumor necrosis factor-alpha was associated with hemiplegia for babies who were born at <32 weeks of gestation (odds ratio, 2.38; 95% CI, 1.02-5.58). Overall, the presence of any cytokine polymorphism was associated with cerebral palsy (odds ratio, 1.37; 95% CI, 1.02-1.84)., Conclusion: Carriage of polymorphisms in the tumor necrosis factor-alpha and mannose-binding lectin genes are associated with an increased risk of cerebral palsy.

Objective: To investigate the association between cerebral palsy and direct evidence for perinatal exposure to neurotropic viruses., Design: Population based case-control study., Setting: Adelaide Women's and Children's Hospital Research Laboratory., Participants and Main Outcome Measures: Newborn screening cards of 443 white case patients with cerebral palsy and 883 white controls were tested for viral nucleic acids from enteroviruses and herpes viruses by using polymerase chain reaction. Herpes group A viruses included herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus 8 (HHV-8), and herpes group B viruses included varicella zoster virus (VZV) and human herpes viruses 6 and 7 (HHV-6 and HHV-7)., Results: The prevalence of viral nucleic acids in the control population was high: 39.8% of controls tested positive, and the prevalence was highest in preterm babies. The detection of herpes group B viral nucleic acids increased the risk of developing cerebral palsy (odds ratio 1.68, 95% confidence interval 1.09 to 2.59)., Conclusions: Perinatal exposure to neurotropic viruses is associated with preterm delivery and cerebral palsy.

Objective: This study was undertaken to investigate associations between inherited thrombophilic polymorphisms and cerebral palsy (CP) in a large case-control study., Study Design: This is a population-based case-control study. Genomic DNA from newborn screening cards of 443 white CP cases and 883 white controls was tested for factor V Leiden (FVL, G1691A), prothrombin gene mutation (PGM, G20210A), and methylenetetrahydrofolate reductase (MTHFR) C677T and MTHFR A1298C., Results: MTHFR C677T was associated with an increased risk of developing any CP (32-36 weeks' gestation, homozygous odds ratio [OR] 2.55, 95% CI 1.12-5.74; heterozygous OR 1.91, 95% CI 1.01-3.66). MTHFR C677T was also associated with diplegia at both less than 32 weeks' gestation (homozygous OR 2.76, 95% CI 1.21-6.12) and all gestations (heterozygous OR 1.58 95%, CI 1.02-2.45). For children less than 32 weeks, FVL homozygosity may be associated with an increase in the risk of developing quadriplegia (OR 9.12, 95% CI 0.86-53.71). MTHFR A1298C (heterozygous) was associated with a reduced risk of diplegia developing at 32 to 36 weeks' gestation (OR 0.16, 95% CI 0.02-0.70). There were no associations between any type of CP and thrombophilia for children born 37 weeks or greater. Heterozygous PGM and homozygous MTHFR C677T combined were associated with quadriplegia at all gestational ages (OR 5.33, 95% CI 1.06-23.25)., Conclusion: MTHFR C677T approximately doubles the risk of CP in preterm infants. A combination of homozygous MTHFR C677T and heterozygous PGM increases the risk of quadriplegia 5-fold at all gestational ages.