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Research question Despite the increasing use of preimplantation genetic testing (PGT) for aneuploidy and monogenic diseases, for children conceived using PGT there is limited follow-up beyond 2 years of age. This study examined the health, well-being and development of school-aged children (5–8 years old) conceived following PGT. Design Retrospective cohort study of children conceived after IVF with PGT (exposed cohort) and children conceived after IVF without PGT (unexposed cohort) at two IVF clinics in Melbourne, born between 2000 and 2008, recruited with a 1:2 ratio. Mothers of the children completed a questionnaire asking child-specific questions regarding health and well-being, mental health, development, educational achievement and family-specific questions regarding family functioning and parent–child attachment. Results A total of 155 participants were recruited to the PGT cohort and 303 participants to the IVF-only cohort. There were no differences between the two cohorts with regards to maternal characteristics, birth defect frequency and pregnancy characteristics, apart from delivery by Caesarean section, which was more frequent in PGT singletons (55%) compared with IVF-only singletons (36%). While no significant differences between the PGT and IVF-only cohorts were found for the majority of general health and psychological scales, there were differences when compared with population data. Children in the exposed cohort appeared to have more positive outcomes in many of the measures. Conclusion The data from this study suggest that PGT does not cause adverse outcomes in children. However, the nature (self-report) and small sample size of the study must be taken into consideration when interpreting the data.

Genomic newborn screening raises practical and ethical issues. Evidence is required to build a framework to introduce this technology safely and effectively. We investigated the choices made by a diverse group of parents with newborns when offered tiered genomic information from exome sequencing. This population-derived cohort comprised infants with congenital deafness. Parents were offered exome sequencing and choice regarding the scope of analysis. Options were choice A, diagnostic analysis only; choice B, diagnostic analysis plus childhood-onset diseases with medical actionability; or choice C, diagnostic analysis plus childhood-onset diseases with or without medical actionability. Of the 106 participants, 72 (68%) consented to receive additional findings with 29 (27.4%) selecting choice B and 43 (40.6%) opting for choice C. Family size, ethnicity, and age of infant at time of recruitment were the significant predictors of choice. Parents who opted to have additional findings analysis demonstrated less anxiety and decisional conflict. These data provide evidence from a culturally diverse population that choice around additional findings is important and the age of the infant when this choice is offered impacts on their decision. We found no evidence that offering different levels of genomic information to parents of newborns has a negative psychological impact.

Objective To determine the health outcomes for adults aged 22–35 years old who were conceived via assisted reproduction technology (ART) compared with adults of the same age conceived without use of ART. Design Cohort study. Setting Not applicable. Patient(s) Adult men and women aged 22–35 years who were conceived with and without use of ART. Intervention(s) Questionnaire and clinical review. Main Outcome Measure(s) Vascular structure (carotid artery intima-media thickness, pulse wave velocity), vascular function (blood pressure), metabolic markers (fasting blood glucose, insulin, and standard lipid profiles), anthropometric measurements, and respiratory function (spirometry). Result(s) The mean age of the 193 ART and 86 non-ART participants was 27.0 and 26.9 years, respectively. There were no substantial intragroup differences in demographics or vascular intermediate phenotypes, metabolic parameters, or anthropometric measures, before or after adjusting for perinatal factors and a quality of life measure with four domains. Diastolic blood pressure was lower in the ART men than the non-ART men (adjusted mean difference −4.4 mm Hg, 95% CI, −8.7 to −0.1). The ART group reported a higher prevalence of ever having asthma, (40.8% vs. 28.6%; odds ratio 1.7; 95% CI, 1.0–3.0), but expiratory flow rates were similar. Conclusion(s) This study of the health of 193 adults conceived via ART, the largest to date globally, found no evidence of increased vascular or cardiometabolic risk, or growth or respiratory problems in the ART group compared with a non-ART group from the same source population. Follow-up observation for reproductive and later-onset adverse health effects remains important.

Background During the coronavirus disease 2019 (COVID-19) pandemic, concerns have been raised regarding the increased risk of perioperative mortality for patients with COVID-19, and the transmission risk to healthcare workers, especially during endonasal neurosurgical operations. The Pituitary Society has produced recommendations to guide management during this era. We sought to assess contemporary neurosurgical practice and the effects of COVID-19. Methods A multicenter prospective observational cohort study was conducted at 12 tertiary neurosurgical units (United Kingdom and Ireland). Data were collected from March 23 to July 31, 2020, inclusive. The data points collected included patient demographics, preoperative COVID-19 test results, operative modifications, and 30-day COVID-19 infection rates. Results A total of 124 patients were included. Of the 124 patients, 116 (94%) had undergone COVID-19 testing preoperatively (transsphenoidal approach, 97 of 105 [92%]; expanded endoscopic endonasal approach, 19 of 19 [100%]). One patient (1 of 116 [0.9%]) had tested positive for COVID-19 preoperatively, requiring a delay in surgery until the infection had been confirmed as resolved. Other than transient diabetes insipidus, no other complications were reported for this patient. All operating room staff had worn at least level 2 personal protective equipment. Adaptations to surgical techniques included minimizing drilling, draping modifications, and the use of a nasal iodine wash. At 30 days postoperatively, no evidence of COVID-19 infection (symptoms or positive formal testing results) were found in our cohort and no mortality had occurred. Conclusions Preoperative screening protocols and operative modifications have facilitated endonasal neurosurgery during the COVID-19 pandemic, with the Pituitary Society guidelines followed for most of these operations. We found no evidence of COVID-19 infection in our cohort and no mortality, supporting the use of risk mitigation strategies to continue endonasal neurosurgery in subsequent pandemic waves.

PurposePopulation-based carrier screening for fragile X syndrome (FXS) is still not universally endorsed by professional organizations due to concerns around genetic counseling for complex information and potential for psychosocial harms.MethodsWe determined uptake levels, decision making, and psychosocial impact in a prospective study of pregnant and nonpregnant Australian women offered FXS carrier screening in clinical settings. Women received pretest genetic counseling, and completed questionnaires when deciding and one month later.ResultsOf 1,156 women recruited, 83.1% returned the first questionnaire with 70.6% nonpregnant and 58.8% pregnant women choosing testing (χ2=16.98, P

The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine recently recommended offering genetic counseling and diagnostic testing for enlarged nuchal translucency at ≥3.0 mm, regardless of previous negative screening with noninvasive prenatal testing.This study aimed to perform a population-based, individual record linkage study to determine the optimal definition of an enlarged nuchal translucency for the detection of atypical chromosome abnormalities.This was a retrospective study of women resident in Victoria, Australia, undergoing combined first-trimester screening during the 24-month period from January 2015 to December 2016. Linkages between statewide results for combined first-trimester screening, prenatal diagnostic procedures, and postnatal cytogenetic results from products of conception and infants up to 12 months of age were used to ascertain the frequency and type of chromosome abnormality by gestation and nuchal translucency measurement. An atypical chromosome abnormality was defined as any major chromosome abnormality other than whole chromosome aneuploidy involving chromosomes 21, 18, 13, X, and Y.Of the 81,244 singleton pregnancies undergoing combined first-trimester screening, 491 (0.60%) had a nuchal translucency of ≥3.5 mm, 534 (0.66%) had a nuchal translucency of 3.0 to 3.4 mm, and 80,219 (98.74%) had a nuchal translucency of3.0 mm. When grouped by nuchal translucency multiples of the median (MoM), 192 (0.24%) had a nuchal translucency of ≥3.0 MoM, 513 (0.63%) had a nuchal translucency of 1.9 to 2.9 MoM, and 80,539 (99.13%) had a nuchal translucency of1.9 MoM. A total of 1779 pregnancies underwent prenatal or postnatal diagnostic testing, of which 89.60% were performed by whole-genome single-nucleotide polymorphism chromosomal microarray. The frequency of total major chromosome abnormalities was significantly higher in the group with a nuchal translucency of ≥3.5 mm (147 of 491, 29.94%) than the group with a nuchal translucency of 3.0 to 3.4 mm (21 of 534, 3.93%) or a nuchal translucency of3.0 mm (71 of 80,219, 0.09%) (P.001). There were 93 atypical chromosome abnormalities in the total screened cohort. The frequency of an atypical chromosome abnormality was 4.07% (95% confidence interval, 2.51-6.22), 0.37% (95% confidence interval, 0.05-1.35), and 0.09% (95% confidence interval, 0.07-0.11) in the groups with a nuchal translucency of ≥3.5 mm, 3.0 to 3.4 mm, and3.0 mm, respectively. The frequency of atypical chromosome abnormalities was 4.69% (95% confidence interval, 2.17-8.71), 2.53% (95% confidence interval, 1.36-4.29), and 0.09% (95% confidence interval, 0.07-0.11) in the groups with a nuchal translucency of ≥3.0 MoM, 1.9 to 2.9 MoM, and1.9 MoM, respectively. When defining thresholds for offering diagnosis with chromosomal microarray at 11 to 13 weeks, both a nuchal translucency threshold of 1.9 MoM and a fixed threshold of 3.0 mm captured 22 of 93 fetuses (23.7%) with an atypical chromosome abnormality. Of these, 50.0% had a coexisting fetal abnormality on ultrasound. However, the gestation-specific threshold of 1.9 MoM had a better specificity than 3.0 mm. The positive predictive value of an enlarged nuchal translucency for any atypical chromosome abnormality was 1 in 47 for nuchal translucency of3.0 mm and 1 in 32 for nuchal translucency of1.9 MoM. Our nuchal translucency threshold of 1.9 MoM captured 0.87% of fetuses, thus approximating the 99th centile.A gestational age-adjusted nuchal translucency threshold of 1.9 MoM or 99th centile is superior to the fixed cutoff of 3.0 mm for the identification of atypical chromosome abnormalities. The risk of an atypical chromosome abnormality in a fetus with an enlarged nuchal translucency is more than tripled in the presence of an additional ultrasound abnormality.

The use of donor sperm is increasing, yet limited information is available about the health and development of children conceived from donor sperm. This retrospective descriptive study aimed to assess health and development in a cohort of school-aged children who were conceived using donor sperm. Participants included 224 children, aged 5-11 years, who were conceived using donor sperm. Participants' mothers completed a questionnaire comprising validated scales examining their child's current and past physical, psychosocial and mental health, healthcare needs and child development, as well as the mothers' health and wellbeing. At the conclusion of the study, the response rate was 296 out of 407 (72.7%), with a participation rate of 224 out o 407 (55.0%). Compared with the normative Australian population, sperm donor-conceived children had similar physical, psychosocial and mental health and development. A modest increase in healthcare needs was evident. The study concludes that in school-aged children conceived using donor sperm, most aspects of child health and wellbeing are similar to the general population.

Reproductive genetic carrier screening identifies couples with an increased chance of having children with autosomal and X-linked recessive conditions. Initially only offered for single conditions to people with a high priori risk, carrier screening is becoming increasingly offered to individuals/couples in the general population for a wider range of genetic conditions. Despite advances in genomic testing technology and greater availability of carrier screening panels, there is no consensus around which types of conditions to include in carrier screening panels. This study sought to identify which types of conditions parents of children with a genetic condition believe should be included in carrier screening. Participants (n = 150) were recruited through Royal Children's Hospital (RCH) Melbourne outpatient clinics, the Genetic Support Network of Victoria (GSNV) and a databank of children with hearing loss (VicCHILD). This study found that the majority of participants support offering carrier screening for: neuromuscular conditions (n = 128/134, 95.5%), early fatal neurodegenerative conditions (n = 130/141, 92.2%), chronic multi-system disorders (n = 124/135, 91.9%), conditions which cause intellectual disability (n = 128/139, 92.1%) and treatable metabolic conditions (n = 120/138, 87.0%). Views towards the inclusion of non-syndromic hearing loss (n = 88/135, 65.2%) and preventable adult-onset conditions (n = 75/135, 55.6%) were more mixed. Most participants indicated that they would use reproductive options to avoid having a child with the more clinically severe conditions, but most would not do so for clinically milder conditions. A recurring association was observed between participants’ views towards carrier screening and their lived experience of having a child with a genetic condition.\ud \ud

Background pregnancy alcohol research relies on self-reports of alcohol consumption. Reporting bias may contribute to ambiguous and conflicting findings on fetal effects of low to moderate pregnancy alcohol exposure. Objective this study aimed to identify the determinants which would enable women to provide accurate data in surveys of alcohol use in pregnancy. Design and participants six focus groups were held with a total of 26 pregnant women and new mothers. Participants reviewed a set of alcohol survey questions followed by a guided discussion. Transcripts were analysed using inductive content analysis. Setting public hospital antenatal clinics and Mother & Child Health Centres, Melbourne, Victoria, Australia. Findings women׳s emotional responses were generally favourable, although the potential for anxiety and fear of judgement was acknowledged. Barriers to accurate self-report were recall, complexity and use of subjective language. Facilitators were appropriate drink choices, occasional drinking options and contextualising of questions. Confidentiality and survey method, including a preference for methods other than face-to face, were also important factors. Key conclusions and implications for practice questions embedded in clear context may reduce anxiety around questions about alcohol use in pregnancy. Methods using shorter recall periods, a list of drinks choices, measures of special occasion drinking and minimising complex and subjective language will increase accurate self-report. A setting perceived as confidential and anonymous may reduce a desire to provide socially acceptable answers.

Vessel size index (Rv, μm) has been proposed as a quantitative magnetic resonance imaging (MRI) derived imaging biomarker in oncology, for the non-invasive assessment of tumour blood vessel architecture and vascular targeted therapies. Appropriate pre-clinical evaluation of Rv in animal tumour models will improve the interpretation and guide the introduction of the biomarker into clinical studies. The objective of this study was to compare Rv measured in vivo with vessel size measurements from high-resolution X-ray computed tomography (μCT) of vascular corrosion casts measured post mortem from the same tumours, with and without vascular targeted therapy. MRI measurements were first acquired from subcutaneous SW1222 colorectal xenografts in mice following treatment with 0 (n = 6), 30 (n = 6) or 200 mg/kg (n = 3) of the vascular disrupting agent ZD6126. The mice were then immediately infused with a low viscosity resin and, following polymerisation and maceration of surrounding tissues, the resulting tumour vascular casts were dissected and subsequently imaged using an optimised μCT imaging approach. Vessel diameters were not measurable by μCT in the 200 mg/kg group as the high dose of ZD6126 precluded delivery of the resin to the tumour vascular bed. The mean Rv for the three treatment groups was 24, 23 and 23.5 μm respectively; the corresponding μCT measurements from corrosion casts from the 0 and 30 mg/kg cohorts were 25 and 28 μm. The strong association between the in vivo MRI and post mortem μCT values supports the use of Rv as an imaging biomarker in clinical trials of investigational vascular targeted therapies., Highlights ► Non-invasive quantitation of vessel calibre in tumour xenografts in vivo ► Assessment of tumour vessel calibre response to a vascular disrupting agent ► Generation of vascular corrosion casts from the same tumours imaged by MRI ► Quantitation of vessel calibre from corrosion casts by microCT ► Excellent agreement between the in vivo MRI and post mortem microCT vessel calibres

Objective To compare obstetric and perinatal outcomes of singleton births after assisted reproductive technology (ART) with blastocyst transfer (days 5 to 6) versus nonblastocyst transfer (days 2 to 4). Design Retrospective cohort study. Setting Monash IVF. Patient(s) 4,202 women who conceived using in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) between 2004 and 2009. Intervention(s) Records analysis of fresh and frozen-thawed embryo transfers resulting in singleton births of at least 20 weeks' gestation. Main Outcome Measure(s) Perinatal outcomes: preterm birth, low birthweight, very low birthweight, small for gestational age, large for gestational age, preeclampsia, antepartum hemorrhage, placental abruption, placenta previa, and postpartum hemorrhage; and covariates: maternal age, year of birth of the baby, private health insurance status, maternal body mass index, smoking status, parity, gender of baby, and variations in treatment procedures. Result(s) Multivariate analysis found no statistically significant difference between transfers on days 5 and 6 and days 2 and 4 for all maternal and perinatal outcomes. There were modest increases in the adjusted odds ratios for preeclampsia (adjusted odds ratio 1.72, 99% confidence interval 0.93–3.20) and placenta previa (1.65, 0.92–2.98). Conclusion(s) Obstetric and perinatal outcomes after blastocyst transfer on days 5 to 6 are similar when compared with embryo cleavage-stage transfers on days 2 to 4.

Purpose: To compare the number and types of chromosome abnormalities prenatally diagnosed and the number of invasive procedures between current prenatal testing pathways and a pathway where noninvasive prenatal diagnosis for Down syndrome replaces Down syndrome screening tests. Methods: Numbers and types of chromosome abnormalities for each referral category were extracted from prenatal diagnostic testing reports routinely collected in Victoria, Australia, in 2006 and 2007. These data were then applied to the proposed implementation strategy. Results: If noninvasive prenatal diagnosis for Down syndrome had replaced Down syndrome screening tests in 2006 and 2007, in Victoria, there would have been 25 (7%) additional Down syndrome diagnosed, 6896 (84%) fewer invasive procedures, and 231 (56%) non-Down syndrome chromosome abnormalities no longer detected. These include trisomy 13, trisomy 18, sex chromosome abnormalities, balanced and unbalanced rearrangements, polyploidy, and mosaic results. Conclusions: The potential loss of information about chromosome abnormalities other than Down syndrome with noninvasive prenatal diagnosis compared with full karyotyping with traditional prenatal diagnosis should be considered when planning for the implementation of new technologies.

To examine utilization of genetic counseling after diagnosis of a birth defect in 2004, and trends in utilization from 1991 to 2004.Birth defects data for births in 2004 were linked to genetic counseling data to determine utilization of genetic counseling in Victoria, Australia. Variability in utilization was determined according to the need for genetic counseling (as indicated by the particular birth defect), and demographic and perinatal variables. Trends in utilization were determined by comparing 2004 data with that of earlier studies using the same data sources for birth defects cohorts in 1991, 1993, and 1995.Frequency of overall utilization was 20% and was not affected by maternal country of birth, socioeconomic advantage/disadvantage, or region of residence. Higher-than-average utilization was strongly predicted by "high-need" (48.4%), infant death (stillbirth 50%, postnatal death 50.4%), or birth in a tertiary level hospital (28.5%). There was an upward trend in the proportion of the high-need group using genetic counseling, progressively increasing from 39.7% in the 1991 cohort to 42.5% in the 1993 cohort, 46.5% in the 1995 cohort, to a high of 48.4% in the 2004 cohort.Utilization by those who most need it has gradually increased from 1991 to 2004, with no inequity of access apparent in the most recent cohort. Further studies are needed to determine whether high-need families not using genetic counseling are not doing so because of chance or choice.

Objective To report preterm birth and small for gestational age (SGA) rates from assisted reproduction technologies (ART) patients with ovarian endometriomata compared with control groups. Design Retrospective cohort study. Setting Tertiary university affiliated ART center and Perinatal Data Collection Unit (PDCU). Patient(s) Every woman who had an ART singleton baby born between 1991 and 2004 had her database record assessed (N = 4382). Control groups included 1201 singleton babies from ART patients without endometriosis and 2400 randomly selected women from the PDCU database of 850,000 births. Intervention(s) There were 95 singleton ART babies from patients with ovarian endometriomata and 535 ART singleton babies from patients who had endometriosis but no ovarian endometriomata. Main Outcome Measure(s) Preterm birth rates and SGA birth rates. Result(s) Preterm birth rate increased only in the ovarian endometriomata group when compared with community birth records (n = 850,000). Furthermore, ART patients with ovarian endometriomata had a statistically significantly increased likelihood of having a SGA baby when compared with other forms of endometriosis. Conclusion(s) Rates of preterm birth and SGA babies doubled in infertility patients with ovarian endometriomata who required ART.

Background: To fully assess predictive genetic testing programs, it is important to assess outcomes over periods of time longer than the 1-year follow-up reported in the literature. Methods: We conducted a 3-year study of individuals who received predictive genetic test results for previously identified familial mutations in Australian Familial Cancer Clinics. Questionnaires were sent before attendance at the familial cancer clinic and 2 weeks, 4 months, 1 year, and 3 years after receiving test results. Psychological measures were included each time, and preventive behaviors were assessed at baseline and 1 and 3 years. Psychological measures were adjusted for age, gender, and baseline score. Results: The study included 19 carriers and 54 non-carriers. We previously reported an increase in mean cancer-specific distress in carriers at 2 weeks with a return to baseline levels by 12 months. This level was maintained until 3 years. Non-carriers showed sustained decreases after testing with a significantly lower level at 3 years compared with baseline (P < 0.001). These scores tended to be lower than those for carriers at 3 years (P = 0.09). Mean depression and anxiety scores did not differ between carriers and non-carriers and, at 3 years, were similar to baseline. All carriers and 7% of non-carriers had had a colonoscopy by 3 years, and 69% of 13 female carriers had undergone gynecological screening in the previous 2 years. Prophylactic surgery was rare. Conclusion: This report of long-term data indicates appropriate screening and improved psychological measures for non-carriers with no evidence of undue psychological distress in carriers of hereditary nonpolyposis colorectal cancer mutations.

Perinatal outcomes, such as preterm delivery, low birth weight and some obstetric complications, are increased significantly after in-vitro fertilization (IVF) compared with spontaneously conceived pregnancies. The degree of difference is greater for singletons than for twins, especially with regard to preterm delivery which is increased two fold in IVF singletons and by 40% in twins. It is difficult to obtain accurate outcome information because of unmeasured confounders such as smoking status and fetal reduction. It is also unknown whether IVF technologies or patient infertility is the major contributor to adverse outcomes. Birth defects are increased, shown in a number of systematic reviews, and there has been a particular interest in imprinting syndromes. Epigenetic modifications may play a larger role in IVF outcomes, as yet unidentified. There is no apparent increase in adverse outcomes in children up to adolescence, although further studies are needed to examine longer-term risks, including those for cancer.

Objective:To describe patterns of uptake of prenatal diagnostic testing and prenatal detection rates for Down syndrome in Victoria with regard to mater nal age and prenatal screening practices. Methods: Analysis of routinely collected statewide datasets for 1992 to 2002, containing detailed information on all prenatal diagnoses, births and birth defects. Results: Utilisation of prenatal diagnosis in women less than 37 years has increased significantly (p

Objectives: To determine the changes since 1996 in knowledge of folate for the prevention of neural tube defects (NTDs) among women of child-bearing age and measure the residual effect of an earlier consumer-directed information campaign. Design: A community randomised trial with three matched pairs of geographically distinct local government areas in Victoria. Intervention: Printed information recommending folate intake to decrease the risk of NTDs was disseminated in 1997 to women of child-bearing age. Main outcome measure: The proportion of women aware of the association between folate and spina bifida was established in 1996, 1997 and 2000 (approximately 200 respondents per local government area in each survey). Results: 12.5% (adjusted for population sampling fraction) of 1,196 women interviewed in 1996, prior to the intervention, were aware of folate and NTDs. Independent surveys after the intervention in 1997 and again in 2000 showed that this had increased to 17.4% (n=1204) and 30.2% (n=1227) respectively. The intervention had a significant impact on folate awareness (a 4% difference in 1997 and a residual 3.3% in 2000, ORadj= 1.24, 95% Cl 1.19–1.37, p=0.007). Conclusions and implications: There has been a continuing increased awareness of folate in women of child-bearing age since 1996. Within this setting, the provision of printed educational material in a brief intervention in 1997 has caused enduring increased awareness of the association between folate and NTDs. The need for ongoing health promotion action on folate remains.

he intake of folate by women in the periconceptional period is effective in preventing neural tube defects (NTDs) in both the fetuses of women who have not already had a pregnancy affected by a NTD and those who have. 1 Abstract Objectives: To measure population prevalence and determine potential predictors of neural tube defects. Method: Analysis of all births reported to a mandated collection of perinatal data, and terminations prior to 20 weeks' gestation that have been reported to a data collection of birth defects in Victoria from 1983 to 1997. Prevalence at birth and risk ratios of infant and maternal characteristics associated with neural tube defects were calculated. Results: Prevalence of spina bifida has remained steady for 15 years and was 8.8/ 10,000 in 1997. Anencephaly increased to 7.9/10,000 in 1997. After exclusion of pregnancy terminations, the 1997 birth prevalence was 4.5/10,000 for spina bifida and 2.4/10,000 for anencephaly. Neural tube defects are identified in 1 in 1600 fetuses, the risk being significantly higher for epileptic women (Adjusted Odds Ratio (AOR)= 3.70, 95% CI 2.25-6.07), multiple births (AOR=4.56, 95%CI 3.46-6.02), teenage mothers (AOR=1.47, 95% CI 1.09- 2.00) compared with those aged 25-29, and women with three or more previous pregnancies (AOR=1.40, 95% CI 1.10- 1.78). The risk was lower for women of East Asian (AOR=0.70, 95% CI 0.49-1.00) and Middle Eastern origin (AOR=0.60, 95% CI 0.35-1.02) and these differences were approaching statistical significance. Conclusion: Total prevalence of neural tube defects did not decline up to 1997. Implications: It is unlikely that targeting 'at risk' groups identified in this study would make a difference to neural tube defect incidence. However, consideration could be given to identifying larger 'at risk' groups such as those with homocysteine metabolism defects.

Summary HFE -associated hereditary haemochromatosis is a recessive, iron-overload disorder that affects about one in 200 north Europeans and that can be easily prevented. However, genetic screening for this disease is controversial, and so we assessed whether such screening was suitable for communities. Cheek-brush screening for the Cys282Tyr HFE mutation was offered to individuals in the workplace. Outcomes were assessed by questionnaires before and after testing. 11 307 individuals were screened. We recorded no increase in anxiety in individuals who were homozygous for the Cys282Tyr mutation or non-homozygous. Self-reported tiredness before testing was significantly higher in homozygous participants than in non-homozygous participants (χ 2 test, p=0·029). Of the 47 homozygous individuals identified, 46 have taken steps to treat or prevent iron accumulation. Population genetic screening for HFE -associated hereditary haemochromatosis can be practicable and acceptable.

To the Editor: A recent series of observations has suggested a linkbetween in vitro fertilization (IVF) and imprinting disorders, such as Beckwith-Wiedemann syndrome (BWS [MIM 130650]) and Angelman syndrome (MIM 105830). BWS is a model imprinting disorder and is characterized by prenatal and/or postnatal overgrowth, macroglossia, abdominal-wall defects, neonatal hypoglycemia, hemihypertrophy, ear abnormalities, and an increased risk of embryonal tumors (DeBaun et al. 2002). An analysis of BWS registries from three centers has shown the proportion of individuals with BWS conceived using IVF to be 3/65 (DeBaun et al. 2003), 6/149 (Maher et al. 2003), and 6/149 (Gicquel et al. 2003). These data suggest that ∼4% of individuals with BWS are conceived using IVF, a figure greater than the generally accepted usage of IVF in these centers. Further interpretation of these results has been limited because of a reliance by these studies on case records and questionnaire data to determine the method of conception in BWS cases, a lack of the use of appropriate controls, and a statistical significance that was either borderline (Gicquel et al. 2003; Maher et al. 2003) or not mentioned (DeBaun et al. 2003). A recent review of the epidemiology and molecular biology behind these and other related studies has highlighted the need for case-control studies in this area (Niemitz and Feinberg 2004). We report here the results of what we believe is the first case-control study done to test the null hypothesis that there is no difference between the rate of IVF in BWS cases and that in non-BWS controls, in an Australian population. The present study was possible because the State of Victoria, Australia, is serviced by a single clinical genetics service and laboratory providing molecular tests for BWS. This allowed complete ascertainment of children born in Victoria between 1983 and 2003 and diagnosed with BWS by a clinical geneticist. Only cases meeting the DeBaun criteria (DeBaun and Tucker 1998) were included in this study. Appropriate controls were obtained using data from the Victorian Perinatal Data Collection Unit, which registers all births of >19-wk gestation. For each BWS case, four live-born controls were randomly selected from babies born within 1 mo of that case, in which parity was 1 and the maternal age was within 1 year of the risk-set case. Manual record linkage was then used to determine if the BWS cases and the controls were recorded in the databases of the providers of IVF services in Victoria, with the use of maternal names and the dates of birth of mothers and babies. Ethics approval was obtained from all sites providing data. Statistical significance of differences in proportions between groups was assessed using Epi Info, with results expressed as odds ratios (ORs) and as Fisher's-exact-test two-sided P values to account for cell sizes

Women who are the most difficult to trace after amniocentesis or chorion villus sampling are often those who have had an adverse pregnancy outcome. To calculate total fetal loss figures for use in prenatal counselling we have followed in a multicentre study 100% of women who had undergone these procedures. Early spontaneous loss (within three weeks of the procedure) and total spontaneous loss were much lower after amniocentesis (0.2% and 1.3%, respectively) than after chorion villus sampling (1.2% and 2.9%). Four spontaneous fetal losses among the 20 pregnancies that were the most difficult to follow-up increased the loss rate by 0.5% for chorion villus sampling. Risk of early fetal loss after chorion villus sampling was related to experience of the operator (relative risk [RR] 4.3, p = 0.003), and total fetal loss was lower in pregnancies tested at 10 weeks' or more gestational age compared with those tested before 10 weeks' (RR 0.4, p = 0.01). A table showing the frequency of each of the seven possible outcomes after amniocentesis and chorion villus sampling is useful in counselling those considering one or other test.

Ewing's sarcoma family of tumors is part of a rare group of malignant neoplasms with small blue, round-cell morphology on hematoxylin and eosin stain, expressing CD99, C-Kit, and Bcl2, and sharing the presence of the translocation t(11:22). Extraskeletal Ewing's sarcoma is a rare disease that typically involves the soft tissues of the trunk or extremities. We describe a case of extraskeletal Ewing's sarcoma presenting as a mediastinal mass in a 16-year-old boy.

CONCLUSIONS: These results suggest the adverse birth outcomes of ART are associated with fresh embryo transfers and therefore embryology laboratory procedures affecting the embryos are not the cause because they are not seen with FET. The adverse effects must operate via the woman. If these involve ovarian stimulation or anesthesia for oocyte collection they may be able to be modified to improve birth outcomes. The other implication is that FET should be more widely used.

Objective To assess trends in the prevalence of Down syndrome (DS) from 1986 to 2004 in Victoria, Australia (population ∼5 million). Study design The Victorian Birth Defects Register and the Prenatal Diagnosis Database were linked to ascertain all cases of DS. Total and birth prevalence estimates were calculated per year and presented as 3-year moving averages. Results The total number of cases of DS increased from 113 in 1986 to 188 in 2004. The number of births declined over the first decade of the study, particularly in younger women, but total numbers have fluctuated between 45 and 60 births since 1996. In women under age 35 years, total prevalence was 10/10,000 until 1997 and then increased to 12.5/10,000. In older women, total prevalence increased from 70/10,000 to 90/10,000 in this time frame. Birth prevalence declined at first but remained relatively stable in the later years of the study. The proportion of cases diagnosed prenatally increased from 3% to 60% in younger women. Conclusions Our findings demonstrate the continuing need to devote resources to support individuals with DS and their families.