School performance for children with cleft lip and palate: a population-based study.

BACKGROUND: Educational attainment is important in shaping young people's life prospects. To investigate whether being born with orofacial cleft (OFC) affects school performance, we compared school test results between children born with and without OFC. METHODS: Using record-linked datasets, we conducted a population-based cohort study of children liveborn in Western Australia 1980-2010 with a diagnosis of OFC on the Register of Developmental Anomalies, and a random sample of 6603 children born without OFC. We compared odds ratios for meeting national minimum standards in five domains (reading, numeracy, writing, spelling, grammar and punctuation), and adjusted OR (aOR) for children with cleft lip only (CLO), cleft lip and palate (CL + P) and cleft palate only (CPO) for each domain. RESULTS: Results from two testing programs (WALNA and NAPLAN) were available for 3238 (89%) children expected to participate. Most met the national minimum standards. Compared with children without OFC, children with CPO were less likely to meet minimum standards for NAPLAN reading (aOR 0.57 [95%CI 0.34, 0.96]) grammar and punctuation (aOR 0.49 [95%CI 0.32, 0.76]), WALNA writing (aOR 0.66 [95%CI 0.47, 0.92]), and WALNA and NAPLAN numeracy (aOR 0.64 [95%CI 0.43, 0.95] and aOR 0.47 [95%CI 0.28, 0.82]), respectively. Children with CL + P had significantly lower odds for reaching the spelling standard in NAPLAN tests (aOR 0.52 [95%CI 0.29, 0.94]). Children with CLO had similar odds for reaching all minimum standards. CONCLUSION: Children born with OFC, particularly children with CPO, should be monitored to identify learning difficulties early, to enable intervention to maximize school attainment.

Maternal first trimester serum levels of free-beta human chorionic gonadotrophin and male genital anomalies.

STUDY QUESTION: Are maternal first trimester levels of serum free-beta hCG associated with the development of hypospadias or undescended testis (UDT) in boys? SUMMARY ANSWER: Overall, first trimester maternal levels of serum free-beta hCG are not associated with hypospadias or UDT. However, elevated levels were found in severe phenotypes (proximal hypospadias and bilateral UDT) suggesting an altered pathway of hormonal release in early pregnancy. WHAT IS KNOWN ALREADY: Human chorionic gonadotrophin peaks in first trimester of pregnancy stimulating fetal testosterone production, which is key to normal male genital development. Endocrine-disrupting insults early in pregnancy have been associated with increased risk of common genital anomalies in males such as hypospadias and UDT. One plausible etiological pathway is altered release of hCG. STUDY DESIGN, SIZE, DURATION: We conducted a record-linkage study of two separate populations of women attending first trimester aneuploidy screening in two Australian states, New South Wales (NSW) and Western Australia (WA), in 2006-2009 and 2001-2003, respectively. PARTICIPANTS/MATERIALS, SETTING, METHODS: Included were women who gave birth to a singleton live born male infant. There were 12 099 boys from NSW and 10 518 from WA included, of whom 90 and 77 had hypospadias; and 107 and 109 UDT, respectively. Serum levels of free-beta hCG were ascertained from laboratory databases and combined with relevant birth outcomes and congenital anomalies via record linkage of laboratory, birth, congenital anomalies and hospital data. Median and quartile levels of gestational age specific free-beta hCG multiple of the median (MoM) were compared between affected and unaffected boys. Logistic regression was used to evaluate the association between levels of free-beta hCG MoM and hypospadias or UDT, stratified by suspected placental dysfunction and co-existing anomalies. Where relevant, pooled analysis was conducted. MAIN RESULTS AND THE ROLE OF CHANCE: There was no difference in median hCG levels amongst women with an infant with hypospadias (NSW = 0.88 MoM, P = 0.83; WA = 0.84 MoM, P = 0.76) or UDT (NSW = 0.89 MoM, P = 0.54; WA = 0.95 MoM, P = 0.95), compared with women with an unaffected boy (NSW = 0.92 MoM; WA = 0.88 MoM). Low (<25th centile) or high (>75th centile) hCG levels were not associated with hypospadias or UDT, nor when stratifying by suspected placental dysfunction and co-existing anomalies. However, there was a tendency towards high levels for severe types, although confidence intervals were wide. When combining NSW and WA results, high hCG MoM levels (>75th centile) were associated with increased risk of proximal hypospadias (odds ratio (OR) 4.34; 95% CI: 1.08-17.4) and bilateral UDT (OR 2.86; 95% CI: 1.02-8.03). LIMITATIONS, REASONS FOR CAUTION: There were only small numbers of proximal hypospadias and bilateral UDT in both cohorts and although we conducted pooled analyses, results reported on these should be interpreted with caution. Gestational age by ultrasound may have been inaccurately estimated in small and large for gestational age fetuses affecting hCG MoM calculation in those pregnancies. Despite the reliability of our datasets in identifying adverse pregnancy outcomes, we did not have pathology information to confirm tissue lesions in the placenta and therefore our composite outcome should be considered as a proxy for placental dysfunction. WIDER IMPLICATIONS OF THE FINDINGS: This is one of the largest population-based studies examining the association between maternal first trimester serum levels of free-beta hCG and genital anomalies-hypospadias and UDT; and the first to compare specific phenotypes by severity. Overall, our findings does not support the hypothesis that alteration in maternal hCG levels is associated with the development of male genital anomalies; however, high hCG free-beta levels found in severe types suggest different underlying etiology involving higher production and secretion of hCG. These findings require further exploration and replication. STUDY FUNDING/COMPETING INTERESTS: This work was funded by the National Health and Medical Research Council (NHMRC) grant APP1047263. N.N. is supported by a NHMRC Career Development Fellowship APP1067066. C.B. was supported by a NHMRC Principal Research Fellowship #634341. The funding agencies had no role in the design, analysis, interpretation or reporting of the findings. There are no competing interests. TRIAL REGISTRATION NUMBER: Not applicable.

First Measurement of Electron Neutrino Appearance in NOvA.

We report results from the first search for ν_{µ}→ν_{e} transitions by the NOvA experiment. In an exposure equivalent to 2.74×10^{20} protons on target in the upgraded NuMI beam at Fermilab, we observe 6 events in the Far Detector, compared to a background expectation of 0.99±0.11(syst) events based on the Near Detector measurement. A secondary analysis observes 11 events with a background of 1.07±0.14(syst). The 3.3σ excess of events observed in the primary analysis disfavors 0.1π<δ_{CP}<0.5π in the inverted mass hierarchy at the 90% C.L.

Hospital utilization, costs and mortality rates during the first 5 years of life: a population study of ART and non-ART singletons.

STUDY QUESTION: Do singletons conceived following assisted reproduction technologies (ARTs) have significantly different hospital utilization, and therefore costs, compared with non-ART children during the first 5 years of life? SUMMARY ANSWER: ART singletons have longer hospital birth-admissions and a small increased risk of re-admission during the first 5 years of life resulting in higher costs of hospital care. WHAT IS KNOWN ALREADY: ART singletons are at greater risk of adverse perinatal outcomes compared with non-ART singletons. Long-term physical and mental health outcomes of ART singletons are generally reassuring. There is a scarcity of information on health service utilization and the health economic impact of ART conceived children. STUDY DESIGN, SIZE, DURATION: A population cohort study using linked birth, hospital and death records. Perinatal outcomes, hospital utilization and costs, and mortality rates were compared for non-ART and ART singletons to 5 years. Adjustments were made for maternal age, parity, sex, birth year, socioeconomic status and funding source. Australian Diagnosis Related Groups cost-weights were used to derive costs. All costs are reported in 2009/2010 Australian dollars. PARTICIPANTS/MATERIALS, SETTING, METHODS: All babies born in Western Australia between 1994 and 2003 were included; 224 425 non-ART singletons and 2199 ART conceived singletons. Hospital admission and death records in Western Australia linked to 2008 were used. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, ART singletons had a significantly longer length of stay during the birth-admission (mean difference 1.8 days, P < 0.001) and a 20% increased risk of being admitted during the first 5 years of life. The average adjusted difference in hospital admission costs up to 5 years of age was $2490, with most of the additional cost occurring during the birth-admission ($1473). The independent residual cost associated with ART conception was $342 during the birth-admission and an additional $548 up to 5 years of age, indicating that being conceived as an ART child predicts not only higher birth-admission costs but excess costs to at least 5 years of age. LIMITATIONS, REASONS FOR CAUTION: This study could not investigate the impact of different ART practices and techniques on perinatal outcomes or hospital utilization, nor could it adjust for parental characteristics such as cause of infertility and treatment-seeking behaviour. This study related to ART treatment undertaken before 2003. WIDER IMPLICATIONS OF THE FINDINGS: Clinicians and patients should be aware of the risk of poorer perinatal outcomes and increased hospitalization of ART singletons compared with non-ART singletons. These differences are significant enough to affect health-care resource consumption, but are substantially and significantly less than those associated with ART multiple birth infants. Understanding the short- and long-term health services and economic impact of ART is important for setting the research agenda in ART, for informing economic evaluations of infertility and treatment strategies, and for providing an important input to clinical and administrative decision making. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was used to undertake this study and the authors report no conflicts of interest. A number of the authors receive Research Grants to their institutions from the Australian Government. G.M.C. receives grant support to her institution from the Australian Government, Australian Research Council (ARC) Linkage Grant No LP1002165; ARC Linkage Grant Partner Organisations are IVFAustralia, Melbourne IVF and Queensland Fertility Group. V.P.H. is employed as an Economics Research Associate on the same grant. TRIAL REGISTRATIONS NUMBER: NA.

Alcohol-use disorders during and within one year of pregnancy: a population-based cohort study 1985-2006.

OBJECTIVES: To examine alcohol-use disorders in pregnant women and the extent of under-reporting. DESIGN: Population-based cohort study. SETTING: Western Australia. POPULATION: Women with a birth recorded on the Western Australian Midwives Notification System (1985-2006). METHODS: Mothers with an International Classification of Diseases 9/10 alcohol-related diagnosis, indicating heavy alcohol consumption, recorded on population-based health datasets (non-Aboriginal n=5,839; Aboriginal n=2,583) were identified through the Western Australian data-linkage system. This 'exposed' cohort was frequency matched (on maternal age, year of birth of offspring, Aboriginal status) with comparison mothers without an alcohol-related diagnosis (non-Aboriginal n=33,979; Aboriginal n=8,005). MAIN OUTCOME MEASURES: Trends in maternal alcohol diagnoses in relation to pregnancy for non-Aboriginal and Aboriginal women. The proportion of children diagnosed with fetal alcohol syndrome (FAS) who had a mother with an alcohol diagnosis recorded during pregnancy. RESULTS: The proportion of Aboriginal mothers in Western Australia with an alcohol diagnosis (23.1%) is ten times greater than for non-Aboriginal mothers (2.3%). There has been a six-fold increase in the percentage of non-Aboriginal births with a maternal alcohol diagnosis recorded during pregnancy and a 100-fold increase for Aboriginal births. Around 70% of the mothers of children diagnosed with FAS did not have an alcohol diagnosis recorded during pregnancy and 18% of the mothers had no record of an alcohol diagnosis. CONCLUSIONS: Maternal alcohol exposure during pregnancy is significantly under-ascertained. Given the severe risks to the fetus from heavy prenatal alcohol exposure, assessment and recording of alcohol use should be routinely undertaken in maternity and other health settings.

Heavy prenatal alcohol exposure and increased risk of stillbirth.

OBJECTIVE: To investigate the association between heavy prenatal alcohol exposure and stillbirth. DESIGN: Data linkage cohort study. SETTING: Western Australia (WA). POPULATION: The exposed cohort included mothers with an alcohol-related diagnosis (International Classification of Diseases, ninth/tenth revisions) recorded in health data sets and all their offspring born in WA (1983-2007). Mothers without an alcohol-related diagnosis and their offspring comprised the comparison cohort. METHODS: Exposed and comparison mothers were identified through the WA Data Linkage System. Odds ratios for stillbirth at 20+ weeks of gestation were estimated by logistic regression, stratified by Aboriginal status. MAIN OUTCOME MEASURES: The proportion of stillbirths at 20+ weeks of gestation is presented per 1000 births, as well as adjusted odds ratios (aOR) and 95% confidence intervals (95% CI), and population-attributable fractions. RESULTS: Increased odds of stillbirth were observed for mothers with an alcohol-related diagnosis at any stage of their life for both non-Aboriginal (aOR 1.36; 95% CI 1.05-1.76) and Aboriginal (aOR 1.33; 95% CI 1.08-1.64) births. When an alcohol diagnosis was recorded during pregnancy, increased odds were observed for non-Aboriginal births (aOR 2.24; 95% CI 1.09-4.60), with the highest odds of Aboriginal stillbirth occurring when an alcohol diagnosis was recorded within 1 year postpregnancy (aOR 2.88; 95% CI 1.75-4.73). The population-attributable fractions indicate that 0.8% of non-Aboriginal and 7.9% of Aboriginal stillbirths are the result of heavy alcohol consumption. CONCLUSIONS: Prevention of heavy maternal alcohol use has the potential to reduce stillbirths. The lack of an association between exposure during pregnancy and Aboriginal stillbirth in this study needs further investigation.

Search for Lorentz invariance and CPT violation with the MINOS far detector.

We searched for a sidereal modulation in the MINOS far detector neutrino rate. Such a signal would be a consequence of Lorentz and CPT violation as described by the standard-model extension framework. It also would be the first detection of a perturbative effect to conventional neutrino mass oscillations. We found no evidence for this sidereal signature, and the upper limits placed on the magnitudes of the Lorentz and CPT violating coefficients describing the theory are an improvement by factors of 20-510 over the current best limits found by using the MINOS near detector.

Community Priority setting for Fetal Alcohol Spectrum Disorder Research in Australia.

INTRODUCTION: Fetal Alcohol Spectrum Disorder (FASD) is a neurodevelopmental disorder caused by prenatal alcohol exposure (PAE). FASD research is a rapidly growing field that crosses multiple disciplines. To ensure research is relevant and meaningful for people living with FASD, their families, and the broader public there is a need to engage community members in setting priorities for research. OBJECTIVES: Our primary objective was to formally identify the views of people living with FASD, their parents/caregivers, service providers, and the general community on the research priorities for FASD and alcohol use in pregnancy in Australia. Our secondary objective was to provide an overview of current research in the highest priority areas identified. METHODS: The approach for this study involved two community surveys and a consensus workshop, followed by a rapid literature review. Survey responses (n = 146) were collected and grouped using qualitative thematic analysis. The themes identified were then ranked in a second survey (n = 45). The 22 highest ranked themes were considered in a workshop with 21 community members, and consensus on the top ten priority areas was sought. The priority areas were grouped into conceptually similar topics and rapid literature reviews were undertaken on each. RESULTS: A diverse range of priorities was identified within key areas of prevention, diagnosis, and therapy. On request from participants, separate priority lists were developed by Aboriginal and non-Aboriginal participants. CONCLUSION: There is need for a national network of researchers to take forward the research commenced by the Centre of Research Excellence, FASD Research Australia, in addressing community priorities. KEY WORDS: Community, priorities, FASD, rapid review, Australia.

Search for muon-neutrino to electron-neutrino transitions in MINOS.

This Letter reports on a search for nu(mu) --> nu(e) transitions by the MINOS experiment based on a 3.14x10(20) protons-on-target exposure in the Fermilab NuMI beam. We observe 35 events in the Far Detector with a background of 27+/-5(stat)+/-2(syst) events predicted by the measurements in the Near Detector. If interpreted in terms of nu(mu) --> nu(e) oscillations, this 1.5sigma excess of events is consistent with sin2(2theta(13)) comparable to the CHOOZ limit when |Delta m2|=2.43x10(-3) eV2 and sin2(2theta(23))=1.0 are assumed.

The effect of maternal alcohol consumption on fetal growth and preterm birth.

OBJECTIVE: To investigate the relationship between prenatal alcohol exposure and fetal growth and preterm birth and to estimate the effect of dose and timing of alcohol exposure in pregnancy. DESIGN: A population-based cohort study linked to birth information on the Western Australian Midwives Notification System. SETTING: Western Australia. POPULATION: A 10% random sample of births restricted to nonindigenous women who had delivered a singleton infant (n= 4719) in 1995-1997. METHODS: The impact of alcohol consumption in pregnancy on fetal growth (small-for-gestational-age [SGA] and large-for-gestational-age infants [LGA]) and preterm birth (<37 weeks of gestation) was assessed using multivariate logistic regression analysis and adjusting for confounding factors. MAIN OUTCOME MEASURES: Odds ratios and 95% CI, attributable risk, and population attributable risk were calculated. RESULTS: The percentage of SGA infants and preterm birth increased with higher levels of prenatal alcohol exposure; however, the association between alcohol intake and SGA infants was attenuated after adjustment for maternal smoking. Low levels of prenatal alcohol were not associated with preterm birth; however, binge drinking resulted in a nonsignificant increase in odds. Preterm birth was associated with moderate and higher levels of prenatal alcohol consumption for the group of women who ceased drinking before the second trimester. This group of women was significantly more likely to deliver a preterm infant than women who abstained from alcohol (adjusted OR 1.73 [95% CI 1.01-3.14]). CONCLUSIONS: Alcohol intake at higher levels, particularly heavy and binge drinking patterns, is associated with increased risk of preterm birth even when drinking is ceased before the second trimester. This finding, however, is based on small numbers and needs further investigation. Dose and timing of prenatal alcohol exposure appears to affect preterm delivery and should be considered in future research and health education.

Expectations prior to epilepsy surgery: an exploratory comparison of men and women.

Although the clinical goal of resective epilepsy surgery is seizure freedom, patients have a wide set of expectations for this invasive procedure. The goal of this study was to evaluate potential gender differences in expectations among patients undergoing resective epilepsy surgery. Ratings of the importance of 12 potential impacts ("expectations") of resective surgery were analyzed in a seven-center cohort study including 389 adults aged 16 and older who underwent resective epilepsy surgery. Men and women both ranked anticipated changes in driving and memory as the most important presurgical expectations. Women rated driving, physical activity limitations, and economic worries as less important, and fatigue and pregnancy concerns as more important than did men (p's< or =0.05). Exploratory factor analysis indicated a different pattern of associations among the 12 importance items for men and women. Whether gender differences in presurgical values are associated with outcomes needs exploration.

Fetal growth and the risk of childhood non-CNS solid tumours in Western Australia.

Using population-based linked health data, we investigated whether the risk of certain childhood non-CNS solid tumours (n=186) was associated with intra-uterine growth. The risk of retinoblastoma and rhabdomyosarcoma, but not other tumour types, was positively associated with increased growth, suggesting a possible role of fetal growth factors. Larger studies are needed.

The impact of having a sibling with an intellectual disability: parental perspectives in two disorders.

BACKGROUND: The potential effects on other children when there is a child with intellectual disability (ID) in the family are being increasingly recognized. This study describes the impact of having a sibling with Down syndrome or Rett syndrome using a questionnaire completed by parents. METHODS: The parents of 186 Western Australian children with Down syndrome and 141 Australian girls and women with Rett syndrome participated in the study. Patterns of reporting disadvantages and/or benefits were compared across a number of child and family variables (age, functional ability and birth order of the affected child, number of siblings and number of parents in the family home) and by socio-economic status as measured by the index of relative socio-economic disadvantage and by area of residence. Parents' responses to open-ended questions about the benefits and/or disadvantages for siblings of their child were analysed for themes. RESULTS: The majority of parents in the Rett syndrome and Down syndrome groups reported both disadvantages and benefits for siblings. In the Rett syndrome group, families from outer regional areas were the least likely to mention disadvantages and those with a smaller family more likely to note disadvantages. In both groups, more socio-economically advantaged families were more likely to report disadvantages. In the Down syndrome group, benefits were also more commonly reported by parents who were socio-economically advantaged, and by larger and two-parent families. Major disadvantages for siblings centred around parental and personal time constraints, relationships and socializing, restrictions, parental emotion and burden of helping. Major benefits were related to personality characteristics. CONCLUSION: Parents identified both benefits and disadvantages to the siblings of their child with either Rett syndrome or Down syndrome. It is important that these findings are incorporated into any discussion around the impact on the family of a child diagnosed with an ID.

Dietary folate and nonneural midline birth defects: no evidence of an association from a case-control study in Western Australia.

In a population-based case-control study of dietary folate and neural tube defects, information was collected by interview and self-administered questionnaires from the mothers of cases with only neural tube defects, from the mothers of matched control infants with defects other than neural tube defects, and from the mothers of matched live-born infants with no birth defects. The association of midline birth defects (excluding neural tube defects) with dietary folate intake in the first 6 weeks of pregnancy was assessed by restricting the analysis to the 59 mothers of infants with midline defects in the first control group and comparing them with their matched control infants in the second control group. The crude and adjusted odds ratios for dietary folate and for folic acid supplementation were close to one, and all confidence intervals embraced unity. These data do not provide evidence of an association between midline birth defects (excluding neural tube defects) and either dietary folate or folic acid supplementation.

Craniosynostosis in Western Australia, 1980-1994: a population-based study.

A craniomaxillofacial unit was established recently in Western Australia, and a study was carried out to provide some baseline characteristics of primary craniosynostosis in Western Australia and to investigate whether there has been any significant temporal change in birth prevalence. A case control study was conducted, using cases identified from a population-based register of birth defects, and a random sample of all births without a birth defect formed the control group. All subjects were born in Western Australia over the period 1980-1994 inclusive. The prevalence of craniosynostosis over the period 1980-1994 in Western Australia was 5.06 per 10,000 births. There was a significant linear increase in lambdoid synostosis over this period of 15.7% per year. Craniosynostosis was significantly more common among male infants, infants born preterm (<37 weeks gestation), breech presentation or presentations other than vertex, and infants born to fathers 40 years of age or older, even after accounting for known autosomal dominant syndromes. Other major birth defects were found in 11.2% of children with nonsyndromic craniosynostosis. Only 43 children (25.3%) with craniosynostosis were reported to have been seen by a geneticist. Thus, the prevalence of craniosynostosis in Western Australia is among the lowest reported. There is no current explanation for the increase in lambdoid synostosis. The increased risk of so-called nonsyndromic craniosynostosis with paternal age raises the possibility of undiagnosed new dominant mutations. This, along with the excess of other birth defects in children with craniosynostosis emphasises the need to ensure that these families are offered genetic counseling.

Population screening for cystic fibrosis in Western Australia: community response.

We measured acceptance of carrier testing for cystic fibrosis in the community when offered in a primary care setting, determined variables influencing acceptance, and assessed knowledge of cystic fibrosis 3-6 months later. A total of 5,102 individuals age 18-50 years attending general practices or a family planning clinic in Western Australia completed questionnaires about knowledge of cystic fibrosis and the State Anxiety Inventory. Testing for the delta F508 gene was offered. After 3-6 months, carriers, a sample of consenting participants who were not tested, and a sample of test-negative participants were sent a further questionnaire; 43.5% of participants chose to be tested for cystic fibrosis carrier status. Women, younger people, people with higher education, people without children, and people planning to have children were more likely to be tested. After 3-6 months, carriers gave correct responses to questions about cystic fibrosis more frequently than those who tested negative or were not tested; 82.2% of carriers knew that they were definitely a carrier and 31.1% of test-negative individuals believed they were definitely not carriers. Thus, population carrier screening for cystic fibrosis offered in a community setting in Western Australia was acceptable to almost half of those offered testing, particularly younger people and those planning to have children, for whom knowledge of carrier status could be useful in making reproductive decisions. There was evidence that tested individuals recalled information in a way that minimised their risk of being a carrier.

Skeletal abnormalities in Rett syndrome: increasing evidence for dysmorphogenetic defects.

The presence of metatarsal and metacarpal abnormalities in some individuals has raised the possibility that Rett syndrome is, in fact, a multiple congenital abnormalities/mental retardation (MCA/MR) syndrome. We have conducted radiological examination of 17 cases of Rett syndrome in Western Australia. Short fourth and/or fifth metatarsals were identified in 65% of cases and short fourth and/or fifth metacarpals in 57%. Metatarsal (P = 0.045) and metacarpal (P = 0.006) shortness were significantly more common in girls 14 years or older. Negative ulnar variance (found in 79% of cases) appeared to be independent of age. Reduced bone density in the hands was found in 86% of cases. A nationwide study using the Australian Rett Syndrome Database is planned to follow up these findings and compare them with findings from a control group. The confirmation of these abnormalities in a high proportion of cases may provide morphologic markers to assist in the diagnosis of Rett syndrome and perhaps provide a further avenue of research into the pathogenesis of this disorder.

Metacarpophalangeal pattern profile and bone age in Rett syndrome: further radiological clues to the diagnosis.

Hand radiographs of 100 girls representing 73% of the known Australian population of girls with Rett syndrome, age 20 years or less, were available for this study. Control radiographs were matched for age, sex, and laterality. Bone age was assessed against standard radiographs in Greulich and Pyle [1959: Radiographic Atlas of Skeletal Development of the Hands and Wrist, 2nd ed.]. A metacarpophalangeal pattern (MCPP) profile comparing the relative lengths of the hand bones with mean population norms by age was produced by converting the length of each of the 19 metacarpal and phalangeal bones into a Z score. In girls less than 15 years old, bone age was more advanced in Rett syndrome than in age-matched control girls (left hand P = 0.03, right hand 0.004), but was most advanced in the younger group and normalized with age. In Rett syndrome, the mean Z score for the 19 metacarpal and phalangeal bones was 1.0 in children under 5 years, -0.27 in those aged 5-11 years, and -1.7 in those aged 12 years and over. This variation between age groups was much greater than in the controls. The dips in the MCPP profile occurred at MC2 and D1, and the peaks at M5, P5, and M4. An MCPP profile may provide an additional aid to diagnosis in cases of Rett syndrome where all the criteria are not met, but in children under age 5 years, advanced bone age may be more helpful as a marker.

Decreased mu-opioid receptor binding in the globus pallidus of rats treated with chronic haloperidol.

RATIONALE: Chronic neuroleptic treatment produces a movement disorder in rats characterized by vacuous chewing movements (VCMs). Neuroleptics also produce a variety of changes in opioid neurotransmission in several regions of the basal ganglia. Rats with the VCM syndrome show elevated mRNA for enkephalin in striatopallidal neurons, suggesting a possible role for enkephalin in the pathophysiology of VCMs. OBJECTIVE: This study investigated the role of mu-opioid receptor density in the basal ganglia on the expression of VCMs. METHODS: Rats were treated with haloperidol for 24 weeks and withdrawn for 9 weeks. Mu (m) receptors were labeled with [3H]-DAMGO. RESULTS: Haloperidol treatment produced a significant reduction in mu-receptor binding in the globus pallidus (P<0.05). There was, however, no relationship between mu-opioid receptor density and VCMs in this or any other region of the basal ganglia. CONCLUSION: These results replicate prior findings of a neuroleptic-induced reduction in [3H]-DAMGO binding in the globus pallidus. The lack of association between VCMs and [3H]-DAMGO binding in the globus pallidus or any other region suggests that prior reports of enkephalinergic mRNA changes in the striatum are not accompanied by compensatory changes in postsynaptic neurons.