A cytogenetic register of down syndrome in Lebanon

OBJECTIVES: To provide data on the cytogenetics and epidemiology of Down syndrome in our community. METHODS: All cases of Down syndrome diagnosed cytogenetically were entered over a period of 5 years together with data regarding age at referral, parental ages and parity. RESULTS: A total of 280 cases were entered. In postnatal cases, the mean maternal age was 32.19 years and 41.5% of mothers were over 35 years. Only 47.3% of Down syndrome children were diagnosed at less than 1 month of age. The male to female sex ratio of 1.66 is significantly more elevated than that reported in larger registers. CONCLUSIONS: Because of problems inherent to Lebanon, this register does not have a high level of ascertainment, however it appears that the emphasis in a potential prevention programme should be placed on education, information and family planning.     

The burden of genetic disorders in India and a framework for community control

With a very large population and high birth rate, and consanguineous marriage favoured in many communities, there is a high prevalence of genetic disorders in India. An estimated 495,000 infants with congenital malformations, 390,000 with G6PD deficiency, 21,400 with Down syndrome, 9,000 with beta-thalassaemia, 5,200 with sickle cell disease, and 9,760 with amino acid disorders are born each year. The prevalence of late-onset multi-factorial disorders (including coronary artery disease, hypertension and psychiatric disorders) is also large. Due to inadequate diagnostic, management and rehabilitation facilities, the burden of these disorders is greater than in Western countries. Although genetic diseases receive little attention from the health services, research funding by the government has been liberal. Community control of common disorders like thalassaemia, Down syndrome, neural tube defects, and muscular dystrophies deserves high priority, and genetic services should be integrated into the existing primary health care and medical services. Most genetic counselling would have to be provided through training physicians who staff the district and medical school hospitals. To ensure future progress, there is a need to establish additional departments of medical genetics in medical schools.     

Parents' satisfaction with medical and social assistance provided to children with Down syndrome: experience in Estonia

OBJECTIVE: Parents of children with mental or physical disabilities have been assumed to live more stressful lives than other parents, and people with Down syndrome (DS) may get second-rate care because of their diagnosis. The aim of this work is to investigate the extent of parents' satisfaction with medical and social services in Estonia provided for the DS individuals and their families. METHODS: From 1999 to 2001, fifty-nine DS families answered questionnaires in which we inquired about their satisfaction with medical and social assistance. RESULTS: We found that satisfaction with the quality of the information about DS is low, and most of the parents are not satisfied with the social benefits and rehabilitation options. CONCLUSIONS: The DS families need more medical information about this syndrome.The medical staff has to learn more about how to deliver bad news and how to support parents. More work needs to be done in the area of rehabilitation options and social assistance.     

High distress in parents whose children undergo predictive testing for long QT syndrome

OBJECTIVES: To assess the psychological effect of predictive testing in parents of children at risk for long QT syndrome (LQTS) in a prospective study. METHODS: After their child was clinically screened by electrocardiography and blood was taken for DNA analysis, and shortly after delivery of the DNA test result, 36 parents completed measures of psychological distress. RESULTS: 24 parents were informed that at least one of their children is a mutation carrier. Up to 50% of the parents of carrier children showed clinically relevant high levels of distress. Parents who were familiar with the disease for a longer time, who had more experiences with the disease in their family and who received positive test results for all their children were most distressed. CONCLUSIONS: Predictive ECG testing together with DNA testing has a profound impact on parents whose minors undergo predictive testing for LQTS.     

Down syndrome and parity

OBJECTIVE: To investigate the effect of parity on Down syndrome (DS). METHODS: The study was conducted on data from Northeast Italy (NEI) (1981-1996) and Sicily (ISMAC) (1991-1996) Congenital Malformation Registries. In these areas, all DS births are recorded and confirmed by chromosomal analysis; the NEI Registry also registers pregnancy terminations (TOPs) after prenatal diagnosis of DS. In order to estimate the effect of parity independently of the mother's age and to reduce the truncation effect, different age classes and three classes of parity (1, 2-4, >4) were defined. RESULTS: The study sample consisted of 1,088 consecutive newborns and 169 consecutive fetuses affected by DS. In both NEI and ISMAC samples, we found a significantly increased risk of having a DS child for multiparas > or =35 years of age. In the NEI sample, the inclusion of TOP data did not seem to modify this finding. In the ISMAC sample, a significantly reduced risk for primiparas was found at all ages. CONCLUSIONS: Our data confirm a higher risk of having a DS child in women with parity >4. As this effect is evident only in women > or =35 years age, its practical impact is null because these women are usually offered prenatal diagnosis in any case. However, the mechanisms involved, if this association is true, are very intriguing and the observation should stimulate scientific studies allowing a better knowledge of the nondisjunction mechanism.     

Preconceptional screening of couples for carriers of cystic fibrosis: a prospective evaluation of effects, costs and savings for different mutation detection methods

OBJECTIVE: The aim of this study was to perform a prospective evaluation of the effects, costs and savings of a preconceptional screening programme of couples for carriers of cystic fibrosis (CF). METHODS: A decision model for both single-entry two-step (SETS) and double-entry two-step (DETS) couple screening was constructed. Two mutation detection methods were considered: allele-specific oligonucleotide (ASO) hybridisation screening of 32 mutations, with a sensitivity of 90%, and denaturing gradient gel electrophoresis (DGGE), with a sensitivity of 98%. In our model, the following combinations were used: (1) ASO for both steps; (2) DGGE for both steps, and (3) ASO for the first step and DGGE for the second step. The model is demonstrated using figures from the Netherlands, where there is a carrier frequency of 1:30. We estimated the value of different choices and probabilities in a decision tree and determined the costs of screening for CF and the costs of the illness itself. RESULTS: We found that with most of the combinations of mutation detection methods, SETS couple screening could offer positive net savings in the Netherlands. The ASO/DGGE combination resulted in the highest net savings. DETS couple screening for all combinations, including testing with DGGE in both steps, did not show a positive cost-savings balance at all, not even with an uptake rate of 100%. The maximum number of carrier couples identified when screening 100,000 couples with the ASO/DGGE combination was 98 (SETS). This could result in about 25 fewer children born with CF each year in the Netherlands, under the following assumptions: (1) each couple has two children and 10% of couples are unable to have children; (2) of detected carrier couples, 15% decide not to have children and 85% make use of prenatal diagnosis; (3) of those fetuses diagnosed with CF, 80% are aborted, and (4) prenatal diagnosis carries a 0.75% risk of iatrogenic abortion. CONCLUSIONS: The results of this evaluation show that there are no financial objections to the preconceptional screening of couples in the Netherlands when the above-mentioned assumptions apply; thus, further evaluation can concentrate on the balance of the non-economic consequences of screening for participants and for society.     

ECLAMC: the Latin-American collaborative study of congenital malformations

DEFINITION: ECLAMC ('Estudio Colaborativo Latino Americano de Malformaciones Congenitas') is a program for the clinical and epidemiological investigation of risk factors in the etiology of congenital anomalies in Latin-American hospitals, using a case-control methodological approach. It is a voluntary agreement among professionals lacking institutional base as well as designated budgets. ECLAMC has been usually funded by research-funding agencies rather than public health ministries. The National Research Councils of Argentina and Brazil have been the main sources of support during its 36 years of existence. Since vital and health statistics are unreliable in South America, ECLAMC collects all the information required for the denominators in a hospital-based sample of births. ECLAMC can be defined as a continental network of persons interested in research and prevention of birth defects. HISTORY AND EVOLUTION: From the institutional point of view, ECLAMC has had headquarters in diverse centers of Argentina and Brazil, but always as an independent research project, without a defined administrative link. ECLAMC began operating in 1967, as an investigation limited to the city of Buenos Aires, Argentina, and it gradually expanded until covering all the 10 countries of South America as well as Costa Rica and the Dominican Republic. Even though ECLAMC has maintained essentially the same original experimental design since 1967, due to the data accumulated by the program, the increasing experience as well as the development in science, technical modifications occurred including a DNA bank and a fully informatized data handling system. Since 1974 ECLAMC has been a founder member of the International Clearinghouse for Birth Defects Monitoring Systems; since 1994 a WHO Collaborating Center for the Prevention of Congenital Malformations, and since 2000 a collaborating member of the NIH Global Netwok for Women's and Children's Health Research. METHODOLOGY: The maternity hospital network of ECLAMC examines around 200,000 births per year. All major and minor anomalies diagnosed at birth in infants weighing 500 g or more are registered according to a manual of procedures. The next non-malformed baby of the same sex born in the same hospital is selected as a control subject for each case. Thus, a one-to-one healthy control group matched by sex, time and place of birth is obtained. As a system of epidemic surveillance, ECLAMC systematically observes the fluctuations in the frequencies of different malformations and, in the case of an alarm for a probable epidemic of a given malformation, at a given moment, and given area, it acts to identify its cause. As termination of pregnancy has severe legal restrictions in South America, prevention of birth defects should concentrate on primary, preconceptional and tertiary measures. Tertiary measures aim to avoid complications of the affected patients from the medical, psychological, and social standpoints.     

Public experiences, knowledge and expectations about medical genetics and the use of genetic information

OBJECTIVE: The objectives of this study were (1) to explore public experiences, genetic knowledge, expectations of future medical genetic developments, and the attitudes towards the use of genetic information, and (2) to determine whether there are subject characteristics associated with these variables. METHODS: Participants (n = 1,308, age > or = 25 years) of a Dutch consumer panel were sent a questionnaire, specifically designed for this study. RESULTS: Response was 63% (817/1,308). A minority of respondents reported to know someone with a hereditary disease (34%) or to have used a genetic test (8%). Overall, 57% perceived a lack of genetic knowledge. In multivariate analyses, high self-rated knowledge, younger age, having heard of genetic testing, high educational level, female gender, having children living at home, being a health professional, and familiarity with genetic testing were positively associated with genetic knowledge. Future expectations of the consequences of developments in medical genetics varied between the subjects. The great majority expected great benefits for medical practice such as an increasing use of genetic aspects of disease for diagnosis or prevention. One fifth, mainly older people, anticipated a negative impact of genetic developments on society. The results also show that most people are reserved to share their genetic information with others, especially with regard to the wider public domain (e.g. industry and insurers) and employers. Remarkably, respondents were more willing to share their genetic information with scientific researchers (68%) than with their relatives (54%). CONCLUSION: This study suggests that although one fifth anticipates negative consequences of genetic developments, the great majority has high expectations about the increasing use of genetics in prevention, diagnosis and treatment of diseases. In developing educational programmes about genetic innovations in medicine, policymakers will have to take into account pre-existing lay knowledge, views and expectations of different groups of citizens towards these developments.     

Campaign to control genetic blood diseases in Bahrain

Genetic blood diseases are frequent in Bahrain as in all Middle Eastern countries. Previous neonatal screening in 1984-1985 showed that the birth prevalence of sickle cell disease (SCD) was 2.1%, of sickle cell trait 11% and of glucose-6-phosphate dehydrogenase (G6PD) deficiency 25%. The Ministry of Health recognized the importance of controlling these diseases. In 1984, the first genetic clinic was established, which started the educational campaigns. Information booklets were prepared and distributed widely in schools and clubs in an attempt to increase awareness about these diseases among students and the public. In 1991, the Bahrain Hereditary Anemia Society was formed. In 1992, the Minister of Health formed a national committee for the prevention of genetic diseases in Bahrain. Screening of all pregnant women began, followed by newborn testing if the mother was found to be a carrier. In 1993, a premarital counseling (PMC) service was organized and in 1998, a student-screening project began. At this stage, we want to update the national birth prevalence figure by screening Bahraini newborns for these genetic diseases. This will help to design prevention programs and to measure the effect of health education on the previous birth prevalence figure. SUBJECTS AND METHODS: A newborn screening study was conducted to determine the effects of this long-term campaign (16-18 years). Cord blood samples from 2,000 Bahraini newborns were tested for hemoglobinopathies and G6PD deficiency using HPLC. RESULTS: 18 newborns were found to have SCD. The new birth prevalence figure for SCD in Bahrain is 0.9%, which indicates a 60% decline in the birth prevalence rate. CONCLUSION: With the continuation of education, awareness campaigns, screening of carriers and PMC, we expect the number of affected children born to be reduced tremendously over the next few years.     

Genetic disorders in haematological practice in India

Haemoglobinopathies represent a significant national health burden in India. The distribution of specific disorders varies geographically and by community. Heterozygote frequencies of beta-thalassaemia range from 1 to 15%, resulting in an estimated 20 million carriers. HbS is mainly present in tribal and non-caste communities, with carrier prevalences of up to 40%. By comparison, alpha-thalassaemia carriers are found in both the caste and tribal communities, and can reach a frequency of >90% in the latter case. Community control of haemoglobinopathies relies mainly on out-reach education programmes and genetic counselling, with antenatal diagnosis offered in specific major centres. Only partial data are available on the prevalence of haemophilia, but it has been estimated that there are some 50,000 affected individuals nationwide, with an additional 1,500 new cases born each year. RFLP-based techniques have been established to detect mutations in the factor VIII and IX genes, enabling the limited introduction of carrier detection and antenatal diagnosis.     

Study of 224 cases of oligohydramnios and congenital malformations in a series of 225,669 consecutive births

OBJECTIVES: To provide data on oligohydramnios associated with congenital anomalies in 225,669 consecutive pregnancies. MATERIAL AND METHODS: The malformations in this study came from births of known outcome recorded in our registry of congenital malformations. Routine ultrasonographic examination was performed. Diagnosis of oligohydramnios was made ultrasonographically. For each case, a control was chosen. RESULTS: The prevalence of this association was 0.99 per thousand (224 cases). A case-control study allowed the examination of genetic and environmental factors for the origin of oligohydramnios associated with congenital malformations. Diagnosis of oligohydramnios associated with congenital malformations was made prenatally in 32.6% of the cases; 12.0% of the infants were stillborn. Fifty-nine percent of the cases had more than one malformation, 13.8% had a chromosomal aberration, and 27.6% had multiple malformations that do not constitute a syndrome. The more frequent malformations associated with oligohydramnios were urinary, musculoskeletal, digestive and cardiac. There was increased parental consanguinity. The frequency of oligohydramnios and congenital anomalies among first-degree relatives was 4.5% and first-degree relatives had more malformations than controls (8.0 vs. 3.1%, p < 0.05). Threatened abortions and diabetes mellitus were significantly more frequent among mothers of the children with congenital malformations associated with oligohydramnios than among the controls. CONCLUSIONS: Our study demonstrated that careful fetal examination has to be performed when oligohydramnios is diagnosed as congenital malformations are often associated with oligohydramnios. We recommend the use of fetal chromosome analysis and careful ultrasonographic examination in every pregnancy complicated by oligohydramnios.     

The molecular spectrum of beta-thalassemia and abnormal hemoglobins in the allochthonous and autochthonous dutch population

The prevalence at birth of hemoglobin defects in the autochthonous North-European population is low. However, the long immigration and colonial history of the Netherlands has resulted in a group of about 1-2 million 'autochthonous' inhabitants, with Asian, South-European or African ancestors, in whom a moderate birth prevalence of globin gene mutations can be expected. Furthermore, at least 10% of the Dutch population consists of recent immigrants from different countries with high birth prevalence of hemoglobinopathies. Because of the endogamous partner choice, which is prevalent in this population, the risk for homozygous progeny remains elevated. At least 100,000 carriers of hemoglobinopathies of recent allochthonous origin are present in the Netherlands, and the number of homozygous children is rising. Prevention by prenatal diagnosis requires a suitable protocol and knowledge about the molecular defects present in the country. Therefore we have analyzed a large number of patients and carriers, both at the hematological and at the DNA level. Our survey revealed 47 different beta-thalassemia determinants, characterized on 223 independent chromosomes from individuals of different ethnic origins. As expected, the most prevalent mutations were largely represented. The cd39 (C-->T) mutation was found in 70% of the immigrants from Morocco, Sardinia and other Central-West-Mediterranean regions while the IVS-I-110 (G-->A) was prevalent in the East-Mediterranean populations. The IVS-I-5 (G-->C) mutation was found in 45% of the patients of Indonesian origin. We also registered 308 independent chromosomes with common structural defects (HbS, HbC, HbE, Hb Lepore, Hb Constant Spring and HbD Punjab) and 33 chromosomes with 19 different, less frequent, rare or very rare mutants. Seven structural mutants were described for the first time and published separately. Furthermore, 139 independent chromosomes with deletional and nondeletional alpha-thalassemia defects were characterized.     

Risk factors for neonatal mortality in low-income population subgroups in Karachi, Pakistan

This paper assesses the risk factors for neonatal mortality (0-28 days of life) for full-term singleton live births. The study sample comprised 1,011 ever-married women who were residents of four multi-ethnic, multi-religious low-income areas of Karachi, Pakistan during 1995. The analysis sample was restricted to 4,488 live births to 912 women. Results showed that 4.8% (n = 217) of all births ended in death in the neonatal period, and 76% (n = 164) of these neonatal deaths occurred in the first week of life. While neonatal mortality rates had declined appreciably over time, a large proportion of neonatal deaths were clustered in a small group of women. The univariate analysis showed a statistically significant association between a number of maternal-level parameters (e.g., mother's age at birth, level of formal education, employment status, religious affiliation, and consanguinity) and child-level parameters (e.g., birth order, birth interval, survival status of the preceding child, sex of the neonate, year of death). At the multivariate level, consanguinity, birth order and year of death were found to be statistically significant risk factors for neonatal mortality analyses despite adjustment for death clustering. The study highlights the importance of inbreeding as a determinant of early offspring death, and points to the need for better understanding of why deaths are clustered in certain families. Given the widespread practice of close cousin marriages in Pakistan across all socio-economic groups, there is a need to validate the findings in less economically disadvantaged population subgroups within the country.     

A survey on inborn errors of metabolism in 323 neonates from the state of Rio de Janeiro, Brazil

Inborn errors of metabolism (IEM) are a relevant cause of morbidity and death among children, and neonates in particular. However, little is known about the prevalence of these disorders in Brazilian newborns. Our laboratory of IEM (LABEIM) at the Department of Biochemistry, Institute of Chemistry, Federal University of Rio de Janeiro (UFRJ), has been working on the diagnosis of IEM since 1988. Out of 3,300 patients (90% children), screened and evaluated from 1989 to 2,000 because of a high clinical suspicion of having an IEM, 323 (9.8%) were neonates. Patients came from different regions of the state of Rio de Janeiro, in which lives approximately 8.5% of the total Brazilian population. Chemical tests, various chromatographic techniques and enzyme assays were performed in urine, plasma and in some cases, cerebrospinal fluid (CSF). This study describes our laboratory and the experience with the 323 investigated neonates, among which 28 cases (8.7%) of IEM were identified and 18 (5.6%), strongly suspected. All these cases were related mainly to the metabolism of amino acids, organic acids, lysosomal enzymes and carbohydrates. Furthermore, data on population, community and health services are presented.     

Attitudes toward genetic counseling in the United Arab Emirates

AIMS: To assess the level of understanding of genetic advice given in the Genetic Clinic and attitudes toward consanguineous marriages, and prenatal, abortion and preconception diagnoses. METHODS: One hundred couples underwent structured interviews, and various social and educational data, reason for referral and diagnosis and advice given were recorded. Three months later, the couples were asked open-ended questions about the perceived causation of the disease, recurrence risk, plans for births, and prenatal, abortion and preconception diagnoses. RESULTS: Half of the couples acknowledged a genetic basis for their child's condition but only 10 remembered the risk given to them. There was a high correlation between educational level and remembering the risk, and the number of healthy children and future plans for further children. Almost half preferred consanguineous marriages and only 10% agreed with prenatal diagnosis and abortion, while 75% agreed with carrier screening and preconception diagnosis in affected families. CONCLUSION: Effective genetic counseling in this community requires an informed educated population and introduction of carrier screening and preconception diagnosis in affected families.     

Global prevention of all folic acid-preventable spina bifida and anencephaly by 2010

Folic acid-preventable spina bifida and anencephaly are pandemic, affecting 225,000 children a year. These birth defects are as preventable as polio. As we near the eradication of polio, it is time to make the commitment to global prevention of all folic acid-preventable spina bifida and anencephaly (FA-P SBA) by 2010. Folic acid fortification of centrally processed foods, such as wheat and corn flour, could immediately prevent all of these birth defects for much of the world's population. These fortification programs will also help adults by increasing serum folate concentration, eradicating folate deficiency anemia, providing human genome stability and reducing homocysteine serum concentration, which will probably prevent heart attacks and strokes, and may prevent colon cancer and Alzheimer's disease. Where there is no centrally processed and distributed food to fortify, intense efforts must be made to increase consumption of synthetic folic acid through vitamin supplements. Geneticists can play a major role in preventing FA-P SBA by helping to create the political will in each country to implement fortification and supplement programs to eliminate disease caused by the current pandemic of folate deficiency.     

Wavelet analysis of stagnation point flow of non-Newtonian nanofluid

The wavelet approach is introduced to study the influence of the natural convection stagnation point flow of the Williamson fluid in the presence of thermophysical and Brownian motion effects. The thermal radiation effects are considered along a permeable stretching surface. The nonlinear problem is simulated numerically by using a novel algorithm based upon the Chebyshev wavelets. It is noticed that the velocity of the Williamson fluid increases for assisting flow cases while decreases for opposing flow cases when the unsteadiness and suction parameters increase, and the magnetic effect on the velocity increases for opposing flow cases while decreases for assisting flow cases. When the thermal radiation parameter, the Dufour number, and Williamson's fluid parameter increase, the temperature increases for both assisting and opposing flow cases. Meanwhile, the temperature decreases when the Prandtl number increases. The concentration decreases when the Soret parameter increases, while increases when the Schmidt number increases. It is perceived that the assisting force decreases more than the opposing force.The findings endorse the credibility of the proposed algorithm, and could be extended to other nonlinear problems with complex nature.     

Mixed convection boundary layers in the stagnation-point flow toward a stretching vertical sheet

An analysis is made for the steady mixed convection boundary layer flow near the two-dimensional stagnation-point flow of an incompressible viscous fluid over a stretching vertical sheet in its own plane. The stretching velocity and the surface temperature are assumed to vary linearly with the distance from the stagnation-point. Two equal and opposite forces are impulsively applied along the x-axis so that the wall is stretched, keeping the origin fixed in a viscous fluid of constant ambient temperature. The transformed ordinary differential equations are solved numerically for some values of the parameters involved using a very efficient numerical scheme known as the Keller-box method. The features of the flow and heat transfer characteristics are analyzed and discussed in detail. Both cases of assisting and opposing flows are considered. It is observed that, for assisting flow, both the skin friction coefficient and the local Nusselt number increase as the buoyancy parameter increases, while only the local Nusselt number increases but the skin friction coefficient decreases as the Prandtl number increases. For opposing flow, both the skin friction coefficient and the local Nusselt number decrease as the buoyancy parameter increases, but both increase as Pr increases. Comparison with known results is excellent.     

Detection of Congenital Anomalies by Fetal Ultrasonographic Examination across Europe

Objectives: Birth defects are a major health burden. Primary prevention is at present emerging, i.e. folate supplementation. When it is not possible, as is still the case for most birth defects, research is needed to determine how an optimal provision of prenatal diagnosis and use of services can be achieved. Ultrasound scans in the midtrimester of pregnancy are now a routine part of antenatal care in most European countries. The objective of this study was to evaluate the prenatal diagnosis of congenital anomalies by fetal ultrasonographic examination across Europe. Methods: Data from 20 registries of congenital malformations in 12 European countries were included. The prenatal ultrasound screening programs in the countries ranged from no routine screening to 3 fetal scans offered, including 2 for biometric purposes and 1 for search of congenital anomalies, the anomaly scan. Results: There were 8,126 cases with congenital anomalies with an overall prenatal detection rate of 44.3%. Termination of pregnancy was performed in 1,657 cases (21.8%). There was significant variation in the prenatal detection rate between regions with the lowest detection rate in registries of countries without routine fetal screening (Denmark and The Netherlands) and the highest detection rate in registries of countries with at least 1 anomaly scan (France, Germany, Italy, Spain, UK). However, there were large variations among the registries with a high detection rate. There were significant differences in the prenatal detection rate and proportion of induced abortions between isolated anomalies and associated anomalies (chromosomal aberrations, recognized syndromes, and multiple without chromosomal aberrations or recognized syndromes). Conclusions: Prenatal detection rate of congenital anomalies by fetal scan varies significantly between registries of European countries even with the same screening policy. Prenatal detection of congenital anomalies is significantly higher when associated malformations are present. The rate of induced abortions varies between registries of countries even with the same detection rate of congenital anomalies. The variation described may be due to cultural and policy differences. Copyright 2002 S. Karger AG, Basel     

Prenatal screening and the reduction of birth defects in populations

OBJECTIVES: Birth defects occur in populations in 3-5% of births. This paper assesses whether population-wide screening programmes for pregnant women would be likely to result in major decreases in the prevalence of birth defects. METHOD: Relevant literature on this question is reviewed and synthesized. RESULTS: Given certain assumptions, a decrease from 3-5 to 2-4% in the prevalence of defects at birth may be possible. The resources required to put in place an appropriately delivered programme to achieve this are substantial. CONCLUSIONS: As well as the potential benefit of a decrease, there are opportunity costs, and potential serious harms. Unless undertaken in a carefully planned and monitored way, a population-based birth defects reduction programme is likely to bring harm and anxiety rather than benefit.