Următorul pas în monitorizare – Registrul Național al Anomaliilor Congenitale din România (RN-CAR)

Introduction

Fetal malformations represent an important public health issue, being associated with a significant burden of morbidity and mortality, both in terms of the afflicted patients and their families, with a significant social and human cost. Congenital malformations are still a source of patient anxiety and concern, despite impressive improvements that have resulted from advances in medical science, including advances in neonatology and pediatric surgery. A thorough understanding of the etiology of these malformations generally allows patients to make informed decisions about whether they should proceed with a corrective operation, bearing in mind the anticipated outcomes and potential problems. Detection of just one fetal malformation requires a thorough diagnostic survey of the entire fetus, as malformations are generally not isolated; they may present as an isolated organ system or structural malformation or may occur concurrently, due to shared development and common growth periods. Statistics derived from congenital anomaly registries are potentially valuable health and management data and can be used in public health inferences such as service delivery, preventive medicine and clinical management of the infant. Congenital anomaly registers are not only a diagnostic instrument, but they have also proved their worth in the field of scientific and clinical research. The registry of congenital anomaly is a program that gathers the causes of congenital defects and malformations observed during pregnancy and in newborn children. The majority of embryonic and fetal development disorders taken one by one have significant low frequencies. From this point of view, these types of malformation fall under the rare diseases category. For this reason, it is important that the registry gathers multidisciplinary and cooperative network in which doctors from hospitals throughout each country, from different areas, participate. The most important objective is to find out the causes and the incidence of alterations in embryonic and fetal development. This is the first step in order to ensure that the development is not altered by establishing public healthcare measures.

In Europe, there are several countries that have developed national registries. These data are gathered and centralized with the help of EUROCAT – European network of population-based registries for the epidemiological surveillance of congenital anomalies. The main EUROCAT objectives are providing essential epidemiological data on congenital anomalies, teratogenic factors early warning, evaluating the primary prevention, and offering information and resources for the population and the healthcare professionals.

In this paper, we would like to discuss the benefits and the practical necessity of a national congenital anomaly registry in our country.

Worldwide registries

Several models of congenital anomalies databases have demonstrated adequate efficiency. They include the technical databases, which provide data for surveillance, studies, evaluation of risk factors, prioritization of policymaking and planning. Some strategies for the sustainable development of the databases have emerged. Surveillance systems are ongoing activities, inherently important to the operation and well-being of national healthcare systems, and serve as demanding hardware for the further upgrading and modernization of healthcare databases. The surveillance databases are the prime source for periodic analyses, evaluation of policy interventions, including demonstration of their achievements or failure, and have value for evidence-informed comprehensive planning for quality of care, production of public health documents, improving health information, facilities for auditing, and public availability of governmental information.

In the United States of America, several states maintain registries of birth defects and fetal anomalies. The database dates from the 1950s. The registry maintained by the Center for Disease Control and Prevention (CDC) includes data on the 14 million births up to 2003. The accumulated experienced helped those interested in building better models and decision support systems.

The Canadian Enhanced Congenital Anomalies Surveillance System (ECASS) database contains information on pregnancies with a diagnosis of fetal anomaly dating from 1999-2010 from seven provinces. Variables recorded in ECASS include maternal and newborn personal identifiers, demographic data, fetal and newborn birth weight, fetal and newborn gestational age, fetal and newborn gender, maternal conditions, pregnancy screening and diagnosis procedures, maternal and fetal diagnosis of infection, pregnancy terminations, pregnancy outcomes, the number of outpatient visits and hospitalizations during pregnancy, newborn delivery mode, the newborn’s condition at delivery, temporary codes related to testing, newborn’s conditions at birth and initial hospitalizations, and the vital event and cause of death.

France, the United Kingdom, Spain and Italy are just some of the countries that have consistent anomaly registries that contribute to EUROCAT and adhere to the same purposes (Figure 1). There are elaborated guidelines for data collection, coding and classification. It is strongly encouraged that the data are used for research purposes and epidemiological surveillance.

Epidemiology and incidence of congenital malformations

Congenital malformations are abnormalities of a structural or functional nature which originate during intrauterine life and can be assessed prenatally, at birth, or at any time during the postnatal period. These can be identified as simple or multiple, not related with a numerical chromosomal anomaly. Of all recognized human congenital anomalies, approximately 20-25% are chromosomal, or with a genetic imprint. Structural abnormalities represent a very heterogeneous group that includes the most serious and numerous CHDs (congenital heart diseases), the CNS (central nervous system) malformations, facial clefts, limb deficiencies, body wall defects, gastrointestinal abnormalities, renal agenesis, severe skeletal malformations, and several well-defined malformations with or without known chromosomal or non-chromosomal syndromes. The International Federation of Obstetrics and Gynecology (FIGO) defined two types of malformations. Minor or soft malformations are deviations from the normal morphology that have neither functional consequences, nor cause social stigmatization. Major or hard malformations are anomalies that may require surgical correction and may have attendant psychological, social and economic complications^(2-7).

In European countries, the overall congenital malformation (CM) incidence ranges from 3 to 4.5 per 100 live births, particularly in Western Europe (4-5 per 100 live births) and in the Mediterranean countries. CMs are the leading cause of perinatal mortality in Europe, especially in Nordic countries, and the second leading cause of infant mortality after premature births. The total mortality related to congenital malformations has not decreased in recent years, because the rate of prenatal diagnosis has no effect on the number of pregnancies with lethal malformations. The trend has been stable over the past 25-30 years because of low rates of voluntary interruptions of pregnancy in the presence of fetal congenital anomalies in Western Europe, except in the Mediterranean countries^(8-16).

Birth defects kill thousands of high-risk neonates each year in developing countries. The babies who are born with congenital anomalies and survive through the first years may have lifelong mental and physical disabilities. This percentage of congenital malformations ranges between 2.13% and 7.26%. Among these, around 25% have metabolic malformations^(17-26).

According to World Health Organization (WHO), in Romania there were more than 4000 live births with congenital anomalies in 2022⁽¹⁾.

Benefits and impact of a national registry

The national congenital malformation national registry would enable the provision of important information about congenital malformations at the population level. It would provide information to help understand the prevalence of different pathologies in the community. It would also give a guide to the types and number of services that are needed to be provided for children with different malformations in ordinary community services⁽²⁶⁾. Also, the turnover of patients with the different congenital anomalies could be calculated using the rate of deaths and the hospital admissions from the data in the registry. As seen in different medical fields, it will provide a uniform etiological classification corelated with the causal factors associated with congenital pathologies at the population level⁽²⁷⁾. Information gathered from a national registry could estimate and evaluate the impact of health and social service interventions⁽²⁸⁾. The National Congenital Anomaly Registry can serve as the starting point in all congenital pathologies encountered later in childhood. It could be the infrastructure to communicate between medical centers and to provide childcare for different pathologies in dedicated centers.

A national congenital malformation registry can be established by administrative order. As an alternative, the voluntary participation of all healthcare providers is particularly encouraged^(29,30). Patient information is then necessary to review regional, provincial and national rates of remaining physical and/or developmental illness. Accessible information regarding all pathologies is useful. Health professionals are in an excellent position to monitor these malformations over the course of the lifetime of afflicted patients^(31-35).

The impact of a registry is both specific (for the population of registrars) and general – for national public health in general. It can be assumed that the electronic congenital malformation registry will have an impact on the international level – on a European and global scale. It should increase the interest of researchers in the quality of the database and further processing and results^(36-38). In addition to the indirect benefit for public health in the fields of prevention, genetic research and prenatal diagnosis – influencing national demographic indicators, we can summarize the impact of a central electronic registry of congenital malformations from several perspectives in Figure 4.

Ethical and legal considerations

The use of genetic and congenital malformations registries in research, genetic counseling and management decisions involves a range of ethical problems, including those related to accuracy and interpretation of information, informed consent, issues of privacy, confidentiality, intellectual property, and ownership of genetic material, potential misuse and misinterpretation of information, services outside the consensual framework of genetic and congenital malformations services^(37,39). The law has a comprehensive impetus to protect human genetics research and practice from an array of antisocial activities. The law imposes responsibilities upon parents, relatives, researchers, other healthcare providers, insurance providers and employers with respect to reproductive genetics and congenital malformations^(40-42).

Data privacy and confidentiality have long been central notions in scientific research involving human beings, in which the goal of research often involves the recording and use of personal information in a manner that preserves individual privacy⁽⁴³⁾. The demands of privacy and research often pull in opposite directions. On one hand, researchers often require information with individually identifying details to calculate incidence rates, analyze demographic trends, and assess disease causation^(44,45). In addition, there are compelling ethical obligations to protect people’ privacy and maintain strict confidentiality of any information about individuals obtained during research⁽⁴⁶⁾.

Data collection and management

The management of the National Congenital Malformation Registry system involves in the first place the inclusion criteria in the database. This includes all types of prenatal diagnosis, determination of eligible births, or cases of pregnancy termination to be registered. Collaboration of key institutions for data collection, development of data collection sheet and multidisciplinary approach are important for optimal results. The data enquire cannot be made completely anonymous due to the risk of repeated enrolment.

The data will be primarily collected by accessing the registries of hospitals that are willing to enroll the patients. The computer database will be filled after the medical personnel will evaluate the patient’s medical folder available at that moment or will complete with new data the patient’s preexisting file. Additionally, the research team, including the main investigator, regularly monitors the registers on a regular basis. Data quality checks will be carried out by these investigators. To have a complete description of the presented anomalies, the teams will include obstetricians, sonographers, geneticist, neonatologists, pathologist and pediatricians, so there could be a correlation between ultrasound findings, the genetic disorder and (if the case permits) the pathological anatomy elements.

Discussion

The establishment of a National Congenital Malformation Registry has been identified as one of the components of a comprehensive approach to the prevention of congenital malformations^(47,48). This registry aims to determine the prevalence of malformations, report rates, trends, types, frequency and areas where a clustering of the problem could be analyzed in detail to affect future public health programs^(49-51). The registry could be used to develop an optimum periconceptual care protocol for appropriate safe motherhood, newborn, and childhood care implementation. It also aims to prevent the dreadful consequences of birth defects, such as stigma and discrimination, and the lifetime burden carried by affected persons, families and society^(13,52).

Outcome and monitoring of congenital malformations, with and without intervention, help in the following ways: providing service in an optimal way, improving overall health policy activities, and identifying the existing needs of the community^(53,54). This information can then help to develop, streamline and implement newer future strategies for primary, secondary and tertiary prevention of congenital anomalies. The congenital malformation detection rate can be projected internationally, nationally, regionally and in rural-urban areas^(55-58). Additionally, it can provide a cost-effective way of active case finding, managing early diagnosis and treatment at the primary level (for example, tube defects, cleft-lip, anterior meningomyelocele in a neonate), while also improving the available management goal.

There are no public policies providing stipulations aimed at protecting the interests of the child who is likely to be born with congenital malformations. The inclusion of parents’ plans for childbirth based on clinical data about their future child and evaluation of risks has reduced the number of abortions after 22 weeks of gestation or refusal of complications during or after birth by elective indication^(59-63). Providing a fetal diagnosis late in pregnancy brings on a social, ethical and medical-juridical impact.

A surveillance system will contribute to informed decision-making, with respect to where to target resources, including the exploration of evolving technology, for the prevention, diagnosis and treatment⁽⁶⁴⁾. Equally, where certain policies, such as the addition of harm reduction vaccines for infectious diseases to the National Immunization Program, have been introduced, we are able to provide data that will inform our evaluation of the appropriateness and success of such a change in policy⁽⁶⁵⁾. Further data from the EUROCAT register in this specific area have allowed the presentation of more complex information – e.g., the relation between trends in seasonal influenza strains and the occurrence of congenital malformation (such as congenital cataract), pointing towards co-circulating cytotoxic virus strains in infants, and supporting specific interventions in pregnant women^(66-68).

A national congenital malformation registry would allow for better resource allocation and planning. It allows for cost estimation for lifelong care requirements of congenitally malformed children and thus enables policy making in resource allocation⁽⁶⁹⁾. It allows for the estimation of the need for skilled care required for rehabilitation, including post-surgical complication management^(70,71). It may also act as an epidemiological indicator for geographical and temporal patterns, if any, of congenital malformation in the country, permitting corrective action and policy of preventive programs. A national registry would have a strategic role in developing evidence-based simple health policies⁽⁷²⁾.

There are some difficulties that can be encountered in the development of the national registry. Establishing and maintaining the registry require significant financial, technical and human resources. The challenges that can be encountered refers to ensuring an accurate and complete data collection. This is due to inconsistencies in reporting, underreporting, or lack of standardized diagnostic criteria across different regions. A method to minimize these problems is by evaluating the collected data and secondary processing with unified coding. Collecting sensitive health data can raise privacy concerns. Ensuring data security and obtaining the informed consent from participants will be critical to addressing ethical issues. As evaluated in the SWOT analysis, we consider that the benefits of implementing the RN-CAR surpass the difficulties that may be encountered along the way.

To sum up, we consider that it would be beneficial for the Romanian healthcare system to implement a National Congenital Anomaly Registry that has the following goals:

• Support an increase in knowledge on the prevalence of specific congenital malformations and the associated mortality in a specific population.
• Investigate the incidence of different congenital malformations over time, as well as across geographical regions.
• Investigate the long-term effect congenital malformation may have on the health status of the child.
• Support the development and funding of further research.
• Provide evidence to healthcare professionals involved in preconception and prenatal care, where resources should be directed to improve the detection and prevention of a specific congenital malformation.
• Provide information from our country for the parents who are confronting with anomalies during pregnancy.
• Generate the infrastructure for additional databases for congenital anomalies that can extent in the pediatric and adult population.

The aim of this paper is to bring awareness among the medical society regarding the usefulness of the Romanian National Congenital Anomaly Registry (RN-CAR) and to collaborate for the benefit of our patients (www.rncar.ro).

Autor corespondent: Adrian-Valeriu Neacșu E-mail: adrian-valeriu.neacsu@drd.umfcd.ro

CONFLICT OF INTEREST: none declared.

FINANCIAL SUPPORT: none declared.

This work is permanently accessible online free of charge and published under the CC-BY.