The congenital anomalies registered in this study comprise mostly major CAs and do not include some minor anomalies. It is therefore difficult to compare the determined total prevalence in our study with the data from other studies with a specific anomalies inclusion and exclusion list, as well as with a different way of calculation of the prevalence [6,9,10].

The overall total prevalence of CAs in this study was 25.72 per 1,000 births, which is similar to the total prevalence in other studies[11-14], and to the average rate for all full members’ registries of EUROCAT (22.11 per 1000 births over time (1980-2005) [1]. The reported trend in prevalence of CAs is different for the registries. The registries in France, Belgium, Malta, Switzerland, Spain, Croatia and Italy reported increasing rates over time (1980-2005), while others like the British, Irish, Dutch and Danish registries, reported a declining trend.

The present study demonstrated an overall significant upward trend in the prevalence of CAs as a whole (total and live birth prevalence) from 1988 to 2006 in the Pleven region. However, there was a significant increase in the total prevalence only of specific anomalies: digestive system, tumors, gastroschisis and non syndromal dysmorphologic conditions. The potential underlying contributing factors that should be considered for explanation of regional and secular trends are: case ascertainment methods; improving antenatal screening; some demographic and environmental factors [9,15,16].

In this study, due to the relatively consistent methodology used in the registration of CA cases, we think that the case ascertainment and diagnostic methods play a minor role in data collection over time. In our study, the types of CA that have recently demonstrated an upward trend in prevalence have unclear genetics or a minor genetic impact and an important role of environmental factors in their etiology. That is why more attention should be paid to these factors in the future and further epidemiological studies are needed. For example, concerning gastroschisis there is a significant difference in the reported prevalence between EUROCAT registries, suggesting a geographical gradient in the prevalence of this defect [1,9]. The phenomenon of increasing gastroschisis prevalence in Europe (1980-2002), according to some authors [17], is not restricted to younger mothers only. In the present study, the upward trend in gastroschisis prevalence is without a rise in the proportion of teenage mothers. There is evidence that maternal exposure to vasoconstrictive drugs and cigarette smoking may increase the risk of gastroschisis and small intestinal atresia [18]. This hypothesis is suitable to be tested in a future study, in relation to the changes in socioeconomic status of the Bulgarian population over the study period and expansion of some habits such as cigarette smoking.

The most common type of CAs we found were cardiac defects (16.7% of all anomalies), with a total prevalence rate of 4.3 per 1,000 births. The overall prevalence rate of CHD reported by EUROCAT over the period (1990-2005) was 6.77 per 1,000 births, with a variation of the rate seen across the different registries (from 4.49 per 1,000 for Zagreb, Croatia to 8.71 per 1,000 for Odense, Island of Fyn, Denmark) [1]. This variation reflects the difference of the availability and accuracy of antenatal diagnosis, the ascertainment of late post neonatally diagnosed cardiac defects, the possibility for close relation with a pediatric cardiologist and the expertise to accurately diagnose [9].

Neural tube defects are among the most common CAs that cause fetal and neonatal death around the world [5,19]. EUROCAT reported the overall prevalence rate of NTD at 1.05 per 1,000 births over the period 1990-2005 (Zagreb, Croatia 0.5 per 1,000 births, Glasgow, Scotland, UK 1.7 per 1,000, Paris, France 1.3 per 1,000) [1]. There is a variation (0% for Malta and Ireland, 22.0% for the Netherlands, 92.0% for France) in the proportion of NTD cases resulting in pregnancy termination, seen across the different registries and countries in Europe, influenced by the differences in screening policies, culture and legislation. The countries that did not have a policy for offering routine scans had a significantly lower prenatal detection rate of NTD [20].

The present study showed a relatively high prevalence rate of NTD in the Pleven region (2.0 per 1,000 births) compared to other registers and parts of Europe [1] and about 20.0% of all registered cases of NTD were detected in terminated pregnancies after prenatal diagnosis. Since in all the cases of prenatal diagnosis of NTD there was termination of the pregnancy, the data demonstrate inadequate prenatal screening for these defects in the Pleven region. Although in recent years the national policy recommended periconceptional folic acid supplementation, the prevalence rate of NTD in the Pleven region remained stable over the study period. These factors raise the issue of introducing an official countrywide policy for routine ultrasound anomaly scanning as an element of prevention approaches.

Our study revealed three important findings: 1) genetic components were identified in approximately 62.0% of all CA cases; 22.0% of all cases had a clear genetic cause (chromosomal 8.0% or single gene defects 14.0%) and 40.0% multifactorial etiology. The data demonstrate a high proportion of affected families with a high recurrence risk, and emphasize the importance of offering genetic counseling and prenatal diagnosis to mothers who have previously had an abnormal baby/pregnancy. 2) The etiology of one-third of the CAs was unknown or unclear. 3) Environmental causes were infrequent (approximately 7.0% of all CA cases).

In other studies [21-23], the reported genetic contribution of CAs is similar: chromosomal abnormalities 6.0-10.0%, single gene defects 7.0-17.0%, multifactorial etiology 20.0-30.0%. Environmental causes have been identified in 5.0-10.0% of birth defects and unknown causes in 40.0-50.0% of all cases. The lower proportion of CAs with unknown etiology established in our study may be due to the lower number of births (from 2,000 to 3,000 annually), which allows an accuracy of diagnosis and reflects the interest to identify a specific etiology.

In conclusion, the epidemiological data of this study suggest that 2.0-3.0% of all births (approximately 1 in 40 births every year) are associated with CAs. The particular pattern of CAs in the Pleven region and the increasing trend in prevalence of specific anomalies, draw attention to the role of specific environmental or may be local risk factors for those anomalies, and require further regional epidemiological studies. The high proportion of genetic factors in the causes of CA emphasize the importance of genetic counseling services as an integral part of preventive medical care.