Aims With remarkable progress in treating childhood cancer over recent years, more and more survivors are reaching adulthood and thus greater attention is being directed to understanding the late complications of surviving cancer, such as effects on educational attainment. Studies so far have provided conflicting results, emphasising the need for a systematic review and meta-analysis. In this first meta-analysis, we therefore aim to assess if any differences across educational outcomes exist in childhood cancer survivors compared to their peers. Methods Medline, EMBASE, ERIC, CINAHL and PsycInfo were searched from inception to 1stMarch 2017. Any survivor with a diagnosis of childhood cancer was eligible. The primary outcome of interest was the level of educational attainment, classified into compulsory, secondary and tertiary levels. The secondary outcome was special educational needs. Subgroup analyses and meta-regression were carried out to assess heterogeneity. This study is registered with PROSPERO(CRD42017057501). Results We identified 3231 publications through our search strategy. 26 studies were eligible for meta-analysis; which included 28 434 childhood cancer survivors, 17 814 matched-controls, 6582 siblings and six population studies from 11 developed nations across the globe. Overall, childhood cancer survivors appeared to be significantly less likely to progress onto secondary level education (pooled OR 1.36 (95% CI 1.26, 1.43, p<0.00001)) or to complete tertiary level education (pooled OR 0.87 (95% CI 0.78, 0.98, p=0.02)),compared to controls. They were also more likely to require special educational needs (pooled OR 2.47 (95% CI 1.91, 3.20, p<0.00001)). Children who survived central nervous system tumours appeared to have worse outcomes compared to other types of cancers, although the latter also showed significantly poorer progression onto secondary level education(pooled OR 1.30 (95%CI 1.20, 1.41, p<0.00001, I2=0%)). Conclusions This is the first comprehensive meta-analysis, which explored educational attainment in childhood cancer survivors and elucidated overall poorer educational outcomes in survivors compared to peers. Poorer outcomes are sustained across different countries, implying that this is an international issue. Armed with these results, the next steps are to understand why childhood cancer survivors perform worse than their peers and how support can be targeted to ensure equal educational attainment.

STUDY QUESTIONDo children born after donor ART have an increased risk of developing childhood cancer in comparison to the general population?SUMMARY ANSWERThis study showed no overall increased risk of childhood cancer in individuals born after donor ART.WHAT IS KNOWN ALREADYMost large population-based studies have shown no increase in overall childhood cancer incidence after non-donor ART; however, other studies have suggested small increased risks in specific cancer types, including haematological cancers. Cancer risk specifically in children born after donor ART has not been investigated to date.STUDY DESIGN, SIZE, DURATIONThis retrospective cohort study utilized record linkage to determine the outcome status of all children born in Great Britain (1992-2008) after donor ART. The cohort included 12 137 members who contributed 95 389 person-years of follow-up (average follow-up 7.86 years).PARTICIPANTS/MATERIALS, SETTING, METHODSRecords of all children born in Great Britain (England, Wales, Scotland) after all forms of donor ART (1992-2008) were linked to the UK National Registry of Childhood Tumours (NRCT) to determine the number who subsequently developed cancer by 15 years of age, by the end of 2008. Rates of overall and type specific cancer (selected a priori) were compared with age, sex and calendar year standardized population-based rates, stratifying for potential mediating/moderating factors including sex, age at diagnosis, birth weight, multiple births, maternal previous live births, assisted conception type and fresh/ cryopreserved cycles.MAIN RESULTS AND THE ROLE OF CHANCEIn our cohort of 12 137 children born after donor ART (52% male, 55% singleton births), no overall increased risk of cancer was identified. There were 12 cancers detected compared to 14.4 expected (standardized incidence ratio (SIR) 0.83; 95% CI 0.43-1.45; P = 0.50). A small, significant increased risk of hepatoblastoma was found, but the numbers and absolute risks were small (<5 cases observed; SIR 10.28; 95% CI 1.25-37.14; P < 0.05). This increased hepatoblastoma risk was associated with low birthweight.LIMITATIONS REASONS FOR CAUTIONAlthough this study includes a large number of children born after donor ART, the rarity of specific diagnostic subgroups of childhood cancer results in few cases and therefore wide CIs for such outcomes. As this is an observational study, it is not possible to adjust for all potential confounders; we have instead used stratification to explore potential moderating and mediating factors, where data were available.WIDER IMPLICATIONS OF THE FINDINGSThis is the first study to investigate cancer risk in children born after donor ART. Although based on small numbers, results are reassuring for families and clinicians. The small but significant increased risk of hepatoblastoma detected was associated with low birthweight, a known risk factor for this tumour type. It should be emphasized that the absolute risks are very small. However, on-going investigation with a longer follow-up is needed.STUDY FUNDING/COMPETING INTEREST(S)This work was funded by Cancer Research UK (C36038/A12535) and the National Institute for Health Research (405526) and supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. The work of the Childhood Cancer Research Group (CCRG) was supported by the charity CHILDREN with CANCER UK, the National Cancer Intelligence Network, the Scottish Government and the Department of Health for England and Wales. There are no competing interests.TRIAL REGISTRATION NUMBERN/A.

Aims Cancer incidence has been investigated in children born after non-donor assisted conception, but incidence in children born after donor assisted conception remain uncertain. This study aimed to determine overall and site specific cancer incidence in a British cohort of children born after assisted conception using donor gametes. Methods This retrospective cohort study utilised records of all 12 186 children born in Britain (England, Wales and Scotland) after all forms of donor assisted conception between 1992 and 2008. Records were linked to the United Kingdom National Registry of Childhood Tumours to determine the number who developed cancer at under 15 years of age by the end of 2008. Overall and site specific cancer rates within the cohort were compared with population based rates in Great Britain over the same time period, stratifying for potential mediating and moderating factors including sex, age at diagnosis, birth weight, multiple births, parity, parental age, assisted conception type and parental infertility cause. Results No overall increased risk of cancer was identified in this population. 12 cancers were detected compared with 14.4 expected (Standardised incidence ratio (SIR) 0.83; 95% confidence interval (CI) 0.43, 1.45). A small but significant increased risk of hepatoblastoma was detected, but numbers were small (<5 cases observed compared with 0.19 cases expected; SIR 10.28; 95% CI 1.25, 37.14) and therefore absolute risk increase was also small (18.9 cases per 1 million person years). This risk was associated with low birth weight. Conclusion There was no overall increased risk of cancer in children born in Great Britain after donor assisted conception over this 16 year study period. A small increased risk of hepatoblastoma was detected, but numbers were small and absolute risks low. Our results mirror those found in a similar cohort of 1 06 000 children born after non-donor assisted conception over the same period in Britain.

To determine the risk of ovarian cancer, including malignant and borderline ovarian tumors, in women who have been exposed to ART. Records from the Human Fertilisation & Embryology Authority (HFEA) of all women who had ART in Britain between 1991-2010, were linked to the National Health Service Central Registers (NHSCR) for England, Wales and Scotland to obtain follow up for cancer outcomes, deaths and emigrations. Reporting to the HFEA is mandatory. Cancer incidence in the cohort was stratified by age and calendar period and compared with expectations derived from annual age-specific national rates over the same period. Data were also stratified for potential mediating/moderating factors such as repeated exposures, age at first exposure, parity and subfertility diagnoses. Trends across categories were evaluated using Poisson regression. With 8.8 years average follow-up, 386 ovarian cancers occurred in 255,786 women. An increased risk of developing an ovarian cancer was observed in the cohort (standardized incidence ratio (SIR) 1.37; 95%CI 1.24-1.51). No increased risk was found with increasing number of cycles of ART (Ptrend=0.80). Increasing risk was found with decreasing parity (Ptrend=0.002), with women who had no live births by the end of treatment being at greatest risk (SIR 1.54; 95%CI 1.34-1.76). Risk was increased for women with a ‘female factor’ cause of infertility (SIR 1.62; 95%CI 1.42-1.84), especially endometriosis (SIR 2.35; 95%CI 1.80-3.07), but ‘male factor’ only infertility was not associated with risk (SIR 1.05; 95%CI 0.86-1.28). Younger age at starting ART carried greater cancer risk (Ptrend<0.0001). The risk of developing an ovarian cancer was strongest 0-3 years after first ART cycle (SIR 1.54; 95%CI 1.27-1.88), but no trend with duration since first treatment was observed (Ptrend=0.30). Increased ovarian cancer risk was observed in this large cohort of women who had ART in Great Britain compared with national rates. The results suggest that this increase is at least partially mediated by patient factors such as low parity and endometriosis. Certain results argue against an association with ART itself (no increased risk in male factor infertility or with increasing number of cycles), but others (increased risk with decreasing age at first exposure and in the first few years after treatment) leave open the possibility that ART might affect risk. Further investigation to support these initial results will include analysis by tumor behavior and histopathological sub-type.

Surveillance is defined as ‘the ongoing systematic collection, analysis, interpretation, and dissemination of data, reflecting the current status of a community or population'.1 Congenital anomaly surveillance is important in improving the health of children,2 and anomaly registers are well established in many high-income countries. The data collected can be used to detect geographical clustering of cases or temporal trends, both of which may indicate change in exposure to harmful environmental agents. The data also serve to inform service planning and medical/epidemiological research. Routine reporting of surveillance data for congenital anomalies in England and Wales has been performed by the National Congenital Anomaly System (NCAS) run by the Office for National Statistics (ONS).3 NCAS notification3 systems were complex, but essentially, there were two tiers, (a) an original system of voluntary notifications (completed by any health professional) using the ‘SD56' reporting form, and (b) contribution of data to the NCAS scheme by regional anomaly registers.4 Regional anomaly registers have been established at different times, with different purposes, and with different funding arrangements. They only started to exchange data with NCAS in 1998, and they are recognised as having more complete case ascertainment5 than the ‘SD56' system. Congenital eye anomalies are an important cause of visual impairment in children worldwide, and are responsible for approximately 15–20% of blindness and severe visual impairment in children.6 The majority of these anomalies have an unknown aetiology, but both genetic and environmental factors have a role.7, 8, 9 The completeness in ascertainment of eye anomalies by NCAS has not been examined since the inclusion of regional register data. The purpose of this study was to compare the number of children identified in a national active surveillance study (ascertained through the British Ophthalmic Surveillance Unit (BOSU)10) with an equivalent NCAS data set. In the BOSU study, ophthalmologists reported all children aged 16 years, newly diagnosed with anophthalmos, microphthalmos, and/or coloboma (AMC). The NCAS data set included children with the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) codes applicable to eye anomalies (ie, Q10 to Q1511). The two methods of case ascertainment were compared using a method described by Rahi and Botting.12 The comparison was restricted to children born in England and Wales between 1 January 2007 and 31 December 2007, and four identifiers were used to match children. Each child in the BOSU data set was assigned one of four outcomes, three in which the child's identifiers matched those in the NCAS data set, and one when no match was present (Table 1). Children in the NCAS data set, but who were not in the BOSU data set, were also identified. Table 1 Results of matching the BOSU and NCAS data sets The BOSU data set included 55 children, but only eight (14.5%) of them were listed in the NCAS data set as having an AMC code (ie, outcome 1; Table 1). The majority of children in the BOSU data set (81.8%) did not match any child in the NCAS data set. Eleven children were in the NCAS data set, but not in the BOSU data set. Children with systemic anomalies were more likely to be on the NCAS register than those without (17.6 vs 9.5%). Children (8%) in the BOSU data set from voluntary notification areas (ie, ‘SD56' system) were matched, compared with 20% from register regions. Two children identified through BOSU with anophthalmos, one bilaterally affected, were registered to NCAS as having systemic abnormalities, but no eye anomalies. All 11 children who were only in the NCAS register were recorded by regional registers. This study shows that there is significant underreporting of eye anomalies to NCAS in England and Wales, with children living in an area served by a regional register being more likely to have been reported then those served by the SD56 system alone. Children with systemic anomalies were also more likely to be reported. This differential case ascertainment not only underestimates the number of children affected, but over emphases the degree of severity. Two other studies have explored completeness of reporting to NCAS of children with eye anomalies ascertained through other methods.12, 13 Both studies were performed before the regional registers started contributing to NCAS, and so they only investigated the passive SD56 system. In the first study, only 22% of children with anophthalmos and microphthalmos identified using multiple sources between 1988 and 1994 were reported to NCAS.13 In the second study, only 10% of children newly diagnosed with cataract reported to BOSU between 1995 and 1996 were also reported to NCAS.12 The low figures in this latter study and in ours may, in part, be due to more complete case ascertainment through BOSU, which uses active surveillance which is known to yield higher case ascertainment rates.14 Since the conclusion of this study, ONS has undertaken a consultation to consider the future of NCAS.15 Response to the consultation proposes that the SD56 system be terminated immediately, and discussions undertaken with the Department of Health for a properly funded, comprehensive national system based on existing regional registries that can provide good quality data on anomalies on both live births, still births, and terminations of pregnancy.16 We support and await the development of such a system; however, we are concerned that, at present, only 50% of births in England are covered by a regional register.17 Eye anomalies can be very difficult to diagnose for the non-specialist, and an increased awareness of the importance and need to report cases by the paediatric eye health community is required. Greater engagement between coordinators of the regional registers and the paediatric eye care professionals would improve reporting, as would the designation of one member of staff in each paediatric eye unit to be responsible for day-to-day monitoring and reporting. Making the reporting mechanism more user-friendly, by allowing direct reporting by secure email, for example, may aid reporting by busy clinicians. For the future, the increasing use of computerised medical records allowing linkage of databases is likely to change the face of public health surveillance, but for the present, national anomaly reporting for eye anomalies remains insensitive to detect changes in frequency and therefore risk factors.

OBJECTIVES:To evaluate the effectiveness of policies and recommendations on folic acid aimed at reducing the occurrence of neural tube defects.DESIGN:Retrospective cohort study of births monitored by birth defect registries.SETTING:13 birth defects registries monitoring rates of neural tube defects from 1988 to 1998 in Norway, Finland, Northern Netherlands, England and Wales, Ireland, France (Paris, Strasbourg, and Central East), Hungary, Italy (Emilia Romagna and Campania), Portugal, and Israel. Cases of neural tube defects were ascertained among liveborn infants, stillbirths, and pregnancy terminations (where legal). Policies and recommendations were ascertained by interview and literature review.MAIN OUTCOME MEASURES:Incidences and trends in rates of neural tube defects before and after 1992 (the year of the first recommendations) and before and after the year of local recommendations (when applicable).RESULTS:The issuing of recommendations on folic acid was followed by no detectable improvement in the trends of incidence of neural tube defects.CONCLUSIONS:Recommendations alone did not seem to influence trends in neural tube defects up to six years after the confirmation of the effectiveness of folic acid in clinical trials. New cases of neural tube defects preventable by folic acid continue to accumulate. A reasonable strategy would be to quickly integrate food fortification with fuller implementation of recommendations on supplements.

The study evaluated the sex distribution of major isolated malformations and common trisomies among a large and geographically varied sample. Eighteen registries from 24 countries contributed cases, which were centrally reviewed and classified in three clinical types as isolated, associated, or syndromic. We selected cases of 26 major defects (n = 108,534); trisomy 21, 18, and 13 (n = 30,114); other syndromes (n = 2,898); and multiple congenital anomalies (n = 24,197), for a total of 165,743 cases. We observed a significant deviation of sex distribution (compared to a sex ratio of 1.06 or male proportion of 51.4%) for 24 of the 29 groups (a male excess in 16, a female excess in 8), and in 8 of such groups these estimates varied significantly across registries. A male excess was noted for two left obstructive cardiac defects (hypoplastic left heart and coarctation of the aorta) and a female excess for all the main types of neural tube defects. A male excess was seen for omphalocele but not gastroschisis. For neural tube defects the female excess tended to be stronger in areas with historically high prevalence for these defects. For 15 of the 26 birth defects the sex distribution differed among isolated, associated, and syndromic cases. Some of these epidemiologic commonalities are consistent with known or putative developmental processes. Further, the geographic variation for some defects may reflect local prevalence rates and risk factors. Finally, the findings underscore the need for clinical classification (e.g., into isolated, multiple, syndromes) in studies of birth defects. Published 2005 Wiley-Liss, Inc.

Concern about apparent increases in the prevalence of hypospadias--a congenital male reproductive-tract abnormality--in the 1960s to 1980s and the possible connection to increasing exposures to endocrine-disrupting chemicals have underlined the importance of effective surveillance of hypospadias prevalence in the population. We report here the prevalence of hypospadias from 1980 to 1999 in 20 regions of Europe with EUROCAT (European Surveillance of Congenital Anomalies) population-based congenital anomaly registers, 14 of which implemented a guideline to exclude glanular hypospadias. We also report data from the England and Wales National Congenital Anomaly System (NCAS). Our results do not suggest a continuation of rising trends of hypospadias prevalence in Europe. However, a survey of the registers and a special validation study conducted for the years 1994-1996 in nine EUROCAT registers as well as NCAS identified a clear need for a change in the guidelines for registration of hypospadias. We recommend that all hypospadias be included in surveillance, but that information from surgeons be obtained to verify location of the meatus, and whether surgery was performed, in order to interpret trends. Investing resources in repeated special surveys may be more cost-effective than continuous population surveillance. We conclude that it is doubtful whether we have had the systems in place worldwide for the effective surveillance of hypospadias in relation to exposure to potential endocrine-disrupting chemicals.

Objective Firstly, to assess the completeness of ascertainment in die National Congenital Anomaly System (NCAS), the basis for congenital anomaly surveillance in England and Wales, and its variation by defect geographical area, and socioeconomic deprivation. Secondly, to assess die impact of the lack of data on pregnancies terminated because of fetal anomaly.Design Comparison of the NCAS with four local congenital anomaly registers in England.Setting Four regions in England covering some 109 000 annual births.Participants Cases of congenital anomalies registered in the NCAS (live births and stillbirths) and independently registered in the four local registers (live births, stillbirths, fetal losses from 20 weeks' gestation, and pregnancies terminated after prenatal diagnosis of fetal anomaly).Main outcome measure The ratio of cases identified by the national register to those in local registry files, calculated for different specified anomalies, for whole registry areas, and for hospital catchment areas within registry boundaries.Results Ascertainment by the NCAS (compared with data from local registers, from which terminations of pregnancy were removed) was 40% (34% for chromosomal anomalies and 42% for non-chromosomal anomalies) and varied markedly by defect, by local register, and by hospital catchment area, but not by area deprivation. When terminations of pregnancy were included in the register data, ascertainment-by NCAS was 27% (19% for chromosomal anomalies and 31% for non-chromosomal anomalies),and the geographical variation was of a similar magnitude.Conclusion The surveillance of congenital anomalies in England is currently inadequate because ascertainment to the national register is low and non-uniform and because no data exist on termination of pregnancy resulting from prenatal diagnosis of fetal anomaly.

Background: Reported rises in the prevalence of hypospadias and other abnormalities of the male reproductive system may be a result of exposure to endocrine disrupting chemicals. Aims: To analyse the relation between risk of hypospadias and maternal occupation, particularly with regard to exposure to potential endocrine disrupting chemicals (EDCs). Methods: Data (1980–96) from the National Congenital Anomaly System (NCAS) were used to analyse the proportion of all congenital anomaly cases (n = 35 962) which were notified with hypospadias (n = 3471) by occupational codes (348 individual job titles) and by categories of exposure to potential EDCs from a job exposure matrix. Results: Five individual occupations (of 348) showed nominally statistically significant excesses, none of which had possible or probable exposure to potential EDCs. Odds ratios for “possible” or “probable” compared to “unlikely” exposure to potential EDCs did not show statistically significant increases in any of the EDC categories after adjustment for social class of the mother and father, nor was there evidence of an upward trend in risk with likelihood of exposure. In the 1992–96 time period odds ratios were increased for hairdressers (the largest group exposed to potential EDCs) and for probable exposure to phthalates (of which hairdressers form the largest group) before social class adjustment. Conclusions: There was little evidence for a relation between risk of hypospadias and maternal occupation or occupational exposure to potential EDCs, but as the exposure classification was necessarily crude, these findings should be interpreted with caution.

A study to assess the association between the prevalence of hypospadias and maternal occupational exposure to potential endocrine-disrupting chemicals was carried out using data from the congenital anomaly register of the Office for National Statistics. The occupation of the mother is recorded in this register and to facilitate the assessment of maternal occupational exposure, a specific job-exposure matrix for potential endocrine-disrupting chemicals was developed. Seven categories of contaminants were evaluated (pesticides, polychlorinated organic compounds, phthalates, alkylphenolic compounds, bi-phenolic compounds, heavy metals and other substances). Maternal occupations were all coded using the 1980 version of Categories of Occupations. Three occupational hygienists assessed the likelihood of exposure (unlikely, possible, probable) to these seven substance groups for all 348 possible job titles independently. Almost 30% of the job titles were classified as exposed to at least one substance category (possible or probable), with approximately 16% of the job titles being probably exposed to at least one substance category. Some examples of occupations with probable exposure to potential endocrine-disrupting chemicals include: farm workers, electricians, workers in the plastics industry, painters, printers, hairdressers, dental practitioners, laboratory workers, textile workers and cleaners. It is recognized that there are a lot of limitations to the use of job-exposure matrices in general and with the matrix presented in this paper in particular. However, the matrix forms the basis on which further developments on occupational exposure assessment of potential endocrine-disrupting chemicals could be founded. In addition, the job-exposure matrix has identified areas where more exposure information is required. For example, exposure to potential endocrine-disrupting chemicals can occur in occupations such as hairdressing and workers in beauty salons, where the working population is more likely to be female and for which little data exist on levels of exposure.

Study objective-To provide an international perspective on the impact of congenital anomalies on infant mortality from 1950 to 1994.Design-Population-based study based on data obtained from vital statistics reported to the World Health Organisation. Settings-36 countries from Europe, the Middle East, the Americas, Asia, and the South Pacific.Results-On average, infant mortality declined 68.8 per cent from 1950 to 1994. In the countries studied, infant mortality attributable to congenital anomalies decreased by 33.4 per cent, although it recently increased in some countries in Central and Latin America and in Eastern Europe. Anomalies of the heart and of the central nervous system accounted for 48.9 per cent of infant deaths attributable to congenital anomalies. During 1990-1994, infant mortality attributable to congenital anomalies was inversely correlated to the per capita gross domestic product in the countries studied. At the same time, the proportion of infant deaths attributable to congenital malformations was directly correlated with the per capita gross domestic product.Conclusions-Congenital malformations account for an increasing proportion of infant deaths in both developed and developing countries. Infant mortality attributable to congenital anomalies is higher in poorer countries although as a proportion of infant deaths it is greater in wealthier countries. Conditions such as spina bifida, whose occurrence can be reduced through preventive strategies, still cause many infant deaths. The apparent increase of infant mortality because of congenital anomalies in some countries should be investigated to confirm the finding, find the causes, and provide prevention opportunities.

The late 1960s and early 1970s saw major changes in access to birth control. This article reviews trends in fertility and contraception between 1976 when the Family Formation Survey was undertaken and 1998, the latest year for which data are available. There has been an increase in mean age at childbirth over the period. Some of this increase is possibly a result of childbearing in second and subsequent relationships when the women will be older on average. This also has had an impact on their patterns of contraception use. Teenage pregnancy is high on the Government's agenda. Teenage pregnancy continues at constant levels. As the estimated age of first intercourse decreases, there is a continued need for sufficient, accessible and appropriate family planning services.

Objectives To measure the changes in fc,late consumption and the prevalence of neural tube defects in the British and Irish populations during the past two decades.Design Ecological study.Main outcome measures Average daily dietary folate consumption for Britain for the period 1980-1996 was estimated from the National Food Survey. Annual neural tube defect prevalences for the same period were obtained from the Oxford Record Linkage Study Neural Tube Defect register, the Glasgow EUROCAT register, and the three Irish EUROCAT registers (Belfast, Dublin and Galway).Results Dietary folate consumption increased on average by 1.6% per annum in Scotland and 1.4% in England during the study period. The annual rate of decline of neural tube defect prevalence averaged 10.4% in the Irish population, 8.2% in Glasgow, and 5.2% in Oxfordshire and West Berkshire.Conclusions The decline in neural tube defect prevalence observed in all British and Irish populations since the early 1970s continued with the introduction of folate fortification of cereals, which produced measurable increases in average daily folate consumption. Further declines in neural tube defect prevalence may be achieved by targeted folate supplementation during the periconceptual period.

Periconceptional folate supplementation has been encouraged in the UK since the early 1990s, but no concurrent decline in neural-tube-defect pregnancies has been observed by regional congenital anomaly registers.

Data provided by nine registries based in European and Latin America countries were analyzed to assess whether there is an excess of malformations in twins compared to singletons. Specific congenital malformations were coded according to the ninth revision of the International Classification of Diseases (ICD). Malformation rates and rate ratios (RR) for twins compared to singletons were calculated for each registry, and the homogeneity of the RRs was tested using the test of Breslow and Day. If departure from homogeneity in the different registries was not significant, registry-adjusted RRs with 95% confidence intervals were calculated. Overall, among 260,865 twins, 5,572 malformations were reported. A total of 101 different types of malformations or groups of defects was identified, and a homogeneous estimate of the RRs among registries was found for 91.1% of the malformations. Thirty-nine of the 92 malformations with homogeneous estimates of RRs were more common in twins than in singletons. For the remaining nine malformations, heterogeneous estimates of RRs were obtained. This study confirms the majority of already known associations and further identifies previously unreported malformations associated with twins. In conclusion, there is an excess of malformations in twins compared with singletons, and all anatomical sites are involved. The number of specific malformations associated with twins is higher than that previously reported in smaller studies.

Objective-To examine time trends in neural tube defects (NTD) prevalence from 1987 to 1996 in relation to the primary prevention policies for folic acid supplementation strategies in different countries.Design-Retrospective time trends analysis of NTD prevalence.Setting-11 birth defect registries of congenital malformations participating in the International Clearinghouse for Birth Defects Monitoring System, in the period from 1 July 1987 to 30 June 1996.Subjects-8207 live births, stillbirths and terminated pregnancies affected by anencephaly or spina bifida registered by the 11 participating centres 1987-1996.Outcome measures-Prevalence rate ratios based on the annual rates, using the Poisson regression model.Results-During the study period a significant fall in prevalence rates for all NTD is present in Atlanta (USA), England and Wales, Hungary and japan, and a significant rise in Norway and South America. After adjusting for the secular trends observed in the earlier years of the study, no significant trend can be attributed to preventive strategies. Data on NTD prevalence are supplemented with information on folate awareness among some of the populations studied.Conclusion-There is no evidence that, up to the middle of 1996, any change in time trend was attributable to the introduction of national folate supplementation policies. The possible effectiveness of folate supplementation policies for the reduction of NTD clearly needs to be tried and studied for several more years. Considering that in the Western world about 50% of pregnancies are unplanned, a policy that rests on action taken before conception can only have limited success. Strategies based on food enrichment, such as was introduced in the USA from the beginning of 1998, may prove to be more successful.

Teenage mothers continue to present challenges to social policy and remain of topical interest to the media. This article discusses trends in teenage conception rates, their outcomes and long term consequences. In 1996, 7 per cent of all births were to girls aged under 20. On average children born to teenage girls have lower birthweights, increased risk of infant mortality and an increased risk of some congenital anomalies. They are less likely to be breastfed and more likely to live in deprived circumstances. These factors in turn influence their health and long term opportunities.