Ambient air pollution and risk of congenital anomalies in England, 1991-1999.

OBJECTIVES: To investigate whether there is an association between risk of congenital anomaly and annual ward level exposure to air pollution in England during the 1990s. METHODS: A geographical study was conducted across four regions of England using population-based congenital anomaly registers, 1991-1999. Exposure was measured as 1996 annual mean background sulphur dioxide (SO(2)), nitrogen dioxide (NO(2)) and particulate matter (PM(10)) concentrations at census ward level (n=1474). Poisson regression, controlling for maternal age, area socioeconomic deprivation and hospital catchment area, was used to estimate relative risk for an increase in pollution from the 10th to the 90th centile. RESULTS: For non-chromosomal anomalies combined, relative risks were 0.99 (95% CI 0.93 to 1.05) for SO(2), 0.97 (95% CI 0.84 to 1.11) for NO(2) and 0.89 (95% CI 0.75 to 1.07) for PM(10). For chromosomal anomalies, relative risks were 1.06 (95% CI 0.98 to 1.15) for SO(2), 1.11 (95% CI 0.95 to 1.30) for NO(2) and 1.18 (95% CI 0.97 to 1.42) for PM(10). Raised risks were found for tetralogy of Fallot and SO(2) (RR=1.38, 95% CI 1.07 to 1.79), NO(2) (RR=1.44, 95% CI 0.71 to 2.93) and PM(10) (RR=1.48, 95% CI 0.57 to 3.84), which is of interest in light of previously reported associations between this cardiac anomaly and other air pollutants. CONCLUSIONS: While air pollution in the 1990s did not lead to sustained geographical differences in the overall congenital anomaly rate in England, further research regarding specific anomalies is indicated.

Prevalence of congenital anomalies in five British regions, 1991-99.

AIMS: To describe trends in total and live birth prevalence, regional differences in prevalence, and outcome of pregnancy of selected congenital anomalies. METHODS: Population based registry study of 839,521 births to mothers resident in five geographical areas of Britain during 1991-99. Main outcome measures were: total and live birth prevalence; pregnancy outcome; proportion of stillbirths due to congenital anomalies; and secular trends. RESULTS: The sample consisted of 10,844 congenital anomalies, giving a total prevalence of 129 per 10,000 registered births (95% CI 127 to 132). Live birth prevalence was 82.2 per 10,000 births (95% CI 80.3 to 84.2) and declined significantly with time. The proportion of all stillbirths with a congenital anomaly was 10.5% (453 stillbirths). The proportion of pregnancies resulting in a termination increased from 27% (289 cases) in 1991 to 34.7% (384 cases) in 1999, whereas the proportion of live births declined from 68.2% (730 cases) to 58.5% (648 cases). Although similar rates of congenital anomaly groups were notified to the registers, variation in rates by register was present. There was a secular decline in the total prevalence of non-chromosomal and an increase in chromosomal anomalies. CONCLUSIONS: Regional variation exists in the prevalence of specific congenital anomalies. For some anomalies this can be partially explained by ascertainment variation. For others (neural tube defects, diaphragmatic hernia, gastroschisis), higher prevalence rates in the northern regions (Glasgow and Northern) were true differences. Live birth prevalence declined over the study due to an increase in terminations of pregnancy.

Congenital anomaly surveillance in England--ascertainment deficiencies in the national system.

OBJECTIVE: Firstly, to assess the completeness of ascertainment in the 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 the 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.

Chromosomal congenital anomalies and residence near hazardous waste landfill sites.

Previous findings of the EUROHAZCON study showed a 33% increase in risk of non-chromosomal anomalies near hazardous waste landfill sites. Here, we studied 245 cases of chromosomal anomalies and 2412 controls who lived near 23 such sites in Europe. After adjustment for confounding by maternal age and socioeconomic status, we noted a higher risk of chromosomal anomalies in people who lived close to sites (0-3 km) than in those who lived further away (3-7 km; odds ratio 1.41, 95% CI 1.00-1.99). Our results suggest an increase in risk of chromosomal anomalies similar to that found for non-chromosomal anomalies.

What parents are told after prenatal diagnosis of a sex chromosome abnormality: interview and questionnaire study.

OBJECTIVE: To investigate how the prenatal diagnosis of a sex chromosome anomaly is first communicated to parents. DESIGN: Health professionals were interviewed by telephone and the conversation was taped; parents were sent questionnaires at 1 month after diagnosis and those who responded were sent another at 6 months. PARTICIPANTS: 29 health professionals who had recently informed parents that a sex chromosome anomaly had been identified in an apparently anatomically normal, viable fetus. 23 mothers and partners who had been informed of such a diagnosis. MAIN OUTCOME MEASURES: Health professionals' knowledge about sex chromosome anomalies and parents' responses to information provided by health professionals. RESULTS: Analysis of the telephone interviews identified great variation in what different healthcare professionals know, think, and say about the same sex chromosome anomaly. The small numbers and the low response rate for the questionnaire (39% for women and 30% for men) meant that statistical analysis was not appropriate. CONCLUSIONS: It is essential for obstetric units to have an established protocol for giving results and for all staff who communicate results to parents to have accurate, up to date information about the condition identified.

Socioeconomic inequalities in risk of congenital anomaly.

AIMS: To investigate socioeconomic inequalities in the risk of congenital anomalies, focusing on risk of specific anomaly subgroups. METHODS: A total of 858 cases of congenital anomaly and 1764 non-malformed control births were collected between 1986 and 1993 from four UK congenital malformation registers, for the purposes of a European multicentre case control study on congenital anomaly risk near hazardous waste landfill sites. As a measure of socioeconomic status, cases and controls were given a value for the area level Carstairs deprivation index, by linking the postcode of residence at birth to census enumeration districts (areas of approximately 150 households). RESULTS: Risk of non-chromosomal anomalies increased with increasing socioeconomic deprivation. The risk in the most deprived quintile of the deprivation index was 40% higher than in the most affluent quintile. Some malformation subgroups also showed increasing risk with increasing deprivation: all cardiac defects, malformations of the cardiac septa, malformations of the digestive system, and multiple malformations. No evidence for socioeconomic variation was found for other non-chromosomal malformation groups, including neural tube defects and oral clefts. A decreasing risk with increasing deprivation found for all chromosomal malformations and Down's syndrome in unadjusted analyses, occurred mainly as a result of differences in the maternal age distribution between social classes. CONCLUSION: Our data, although based on limited numbers of cases and geographical coverage, suggest that more deprived populations have a higher risk of congenital anomalies of non-chromosomal origin and some specific anomalies. Larger studies are needed to confirm these findings and to explore their aetiological implications.

Has advice on periconceptional folate supplementation reduced neural-tube defects?

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.

Risk of congenital anomalies near hazardous-waste landfill sites in Europe: the EUROHAZCON study.

BACKGROUND: Waste-disposal sites are a potential hazard to health. This study is a multicentre case-control study of the risk of congenital anomalies associated with residence near hazardous-waste landfill sites in Europe. METHODS: We used data from seven regional registers of congenital anomalies in five countries. We studied 1089 livebirths, stillbirths, and terminations of pregnancy with non-chromosomal congenital anomalies and 2366 control births without malformation, whose mothers resided within 7 km of a landfill site; 21 sites were included. A zone within 3 km radius of each site was defined as the "proximate zone" of most likely exposure to teratogens. FINDINGS: Residence within 3 km of a landfill site was associated with a significantly raised risk of congenital anomaly (295 cases/511 controls living 0-3 km from sites, 794/1855 living 3-7 km from sites; combined odds ratio 1.33 [95% CI 1.11-1.59], adjusted for maternal age and socioeconomic status). There was a fairly consistent decrease in risk with distance away from the sites. A significantly raised odds ratio for residence within 3 km of a landfill site was found for neural-tube defects (odds ratio 1.86 [1.24-2.79]), malformations of the cardiac septa (1.49 [1.09-2.04]), and anomalies of great arteries and veins (1.81 [1.02-3.20]). Odds ratios of borderline significance were found for tracheo-oesophageal anomalies (2.25 [0.96-5.26]), hypospadias (1.96 [0.98-3.92]), and gastroschisis (3.19 [0.95-10.77]). There was little evidence of differences in risk between landfill sites but power to detect such differences was low. INTERPRETATION: This study shows a raised risk of congenital anomaly in babies whose mothers live close to landfill sites that handle hazardous chemical wastes, although there is a need for further investigation of whether the association of raised risk of congenital anomaly and residence near landfill sites is a causal one. Apparent differences between malformation subgroups should be interpreted cautiously.

47,XXY (Klinefelter syndrome) and 47,XYY: estimated rates of and indication for postnatal diagnosis with implications for prenatal counselling.

Cytogenetic surveys of neonates have found that approximately one boy in 500 is born with an extra sex chromosome. Some of these boys are now being diagnosed when prenatal karyotyping is done for the detection of Down syndrome and other major aneuploidies. This study estimates what proportion of those not detected prenatally will be diagnosed postnatally and what the indications for karyotyping are likely to be. We ascertained all 47,XXY and 47,XYY males detected prenatally and postnatally (during the 4 years 1990-1993) in the three cytogenetic laboratories in the North Thames (West) region. The age at diagnosis and indication for karyotyping were noted for cases diagnosed postnatally. Less than 10 per cent of the estimated number of affected fetuses were detected prenatally. This study suggests that most males born with these chromosome patterns will go through life without being karyotyped, that the commonest indication for a 47,XYY male to be karyotyped will be developmental delay and/or behaviour problems, and that the commonest indication for a Klinefelter male to be karyotyped will be hypogonadism and/or infertility. It would appear that most undiagnosed 47,XXY and 47,XYY males do not look or behave in a manner which prompts testing for a chromosome abnormality.

Room for improvement? Detecting autosomal trisomies without serum screening.

OBJECTIVE: To assess the efficacy of the prenatal screening and diagnostic programme for the detection of the common autosomal trisomies in the North West Thames region prior to the introduction of serum screening. DESIGN: A retrospective study based on reports made to the North West Thames Regional Health Authority Congenital Malformation Register. SUBJECTS: 235 pregnancies of women delivered in units in the North West Thames region over a two-year period (1990-91) whose babies or fetuses were diagnosed as having Down, Edwards or Patau syndrome. RESULTS: 33% of Down syndrome, 68% of Edwards syndrome and 52% of Patau syndrome were diagnosed prenatally (before 28 weeks) in the region without the use of serum screening. CONCLUSIONS: Using maternal age and routine ultrasound as screening methods, units in the region are prenatally diagnosing significantly fewer Down syndrome babies than are those in authorities using serum screening. The use of maternal age and ultrasound screening is more effective for the antenatal detection of the other autosomal trisomies than it is for the detection of Down syndrome. It is not yet clear to what extent serum screening might be expected to increase the detection rate for these conditions.

Women's choices for fetal chromosome analysis.

Five hundred and eighty women aged 35 or more at the expected date of delivery were offered the chance to join the MRC trial comparing CVS and amniocentesis at Queen Charlotte's Hospital. After a 1 h non-directive counselling session, they were asked to choose between having no test, having amniocentesis, or joining the trial in the hopes of having CVS (or in some cases having CVS outside the trial). The majority of women chose to have some test, and CVS was a more popular choice than amniocentesis.