The American Association for Thoracic Surgery (AATS) 2023 Expert Consensus Document: Recommendation for the care of children with trisomy 13 or trisomy 18 and a congenital heart defect.

OBJECTIVES: Recommendations for surgical repair of a congenital heart defect in children with trisomy 13 or trisomy 18 remain controversial, are subject to biases, and are largely unsupported with limited empirical data. This has created significant distrust and uncertainty among parents and could potentially lead to suboptimal care for patients. A working group, representing several clinical specialties involved with the care of these children, developed recommendations to assist in the decision-making process for congenital heart defect care in this population. The goal of these recommendations is to provide families and their health care teams with a framework for clinical decision making based on the literature and expert opinions. METHODS: This project was performed under the auspices of the AATS Congenital Heart Surgery Evidence-Based Medicine Taskforce. A Patient/Population, Intervention, Comparison/Control, Outcome process was used to generate preliminary statements and recommendations to address various aspects related to cardiac surgery in children with trisomy 13 or trisomy 18. Delphi methodology was then used iteratively to generate consensus among the group using a structured communication process. RESULTS: Nine recommendations were developed from a set of initial statements that arose from the Patient/Population, Intervention, Comparison/Control, Outcome process methodology following the groups' review of more than 500 articles. These recommendations were adjudicated by this group of experts using a modified Delphi process in a reproducible fashion and make up the current publication. The Class (strength) of recommendations was usually Class IIa (moderate benefit), and the overall level (quality) of evidence was level C-limited data. CONCLUSIONS: This is the first set of recommendations collated by an expert multidisciplinary group to address specific issues around indications for surgical intervention in children with trisomy 13 or trisomy 18 with congenital heart defect. Based on our analysis of recent data, we recommend that decisions should not be based solely on the presence of trisomy but, instead, should be made on a case-by-case basis, considering both the severity of the baby's heart disease as well as the presence of other anomalies. These recommendations offer a framework to assist parents and clinicians in surgical decision making for children who have trisomy 13 or trisomy 18 with congenital heart defect.

[Prenatal diagnosis and outcome of pregnancy for women with high risks by screening of fetal free DNA from peripheral blood samples].

OBJECTIVE: To analyze the results of prenatal diagnosis and outcome of pregnancy for women with a high risk for fetal aneuploidies. METHODS: A total of 747 cases of prenatal diagnosis by amniocentesis due to high risks by non-invasive prenatal testing (NIPT) were selected from January 2015 to March 2022 in the Drum Tower Hospital Affiliated to Nanjing University Medical School. The amniotic fluid samples were subjected to chromosomal karyotyping and/or chromosomal microarray analysis. All cases were followed up by searching the birth information or telephone calls, and the results were recorded. 2 test or F test were used for comparing the difference between the groups. RESULTS: Among the 747 pregnant women with a high risk by NIPT, 387 were true positives, and the overall positive predictive value (PPV) was 51.81%. The PPVs for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13) and sex chromosome aneuploidies (SCA) were 80.24% (199/248), 60% (48/80), 14% (7/50) and 38.97% (106/272), respectively. The PPV for T21 was significantly higher than T18 and T13 (χ2 = 85.216, P < 0.0001). The PPV for other chromosomal aneuploidies and copy number variations (CNVs) were 11.11% (5/45) and 40.74% (22/52), respectively. The PPV for increased X chromosomes was significantly higher than X chromosome decreases (64.29% vs. 22.22%, χ2 = 5.530, P < 0.05). The overall PPV for elder women (≥ 35 years old) was significantly higher than younger women (69.35% vs. 42.39%, χ2 = 49.440, P < 0.0001). For T21 and T18, the PPV of Z ≥ 10 group was significantly higher than that for 3 ≤ Z < 5 group or 5 ≤ Z < 10 group (P < 0.05). Among 52 cases with a high risk for CNVs, the PPV for the ≤ 5 Mb group was significantly higher than the 5 Mb < CNVs < 10 Mb or > 10 Mb groups (60% vs. 30%60% vs. 23.53%, P < 0.05). Among the 387 true positive cases, 322 had opted for induced labor, 53 had delivered with no abnormal growth and development, and 12 were lost during the follow-up. CONCLUSION: The PPVs for common chromosomal aneuploidies are related to the age and Z value of the pregnant women, which were higher in the elder group and higher Z value group. In addition, the PPV is associated with high risk types. The PPV for T21 was higher than T18 and T13, and that for 45,X was lower than 47,XXX, 47,XYY or 47,XXY syndrome. NIPT therefore has relatively high PPVs for the identification of chromosomal CNVs.

[Genetic analysis of the false positive trisomy 7 and false negative trisomy 18 by NIPT-PLUS].

OBJECTIVE: To explore the cause of inconsistency between the results of trisomy 7 by expanded non-invasive prenatal testing (NIPT-PLUS) and trisomy 18 by prenatal diagnosis. METHODS: A pregnant woman who received genetic counseling at Jiaozuo Maternal and Child Health Care Hospital on July 5, 2020 was selected as the study subject. NIPT-PLUS, systematic ultrasound and interventional prenatal testing were carried out. The middle segment and root of umbilical cord, center and edge of the maternal and fatal surface of the placenta were sampled for the validation by copy number variation sequencing (CNV-seq). RESULTS: The result of NIPT-PLUS indicated that the fetus has trisomy 7. Systematic ultrasound has shown multiple malformations including atrioventricular septal defect, horseshoe kidney, and rocker-bottom feet. However, QF-PCR, chromosomal karyotyping analysis, and CNV-seq of amniotic fluid samples all showed that the fetus was trisomy 18. Validation using multiple placental samples confirmed that the middle segment of the umbilical cord contains trisomy 18, the center of the placenta contained trisomy 7, and other placental sites were mosaicism for trisomy 7 and trisomy 18. Notably, the ratio of trisomy 18 became lower further away from the umbilical cord. CONCLUSION: The false positive results of trisomy 7 and false negative trisomy 18 by NIPT-PLUS was probably due to the existence of placental mosaicism. Strict prenatal diagnosis is required needed aneuploidy is detected by NIPT-PLUS to exclude the influence of placental mosaicisms.

Artificial intelligence for prenatal chromosome analysis.

This review article delves into the rapidly advancing domain of prenatal diagnostics, with a primary focus on the detection and management of chromosomal abnormalities such as trisomy 13 ("Patau syndrome)", "trisomy 18 (Edwards syndrome)", and "trisomy 21 (Down syndrome)". The objective of the study is to examine the utilization and effectiveness of novel computational methodologies, such as "machine learning (ML)", "deep learning (DL)", and data analysis, in enhancing the detection rates and accuracy of these prenatal conditions. The contribution of the article lies in its comprehensive examination of advancements in "Non-Invasive Prenatal Testing (NIPT)", prenatal screening, genomics, and medical imaging. It highlights the potential of these techniques for prenatal diagnosis and the contributions of ML and DL to these advancements. It highlights the application of ensemble models and transfer learning to improving model performance, especially with limited datasets. This also delves into optimal feature selection and fusion of high-dimensional features, underscoring the need for future research in these areas. The review finds that ML and DL have substantially improved the detection and management of prenatal conditions, despite limitations such as small sample sizes and issues related to model generalizability. It recognizes the promising results achieved through the use of ensemble models and transfer learning in prenatal diagnostics. The review also notes the increased importance of feature selection and high-dimensional feature fusion in the development and training of predictive models. The findings underline the crucial role of AI and machine learning techniques in early detection and improved therapeutic strategies in prenatal diagnostics, highlighting a pressing need for further research in this area.

Causes of death in individuals with trisomy 18 after the first year of life.

Mortality in individuals with trisomy 18 has significantly decreased over the past 20 years, but there is scant literature addressing the prognosis and cause of death in individuals with trisomy 18 and survival past the first year of life (YOL). This study analyzed factors associated with mortality and cause of death in a retrospective cohort of 174 individuals with trisomy 18 and survival past the first YOL, the largest such series to date. Data were collected via retrospective survey of parents of affected individuals. Prenatal diagnosis of trisomy 18; postnatal respiratory distress; maternal age > 35 years; birthweight <2000 g; brain and spinal cord defect(s); atrial and/or ventricular septal defect(s); inability to feed orally without medical assistance; and failure to meet sitting and rolling milestones were associated with mortality in this sample. Cause of death was compared between our cohort of individuals with trisomy 18 and existing literature on those with mortality before the first YOL. Individuals with trisomy 18 with mortality after the first YOL demonstrated a predominance of infectious (n = 10/22) and postoperative (n = 6/22) contributing causes of death, in contrast to the existing literature, which shows a predominance of cardiopulmonary causes of death (e.g., cardiopulmonary arrest, pulmonary hypertension). These findings demonstrate that individuals with trisomy 18 and survival past the first YOL have unique medical needs, but further research is needed to develop clinical guidelines for this growing population.

Comprehensive phenotyping of fetuses with trisomy 18: a perinatal center experience.

Trisomy 18 is the second most common aneuploidy after trisomy 21. It presents with varying degrees of heterogeneous clinical phenotypes involving multiple organ systems, with a high mortality rate. Clinical assessment of fetal trisomy 18 is always challenging. In this study, we describe the phenotypes of the fetuses with trisomy 18 from a perinatal cohort. We reviewed fetuses with trisomy 18 in referrals for perinatal autopsy over the period of 15 years. A detailed phenotyping of the fetuses with trisomy 18 was executed by perinatal autopsy. Appropriate fetal tissues were obtained to perform genomic testing. We observed trisomy 18 in 16 fetuses (2%) in our cohort of 784 fetal/neonatal losses and a perinatal autopsy was performed on all of them. Abnormal facial profile was the most frequent anomaly (10/16, 62%) followed by anomalies of the extremities (9/16, 56%), and cardiac defects (6/16, 37%). We also observed esophageal atresia, diaphragmatic hernia, and neural tube defect. The study represents one of the largest cohorts of trisomy 18 from a perinatal center from a developing country and highlights the clinical heterogeneity attributed to trisomy 18. We also report a recurrence of trisomy 18 in a family.

Indications, types, and diagnostic implications of prenatal genetic testing in Sub-Saharan Africa: A descriptive study.

OBJECTIVE: To describe indications, test types, and results of prenatal diagnostic genetic amniocentesis among Ethiopian pregnant women. METHODS: This study was a descriptive study on prenatal diagnostic genetic testing among Ethiopian pregnant women with certain indications and it was conducted at St. Paul's Hospital Millennium Medical College (Addis Ababa, Ethiopia) from January 2017 to April 2023. Data on sociodemographic characteristics, genetic testing indications, types, and results were collected electronically. Data were analysed using SPSS version 23. RESULTS: A total of 159 cases were analysed. The commonest indication for genetic testing among the study subjects was major fetal structural anomalies identified on specialized prenatal anatomic scanning of the index pregnancy detected in 71(44.7%) cases. Down syndrome and Edward syndrome were the commonest genetic aberrations detected accounting for 6.3% (10/159) and 4.4% (7/159), respectively. Among the rare genetic aberration detected were Di-George syndrome (0.6%) and Duchenne muscular dystrophy (0.6%). CONCLUSION: Findings of our study underscore the importance of diagnostic prenatal testing in a Sub-Saharan Africa setting, as common (trisomy 21&18) and rare genetic defects were identified using this important prenatal diagnostic testing. Considering the implications of detecting chromosomal abnormalities for future counselling and care, carrier state in parents for some chromosomal anomalies, and planning post-natal management of some abnormalities that are associated with aneuploidies (notably cardiac anomalies), initiation of diagnostic prenatal genetic testing service at tertiary public health facilities should be acted up on.

Screen-positive rate in cell free DNA screening for trisomy 21.

OBJECTIVE: To assess whether the fetal fraction (FF) has an impact on the screen-positive rate (SPR) in cell-free DNA (cfDNA) screening for trisomy 21. METHODS: Retrospective analysis based on samples analyzed using the Harmony® Prenatal Test (Roche Inc). Due to the size of the data set, we focused on the SPR, which was stratified according to the maternal age, weight, gestational age, and FF distribution. RESULTS: The study cohort consisted of 364,881 patients, including 2614 with a high-risk-result. Median maternal and gestational ages were 34.6 years and 12.4 weeks. FF was dependent on maternal age, weight, and gestational age. SPR was 0.72% and it was independent of maternal weight but was dependent on maternal age. There was a positive but weak association between the FF and the SPR until the FF reached 20.0% (OR p = 1.021, p < 0.001, Nagelkerkes r2 = 0.001). This group included 357,800 pregnancies or 98.1% of the study population. In the group of pregnancies with a FF > 20%, the association was stronger (OR 1.099, p < 0.001, Nagelkerkes r2 = 0.042). CONCLUSION: The SPR in cfDNA screening for trisomy 21 was relatively constant up to a FF of about 20%.

Clinical Potential of Expanded Noninvasive Prenatal Testing for Detection of Aneuploidies and Microdeletion/Microduplication Syndromes.

OBJECTIVE: We aimed to evaluate the clinical performance of expanded noninvasive prenatal testing (NIPT-Plus) for the detection of aneuploidies and microdeletion/microduplication syndromes. METHODS: A total of 7177 pregnant women were enrolled in the study from June 2020 to March 2022 at Xijing Hospital, China. Cases with NIPT-Plus-positive results were further confirmed by chromosomal karyotyping and a chromosomal microarray analysis. RESULTS: A total of 112 positive cases (1.56%) were identified by NIPT-Plus, including 60 chromosome aneuploidies and 52 microdeletion/microduplication syndromes. Ninety-five cases were validated by amniocentesis, and 57 were confirmed with true-positive results, comprising 18 trisomy 21, 4 trisomy 18, 1 trisomy 13, 17 sex chromosome aneuploidies, 1 other aneuploidy, and 16 microdeletion/microduplication syndromes. The positive predictive value of total chromosomal abnormalities was 60% (57/95). For trisomy 21, trisomy 18, trisomy 13, sex chromosome aneuploidies, other aneuploidies and microdeletion/microduplication syndromes, the sensitivity was all 100%, the specificity was 100, 99.986, 100, 99.888, 99.958, and 99.636%, and the positive predictive value was 100, 80, 100, 68, 25, and 38.10%, respectively. For all clinical characteristics, the abnormal maternal serum screening group was found to have the highest prevalence of chromosomal abnormalities (1.54%), and the ultrasound abnormality group presented the highest positive predictive value (73.33%). CONCLUSIONS: NIPT-Plus has great potential for the detection of aneuploidies and microdeletion/microduplication syndromes owing to its high sensitivity, safety, and specificity, which greatly reduces unnecessary invasive procedures and the risk of miscarriage and allows informed maternal choice.

[Retrospective analysis of cell-free fetal DNA prenatal testing of maternal peripheral blood].

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies, chromosomal microdeletions and microduplications using cell-free fetal DNA from peripheral blood samples of pregnant women. METHODS: A total of 15 237 pregnant women who had undergone NIPT testing at the Maternity and Child Health Care Hospital of Zaozhuang from February 2015 to December 2021 were enrolled in this study. For those with a high risk by NIPT, amniotic fluid samples were collected for G-banding chromosomal karyotyping analysis and chromosomal microarray analysis to verify the consistency of NIPT with results of prenatal diagnosis. All of the women were followed up by telephone for pregnancy outcomes. RESULTS: Among the 15 237 pregnant women, 266 (1.75%) were detected with a high risk for fetal chromosomal abnormality were detected. Among these, 79 (29.7%) were at a high risk for T21, 26 (9.77%) were at a high risk for T18, 9 (3.38%) were at a high risk for T13, 74 (27.82%) were at a high risk for sex chromosome aneuploidies, 12 (4.51%) were at a high risk for other autosomal aneuploidies, and 66 (24.81%) were at a high risk for chromosomal microdeletions or microduplications. 217 women had accepted invasive prenatal diagnosis and respectively 50, 13, 1, 25, 1 and 18 were confirmed with T21, T18, T13, sex chromosome aneuploidies, autosomal aneuploidies and microdeletions/microduplications, and the positive predictive values were 75.76%, 68.42%, 11.11%, 40.32%, 10% and 35.29%, respectively. For 13 042 women (85.59%), the outcome of pregnancy were successfully followed up. During the follow-up, one false negative case of T21 was discovered. No false positive cases for T13 and T18 were found. CONCLUSION: NIPT has a sound performance for screening T13, T18 and T21, and is also valuable for screening other autosomal aneuploidies, sex chromosome aneuploidies and chromosomal microdeletions/microduplications.

The common trisomy syndromes, their cardiac implications, and ethical considerations in care.

PURPOSE OF REVIEW: To review the incidence of congenital heart disease in the trisomies, highlight the history of cardiac surgery in trisomy 21 comparing it to the increase in cardiac surgery in trisomies 13 and 18, discuss ethical issues specific to trisomies 13 and 18, and suggest a pathway of shared decision-making in the management of congenital heart disease in trisomy 13 and 18, specifically congenital heart surgery. RECENT FINDINGS: Congenital heart disease is prevalent in the trisomies and the management of these defects, especially surgical intervention, has changed. In the late 20th century, survival after cardiac surgery in trisomy 21 vastly improved, significantly decreasing morbidity and mortality secondary to pulmonary hypertension. Similarly, procedures and surgeries have been performed with increasing frequency in trisomy 13 and 18 patients and concomitantly, survival in this patient population is increasing. Yet across the United States, the willingness to perform cardiac surgery in trisomy 13 and 18 is variable, and there is ethical controversy about the correct action to take. To address this concern, a shared decision-making approach with an informed parent(s) is advised. SUMMARY: As the care and management of congenital heart disease changed in trisomy 21, so too it has with trisomy 13 and 18. Physicians and parents should develop goal-directed treatment plans balancing the risk versus benefit and consider cardiac surgical repair if feasible and beneficial.

Prenatal diagnosis of mosaic trisomy 18 and maternal uniparental disomy 18 by amniocentesis in a pregnancy associated with cytogenetic discrepancy in various tissues and a favorable fetal outcome.

OBJECTIVE: We present prenatal diagnosis of mosaic trisomy 18 and maternal uniparental disomy (UPD) 18 in a pregnancy with a favorable fetal outcome. CASE REPORT: A 34-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age, and the result was 47,XY,+18 [4]/46,XY [25] in cultured amniocytes. Simultaneous array comparative genomic hybridization (aCGH) on uncultured amniocytes revealed 65% mosaicism for trisomy 18. Prenatal ultrasound was normal. She consulted our hospital and underwent repeat amniocentesis at 22 weeks of gestation, and the result revealed a karyotype of 47,XY,+18 [9]/46,XY [12] in cultured amniocytes. Simultaneous aCGH on uncultured amniocytes revealed arr 18p11.32q23 × 2.4 (log2 ratio = 0.3) consistent with 40% mosaicism for trisomy 18. Parental karyotypes were normal. Quantitative fluorescent polymerase chain reaction (QF-PCR) analysis on the DNA extracted from parental bloods and uncultured amniocytes confirmed maternal uniparental heterodisomy of chromosome 18. At 26 weeks of gestation, she underwent the third amniocentesis which revealed a karyotype of 47,XY,+18 [7]/46,XY [19] in cultured amniocytes. Simultaneous aCGH on uncultured amniocytes revealed arr 18p11.32q23 × 2.4 (log2 ratio = 0.27) consistent with 40% mosaicism for trisomy 18. Interphase fluorescence in situ hybridization (FISH) on uncultured amniocytes revealed 38% (38/100 cells) mosaicism for trisomy 18. The woman was advised to continue the pregnancy, and a 2620-g phenotypically normal male baby was delivered at 40 weeks of gestation. At birth, the karyotypes of cord blood, umbilical cord and placenta were 47,XY,+18 [14]/46,XY [26], 47,XY,+18 [9]/46,XY [31] and 47,XY,+18 (40/40 cells), respectively. When follow-up at age 2½ months, the neonate was phenotypically normal. The peripheral blood had a karyotype of 47,XY,+18 [28]/46,XY [12], and interphase FISH analysis on buccal mucosal cells detected 6.4% (7/93 cells) mosaicism for trisomy 18, compared with 0% (0/100 cells) in the normal control. When follow-up at age seven months, the neonate was normal in development, and the peripheral blood had a karyotype of 47,XY,+18 [18]/46,XY [22]. CONCLUSIONS: Mosaic trisomy 18 at amniocentesis can be associated with cytogenetic discrepancy in various tissues, UPD 18 and a favorable fetal outcome. Prenatal diagnosis of mosaic trisomy 18 should alert the possibility of UPD 18 and include UPD testing.

[Contribution of cytogenetic in the diagnosis of Edwards's syndrome: about 9 cases]. / Apport de la cytogénétique dans le diagnostic du syndrome d'Edwards : à propos de 9 cas.

INTRODUCTION: Trisomy 18 is a constitutional chromosomal disorder defined by the presence of a supernumerary chromosome 18. The diagnosis is suspected clinically and confirmed by cytogenetic analysis. Genetic counseling for patients' families is important. The objective of this study is to report our experience in Medical Genetics Department at the Mohammed VI University Hospital of Oujda in the diagnosis and genetic counseling of trisomy 18 through dysmorphological expertise and cytogenetic analysis. MATERIAL AND METHODS: We report a retrospective descriptive study over a period of four years (2018-2022) of nine patients with polymalformative syndrome suggestive of trisomy 18 who underwent cytogenetic analysis. RESULTS: The median age of patients at diagnosis was 2 days with a male predominance. The mean maternal age at birth of the patients in our series was 40 years. Consanguinity was found in only one patient. All patients had a typical phenotype of trisomy 18. The postnatal constitutional karyotype showed a homogeneous trisomy 18 in all patients. In our series, only one patient is still alive at the age of 7 months, the other 8 patients died with a median postnatal survival of 5 days. CONCLUSION: We underline through this study, the contribution of the medical geneticist in the clinic and cytogenetic diagnostic approach of rare chromosomal affections, in order to provide an adequate genetic counseling to the families.

Incidence and outcome of arrhythmias and electrical disease in patients with Trisomy 18.

Patients with Trisomy 18 have a high incidence of cardiac anomalies and are associated with early death. Because of early mortality, electrical system disease and arrhythmia has been difficult to delineate and the incidence remain unknown. We sought to describe the association and clinical outcomes of electrical system disease and cardiac tachy-arrhythmias in patients with Trisomy 18. This was a retrospective, single institutional study. All patients with Trisomy 18 were included in the study. Patient characteristics, congenital heart disease (CHD), conduction system and clinical tachy-arrhythmia data were collected on all patients. Outcomes including cardiac surgical interventions, electrical system interventions and death were collected until the time of study. Patients with tachy-arrhythmias/electrical system involvement were compared to those without to identify potential associated variables. A total of 54 patients with Trisomy 18 were included in analysis. The majority of patients was female and had associated CHD. AV nodal conduction system abnormalities with either first or second degree AV block were common (15%) as was QTc prolongation (37%). Tachy-arrhythmias were common with 22% of patients having at least one form of tachy-arrhythmia and associated with concomitant conduction system disease (p = 0.002). Tachy-arrhythmias were typically treatable with monitoring or medication with eventual resolution without need for procedural intervention. Although early death was common, there were no causes of death associated with tachy-arrhythmia or conduction system disease. In conclusion, patients with Trisomy 18 have a high incidence of conduction system abnormalities and burden of clinical tachy-arrhythmias. Although frequent, electrical system disease did not affect patient outcome or difficultly of care delivery.

Association between low fetal fraction in cell-free DNA screening and fetal chromosomal aberrations: A systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis of the available literature on low fetal fraction (LFF) in cell-free DNA (cfDNA) screening and the risk of fetal chromosomal aberrations. METHOD: We searched articles published between January 2010 and May 2021 in PubMed and EMBASE databases. Risk of bias was assessed using QUADAS-2. RESULTS: Twenty-seven studies met the inclusion criteria, comprising data of 243,700 singleton pregnancies. Compared to normal fetal fraction, LFF was associated with a higher risk of trisomy 13 (OR 5.99 [3.61-9.95], I 2 of heterogeneity = 0%, n = 22 studies), trisomy 18 (OR 4.46 [3.07-6.47], I 2  = 0%, n = 22 studies), monosomy X (OR 5.88 [2.34-14.78], I 2  = 18%, n = 10 studies), and triploidy (OR 36.39 [9.83-134.68], I 2  = 61%, n = 6 studies), but not trisomy 21 (OR 1.25 [0.76-2.03], I 2  = 36%, n = 23 studies). LFF was also associated with a higher risk of various other types of fetal chromosomal aberrations (OR 4.00 [1.78-9.00], I 2  = 2%, n = 11 studies). Meta-analysis of proportions showed that absolute rates of fetal chromosomal aberrations ranged between 1% and 2% in women with LFF. A limitation of this review is the potential risk of ascertainment bias because of differences in outcome assessment between pregnancies with LFF and those with normal fetal fraction. Heterogeneity in population characteristics or applied technologies across included studies may not have been fully addressed. CONCLUSION: An LFF test result in cfDNA screening is associated with an increased risk of fetal trisomy 13, trisomy 18, monosomy X, and triploidy, but not trisomy 21. Further research is needed to assess the association between LFF and other specific types of fetal chromosomal aberrations.

Otolaryngologic Manifestations of Trisomy 13 and Trisomy 18 in Pediatric Patients.

OBJECTIVE: The survival rate of patients with trisomy 13 and trisomy 18 has increased dramatically over the past two decades. We sought to comprehensively describe the otolaryngologic clinical characteristics and procedures required for these patients at our institution. METHODS: We performed algorithmic identification of patients with a diagnosis of trisomy 13 and trisomy 18 for whom the otolaryngology service provided inpatient or outpatient care at our institution between the dates of February 1997 and March 2021. RESULTS: Of the 47 patients studied, 18 patients had a diagnosis of trisomy 13, and 29 had a diagnosis of trisomy 18. Complete trisomy was present in 44% (8/18) of trisomy 13 patients and 55% (16/29) of trisomy 18 patients. 81% of patients were living at the time of the study. About 94% (44/47) of patients required consultation with another specialty in addition to Otolaryngology. Overall, the most common diagnoses among this cohort were gastroesophageal reflux disease (47%), dysphagia (40%), otitis media (38%), and obstructive sleep apnea (34%). Nearly three-quarters (74%) of patients studied required an otolaryngologic procedure. The most common surgical procedure was tonsillectomy and/or adenoidectomy. Patients with trisomy 18 were significantly more likely to have external auditory canal stenosis and obstructive sleep apnea whereas patients with trisomy 13 were more likely to have cleft lip and palate. CONCLUSIONS: Patients with a diagnosis of trisomy 13 or 18 often require multidisciplinary management and the range of required care spans the breadth of otolaryngology. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:1501-1506, 2023.

Prenatal diagnosis and molecular genetic analysis of recurrent trisomy 18 of maternal origin in two consecutive pregnancies.

OBJECTIVE: We present prenatal diagnosis and molecular genetic analysis of recurrent trisomy 18 of maternal origin in two consecutive pregnancies. CASE REPORT: A 37-year-old, gravida 3, para 1, woman was referred for genetic counseling because of cystic hygroma on ultrasound at 12 weeks of gestation, a previous pregnancy with a fetus with trisomy 18, and an abnormal first-trimester non-invasive prenatal testing (NIPT) result of Z score of 9.74 (normal: -3.0-3.0) in chromosome 18 suggesting trisomy 18 during this pregnancy. The fetus died at 14 weeks of gestation, and a malformed fetus was terminated at 15 weeks of gestation. Cytogenetic analysis of the placenta revealed a karyotype of 47,XY,+18. Quantitative fluorescent polymerase chain reaction (QF-PCR) assays on the DNA extracted from parental bloods and umbilical cord determined a maternal origin of trisomy 18. One year previously, the woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age of 36 years. Amniocentesis revealed a karyotype of 47,XX,+18. Prenatal ultrasound was unremarkable. The mother had a karyotype of 46,XX, and the father had a karyotype of 46,XY. QF-PCR assays on the DNA extracted from parental bloods and cultured amniocytes determined a maternal origin of trisomy 18. The pregnancy was subsequently terminated. CONCLUSION: NIPT is useful for rapid prenatal diagnosis of recurrent trisomy 18 under such a circumstance.