Trends in congenital anomalies in Europe from 1980 to 2012.

BACKGROUND: Surveillance of congenital anomalies is important to identify potential teratogens. METHODS: This study analysed the prevalence of 61 congenital anomaly subgroups (excluding chromosomal) in 25 population-based EUROCAT registries (1980-2012). Live births, fetal deaths and terminations of pregnancy for fetal anomaly were analysed with multilevel random-effects Poisson regression models. RESULTS: Seventeen anomaly subgroups had statistically significant trends from 2003-2012; 12 increasing and 5 decreasing. CONCLUSIONS: The annual increasing prevalence of severe congenital heart defects, single ventricle, atrioventricular septal defects and tetralogy of Fallot of 1.4% (95% CI: 0.7% to 2.0%), 4.6% (1.0% to 8.2%), 3.4% (1.3% to 5.5%) and 4.1% (2.4% to 5.7%) respectively may reflect increases in maternal obesity and diabetes (known risk factors). The increased prevalence of cystic adenomatous malformation of the lung [6.5% (3.5% to 9.4%)] and decreased prevalence of limb reduction defects [-2.8% (-4.2% to -1.5%)] are unexplained. For renal dysplasia and maternal infections, increasing trends may be explained by increased screening, and deceases in patent ductus arteriosus at term and increases in craniosynostosis, by improved follow up period after birth and improved diagnosis. For oesophageal atresia, duodenal atresia/stenosis and ano-rectal atresia/stenosis recent changes in prevalence appeared incidental when compared with larger long term fluctuations. For microcephaly and congenital hydronephrosis trends could not be interpreted due to discrepancies in diagnostic criteria. The trends for club foot and syndactyly disappeared once registries with disparate results were excluded. No decrease in neural tube defects was detected, despite efforts at prevention through folic acid supplementation.

Management and outcomes of neonates with down syndrome admitted to neonatal units.

BACKGROUND: Neonates with Down syndrome have an increased risk of being admitted to a neonatal unit compared with unaffected neonates. We aimed to estimate the proportion of neonates with Down syndrome admitted to a neonatal unit and compare their management and outcomes with other neonatal admissions. METHODS: Case-control study of neonates born from 2009 to 2011 admitted to 122 NHS Neonatal Units in England using data from the National Down Syndrome Cytogenetic Register and the National Neonatal Research Database. For each neonate with Down syndrome, three neonates admitted to the same unit in the same month and born at the same gestation were identified. RESULTS: Forty-six percent of neonates with Down syndrome were admitted to a neonatal unit. Boys were more likely to be admitted than girls (odds ratio = 1.7; 95% confidence interval, 1.4-2.0). Neonates with Down syndrome required more intensive or high dependency care compared with unaffected neonates (37% vs. 27%. p < 0.01) and stayed in neonatal units for longer (11 days vs. 5 days, p < 0.01). A total of 31% of neonates with Down syndrome required respiratory support compared with 22% (p < 0.001) of unaffected neonates, and 11% were discharged requiring oxygen supplementation compared with 3% (p < 0.001) of unaffected neonates. A total of 3% of neonates with Down syndrome died in a neonatal unit compared with 1% (p = 0.01) of unaffected neonates. CONCLUSION: Neonates with Down syndrome are more likely than unaffected neonates to be admitted to a neonatal unit, have a prolonged stay, and be discharged home on supplemental oxygen. Birth Defects Research (Part A) 106:468-474, 2016. © 2016 Wiley Periodicals, Inc.

Accuracy of reporting abortions with Down syndrome in England and Wales: a data linkage study.

BACKGROUND: The number of abortions of fetuses with Down syndrome in England and Wales reported by the Department of Health (DH) differs from that reported by the National Down Syndrome Cytogenetic Register (NDSCR). The aim of this study was to investigate the reasons for this. METHODS: Abortions in 2011 and 2012 from DH were matched to those from NDSCR. The number of cases not reported to either source was estimated. RESULTS: An estimated 2240 abortions of fetuses with Down syndrome occurred in 2011/12; NDSCR estimated 2208 and DH 1100. One thousand and six abortions were identified in both data sets, including 145 (14%) which were not recorded by DH as having Down syndrome. Abortions in NDSCR that were not matched in DH occurred throughout England and Wales and at all gestational ages. An estimated 61 abortions of fetuses with Down syndrome were not reported to DH or NDSCR. CONCLUSIONS: The number of abortions of fetuses with Down syndrome reported by the NDSCR is more complete than that reported by the DH. DH data for abortions with other congenital anomalies are also likely to be underestimates, and more accurate estimates are available from BINOCAR regional congenital anomaly registers.

Congenital anomalies associated with trisomy 18 or trisomy 13: A registry-based study in 16 European countries, 2000-2011.

The aim of this study was to examine the prevalence of trisomies 18 and 13 in Europe and the prevalence of associated anomalies. Twenty-five population-based registries in 16 European countries provided data from 2000-2011. Cases included live births, fetal deaths (20+ weeks' gestation), and terminations of pregnancy for fetal anomaly (TOPFAs). The prevalence of associated anomalies was reported in live births. The prevalence of trisomy 18 and trisomy 13 were 4.8 (95%CI: 4.7-5.0) and 1.9 (95%CI: 1.8-2.0) per 10,000 total births. Seventy three percent of cases with trisomy 18 or trisomy 13 resulted in a TOPFA. Amongst 468 live born babies with trisomy 18, 80% (76-83%) had a cardiac anomaly, 21% (17-25%) had a nervous system anomaly, 8% (6-11%) had esophageal atresia and 10% (8-13%) had an orofacial cleft. Amongst 240 Live born babies with trisomy 13, 57% (51-64%) had a cardiac anomaly, 39% (33-46%) had a nervous system anomaly, 30% (24-36%) had an eye anomaly, 44% (37-50%) had polydactyly and 45% (39-52%) had an orofacial cleft. For babies with trisomy 18 boys were less likely to have a cardiac anomaly compared with girls (OR = 0.48 (0.30-0.77) and with trisomy 13 were less likely to have a nervous system anomaly [OR = 0.46 (0.27-0.77)]. Babies with trisomy 18 or trisomy 13 do have a high proportion of associated anomalies with the distribution of anomalies being different in boys and girls.

Down syndrome birth weight in England and Wales: Implications for clinical practice.

The aim of this study was to determine if syndrome-specific birth weight charts were beneficial for babies with Down syndrome in England and Wales. Birth weights of 8,825 babies with Down syndrome born in England and Wales in 1989-2010 were obtained from the National Down Syndrome Cytogenetic Register. Birth weight centiles for 30-42 weeks gestation by sex were fitted using the LMS method and were compared to those for unaffected babies from the UK-WHO growth charts. For babies born with Down syndrome the median birth weight from 37 to 42 weeks was 2,970 g (10th-90th centile: 2,115-3,680) for boys and 2930 g (2,100-3,629) for girls, and the modal age of gestation was 38 weeks, 2 weeks earlier than for unaffected babies. At 38 weeks gestation they were only slightly lighter than unaffected babies (159 g for boys and 86 g for girls). However at 40 weeks gestation the shortfall was much greater (304 g and 239 g, respectively). In neonates with Down syndrome there is little evidence of growth restriction before 38 weeks gestation, so up to this age it is appropriate to use the UK-WHO birth weight charts. Thereafter birth weight is below that of unaffected babies and it should be plotted on the UK Down syndrome growth charts.

Occupational Exposure to Hydrazine and Subsequent Risk of Lung Cancer: 50-Year Follow-Up.

PURPOSE: Hydrazine is carcinogenic in animals, but there is inadequate evidence to determine if it is carcinogenic in humans. This study aimed to evaluate the association between hydrazine exposure and the risk of lung cancer. METHODS: The cause specific mortality rates of a cohort of 427 men who were employed at an English factory that produced hydrazine between 1945 and 1971 were compared with national mortality rates. RESULTS: By the end of December 2012 205 deaths had occurred. For men in the highest exposure category with greater than two years exposure and after more than ten years since first exposure the relative risks compared with national rates were: 0.85 (95% CI: 0.18-2.48) for lung cancer, 0.61 (95% CI: 0.07-2.21) for cancers of the digestive system, and 0.44 (95% CI: 0.05-1.57) for other cancers. CONCLUSIONS: After 50 years of follow up, the results provide no evidence of an increased risk of death from lung cancer or death from any other cause.

Birth prevalence and survival of exomphalos in england and wales: 2005 to 2011.

BACKGROUND: Exomphalos occurs in 2.2 per 10,000 births with 76% of these babies surviving to discharge. The aim of this study was to determine the birth prevalence and survival of babies with this anomaly in England and Wales. METHODS: Six BINOCAR regional congenital anomaly registers in England and Wales (covering 36% of births) between 2005 and 2011 provided cases for this study. Cases included live births, stillbirths (24+ weeks' gestation), late miscarriages (20-23 weeks' gestation), and terminations of pregnancy with fetal anomaly. RESULTS: The overall birth prevalence was 3.8 (95% confidence interval [CI]: 3.6-4.0) per 10,000 births; 1.4 (1.2-1.6) for isolated cases, 1.2 (1.1-1.4) for cases with multiple anomalies, and 1.2 (1.1-1.4) for cases with chromosomal anomalies. The live birth prevalence was 0.8 (0.7-0.9), 0.5 (0.4-0.6), and 0.1 (0.0-0.1) per 10,000 live births, respectively. Edwards syndrome, congenital heart defects, and nervous system anomalies were the most common anomalies associated with exomphalos. A prenatal diagnosis was made in 83% of isolated, 95% of multiple, and 99% of chromosomal cases. Fifty-five percent of isolated and multiple cases were live born, whereas 85% of cases with chromosomal anomalies resulted in a termination of pregnancy with fetal anomaly. The 1-year survival of live born babies with an isolated exomphalos was 92% compared with 81% in cases with multiple anomalies and 27% in cases with chromosomal anomalies (p < 0.001). CONCLUSION: We report a higher birth prevalence than has previously been reported. The proportion of infants surviving with exomphalos remained unchanged over the time period.

Antenatal detection of Edwards (Trisomy 18) and Patau (Trisomy 13) syndrome: England and Wales 2005-2012.

OBJECTIVES: Pregnancies with Edwards or Patau syndrome are often detected through screening for Down's syndrome. We aimed to evaluate the impact of screening for Down's syndrome on the prevalence of live births and antenatal diagnoses of Edwards and Patau syndrome. SETTING: England and Wales, 2005 to 2012. METHODS: Data from the National Down Syndrome Cytogenetic Register, which contains information on nearly all ante- or postnatally diagnosed cases of Edwards or Patau syndrome in which a karyotype was confirmed, were analysed. RESULTS: From 2005 to 2012, 3,941 diagnoses of Edwards syndrome and 1,567 diagnoses of Patau syndrome were recorded (prevalence of 7.0 and 2.8 per 10,000 births respectively). Only 11% (95% confidence interval [CI]: 10-12) of diagnoses of Edwards syndrome and 13% (95% CI: 11-14) of Patau syndrome were live births, resulting in live birth prevalences of 0.8 (95% CI: 0.7-0.8) and 0.4 (95% CI: 0.3-0.4) per 10,000 live births respectively. About 90% of pregnancies with Edwards or Patau syndrome were diagnosed antenatally, and this proportion remained constant over time. The proportion of diagnoses detected before 15 weeks increased from 50% in 2005 to 53% in 2012 for Edwards syndrome, and from 41% in 2005 to 63% in 2012 for Patau syndrome. CONCLUSIONS: Almost 700 women per year had a pregnancy with Edwards or Patau syndrome. Over 90% of these pregnancies were detected antenatally, with the increased use of first trimester screening for Down's syndrome resulting in the reduction in the mean gestational age at diagnosis of these syndromes.

Survival of trisomy 18 (Edwards syndrome) and trisomy 13 (Patau Syndrome) in England and Wales: 2004-2011.

The aim of this study is to determine the survival of live births with trisomy 18 and trisomy 13 and their variants. Information on live births with trisomy 18 or trisomy 13 recorded in the National Down Syndrome Cytogenetic Register (NDSCR) was linked by the NHS Information Centre to obtain information about survival. Survival was known for 326 (88%) of live births with trisomy 18 and 142 (82%) of live births with trisomy 13 born in England and Wales between 2004 and 2011. The median survival time for live births with full trisomy 18 was 14 days and with full trisomy 13 was 10 days, the 3-month survival was 20% and 18%, respectively, and the 1-year survival for both syndromes was 8%. The 1-year survival for live births with trisomy 18 mosaicism (n = 17) was 70%, for those with trisomy 13 mosaicism (n = 5) was 80% and for those with partial trisomy 13 (Robertsonian translocations) (n = 17) was 29%. This study is based on the largest data set on survival for live births with trisomy 18 and trisomy 13. Although median survival for these children is 2 weeks or less, about one in five survive for 3 months or more and about 1 in 12 survive for 1 year or more. We suggest that these survival rates are used in counselling as well as the median survival time.

Socioeconomic inequalities in the rate of stillbirths by cause: a population-based study.

OBJECTIVE: To assess time trends in socioeconomic inequalities in overall and cause-specific stillbirth rates in England. DESIGN: Population-based retrospective study. SETTING: England. PARTICIPANTS: Stillbirths occurring among singleton infants born between 1 January 2000 and 31 December 2007. MAIN OUTCOME MEASURE: Cause-specific stillbirth rate per 10 000 births by deprivation tenth and year of birth. Deprivation measured using the UK index of multiple deprivation at Super Output Area level. METHODS: Poisson regression models were used to estimate the relative deprivation gap (comparing the most and least deprived tenths) in rates of stillbirths (overall and cause-specific). Excess mortality was calculated by applying the rates seen in the least deprived tenth to the entire population at risk. Discussions with our local NHS multicentre ethics committee deemed that this analysis of national non-identifiable data did not require separate ethics approval. RESULTS: There were 44 stillbirths per 10 000 births, with no evidence of a change in rates over time. Rates were twice as high in the most deprived tenth compared with the least (rate ratio (RR) 2.1, 95% CI 2.0 to 2.2) with no evidence of a change over time. There was a significant deprivation gap for all specific causes except mechanical events (RR 1.2, 95% CI 0.9 to 1.5). The widest gap was seen for stillbirths due to antepartum haemorrhages (RR 3.1, 95% CI 2.8 to 3.5). No evidence of a change in the rate of stillbirth or deprivation gap over time was seen for any specific cause. CONCLUSION: A wide deprivation gap exists in stillbirth rates for most causes and is not diminishing. Unexplained antepartum stillbirths accounted for 50% of the deprivation gap, and a better understanding of these stillbirths is necessary to reduce socioeconomic inequalities.

Missed opportunities for diabetes prevention: post-pregnancy follow-up of women with gestational diabetes mellitus in England.

BACKGROUND: Women with gestational diabetes mellitus (GDM) should be followed-up to exclude ongoing diabetes and for prevention of type 2 diabetes. The National Institute for Health and Clinical Excellence (NICE) diabetes in pregnancy guideline recommends checking fasting plasma glucose (FPG) at 6 weeks postpartum (short term), and annually thereafter (long term). AIM: To examine the reported practice regarding GDM follow-up. DESIGN AND SETTING: Nationwide postal survey in England 2008-2009. METHOD: Questionnaires were distributed to a consultant diabetologist and obstetrician in all maternity units, and to a random sample of general practices (approximately 1 in 5). RESULTS: Response rates were: 60% (915/1532) GPs, 93% (342/368) specialists; 80% of GPs and 98% of specialists reported women with GDM had short-term follow-up. More GPs (55%) than specialists (13%) used a FPG test to exclude ongoing diabetes; 26% of GPs versus 89% of specialists thought the hospital was responsible for ordering the test. Twenty per cent of GPs had difficulty in discovering women had been diagnosed with GDM in secondary care. Seventy-three per cent of specialists recommended long-term follow-up; only 39% of GPs recalled women with GDM for this. A minority of GPs and specialists had joint follow-up protocols. CONCLUSION: Follow-up of GDM in England diverged from national guidance. Despite consensus that short-term follow-up occurred, primary and secondary care doctors disagreed about the tests and responsibility for follow-up. There was lack of long-term follow-up. Agreement about the NICE guideline, its promotion and effective implementation by primary and secondary care, and the systematic recall of women with GDM for long-term follow-up is required.

Saving Mothers' Lives: Reviewing maternal deaths to make motherhood safer: 2006-2008. The Eighth Report of the Confidential Enquiries into Maternal Deaths in the United Kingdom.

In the triennium 2006-2008, 261 women in the UK died directly or indirectly related to pregnancy. The overall maternal mortality rate was 11.39 per 100,000 maternities. Direct deaths decreased from 6.24 per 100,000 maternities in 2003-2005 to 4.67 per 100,000 maternities in 2006­2008 (p = 0.02). This decline is predominantly due to the reduction in deaths from thromboembolism and, to a lesser extent, haemorrhage. For the first time there has been a reduction in the inequalities gap, with a significant decrease in maternal mortality rates among those living in the most deprived areas and those in the lowest socio-economic group. Despite a decline in the overall UK maternal mortality rate, there has been an increase in deaths related to genital tract sepsis, particularly from community acquired Group A streptococcal disease. The mortality rate related to sepsis increased from 0.85 deaths per 100,000 maternities in 2003-2005 to 1.13 deaths in 2006-2008, and sepsis is now the most common cause of Direct maternal death. Cardiac disease is the most common cause of Indirect death; the Indirect maternal mortality rate has not changed significantly since 2003-2005. This Confidential Enquiry identified substandard care in 70% of Direct deaths and 55% of Indirect deaths. Many of the identified avoidable factors remain the same as those identified in previous Enquiries. Recommendations for improving care have been developed and are highlighted in this report. Implementing the Top ten recommendations should be prioritised in order to ensure the overall UK maternal mortality rate continues to decline.

Nature of socioeconomic inequalities in neonatal mortality: population based study.

OBJECTIVE: To investigate time trends in socioeconomic inequalities in cause specific neonatal mortality in order to assess changing patterns in mortality due to different causes, particularly prematurity, and identify key areas of focus for future intervention strategies. DESIGN: Retrospective cohort study. SETTING: England. PARTICIPANTS: All neonatal deaths in singleton infants born between 1 January 1997 and 31 December 2007. MAIN OUTCOME MEASURE: Cause specific neonatal mortality per 10 000 births by deprivation tenth (deprivation measured with UK index of multiple deprivation 2004 at super output area level). RESULTS: 18 524 neonatal deaths occurred in singleton infants born in the 11 year study period. Neonatal mortality fell between 1997-9 and 2006-7 (from 31.4 to 25.1 per 10 000 live births). The relative deprivation gap (ratio of mortality in the most deprived tenth compared with the least deprived tenth) increased from 2.08 in 1997-9 to 2.68 in 2003-5, before a fall to 2.35 in 2006-7. The most common causes of death were immaturity and congenital anomalies. Mortality due to immaturity before 24 weeks' gestation did not decrease over time and showed the widest relative deprivation gap (2.98 in 1997-9; 4.14 in 2003-5; 3.16 in 2006-7). Mortality rates for all other causes fell over time. For congenital anomalies, immaturity, and accidents and other specific causes, the relative deprivation gap widened between 1997-9 and 2003-5, before a slight fall in 2006-7. For intrapartum events and sudden infant deaths (only 13.5% of deaths) the relative deprivation gap narrowed slightly. CONCLUSIONS: Almost 80% of the relative deprivation gap in all cause mortality was explained by premature birth and congenital anomalies. To reduce socioeconomic inequalities in mortality, a change in focus is needed to concentrate on these two influential causes of death. Understanding the link between deprivation and preterm birth should be a major research priority to identify interventions to reduce preterm birth.