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, > or =60 microg/L), total brominated exposure (< 10, 10 to < 20, > or =20 microg/L), and bromoform exposure (< 2, 2 to < 4, > or =4 microg/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.

BACKGROUND: Environmental 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. METHODS: The 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. RESULTS: Congenital 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. CONCLUSION: The 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.

Preventing neural tube defects in Europe: a missed opportunity.

Each year, more than 4500 pregnancies in the European Union are affected by neural tube defects (NTD). Unambiguous evidence of the effectiveness of periconceptional folic acid in preventing the majority of neural tube defects has been available since 1991. We report on trends in the total prevalence of neural tube defects up to 2002, in the context of a survey in 18 European countries of periconceptional folic acid supplementation (PFAS) policies and their implementation. EUROCAT is a network of population-based registries in Europe collaborating in the epidemiological surveillance of congenital anomalies. Representatives from 18 participating countries provided information about policy, health education campaigns and surveys of PFAS uptake. The yearly total prevalence of neural tube defects including livebirths, stillbirths and terminations of pregnancy was calculated from 1980 to 2002 for 34 registries, with UK and Ireland estimated separately from the rest of Europe. A meta-analysis of changes in NTD total prevalence between 1989-1991 and 2000-2002 according to PFAS policy was undertaken for 24 registries. By 2005, 13 countries had a government recommendation that women planning a pregnancy should take 0.4mg folic acid supplement daily, accompanied in 7 countries by government-led health education initiatives. In the UK and Ireland, countries with PFAS policy, there was a 30% decline in NTD total prevalence (95% CI 16-42%) but it was difficult to distinguish this from the pre-existing strong decline. In other European countries with PFAS policy, there was virtually no decline in NTD total prevalence whether a policy was in place by 1999 (2%, 95% CI 28% reduction to 32% increase) or not (8%, 95% CI 26% reduction to 16% increase). The potential for preventing NTDs by periconceptional folic acid supplementation is still far from being fulfilled in Europe. Only a public health policy including folic acid fortification of staple foods is likely to result in large-scale prevention of NTDs.

Health professionals' reports of information given to parents following the prenatal diagnosis of sex chromosome anomalies and outcomes of pregnancies: a pilot study.

OBJECTIVES: To examine the association between the information health professionals report providing parents about sex chromosome anomalies (SCAs) and the outcomes of affected pregnancies. METHODS: Telephone interviews were conducted with health professionals who disclosed the prenatal diagnosis of an SCA to parents. The statements they reported providing to parents about the condition were coded as positive, neutral or negative. Outcomes of the pregnancies were obtained from medical records. RESULTS: Six of the 23 pregnancies were terminated. Health professionals reported giving parents of these six cases a greater amount of negative information about an SCA than did the health professionals reporting on the information given to the parents who continued with their pregnancies. Health professionals reported giving a similar amount of positive and neutral information to both groups of parents. CONCLUSION: The results of this pilot study suggest that there is a positive association between the amount of negative information parents are given initially about a sex chromosome anomaly and the decision to terminate the affected pregnancy. This study is limited by its small sample size and reliance on health professionals' self-reports of information provided to parents. Larger, prospective studies in which consultations are tape-recorded and linked to parents' subsequent decision making and adjustment are needed.

Interpreting information: what is said, what is heard--a questionnaire study of health professionals and members of the public.

OBJECTIVE: To investigate how people perceive some of the words and phrases commonly used in prenatal diagnosis counselling. METHODS: A questionnaire containing 25 questions with forced choice answers was administered in the form of a lecture. Respondents were asked to report how worrying they would find different ways of being told about hypothetical anomalies or risks of anomalies in their baby. 581 questionnaires were completed by 372 health professionals and 209 members of the public. The sample was obtained opportunistically. The exact number of non-responders is not known but is estimated to be less than 5%. RESULTS: Respondents reported being particularly worried by the use of genetic jargon and use of the following words: rare, abnormal, syndrome, disorder, anomaly and high risk. They found risk expressed as 1 in X more worrying than when it was expressed as a percentage, and they consistently reacted as if they estimated the chance of an undesired outcome occurring to be greater than that of a desired outcome occurring when both events were equally likely. CONCLUSIONS: The choice of words used to describe a condition or to inform someone about the level of risk of an adverse event occurring may significantly affect how the person perceives that condition or risk.

Outcomes of pregnancies diagnosed with Klinefelter syndrome: the possible influence of health professionals.

OBJECTIVE: To describe the association between the outcomes of pregnancies diagnosed with Klinefelter syndrome (KS) and the specialty of the health professional providing pre- and post-diagnostic counselling. METHOD: Data were extracted from the case notes of the 111 cases of KS diagnosed prenatally between 1986 and 1997 in eight geographical regions in five European countries. The data extracted included: outcome of pregnancy, maternal age, social class, parity, gestational age at diagnosis, year of diagnosis and specialties of the health professionals conducting pre- and post-diagnosis consultations. RESULTS: The overall termination rate was 44% (49/111: 95% confidence interval: 35 to 54). Using multivariable logistic regression analysis, the only significant predictor of continuation of the pregnancy was the specialties of the health professionals conducting post-diagnosis counselling: the affected pregnancy was more likely to continue when post-diagnosis counselling involved only a genetics specialist (relative risk: 2.42 (1.14 to 5.92)). CONCLUSION: There is an association between whether or not a woman terminates a pregnancy affected by an unfamiliar fetal anomaly and the professional background of the health professional providing post-diagnostic counselling. The causal nature of this association remains to be determined.