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BMC Medical Genomics Oct 2023Whole-exome sequencing (WES) significantly improves the diagnosis of the etiology of fetal structural anomalies. This study aims to evaluate the diagnostic value of...
BACKGROUND
Whole-exome sequencing (WES) significantly improves the diagnosis of the etiology of fetal structural anomalies. This study aims to evaluate the diagnostic value of prenatal WES and to investigate the pathogenic variants in structurally abnormal fetuses.
METHODS
We recruited 144 fetuses with structural anomalies between 14 and 2020 and 15 December 2021 in the study. Genetic screening was performed by WES combined with karyotyping and chromosomal microarray analysis. The molecular diagnostic yield of prenatal WES for each type of fetal structural anomaly and the identified pathogenic genes and mutations were reported.
RESULTS
In this study, we retrospectively analyzed the clinical and genetic data of 145 structurally anomalous fetuses. These cases were classified into 9 phenotypic classes based on antenatal ultrasound findings. Thirty-eight pathogenic variants in 24 genes were identified in 35 of the 145 cases, including 14 novel variants in 13 genes (EP300, MYH3, TSC2, MMP9, CPLANE1, INVS, COL1A1, EYA1, TTC21B, MKS1, COL11A2, PDHA1 and L1CAM). Five additional pathogenic variants were classified as incidental findings. Our study showed that the overall diagnosis rate of WES was 28.1% (27/96) in the parent-fetus trio cases and 16.3% (8/49) in the proband-only cases. Fetuses with musculoskeletal anomalies had the highest diagnostic yield (51.4%, 19/37). In addition, FGFR3 and COL1A1 were the most common pathogenic genes.
CONCLUSIONS
Our work expands the mutation spectrum of the genes associated with fetal structural anomalies and provides valuable information for future parental genetic counselling and pregnancy management of the structurally anomalous fetuses.
Topics: Female; Humans; Pregnancy; East Asian People; Exome Sequencing; Fetus; Pregnancy Trimester, First; Prenatal Diagnosis; Retrospective Studies; Ultrasonography, Prenatal; Congenital Abnormalities
PubMed: 37880672
DOI: 10.1186/s12920-023-01697-3 -
Journal of Perinatal Medicine Feb 2022To evaluate the impact of the COVID-19 pandemic on prenatal screening and diagnostic tests.
OBJECTIVES
To evaluate the impact of the COVID-19 pandemic on prenatal screening and diagnostic tests.
METHODS
We conducted a retrospective study with pregnant women attending to the perinatology department of a tertiary referral center. The pre-COVID-19 period between 11 March 2019 and 10 March 2020 and COVID-19 period between 11 March 2020 and 10 March 2021 were evaluated. Both periods were compared in terms of outpatient visits, ultrasound examinations, prenatal screening and diagnostic tests. The correlation of deaths related to COVID-19 pandemic on these parameters was also assessed.
RESULTS
A total of 38,918 patients were examined and 28,452 ultrasound examinations, 26,672 prenatal screening tests and 1,471 prenatal diagnostic tests were performed over two years. During COVID-19 pandemic, number of outpatient visits decreased by 25.2%, ultrasound examinations decreased by 44.2%, prenatal screening tests decreased by 36.2% and prenatal diagnostic tests decreased by 30.7%. Statistically significant correlation was not observed between deaths related to COVID-19 and outpatient visits (p=0.210), ultrasound examinations (p=0.265), prenatal screening (p=0.781) and diagnostic tests (p=0.158). Among indications of prenatal diagnostic tests, maternal anxiety was significantly higher in COVID-19 period (p=0.023). There was significant decrease in the detection of fetuses with trisomy 21 (p=0.047) and a significant increase in the detection of fetuses with Turner syndrome (p=0.017) during COVID-19 period.
CONCLUSIONS
The COVID-19 pandemic has severely impacted antenatal care. Prenatal fetal screening and diagnosis was adversely affected by the pandemic in terms of detecting genetic and structural anomalies.
Topics: Adolescent; Adult; COVID-19; Female; Humans; Pregnancy; Prenatal Diagnosis; Retrospective Studies; Young Adult
PubMed: 34881543
DOI: 10.1515/jpm-2021-0343 -
Ultrasound in Obstetrics & Gynecology :... Nov 2020Celocentesis is an invasive technique that can provide prenatal diagnosis of single-gene disorders, from as early as 7 weeks' gestation. The objective of this study...
OBJECTIVE
Celocentesis is an invasive technique that can provide prenatal diagnosis of single-gene disorders, from as early as 7 weeks' gestation. The objective of this study was to examine the safety of celocentesis.
METHODS
In this prospective study, celocentesis was performed for prenatal diagnosis of hemoglobinopathy in 402 singleton pregnancies in which both parents were carriers of β-thalassemia or sickle cell disease trait. We assessed procedure-related maternal discomfort or pain, success of sampling and obtaining results, pregnancy outcome and postnatal follow-up.
RESULTS
First, celocentesis was carried out at a median gestational age of 8.6 (range, 6.9-9.9) weeks and celomic fluid was successfully aspirated in 99.8% of cases. Second, 67% of women had no or only mild discomfort, 18% had moderate discomfort, 12% had mild-to-moderate pain and 3% had severe pain. Third, prenatal diagnosis from analysis of the celomic fluid was successful in 93.8% cases, and in the last 121 cases, it was always successful. Fourth, in all cases of successful sampling and analysis of celomic fluid, the diagnosis was concordant with results obtained from additional prenatal or postnatal testing. Fifth, in addition to diagnosis of hemoglobinopathy, quantitative fluorescence polymerase chain reaction analysis, which was performed to evaluate maternal contamination using several markers for chromosomes X, Y, 21, 18 and 13, led to the accurate diagnosis of chromosomal aneuploidy. Sixth, in all cases of an affected fetus diagnosed by celocentesis in which the parents chose termination of pregnancy, this was carried out < 10 weeks' gestation. Seventh, in 97.1% (298/307) of the continuing pregnancies there was live birth, in seven (2.3%) there was miscarriage and in two (0.7%) there was loss to follow-up. Eighth, fetal abnormalities were diagnosed in three (1%) cases, including unilateral transverse amputation of the forearm, unilateral moderate hydronephrosis and small-bowel duplication. All neonates were examined by a pediatrician and were found to be phenotypically normal, except for the three cases with a prenatally diagnosed defect.
CONCLUSIONS
Celocentesis can be used for early prenatal diagnosis of genetic abnormalities, and the procedure-related risk of pregnancy complications appears to be low. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Abortion, Eugenic; Adult; Early Diagnosis; Female; Genetic Testing; Gestational Age; Hemoglobinopathies; Humans; Infant, Newborn; Paracentesis; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnancy Trimester, First; Prenatal Diagnosis; Prospective Studies; Ultrasonography, Prenatal
PubMed: 32339311
DOI: 10.1002/uog.22059 -
BMC Medical Genomics Jul 2021DMD/BMD prenatal diagnosis for 931 foetuses.
OBJECTIVE
DMD/BMD prenatal diagnosis for 931 foetuses.
BACKGROUND
DMD is the most common fatal X-linked recessive muscular disease. There is no effective clinical treatment method at present. Accurate gene diagnosis and prenatal diagnosis technology are important ways for early detection, early prevention and early treatment.
METHODS
A total of 931 prenatal diagnoses were performed for pregnant women with a definite family history of DMD or a history of DMD childbirth between 2005 and 2019. This report may be considered the largest DMD prenatal diagnosis report in a single centre worldwide. Multiple ligation-dependent probe amplification (MLPA) and next-generation sequencing were used in combination. Techniques and short tandem repeat (STR) linkage analysis were used to determine the location of the DMD gene mutation in the pregnant woman and then to detect the DMD gene in the foetuses.
RESULTS
There were 872 families in our study. Among all 931 foetuses, 20.73% (193/931) were males expected to develop DMD and 16.33% (152/931) were female carriers. In addition, gonadal mosaicism was observed in 5 mothers, and gene recombination was identified in three foetuses. The results of the prenatal diagnosis were consistent with the results of the CPK analysis, and the results of the prenatal diagnosis were 100% accurate.
CONCLUSIONS
MLPA and Sanger sequencing, when combined with STR linkage analyses, can provide an accurate and rapid prenatal diagnosis. Due to the high de novo rate, prenatal diagnosis and genetic counselling should be given great attention.
Topics: Muscular Dystrophy, Duchenne; Prenatal Diagnosis
PubMed: 34238289
DOI: 10.1186/s12920-021-01024-8 -
Prenatal Diagnosis Jun 2022Prenatal exome sequencing (ES) for monogenic disorders in fetuses with structural anomalies increases diagnostic yield. In England there is a national trio ES service...
BACKGROUND
Prenatal exome sequencing (ES) for monogenic disorders in fetuses with structural anomalies increases diagnostic yield. In England there is a national trio ES service delivered from two laboratories. To minimise incidental findings and reduce the number of variants investigated, analysis uses a panel of 1205 genes where pathogenic variants may cause abnormalities presenting prenatally. Here we review our laboratory's early experience developing and delivering ES to identify challenges in interpretation and reporting and inform service development.
METHODS
A retrospective laboratory records review from 01.04.2020 to 31.05.2021.
RESULTS
Twenty-four of 116 completed cases were identified as challenging including 13 resulting in difficulties in analysis and reporting, nine where trio inheritance filtering would have missed the diagnosis, and two with no prenatal diagnosis; one due to inadequate pipeline sensitivity, the other because the gene was not on the panel. Two cases with copy number variants identified were not detectable by microarray.
CONCLUSIONS
Variant interpretation requires close communication between referring clinicians, with occasional additional examination of the fetus or parents and communication of evolving phenotypes. Inheritance filtering misses ∼5% of diagnoses. Panel analysis reduces but does not exclude incidental findings. Regular review of published literature is required to identify new reports that may aid classification.
Topics: Exome; Female; Fetus; Humans; Pregnancy; Prenatal Diagnosis; Retrospective Studies; Ultrasonography, Prenatal; Exome Sequencing
PubMed: 35506549
DOI: 10.1002/pd.6165 -
Revista Brasileira de Ginecologia E... Dec 2022To describe the clinical results of patients admitted and managed as cases of placenta accreta spectrum (PAS) at a Central American public hospital and the influence...
OBJECTIVE
To describe the clinical results of patients admitted and managed as cases of placenta accreta spectrum (PAS) at a Central American public hospital and the influence of the prenatal diagnosis on the condition.
MATERIALS AND METHODS
A retrospective analysis of PAS patients treated at Hospital Bertha Calderón Roque, in Managua, Nicaragua, between June 2017 and September 2021. The diagnostic criteria used were those of the International Federation of Gynecology and Obstetrics (Fédération Internationale de Gynécologie et d'Obstétrique, FIGO, in French). The population was divided into patients with a prenatal ultrasonographic diagnosis of PAS (group 1) and those whose the diagnosis of PAS was established at the time of the caesarean section (group 2).
RESULTS
During the search, we found 103 cases with a histological and/or clinical diagnosis of PAS; groups 1 and 2 were composed of 51 and 52 patients respectively. Regarding the clinical results of both groups, the patients in group 1 presented a lower frequency of transfusions (56.9% versus 96.1% in group 2), use of a lower number of red blood cell units (RBCUs) among those undergoing transfusions (median: 1; interquartile range: [IQR]: 0-4 versus median: 3; [IQR]: 2-4] in group 2), and lower frequency of 4 or more RBCU transfusions (29.4% versus 46.1% in group 2). Group 1 also exhibited a non-significant trend toward a lower volume of blood loss (1,000 mL [IQR]: 750-2,000 mL versus 1,500 mL [IQR]: 1,200-1,800 mL in group 2), and lower requirement of pelvic packing (1.9% versus 7.7% in group 2).
CONCLUSION
Establishing a prenatal diagnosis of PAS is related to a lower frequency of transfusions. We observed a high frequency of prenatal diagnostic failures of PAS. It is a priority to improve prenatal detection of this disease.
Topics: Pregnancy; Humans; Female; Placenta Accreta; Cesarean Section; Ultrasonography, Prenatal; Retrospective Studies; Prenatal Diagnosis; Placenta
PubMed: 36580936
DOI: 10.1055/s-0042-1758712 -
Contrast Media & Molecular Imaging 2022The purpose was to explore the diagnostic value and application of prenatal magnetic resonance imaging (MRI) and ultrasound (US) in fetal cleft lip and palate.
OBJECTIVE
The purpose was to explore the diagnostic value and application of prenatal magnetic resonance imaging (MRI) and ultrasound (US) in fetal cleft lip and palate.
METHODS
From January 2018 to December 2019, 39 pregnant women without normal fetal maxillofacial structure or with fetal maxillofacial deformity under US examination in our hospital were selected as the study subjects. Not knowing the clinical data of the pregnant women, MRI and US physicians performed diagnostic analysis on the MRI or US images of all the study subjects and analyzed the results of prenatal MRI and US diagnosis and postpartum follow-up to compare the diagnostic efficacy and confidence of MRI and US.
RESULTS
The follow-up found that there were 20 cases of cleft lip, 15 cases of cheilopalatognathus, 3 cases of cleft palate, and 1 case of unilateral cleft lip with alveolar cleft, with a total of 39 cases having cleft lip and palate deformity. MRI and US had the same efficacy in the diagnosis of cleft lip. As for cleft palates, the diagnostic accuracy of MRI (94.87%) was significantly better than that of US (48.72%, < 0.001). The diagnostic confidence of fetal cleft lip and palate by MRI (89.73%) was significantly better than that of US (43.59%, < 0.001). The AUC of US (0.597) was significantly less than that of MRI (0.940), indicating that the diagnostic accuracy of US was not as good as that of MRI ( < 0.05). The sensitivity and 1 - specificity of MRI were significantly higher than those of US.
CONCLUSION
MRI is more accurate than US in the diagnosis of fetal cleft lip and palate, and MRI can be the preferred method for prenatal detection of cleft lip and palate, thus providing more accurate opinions and information for perinatal pregnant women.
Topics: Cleft Lip; Cleft Palate; Female; Gestational Age; Humans; Infant, Newborn; Magnetic Resonance Imaging; Pregnancy; Prenatal Diagnosis; Ultrasonography, Prenatal
PubMed: 35655725
DOI: 10.1155/2022/9410161 -
Medicine Dec 2023Intrauterine microcephaly is a complex and lifelong condition that poses significant ethical challenges for clinicians and parents. The prognosis of microcephaly is...
INTRODUCTION
Intrauterine microcephaly is a complex and lifelong condition that poses significant ethical challenges for clinicians and parents. The prognosis of microcephaly is highly variable and depends on the underlying cause and severity. In addition, microcephaly is often associated with various comorbidities, including intellectual disability, developmental delay, and epilepsy. Ultrasonography (US) is currently the most commonly used imaging modality for detecting microcephaly in the second trimester of pregnancy. However, antenatal brain magnetic resonance imaging (MRI) is increasingly being used as a more sensitive tool to identify structural abnormalities that may suggest a specific diagnosis. In this study, we report a case series of microcephaly diagnosed through the combination of MRI and US.
PATIENT CONCERNS
How to utilize a combination of MRI and US to screen for fetal microcephaly.
DIAGNOSIS
Based on the results of US and MRI examinations, patient 1 was found to have other craniocerebral malformations, patient 2 demonstrated macrogyria, and patient 3 exhibited skull irregularities.
INTERVENTIONS
The pregnancies of all 3 patients were terminated through the induction of labor by injecting Rivanol into the amniotic cavity.
OUTCOMES
The 3 patients were discharged after a period of observation.
CONCLUSION
US is an important tool for diagnosing fetal microcephaly. However, MRI can overcome the limitations of US and detect additional brain structural abnormalities, thereby providing more specific and valuable prenatal diagnostic information. Therefore, combining MRI and US has significant diagnostic value for fetal microcephaly.
Topics: Humans; Pregnancy; Female; Microcephaly; Ultrasonography, Prenatal; Prenatal Diagnosis; Nervous System Malformations; Magnetic Resonance Imaging; Ultrasonography
PubMed: 38115306
DOI: 10.1097/MD.0000000000036623 -
Cold Spring Harbor Perspectives in... Jun 2020Genetic counselors have both the burden and the privilege of supporting patients who are faced with making difficult decisions. In the prenatal setting, genetic... (Review)
Review
Genetic counselors have both the burden and the privilege of supporting patients who are faced with making difficult decisions. In the prenatal setting, genetic counselors are responsible for reviewing a growing list of prenatal testing options for patients with the goal of helping people to anticipate the potential consequences of their decision. Prenatal genetic counselors also support patients in making decisions about the next steps after clinical evaluation has indicated a genetic condition, birth defect, or information of uncertain clinical significance in the fetus. The information provided and choices patients face in the context of prenatal and reproductive genetics can be life-altering, and decisions often must be made within a short window of time. It is imperative that the needs and preferences of each patient are considered and that individuals are empowered to make active decisions that are consistent with their needs and values. Here we will review the history of the role of the genetic counselor in the prenatal setting and will provide strategies and tools for supporting informed patient decision-making in the face of an increasingly complex reproductive genetic testing landscape.
Topics: Decision Making; Female; Genetic Counseling; Genetic Testing; Health Knowledge, Attitudes, Practice; Humans; Patient Preference; Personal Autonomy; Pregnancy; Pregnant Women; Prenatal Diagnosis; Social Support
PubMed: 31615869
DOI: 10.1101/cshperspect.a036509 -
Journal of the American Heart... Aug 2021Background Placental derived cell-free DNA (cfDNA), widely utilized for prenatal screening, may serve as a biomarker for preeclampsia. To determine whether cfDNA...
Background Placental derived cell-free DNA (cfDNA), widely utilized for prenatal screening, may serve as a biomarker for preeclampsia. To determine whether cfDNA parameters are altered in preeclampsia, we conducted a case-control study using prospectively collected maternal plasma (n=20 preeclampsia, n=22 normal) using our in-house validated prenatal screening assay. Methods and Results Isolated cfDNA was quantified, sequenced using Illumina NextSeq 500, and the placental-derived fraction was determined. Clinical and test characteristics were compared between preeclampsia and controls, followed by comparisons within the preeclampsia cohort dichotomized by cfDNA concentration. Lastly, cfDNA parameters in preeclampsia were correlated with markers of disease severity. Maternal age, body mass index, gestational age at delivery, cesarean rate, and neonatal birthweight were expectedly different between groups (≤0.05). The placental-derived cfDNA fraction did not differ between groups (21.4% versus 16.9%, =0.06); however, total cfDNA was more than 10 times higher in preeclampsia (1235 versus 106.5 pg/µL, <0.001). This relationship persisted when controlling for important confounders (OR 1.22, 95% CI 1.04-1.43, =0.01). The dichotomized preeclampsia group with the highest cfDNA concentration delivered earlier (33.2 versus 36.6 weeks, =0.02) and had lower placental-derived fractions (9.1% versus 21.4%, =0.04). Among preeclampsia cases, higher total cfDNA correlated with earlier gestational age at delivery (=0.01) and higher maximum systolic blood pressure (=0.04). Conclusions At diagnosis, total cfDNA is notably higher in preeclampsia, whereas the placental derived fraction remains similar to healthy pregnancies. In preeclampsia, higher total cfDNA correlates with earlier gestational age at delivery and higher systolic blood pressure. These findings may indicate increased release of cfDNA from maternal tissue injury.
Topics: Adult; Biomarkers; Blood Pressure; Body Mass Index; Case-Control Studies; Cell-Free Nucleic Acids; Correlation of Data; Female; Gestational Age; Humans; Maternal Age; Placenta; Pre-Eclampsia; Pregnancy; Prenatal Diagnosis; Reproductive History; Severity of Illness Index
PubMed: 34310191
DOI: 10.1161/JAHA.121.021477