Development Of Prenatal Diagnosis Research Articles

Réflexions éthiques concernant la chirurgie fœtale de réparation des myéloméningocèles

Fetal myelomeningocele surgery was introduced in France in 2014. Developments in prenatal diagnosis of neural tube defects have accompanied the development of prenatal diagnosis. This fetal surgery represents one of the three possible care paths for pregnant women faced with this prenatal diagnosis. The ethical issues of this fetal surgery are discussed and in particular regarding prenatal counselling and patient autonomy of choice.

The Role of Cell-Free Fetal DNA as a Preventative Attempt to Decrease the Severity of Genetic Disorders: A Review

The development of prenatal diagnosis has developed very rapidly over decades. Prenatal screening isapplied to a mother with high-risk pregnancy (threatening the life of the fetus), such as a too-old mother ora too-young mother and having a certain disease in her medical history. Up until now, the curative methodto treat genetic disorder is still developed and perfected. Therefore, a preventative action during pregnancyis important to do, such as Noninvasive Prenatal Testing (NIPT). NIPT method that is widely developedis the circulating cell-free fetal DNA (cffDNA) testing that can be useful for determining the fetal gender,the identification of specific single-gene disorders, blood type, paternity determination, and the potency ofregular use for testing chromosomal abnormalities. The detection of cell-free fetal DNA in the maternal bloodcirculation provides a new expectation for NIPT, especially preventing the severity of genetic disorders.

Management skills required for nursing middle managers in the next generation in perinatal medical care

Learning of management skills is necessary for the training of nursing middle managers in the next generation. However, in perinatal medical care, there have been few studies on management skills for midwives as middle managers. The aim of this study was to determine whether advanced midwives have an awareness of probable future changes in perinatal nursing and what management skills they consider will be required for nursing middle managers in the next generation. This study was a qualitative descriptive design conducted for 761 advanced midwives who work in hospitals having 300 beds or more and having an independent department of nursing during the period from November 2018 to May 2019 in Japan. Self-reported questionnaires were sent after receiving acceptance from directors of nursing and questionnaire forms from 501 midwives in 91 hospitals were analyzed. The proportion of midwives who responded that perinatal care and nursing will change in the next 10 to 20 years was 86.8%, and the items of the top three were increase in the number of pregnant women with a high risk, development of reproductive medicine and development of prenatal diagnosis. According to the responses to the questionnaires, management skills that are required for nursing middle managers in the next generation include the ability to deal with different values of midwives, the ability to train midwives with high ethical values and the ability to cooperate with the community. Midwives recognize the need for systematic training for nursing middle managers in the next generation having a high level of management skill. Key words: Advanced midwives, nursing middle managers in the next generation, management skill, predicted change.

Possibility of hybrid surgery for haemodynamic correction in a child with left heart hypoplasia syndrome: Clinical observation

Owing to the development of prenatal diagnosis and interventional cardiology, newborns can survive complex palliative surgical procedures. Modern methods make it possible to change the principles of treatment for children undergoing haemodynamic correction, the last surgery being Fontan operation, and also stimulate the development of hybrid interventions (catheter procedures and surgical operations in the neonatal period). This article presents the dynamic monitoring of a child diagnosed with left heart hypoplasia syndrome, who underwent Norwood surgery at the age of 2 weeks, followed by restenosis of the distal anastomosis and balloon dilatation of neo-aorta restenosis with installation of a cobalt-chromium balloon-expandable stent (Andrastent XL) along with pararectal left-side access to the infrarenal section of the aorta at 11 months in order to reduce surgical risk and prepare for the next stage of correction (Glenn and Fontan operations).Received 18 March 2020. Revised 10 April 2020. Accepted 17 April 2020.Funding: The study did not have sponsorship.Conflict of interest: Authors declare no conflict of interest.

Epidemiology of orofacial clefts in a Danish county over 35 years – Before and after implementation of a prenatal screening programme for congenital anomalies

In 2004 the Danish National Board of Health changed its screening recommendations. Since 2005 a first trimester screening for Down syndrome and a prenatal ultrasound screening for congenital anomalies in the second trimester of pregnancy has been offered to all pregnant women.The aim of this study was to describe the prevalence of cleft lip with or without cleft palate and cleft palate in a Danish area and to describe associated anomalies and the development in prenatal diagnosis over time. The study was based on data from the EUROCAT Registry for Funen County. The registry is based on multiple data sources and includes information about live births, fetal deaths with a gestational age >20 weeks and terminations of pregnancy after prenatal diagnosis of severe fetal anomaly. The study included all fetuses/infants out of a population of 182,907 births diagnosed with orofacial clefts born between 1980 and 2014. There were 271 cases diagnosed with cleft lip with or without cleft palate and 127 cases diagnosed with cleft palate, giving a prevalence of 14.8 per 10,000 births for cleft lip with or without cleft palate and 6.9 per 10,000 births for cleft palate. There were no significant changes in prevalence over time for the two anomalies, calculated with and without inclusion of genetic and chromosomal cases. Overall 66 cases were diagnosed prenatally (17% of total). For isolated cleft lip with or without cleft palate none of the 157 cases born before 2005 were diagnosed prenatally compared to 34 of 58 cases (59%) born in 2005–2014 (p < 0.01). The proportion of liveborn infants with multiple congenital anomalies also changed after 2005 with 15% (39/266) of all liveborn infants with orofacial clefts born 1980–2004 having multiple anomalies compared to 7% (7/96) in 2005–2014 (p < 0.05).The implementation of the new screening programme in 2005 has given a major change in prenatal detection rate and reduced the proportion of liveborn infants with orofacial clefts classified as multiple congenital anomaly cases. The prevalence of cleft lip with or without cleft palate was higher than reported from many other countries.

Norwegian obstetricians’ experiences of the use of ultrasound in pregnancy management. A qualitative study

ObjectiveTo explore obstetricians’ experiences and views of the use of obstetric ultrasound in clinical management of pregnancy. MethodsA qualitative interview study was undertaken in 2015 with obstetricians (N = 20) in Norway as part of the CROss Country Ultrasound Study (CROCUS). ResultsThree categories developed during analyses. ‘Differing opinions about ultrasound and prenatal diagnosis policies’ revealed divergent views in relation to Norwegian policies for ultrasound screening and prenatal diagnosis. Down syndrome screening was portrayed as a delicate and frequently debated issue, with increasing ethical challenges due to developments in prenatal diagnosis. ‘Ultrasound’s influence on the view of the fetus’ illuminated how ultrasound influenced obstetricians’ views of the fetus as a ‘patient’ and a ‘person’. They also saw ultrasound as strongly influencing expectant parents’ views of the fetus, and described how ultrasound was sometimes used as a means of comforting women when complications occurred. ‘The complexity of information and counselling’ revealed how obstetricians balanced the medical and social aspects of the ultrasound examination, and the difficulties of ‘delivering bad news’ and counselling in situations of uncertain findings. ConclusionThis study highlights obstetricians’ experiences and views of ultrasound and prenatal diagnosis in Norwegian maternity care and the challenges associated with the provision of these services, including counselling dilemmas and perceived differences in expectations between caregivers and expectant parents. There was notable diversity among these obstetricians in relation to their support of, and adherence to Norwegian regulations about the use of ultrasound, which indicates that the care pregnant women receive may vary accordingly.

The International Prenatal Cardiology Collaboration Group - a new concept for global research study.

Congenital heart defects are among the most common congenital defects and contribute substantially to the mortality of newborns and young infants, in spite of well-developed medical and surgical treatments. It is estimated that the mortality of children with congenital heart defects in developing countries is as high as 20%, whereas the incidence of congenital heart defects is approximately 1/100 live births(1). Currently, there is an emphasis on early fetal screening for chromosomal abnormalities and neural tube defects, despite the fact that congenital heart defects are four times more frequent than chromosomal abnormalities and six times more frequent than neural tube defects(2). It should be noted that basic in-utero screening for heart defects is possible as early as the first trimester, which in some cases prompts further work-up and treatment(3). Throughout the world, second trimester screening remains the mainstay of prenatal diagnosis of cardiac anomalies. However, a comprehensive work-up for fetal heart defects can be associated with substantial psychological burden on the mother and her family. Moreover, the prevalence of misdiagnosis can be as high as 36%, thus prompting the need for further training and multidisciplinary team work(4). Furthermore, 33% of heart defects are accompanied by other anomalies(5). In 2006, the Polish Ministry of Health established a Register of Fetal Heart Defects (RFHD). The aim of this initiative was to enable cooperative gathering of data on fetal heart diseases, such as heart defects, significant cardiac arrhythmias, heart failure, heart ectopy and other significant heart conditions. RFHD is an internet database where the user can attach images, movies and other information to a given patient's file. Proofreading is performed by pediatric cardiologists from level C institutions – those that register at least 100 cases of heart defects annually. The data gathered so far have shown that heart defects are the weakest link in prenatal diagnosis. However, as physicians performing prenatal screening gain more experience, the number of diagnosed cases of congenital heart disease has grown steadily, both in Poland and worldwide(6). Analysis of data from Polish institutions confirms the need for multi-center and multidisciplinary collaboration in order to further develop screening for fetal heart defects, as well as to set goals for development of cardiac surgery of newborns. This type of collaboration contributes to both coordinated patient care and complex medical treatment, and is a scientific trend for the 21st century, helping to solve complicated scientific problems(7). Fortunately, the availability of current information and communication technologies allows partnership between different scientific centers around the world to be feasible(8). Therefore, we have established the International Prenatal Cardiology Collaboration Group (www.prenatalcardiology.org) with the aim of bringing together physicians of various specialties who are involved directly in the treatment of pregnant women and their fetuses, for further development of prenatal diagnosis. The IPCCG was established to join current worldwide efforts to improve the standard of care, management and outcomes for fetuses and neonates affected by congenital heart disease. The aim of our group is to establish research studies on a more expansive assembly of patients from different parts of the world. We plan to share our experience and create study protocols. Research to be conducted includes both retrospective and prospective studies, as well as metaanalyses. Through the IPCCG it may also be possible to gather a substantial amount of information on severe and very rare fetal heart defects, such as atrial aneurysms, ventricular aneurysms or coronary fistulas. This can enrich knowledge about these diseases, which can consequently improve patient outcome and contribute to the ever developing field of prenatal cardiology. Collaboration across centers and disciplines is also needed for other reasons. As published recently(9), treatment costs for rare heart conditions have been growing. Furthermore, it has been stressed that multidisciplinary cooperation can help decide which patents should be treated(9, 10). So far, there have been several established multi-center prenatal cardiology programs in Canada and the USA(11). Our aim was to create a similar program of collaboration among not only leading centers worldwide, but also with hospitals that want to further develop the fields of prenatal cardiology and prenatal diagnosis. The perspectives of each specialty are important in creating future standards of practice. We invite all physicians and non-physicians who are involved in prenatal care to collaborate with the IPCCG.

Pränataldiagnostik

During the last few years, there has been a rapid development in prenatal diagnosis. Due to the improvements in sonographic examinations and the introduction of first-trimester screening, the number of invasive prenatal diagnostic procedures has dropped by more than 50 %. Recently, noninvasive prenatal diagnostic tests with cell-free fetal DNA from maternal blood have also become available and will further enhance this development. As invasive prenatal procedures will become less frequent in the near future, the proportion of procedure-related abortions will further decrease.

Progress in prenatal genetic diagnosis: Using cell-free fetal DNA in maternal blood

Non-invasive prenatal testing (Nipt) using cell-free fetal DNA (cffDNA) is an exciting area of development in prenatal diagnosis. CffDNA is found in maternal plasma from 4–5 weeks' gestation, enabling fetal genetic testing from a maternal blood sample, and thus avoiding the miscarriage risk associated with current invasive tests. Nipt is already established in the UK for predicting the rhesus D (RHD) type of the fetus in sensitised RhD-women and fetal sex determination for women who are carriers of sex-linked conditions. applications of Nipt likely to be available in the near future include testing for single gene disorders and chromosomal abnormalities, such as Down's syndrome, as well as routine fetal RHD typing for all RhD negative women. Midwives will play a key role in providing information to women and ensuring new tests are implemented effectively into practice. this article will provide an overview of the current developments in Nipt and discuss some of the ethical and social implications.

Paper 1: The EUROCAT network—organization and processes†

The European Surveillance of Congenital Anomalies (EUROCAT) is a network of population-based congenital anomaly registries in Europe, funded by the European Union, which has been in operation for more than 30 years. It currently surveys more than 1.7 million births per year, including 31% of births in the European Union, and includes almost all population-based European congenital anomaly registries as its members. EUROCAT member registries collect data, ascertained from multiple sources, on all major structural congenital and chromosomal anomalies. EUROCAT surveillance relates to three areas: prevalence, primary prevention, and prenatal screening. This article describes the history of EUROCAT and gives an overview of the current methodology and work of EUROCAT covering the database content and management, coding and classification of anomalies, core surveillance, prevalence tables, statistical monitoring. The monitoring of new developments in prenatal diagnosis, medication during pregnancy, use of folic acid, and investigation of clusters and exposures are overseen by working groups responsible for organizing research and producing regular reports. The EUROCAT Web site includes current data on prevalence rates and prenatal detection rates-an example of information useful to clinicians, public health service managers, and patients.

Current situation and development of prenatal diagnosis in China

Prenatal screening and diagnosis are major methods for control of birth defects, which is a very important problem in China. Here, we review current situation and development of prenatal screening and diagnosis in mainland China, including prenatal screening and prenatal diagnosis of fetal chromosome abnormalities, non-invasive prenatal diagnostic techniques and prenatal diagnosis of monogenic diseases, polygenic disease and congenital metabolic diseases. We also discuss epidemiology of birth defects and genetic diseases in China and related ethical issues of prenatal diagnosis.

The Experience of Operative Management in Jejunoileal Atresia

Purpose: Intestinal atresia is a common cause of neonatal intestinal obstruction. Recently, the survival rate has been increasing from development of prenatal diagnosis, total parenteral nutrition (TPN) and neonatal intensive care. We evaluated the complication rate and cause of mortality after operative management for jejunoileal atresia. Methods: We reviewed 62 patients (36 males, 26 females) with jejuno-ileal atresia who underwent operation from 1998 to 2007. Results: There were 37 patients with jejunal atresia and 25 with ileal atresia. The average gestational age was 256±16.6 days and birth weight was 2,824±620 g. Prenatal diagnosis was performed in 45 patients (72.6%) around gestational age 27 weeks. Within 2nd day after birth, 44 patients (71%) underwent operation. Half of the jejunoileal atresia was type Ⅲa and type Ⅰ was in 8, type Ⅱ was in 3, type Ⅲb was in 12, and type Ⅳ was in 8. The operative treatment was resection & anastomosis in 59 patients and enterotomy & web excision in 3. They started feeding at 12.4±11.5 days after operation on average. The average duration of TPN was 26.7±23.5 days, and the incidence of cholestasis was 30.6%. Hospital days averaged 36.8±26 days. Early complication occurred in 14 patients (intestinal obstruction in 5, sepsis in 4, wound problem in 3, anastomosis leakage in 1, and intraabdominal abscess in 1). Late complication occurred in 7 patients (anastomosis stricture in 4 and intestinal obstruction in 3). There was only one case of mortality due to short bowel syndrome after re-operation for adhesive ileus. Conclusion: The operation for intestinal atresia was successful and aggressive management contributed to a low mortality rate.

Karyotyping or rapid aneuploidy detection in prenatal diagnosis? The different views of users and providers of prenatal care

Developments in prenatal diagnosis raise the question which test strategy should be implemented. However, preferences of women and caregivers are underexposed. This study investigates what kind of prenatal test pregnant women and caregivers prefer and if differences between the groups exist, using self-report questionnaires. Women preferred either karyotyping (50%) or rapid aneuploidy detection (43%). Caregivers opted for the latter (78%). A test targeted on Down syndrome was the least preferred in both groups. We recommend the use of individualised choice for genetic test in prenatal diagnosis, overcoming the existing differences in preferences between women and caregivers.

Gastroschisis and omphalocele: treatments and long-term outcomes

Between February 1994 and April 2004, we treated 40 children with gastroschisis and 26 children with omphalocele. We recorded the course of pregnancy, pre- and post-natal complications, delivery, operation, post-operative therapy, and long-term outcomes. Additionally, we conducted follow-up examinations of 37 of these 66 children (56%). We analysed their abdominal musculature, development, cosmetic result and quality of life. The median duration of follow-up was 6.3 years (range 1-10). In 35/40 children (88%) with gastroschisis and in 18/26 children (69%) with omphalocele, there had been prenatal diagnosis. The average maternal age of 23.9 years in the gastroschisis group was lower than in the omphalocele group (29.9 years). Delivery was by caesarean section in 93% of the gastroschisis group and 65% of the omphalocele group. Outcomes following vaginal delivery were no worse than those after caesarean section. Further, congenital abnormalities were shown in 28% of gastroschisis cases, and were limited to the gastrointestinal tract. Of the omphalocele cases 81% showed further abnormalities. Direct closure of the abdominal wall defect was possible in 31/40 (78%) of the gastroschisis cases and 15/26 (58%) of the omphalocele cases. Mortality in gastroschisis was nil; two children with omphalocele died (8%). Outcomes were better after primary closure than in stepwise reconstruction. Follow-up showed good results in all categories. Developmental delays were rapidly made up after treatment, and 75% of the children had no gastrointestinal problems, or suffered from these rarely. Almost all the children were of normal weight and height, and physical and intellectual development were delayed in only one third of the children. The surgical scar was rated as good or very good in about 80% of the cases. Except for those with severe defects, the children had good ratings for quality of life. Improvements in short-term results of gastroschisis and omphalocele treatment can be attributed to recent developments in prenatal diagnosis and the advancements of centralised perinatal care. Our long-term results clearly demonstrate that initial gastrointestinal problems and developmental delays were made up during the first two years of life. Prenatal counselling can now be more optimistic.

Advances in Neonatal Cardiac Surgery

After completing this article, readers should be able to: 1. Describe the developments that have allowed advances in neonatal cardiac surgery. 2. Describe the diagnostic approach to hypoplastic left heart syndrome (HLHS). 3. Delineate the preoperative management of the neonate who has HLHS. 4. Describe the original Norwood procedure and subsequent modifications. 5. Delineate the optimal therapy in the postoperative period for neonates who have a single ventricle. Advances in the surgical and medical management of children who have congenital heart disease (CHD) have led to a dramatic improvement in overall survival and reduced the long-term sequelae of open-heart surgery. With improved survival and decreased morbidity over the past 2 decades, the early complete repair of complex congenital heart problems in preterm and low-birthweight neonates has gained wider acceptance. Cardiologists and cardiothoracic surgeons now consider and perform complete neonatal repair more frequently than palliative surgery in this patient population. The treatment of hypoplastic left heart syndrome (HLHS) best illustrates the evolution of management strategies to improve survival and long-term outcome. A recent modification of the Norwood operation that involves a right ventricle-to-pulmonary artery conduit has led to much improved early postoperative stability and, in many centers, improved survival to a stage II superior cavopulmonary connection. A multidisciplinary team approach is required to provide the necessary care for this complex patient population. In 1938, Robert Gross at Children’s Hospital in Boston successfully ligated a patent ductus arteriosus, and this procedure—performed against the wishes of surgeon-in-chief William Ladd—opened the era of surgery for CHD. (1) Gross and Hufnagel performed detailed animal experiments to develop a technique for treatment of coarctation of the aorta that involves excision and end-to-end anastomosis. (2) Clarence Craaford of Stockholm, Sweden, had visited Gross to observe his experimental work, and in October 1944, Craaford and Nylin were the first to repair aortic …

FETAL UROLOGY AND PRENATAL DIAGNOSIS: CURRENT THEMES

Isolated case reports of the prenatal detection of urinary tract malformations first appeared in the literature in the late 1970s and by the mid 1980s prenatal diagnosis had already become a firmly established feature of paediatric urological practice throughout the developed world. The rapid development of prenatal diagnosis of urinary tract malformations can be attributed to the relatively high incidence of congenital anomalies within this system and the fact that the common anomalies are usually associated with dilatation or cystic pathology which is readily visualised by ultrasound. Although many aspects of prenatal diagnosis have been clarified by studies undertaken over the last twenty years some important questions have yet to be fully resolved – for example the long term natural history of asymptomatic uropathies such as pelvi ureteric obstruction and the benefit (if any) of prenatal diagnosis in reducing long term burden of chronic renal failure associated with posterior urethral valves.

Congenital Anomalies in the Fetus: Approaches to Examination and Diagnosis

Ongoing developments in prenatal diagnosis, coupled with methods of pregnancy intervention and termination, have brought the demands of fetal medicine to the doorstep of general pathology. The requirements for comprehensive fetal examinations are remarkably diverse, ranging from gross to microscopic to molecular evaluation. Pathologists, as essential members of a diagnostic team that includes ultrasonographers, obstetricians, perinatologists, medical geneticists, nurses, and others, must obtain data and tissue that facilitates diagnosis, either at the time of examination or at a later date, as indications for testing become apparent. To do this, pathologists must understand a wide variety of artifacts, changes unique to the fetus, and congenital disorders, and they should be familiar with the medical-legal and ethical demands of practice. This review introduces practical techniques of dissection; acquisition and preservation of data; and tissue collection, storage, and testing. It also includes recommendations for the operation of a fetal pathology service. Approaches to the study of macerated, disrupted, or hydropic fetuses are given, and the work-up of certain representative conditions (velocardiofacial syndrome, Fanconi anemia, glomerulocystic disease, and trisomy 21) is presented.

Significance of oral health in persons with Down syndrome: a literature review.

Down syndrome (DS) is an autosomal chromosomal anomaly resulting from trisomy of all or a critical part of chromosome 21. It affects approximately 1 in 700 to 800 live births. Despite the development of prenatal diagnosis, the incidence of DS births is predicted to remain static or even to increase over the next decade, partly due to increased maternal age in Western societies. Many of the medical and physiological characteristics of DS have direct consequences for the oral health of subjects affected and indirect consequences for the quality of life of persons with DS and their carers. This article aims to give an overview of the current literature concerning the orofacial problems confronting patients with DS, and to explain the different treatment modalities available.

Analysis of genes that are involved in postnatal mouse cerebral development

This chapter focuses on the technological developments in reproduction. The 1980s marked the beginning of a new era in reproductive technology with developments such as the availability of in vitro fertilization, fetal blood and tissue sampling, and ultrasound examination. By the 1990s, the fetus could be visualized with impressive clarity using modern ultrasound equipment. Biopsy of fetal tissue became a routine procedure with chorionic villus sampling (CVS). Recombinant DNA techniques enabled fetal-specific DNA to be characterized. An important advance made possible through molecular medicine has been the identification of genes involved in human development. Homeobox or HOX genes are a class of genes that can regulate the expression of many other genes. These genes are evolved from common ancestral genes and their subsequent divergence reflects the morphological complexity of the organism in which they are found. Preimplantation genetic diagnosis (PGD) is a recent addition to the prenatal diagnosis options. It is particularly valuable in the scenario in which termination of pregnancy is not acceptable, or a couple with a history of infertility does not want to risk the potential miscarriage or loss of pregnancy that might follow a procedure such as CVS. The approaches used in newborn screening extend from the original 1960s' bacterial inhibition assay (Guthrie test) to the modern tandem mass spectrometry. Tandem mass spectrometry is a new development in newborn screening, allowing the testing for many more diseases. A non-invasive source of fetal tissue is required as the next development in prenatal diagnosis. An early attempt at this involved the identification and isolation of the occasional fetal cells present in the maternal circulation during pregnancy.

Future use and development of prenatal diagnosis. Consumers' attitudes.

The rapid progress of prenatal diagnosis and genetic tests makes it important to investigate attitudes towards this development. A total of 40 women and 20 men with personal experience of prenatal diagnosis for chromosome aberrations were interviewed about their moral opinion of the development. The majority (88 per cent) considered it certain or probable that all new methods developed will also be used in the future. The majority (62 per cent) were hesitant about testing for common disorders, e.g., diabetes mellitus and rheumatoid arthritis, but regarded it justified in some situations. One-third of the individuals (31 per cent) wanted some kind of restrictions for the use of the tests, but only 13 per cent recommended legislation for this purpose. The majority (84 per cent) believed that ethical principles are influenced by scientific progress. In most aspects, the women and their partners had similar attitudes. However, 82 per cent of the women but only 20 per cent of the men considered that the couple itself should decide about prenatal diagnosis. The results demonstrated a considerable respect regarding the difficult choices associated with the development of prenatal diagnosis, also among those who have decided favour of the test. The study indicated a greater need for autonomy among women than among men.