Lenore Abramsky

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 Downs 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.

Preventing neural tube defects in Europe: population based study

Each year, more than 4500 pregnancies in the European Union are affected by neural tube defects. Unambiguous evidence of the effectiveness of periconceptional folic acid in preventing neural tube defects has been available since 1991,1 and improving folate status sufficiently could result in the prevention of more than two thirds of all neural tube defects. We report on trends in the prevalence of neural tube defects up to 2001, in the context of a survey in 16 European countries of periconceptional folic acid policies and their implementation.2 3 Eurocat is a network of population based congenital anomaly registries in Europe (http://www.eurocat.ulster.ac.uk/). A total of 9 273 212 births were surveyed by 31 registries in 16 countries 1980-2001,3 including 8913 babies or fetuses with neural tube defects (anencephaly, spina bifida, or encephalocele): 3298 live births, 844 stillbirths, and 4771 terminations of pregnancy after prenatal diagnosis. In the United Kingdom and Ireland, yearly prevalence of neural tube defects declined, predating any periconceptional folic acid supplementation policy initiatives, from 45 per 10 000 births in 1980 to 10 to 15 per 10 000 in the 1990s (%figure). In contrast, in the rest of Europe the prevalence during the 1980s and thereafter was close to 10 per 10 000 …

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.

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.

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 (SO2), nitrogen dioxide (NO2) and particulate matter (PM10) 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 SO2, 0.97 (95% CI 0.84 to 1.11) for NO2 and 0.89 (95% CI 0.75 to 1.07) for PM10. For chromosomal anomalies, relative risks were 1.06 (95% CI 0.98 to 1.15) for SO2, 1.11 (95% CI 0.95 to 1.30) for NO2 and 1.18 (95% CI 0.97 to 1.42) for PM10. Raised risks were found for tetralogy of Fallot and SO2 (RR=1.38, 95% CI 1.07 to 1.79), NO2 (RR=1.44, 95% CI 0.71 to 2.93) and PM10 (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.

Chlorination disinfection by-products and risk of congenital anomalies in England and Wales

Background Increased risk of various congenital anomalies has been reported to be associated with trihalomethane (THM) exposure in the water supply. Objectives We conducted a registry-based study to determine the relationship between THM concentrations and the risk of congenital anomalies in England and Wales. Methods We obtained congenital anomaly data from the National Congenital Anomalies System, regional registries, and the national terminations registry; THM data were obtained from water companies. Total THM (< 30, 30 to < 60, ≥60 μg/L), total brominated exposure (< 10, 10 to < 20, ≥20 μg/L), and bromoform exposure (< 2, 2 to < 4, ≥4 μg/L) were modeled at the place of residence for the first trimester of pregnancy. We included 2,605,226 live births, stillbirths, and terminations with 22,828 cases of congenital anomalies. Analyses using fixed- and random-effects models were performed for broadly defined groups of anomalies (cleft palate/lip, abdominal wall, major cardiac, neural tube, urinary and respiratory defects), a more restricted set of anomalies with better ascertainment, and for isolated and multiple anomalies. Data were adjusted for sex, maternal age, and socioeconomic status. Results We found no statistically significant trends across exposure categories for either the broadly defined or more restricted sets of anomalies. For the restricted set of anomalies with isolated defects, there were significant (p < 0.05) excess risks in the high-exposure categories of total THMs for ventricular septal defects [odds ratio (OR) = 1.43; 95% confidence interval (CI), 1.00–2.04] and of bromoform for major cardiovascular defects and gastroschisis (OR = 1.18; 95% CI, 1.00–1.39; and OR = 1.38; 95% CI, 1.00–1.92, respectively). Conclusion In this large national study we found little evidence for a relationship between THM concentrations in drinking water and risk of congenital anomalies.

Geographic variation and localised clustering of congenital anomalies in Great Britain

BackgroundEnvironmental pollution as a cause of congenital anomalies is sometimes suspected because of clustering of anomalies in areas of higher exposure. This highlights questions around spatial heterogeneity (clustering) in congenital anomaly rates. If spatial variation is endemic, then any one specific cluster is less remarkable, though the presence of uncontrolled geographically clustered risk factors is suggested. If rates are relatively homogeneous across space other than around specific hazards, then evidence for these hazards causing the clusters is strengthened. We sought to estimate the extent of spatial heterogeneity in congenital anomaly rates in the United Kingdom.MethodsThe study population covered about one million births from five registers in Britain from 1991–1999. We estimated heterogeneity across four geographical levels: register area, hospital catchment, electoral ward, and enumeration district, using a negative binomial regression model. We also sought clusters using a circular scan statistic.ResultsCongenital anomaly rates clearly varied across register areas and hospital catchments (p < 0.001), but not below this level (p > 0.2). Adjusting for socioeconomic deprivation and maternal age made little difference to the extent of geographical variation for most congenital anomaly subtypes. The two most significant circular clusters (of four ano-rectal atresias and six congenital heart diseases) contained two or more siblings.ConclusionThe variation in rates between registers and hospital catchment area may have resulted in part from differences in case ascertainment, and this should be taken into account in geographical epidemiological studies of environmental exposures. The absence of evidence for variation below this level should be interpreted cautiously in view of the low power of general heterogeneity tests. Nevertheless, the data suggest that strong localised clusters in congenital anomalies are uncommon, so clusters around specific putative environmental hazards are remarkable when observed. Negative binomial models applied at successive hierarchical levels provide an approach of intermediate complexity to characterising geographical heterogeneity.

Survival and health in liveborn infants with transposition of great arteries: A population based study

OBJECTIVE To describe treatment, survival, and morbidity for liveborn infants with isolated transposition of great arteries (TGA). DESIGN Population-based data from 7 European registries of congenital malformations (EUROCAT). RESULTS Ninety-seven infants were diagnosed with isolated TGA and livebirth prevalence was 2.0 per 10,000 livebirths. The majority of infants were treated with prostaglandins (83%) and 57% had a catheter atrial septostomia performed. Arterial switch surgery was performed in 78 infants, other or unknown type of surgery was performed in 3 cases, and for 6 infants there was no information on surgery. At 1 year of age 69 infants were alive (71%) and 24 (25%) were dead (4 unknown). There were 10 deaths before surgery and 58% of all deaths took place during the first week. There was no statistically significant regional difference in mortality. Eight infants diagnosed prenatally all survived to 1 year and only 71% of infants diagnosed after birth survived (P = 0.08). Data on morbidity at 1 year of age was available for 57 infants. Fifty-one infants were reported with normal health and development. CONCLUSIONS In this population-based study survival for liveborn infants with TGA is lower than in studies published from tertiary centers. Outcome for survivors at 1 year of age seems favorable.