Prenatal Diagnosis Research Articles

[Efficiency of CNV-seq in detecting fetal DMD gene deletion or duplication in prenatal diagnosis].

Objective: To evaluate the diagnostic efficiency of copy number variation sequencing (CNV-seq) to detect the deletion or duplication of DMD gene in prenatal diagnosis. Methods: A retrospective analysis was carried out on the CNV-seq results of 34 544 fetuses diagnosed in the First People's Hospital of Yunnan Province from January 2018 to July 2023. A total of 156 cases of fetuses were collected, including Group 1:125 cases with family history of Duchenne muscular dystrophy or Becker muscular dystrophy (DMD/BMD), and Group 2:31 cases with no family history but a DMD gene deletion or duplication was detected unexpectedly by CNV-seq. Multiplex ligation-dependent probe amplification (MLPA) was used as a standard method to detect the deletion or duplication. Consistency test was carried out basing on the results of CNV-seq and MLPA of all 156 cases. Results: Comparing to MLPA, CNV-seq had a coincidence rate of 92.3% (144/156) for DMD gene deletion or duplication, with a sensitivity and positive predictive value of 88.2%, with a specificity and negative predictive value of 94.3%, a missed detection rate of 3.8%, and a Kappa value of 0.839. CNV-seq missed 4 cases with deletions and 2 with duplications due to involved fragments less than 100 Kb, among 20 cases of deletions and 6 cases of duplications detected by MLPA in Group 1. In Group 2, the deletions and duplications detected by CNV-seq were 42% (13/31) and 58% (18/31), respectively, in which the percentage of duplication was higher than that in Group 1. Among those 18 cases with duplications, 3 cases with duplication locating in exon 42~67 were likely pathogenic; while 9 cases with duplication covering the 5' or 3' end of the DMD gene, containing exon 1 or 79 and with only one breakpoint within the gene, along with the last 6 cases with duplications locating at chrX: 32650635_32910000 detected only by CNV-seq, which might be judged as variants of uncertain significance. Conclusions: CNV-seq has a good efficiency to detect fetal DMD gene deletion or duplication in prenatal diagnosis, while a further verification test by MLPA is recommended. The duplications on chrX: 32650635_32910000, 5' or 3' end of DMD gene detected by CNV-seq should be carefully verified and assessed because those variants appear to be nonpathogenic polymorphisms.

Prenatal ultrasound diagnostics and socio-psychological support in a complex of rehabilitation measures for patients with congenital cleft maxillofacial region complicated by anomalies of other organs and systems

BACKGROUND.Issues of prenatal ultrasound diagnostics and socio-psychological support in the complex of early rehabilitation of children with clefts of the maxillofacial region, combined with malformations of other organs and systems of the body, complement the algorithm for dynamic observation and rehabilitation treatment of such patients. AIMS.To assess the informed value of prenatal ultrasound diagnostics and socio-psychological support of theof pregnancy and early rehabilitation of a patient with cleft maxillofacial region, combined with malformations of the development of other organs and systems due to a special set of measures in the structure of rehabilitation treatment. MATERIALS AND METHODS.The study was conducted on the basis of the Bonum Medical Center (Ekaterinburg). 823 (33.25%) cases of a combination of cleft of the maxillofacial region with malformations of other organs and systems were studied, identified during the analysis of medical documentation of complex care of 2475 patients with cleftfor 24 years (1998-2022). Epicrises of the course of pregnancy, childbirth, timing of ultrasound diagnostics of the fetus, anamnesis of newborns, timing of routing to the Bonum Center were analyzed. Data from a survey of parents at the initial appointment were studied. RESULTS.Ultrasound examination of the fetus revealed a combination of cleft maxilla with anomalies of other organs and systems in 292 (35.48%) of 823 cases. Major congenital malformations of the fetus were identified during the second - in 99 (33.90%) cases and the third - in 185 (63.36%) pregnancy screenings. When examining mothers during ultrasound diagnostics of the fetus, they were found to have emotional lability. A block of psychocorrective and socially significant measures is proposed from the moment of diagnosis of fetal pathology to the neonatal period. The need for parental participation at all stages of specialized care has been determined. CONCLUSIONS.The system rehabilitation of patients with a cleft of the maxillofacial area, combined with birth defects of other organs and systems, should include prenatal diagnosis of the fetus, as an integral part of a complex of multifunctional measures of restorative treatment. Social and psychological support for the family is necessary at all stages of pregnancy and treatment of the child.

Prenatal Screening and Diagnosis: Time for a Paradigm Shift.

Recent advances in genetics and imaging have ushered in substantial breakthroughs in screening and diagnosis for chromosomal and structural abnormalities. Thus, it is imperative that healthcare providers caring for pregnant individuals should re-examine established practices in prenatal screening and diagnosis. In the past, screening for chromosomal abnormalities was based almost entirely on Down syndrome. Pregnant individuals aged > 35 were considered at "high risk" or of "advanced maternal age" based on age alone; however, the advent of tests with high sensitivity for prenatal detection of chromosomal abnormalities should lead to abandoning that concept, at least from the perspective of chromosomal abnormalities. Given that first-trimester and second-trimester screening will fail to detect between 5 and 20% of Down syndrome, in most situations, non-invasive testing with cell-free DNA should be the first-line screen for Down syndrome. The fact that over 99% of fetuses with Down syndrome will be detected prenatally with cell-free DNA gives other fetal chromosomal and structural abnormalities increasing prominence. Chromosomal microarray analysis (CMA) permits prenatal detection of several clinically important chromosomal aberrations that cannot be detected by karyotype and may exist in structurally normal fetuses with low-risk cell-free DNA screening. As such, CMA should be more readily conducted when invasive testing is performed, regardless of the presence of a structural abnormality. Isolated sonographic "soft markers" have no clinical significance in patients who have normal cell-free DNA screening, can cause unwarranted anxiety and a negative impact on pregnancy, and perhaps it is time to stop discussing them. Detailed first-trimester ultrasound allows early detection of several severe fetal anomalies, and therefore in settings with adequately trained personnel and resources, should be used more frequently. This Opinion traces the evolution of prenatal screening and diagnosis and advocates for a paradigm shift that aligns with recent developments in prenatal screening and diagnostic capabilities.

Additive Effect of Fetal Magnetic Resonance Imaging to Prenatal Ultrasonography in Fetal Congenital Anomalies

OBJECTIVES: In this study, we aimed to assess the diagnostic accuracy of prenatal Ultrasonography (USG) and Magnetic Resonance Imaging (MRI) in fetal congenital anomalies. STUDY DESIGN: A retrospective cross-sectional analysis was conducted on 148 patients who had previously undergone prenatal MRI between January 2013 and May 2023. A total of 185 anomalies in 148 fetuses were evaluated using USG and MRI. The prenatal diagnoses were compared with definitive diagnoses and were classified as diagnosed, partially correct, questionable, or undiagnosed. In addition, USG and MRI findings were compared in terms of their consistency and consolidation. RESULTS: The postnatal evaluation revealed a total of 185 anomalies in 148 fetuses. USG diagnosed 94% of these anomalies, while MRI diagnosed 95.1% of them. Both USG and fetal MRI were able to diagnose 91.9% (n=170) of anomalies during the prenatal period. Fetal MRI provided an additional contribution to USG in the diagnosis of six anomalies (3.24%). CONCLUSION: In fetuses undergoing detailed ultrasonography and specialized neurosonography by experienced professionals, additional fetal anomalies exclusively detected through MRI are now found to be lower than previously documented. However, fetal MRI is presently employed to offer supplementary information, and advice, and assist in clinical decision-making. In the future, extensive prospective studies with standardized protocols for ultrasound imaging of the fetal brain are necessary to better understand the true role of fetal MRI in cases where fetal neurosonography has already been performed.

Applications of artificial intelligence-powered prenatal diagnosis for congenital heart disease.

Artificial intelligence (AI) has made significant progress in the medical field in the last decade. The AI-powered analysis methods of medical images and clinical records can now match the abilities of clinical physicians. Due to the challenges posed by the unique group of fetuses and the dynamic organ of the heart, research into the application of AI in the prenatal diagnosis of congenital heart disease (CHD) is particularly active. In this review, we discuss the clinical questions and research methods involved in using AI to address prenatal diagnosis of CHD, including imaging, genetic diagnosis, and risk prediction. Representative examples are provided for each method discussed. Finally, we discuss the current limitations of AI in prenatal diagnosis of CHD, namely Volatility, Insufficiency and Independence (VII), and propose possible solutions.

Case of Prenatal Diagnosis of a Fetal Pulmonary Arteriovenous Malformation at Term.

In our case, the malformation was diagnosed prenatally at 40 weeks of gestation, and at the age of 14 days, the malformation was removed combined with a segmentectomy of the sixth segment of the left lung. Preoperative diagnostics focus on 3D-CT reconstruction and detailing of the anatomical variations of all arterial and venous vessels, as evident from our case. Treatment includes surgical removal or a minimally invasive interventional approach through the embolization of the vessel afferent to the malformation. After the operation, the child was discharged on the 30th day after birth in good condition and is developing normally. Early operative intervention is of great importance for the favorable outcome of the condition. In our case, this was hypoxemia with a saturation of 70-75%. The rare and often missed prenatal diagnosis of fetal AV malformation is significant for the adequate postnatal treatment and development of affected children.

Prenatal Diagnosis of c.437–1G>A Mutation in the MAN2B1 Gene in a Family With Alpha-Mannosidosis: Unraveling Clinical Presentation and Treatment Outcomes in a Novel Prenatal Case

Prenatal Diagnosis of c.437–1G>A Mutation in the MAN2B1 Gene in a Family With Alpha-Mannosidosis: Unraveling Clinical Presentation and Treatment Outcomes in a Novel Prenatal Case

Outcome of fetal congenital pulmonary malformations: a systematic review and meta-analysis.

To report the outcome of fetuses with a prenatal diagnosis of congenital lung malformation (CLM) diagnosed on ultrasound by performing a comprehensive assessment of these outcomes through a systematic review and meta-analysis. CLMs are a heterogeneous group of anomalies that involve the lung parenchyma and its bronchovascular structures. Their presentation and evolution are variable, from entirely asymptomatic lesions with sonographic regression in utero to hydropic fetuses requiring fetal therapy, intrauterine death or neonatal morbidity. A systematic review was conducted in Medline, Embase and Cochrane databases including studies on fetuses with CLM diagnosed prenatally in order to report the in-utero natural history of these lesions. Thirty-nine studies (2,638 fetuses) were included in the final review. Regression/reduction in size of the lung lesion during pregnancy was reported in 31 % of cases, while its increase in 8.5 % of cases. Intra-uterine death complicated 1.5 % of pregnancies with fetal CLM, while neonatal and perinatal death were 2.2 and 3 %, respectively. Neonatal morbidity occurred in 20.6 % of newborns with CLM; 46 % had surgery, mainly elective. In fetuses with CLM and hydrops, fetal/perinatal loss occurred in 42 %. Assessment of the role of fetal therapy in improving the outcomes of pregnancies complicated by CLM was hampered by the small number of included cases and heterogeneity of type of interventions. Fetuses with CLM prenatally diagnosed have a generally favorable outcome. Conversely, there is a low quality of evidence on the actual role of fetal therapy in improving the outcome of fetuses presenting with these anomalies.

Trisomy 18: Prenatal Diagnosis and Outcome in a Tertiary Care Fetal Medicine Center in South India

AbstractEdwards' syndrome (trisomy 18) is the second most common aneuploidy known in humans, with an overall incidence of 1 in 6,000 live births. It occurs due to the presence of complete or part of an extra copy of chromosome 18 in all or a few body cells of the affected fetus, and it causes major anomalies in the organ systems. Despite this, an accurate diagnosis is often not made antenatally due to its very varied phenotype and the subtle nature of some of the common and consistent findings associated with this condition. This leads to lapses or delays in cytogenetic confirmation as well as delays in decision regarding termination of pregnancies with this mostly lethal fetal aneuploidy. We describe the prenatal profile of 45 confirmed cases of trisomy 18 at a tertiary fetal medicine unit. The presence of a combination of ultrasound (US) findings described in these cases will help alert sonologists and clinicians to suspect this condition and offer a confirmative cytogenetic test without delay for prenatal diagnosis. This study describes the prenatal diagnostic profile of cytogenetically confirmed trisomy 18 cases in a tertiary fetal medicine center in India. A retrospective analysis of records of 45 prenatally diagnosed trisomy 18 cases at a single tertiary fetal medicine center over a period of 11 years was done. Data were collected to describe maternal demography, indication for evaluation, major and minor US findings (trimester-wise), type of invasive test, and gestational age at diagnosis. Outcomes in terms of pregnancy termination, miscarriage, stillbirth, or livebirth were documented. Presenting at a mean maternal age and gestation age of 31.7 years and 22 + 5 weeks, respectively, 41/45 (91%) fetuses showed major and 40/45 (89%) showed minor US findings with an overall US sensitivity of 100%. The most common major US finding was a cardiac anomaly in 26 (57.8%) patients, while clenched fist with pointing index finger, observed in 17 (37.8%) cases, was the most common minor US finding. Fetal growth restriction (FGR) was noted in 20 (44.4%) patients. After cytogenetic confirmation, 37.8% underwent termination, 17.8% had a fetal demise, and only 11.1% had live birth with the longest survival noted at 5.5 months postnatally. Gender was documented in 13 fetuses with a male-to-female ratio of 0.6. A meticulously performed US examination can detect a combination of anomalies that could alert the sonologist to the possibility of trisomy 18. While the US profile could vary among fetuses, an understanding of the spectrum of the anomalies commonly seen in these fetuses would enable caregivers to reach an early accurate diagnosis, and offer appropriate genetic counseling and pregnancy decisions in these cases.

Fetal transposition of the great arteries: 3D virtual and physical models from ultrasound datasets.

Transposition of the great arteries (TGA) is a cyanotic congenital heart disease characterized by ventriculoarterial discordance and atrioventricular concordance with the great arteries in a parallel relationship. Prenatal diagnosis of TGA has implications for postnatal outcomes, allowing for planned delivery and perinatal management. Three-dimensional virtual or physical models of fetal TGA allow better understanding of fetal cardiac anomalies by parents and interactive discussion among the multidisciplinary team (obstetricians, pediatricians, maternal-fetal specialists, pediatric cardiologists, and cardiovascular surgeons), as well as continuing medical education.

Comparison of the performance of NIPT and NIPT-plus for fetal chromosomal aneuploidy and high Z-score increases the positive predictive value.

To evaluate non-invasive prenatal testing (NIPT) and expanded non-invasive prenatal testing (NIPT-plus) for detecting aneuploidies at different sequencing depths and assess Z-score accuracy in predicting trisomies 21, 18, 13, 45X, and 47XXX. Pregnancies with positive NIPT or NIPT-plus results detected at the prenatal diagnosis center of Nanfang Hospital were included in this retrospective study, between January 2017 and December 2022. Invasive prenatal diagnostic results were collected. Logistic regression analyses were used to study the relationship between Z-score and positive predictive value (PPV). Optimal cut-off values were obtained based on receiver operating characteristic analysis, and PPVs were calculated in different groups. We evaluated 1348 pregnant women with positive results, including 930 reported by NIPT and 418 reported by NIPT-plus. NIPT reported significantly more rare chromosomal aneuploidies (RCAs), and NIPT-plus had a significantly higher PPV for trisomy 21 (T21). Logistic regression analyses showed a significant association (P < 0.001) between Z-score and PPVs for T21 and trisomy 18 (T18). A linear relationship was observed between fetal fraction (FF) and Z-values in the true positive cases of T21 and T18.The high Z-score group had significantly higher PPVs than the low Z-score group for T21, T18, trisomy 13, and 47XXX, but not for 45X. The Z-score is helpful in assessing NIPT or NIPT-plus results. Therefore, we suggest including the Z-score and FF in the results. By combining the Z-score, FF, and maternal age, clinicians can interpret NIPT results more accurately and improve personal counsel to reduce patients' anxiety.

Noninvasive prenatal testing for the detection of fetal chromosome 17 microduplication: clinical implications and findings

Background Noninvasive prenatal testing (NIPT) is widely used to screen for fetal aneuploidies. However, there are few reports of using NIPT for screening chromosomal microduplications and microdeletions. This study aimed to investigate the application efficiency of NIPT for detecting chromosomal microduplications.MethodsFour cases of copy number gains on the long arm of chromosome 17 (17q12) were detected using NIPT and further confirmed using copy number variation (CNV) analysis based on chromosome microarray analysis (CMA).ResultsThe prenatal diagnosis CMA results of the three cases showed that the microduplications in 17q12 (ranging from 1.5 to 1.9 Mb) were consistent with the NIPT results. The karyotypic analysis excluded other possible unbalanced rearrangements. The positive predictive value of NIPT for detecting chromosomal 17q12 microduplication was 75.0%.Conclusions NIPT has a good screening effect on 17q12 syndrome through prenatal diagnosis, therefore it could be considered for screening fetal CNV during the second trimester. With the clinical application of NIPT, invasive prenatal diagnoses could be effectively reduced while also improving the detection rate of fetal CNV.

Etiologic evaluation and pregnancy outcomes of fetal growth restriction (FGR) associated with structural malformations

This study aimed to evaluate the etiology and pregnancy outcomes of fetuses underwent invasive prenatal diagnosis for fetal growth restriction (FGR) accompanied by structural malformations. Data from 130 pregnancies referred for prenatal diagnosis for FGR accompanied by structural malformations were obtained between July 2011 and July 2023. Traditional karyotyping was conducted for all the subjects. A total of 37 (28.5%) cases of chromosomal abnormalities were detected by karyotyping, including 30 cases of numerical anomalies and seven cases of unbalanced structural anomalies. Trisomy 18 was the most common abnormalities, accounting for 51.4%, significantly higher than any other chromosomal abnormality. The cohort was predominantly comprised of early-onset FGR (88.5%) compared to late-onset FGR (11.5%). The incidences of chromosomal abnormalities in this two groups were 29.6% (34/115) and 20.0% (3/15), respectively (p > 0.05). The majority (74.6%, 97/130) of the cohort were affected by a single system malformation, with chromosomal abnormalities found in 19.6% (19/97) of cases. In pregnancies of structural malformations involving two and multiple systems, the frequencies were 56.5% (13/23), and 50.0% (5/10), respectively. Single nucleotide polymorphism array (SNP array) was performed in parallel for 65 cases, revealing additional 7.7% cases of copy number variants (CNVs) compared to karyotyping. Polymerase chain reaction (PCR) was used for detection of cytomegalovirus (CMV) DNA in 92 cases. All fetuses with FGR associated with two or more system malformations were either terminated or stillborn, irrespective of chromosomal aberrations. Conversely, 71.8% of pregnancies with a single-system malformation and normal genetic testing results resulted in live births. Furthermore, two (2.2%) cases tested positive for CMV DNA, leading to one termination and one case of serious developmental disorder after birth. Our study suggests that structural malformations associated with FGR are more likely to affect a single organ system. When multiple systems are involved, the incidence of chromosomal abnormalities and termination rates are notably high. We advocate for the use of CMA and CMV DNA examinations in FGR cases undergo invasive prenatal diagnosis, as these tests can provide valuable insights for etiological exploration and pregnancy management guidance.

Prenatal Diagnosis of Vasa Previa in the Second Trimester of Pregnancy Based on Non-typical Ultrasound Findings: A Case Report and Mini-Review of the Literature

Prenatal Diagnosis of Vasa Previa in the Second Trimester of Pregnancy Based on Non-typical Ultrasound Findings: A Case Report and Mini-Review of the Literature

Prenatal Diagnosis and Prognosis of Abdominal Arteriovenous Fistulae: A Comprehensive Case Series and Systematic Review.

This study had two main objectives. Firstly, we conducted a thorough literature review on the prenatal diagnosis of abdominal congenital arteriovenous fistulas (CAVFs) involving the abdominal aorta and hepatic arteries. Secondly, we aimed to provide detailed descriptions of eight additional cases diagnosed at our medical center and assess the outcome of this anomaly for informed counseling. We conducted a systematic search of online databases using specific keywords like "outcome", "ultrasound", "intrahepatic fistulae", and "fetal venous anomalies", focusing on studies published between 1998 and 2023. We selected 10 relevant articles and analyzed 13 cases. Additionally, we conducted a five-year prospective study in two referral centers, identifying eight CAVF cases with an incidence rate of 0.16%. Among the 21 cases evaluated, 11 resulted in live births, all of which received treatment. However, four cases (36.3%) had poor postnatal outcomes and neonatal demise due to heart failure. Prenatal signs of poor fetal hemodynamics, including cardiomegaly or hydrops, were observed in 52.3% of cases, regardless of outcome. Our findings highlight the rarity of this vascular malformation and emphasize the importance of effective treatment to avoid unfavorable outcomes. The long-term effectiveness of prenatal treatment or postnatal embolization remains uncertain, with liver transplantation being considered the most reliable treatment option.

Binder Phenotype—Prenatal Diagnosis, Management, and Postnatal Outcome: Insights from a Case Series and Updated Review of the Literature

AbstractBinder phenotype (BP) or maxillonasal dysplasia is a developmental disorder of the anterior part of the maxilla and nasal complex and is characterized by a short nose with a flat nasal bridge, short columella, acute nasolabial angle, perialar flatness, convex upper lip, and tendency to a class III malocclusion. The etiology of BP is heterogeneous with diverse features and outcomes. The ultrasound features of BP are midfacial hypoplasia with verticalized nasal bones, short columella with flattened tip and alar wings, and the nasofrontal angle measuring &gt;140 degrees. In this case series, we present seven cases of BP detected antenatally, their varied etiology, management, and outcomes with a 2-year follow-up. We conclude that the diagnosis of facial dysmorphisms, such as BP, brings a lot of apprehension and agony in the parents amounting to multiple tests and counseling sessions. Physiognomy which is the normal familial appearance should be considered before concluding whether the observed feature is normal or pathological. Accurate diagnosis, adequate testing, and personalized counseling will help in the prevention of needless termination of pregnancies and ensure an optimal perinatal outcome.

Prenatal Diagnosis of a Case of Asyndromic Tessier Class-7 Bilateral Complete Transverse Facial Cleft: Case Report with Review of Literature

AbstractTransverse or lateral facial clefts are atypical and rare forms of facial clefts identified as Tessier type 7 in the classification system for orofacial clefts. They have an overall incidence of 1 in 60,000 to 300,000 live births. We report a case diagnosed at 22 weeks of gestation. The two-dimensional (2D) ultrasound examination revealed a single live fetus with a persistently open mouth, failure of visualization of lateral commissures, and mild retrognathia. The three-dimensional (3D) surface rendering of the fetal face demonstrated a bilateral horizontal facial cleft that extended from the lateral commissures to the ears. No additional anomalies were identified. Fetal karyotype and whole exome sequencing reports did not reveal any genomic imbalances. The case highlights the importance of 2D oblique and 3D imaging of the fetal face when subtle findings are detected in routine 2D views. A review of the literature is provided to enhance the understanding of the entity.

Prenatal diagnosis of 18p deletion and 8p trisomy syndrome: literature review and report of a novel case

18p deletion syndrome constitutes one of the most frequent autosomal terminal deletion syndromes, affecting one in 50,000 live births. The syndrome has un-specific clinical features which vary significantly between patients and may overlap with other genetic conditions. Its prenatal description is extremely rare as the fetal phenotype is often not present during pregnancy. Trisomy 8p Syndrome is characterized by heterogenous phenotype, with the most frequent components to be cardiac malformation, developmental and intellectual delay. Its prenatal diagnosis is very rare due to the unspecific sonographic features of the affected fetuses. We present a very rare case of a fetus with multiple anomalies diagnosed during the second trimester whose genomic analysis revealed a 18p Deletion and 8p trisomy Syndrome. This is the first case where this combination of DNA mutations has been described prenatally and the second case in general. The presentation of this case, as well as the detailed review of all described cases, aim to expand the existing knowledge regarding this rare condition facilitating its diagnosis in the future.

Diagnostic error during antenatal care visit in selected health facilities of Ethiopia: a survey

Diagnostic error in antenatal care is a critical concern within the broader challenge of diagnostic errors in healthcare. Antenatal care plays a crucial role in ensuring the well-being of both the mother and the developing fetus during pregnancy. As a result, missed or delayed antenatal care visits or diagnosis errors of maternity complications affect both the mother and the baby. Diagnostic errors in this context refer to mistakes or inaccuracies in identifying and interpreting medical conditions, risks, or abnormalities related to the pregnancy. Several factors contribute to diagnostic errors in antenatal care, and understanding these challenges is essential for improving the overall quality of maternal and fetal healthcare. Delivering an improved approach to underrating diagnostic error requires the combined usage of non-technological and technological solutions. Identifying the factors contributing to diagnostic errors among healthcare professionals can lead to targeted interventions, training programs, and system level changes to prevent or minimize such errors. In this study, the prevalence of DE among health care professionals, pregnant women, and their relatives, and the frequency of occurrence of DE among health workers in selected health facilities in Ethiopia has been assessed. The data was collected using a questionnaire. The assessment results show that the major causes of diagnostic errors (mainly incorrect diagnosis) are identified as loss of patient records (36.4%), lack of proper laboratory (22.7%), and an insufficient number of health care professionals (13.6%). The leading effects of diagnostic error recognized are disease aggravation (58.3%) and permanent disability (25.0%). The research shows that providing an accurate diagnosis is crucial for avoiding risky obstetric outcomes and, as a result, reducing morbidity and mortality due to complications of pregnancy.

Renal Pathology of Ciliopathies.

Renal ciliopathies are a group of genetic disorders that affect the function of the primary cilium in the kidney, as well as other organs. Since primary cilia are important for regulation of cell signaling pathways, ciliary dysfunction results in a range of clinical manifestations, including renal failure, cyst formation, and hypertension. We summarize the current understanding of the pathophysiological and pathological features of renal ciliopathies in childhood, including autosomal dominant and recessive polycystic kidney disease, nephronophthisis, and Bardet-Biedl syndrome, as well as skeletal dysplasia associated renal ciliopathies. The genetic basis of these disorders is now well-established in many cases, with mutations in a large number of cilia-related genes such as PKD1, PKD2, BBS, MKS, and NPHP being responsible for the majority of cases. Renal ciliopathies are broadly characterized by development of interstitial fibrosis and formation of multiple renal cysts which gradually enlarge and replace normal renal tissue, with each condition demonstrating subtle differences in the degree, location, and age-related development of cysts and fibrosis. Presentation varies from prenatal diagnosis of congenital multisystem syndromes to an asymptomatic childhood with development of complications in later adulthood and therefore clinicopathological correlation is important, including increasing use of targeted genetic testing or whole genome sequencing, allowing greater understanding of genetic pathophysiological mechanisms.