RESUMEN
Complex chromosomal rearrangements (CCRs) can result in spontaneous abortions, infertility, and malformations in newborns. In this study, we explored a familial CCR involving chromosome 6 by combining optical genomic mapping (OGM) and molecular cytogenetic methodologies. Within this family, the father and the paternal grandfather were both asymptomatic carriers of an identical balanced CCR, while the two offspring with an unbalanced paternal-origin CCR and two microdeletions presented with clinical manifestation. The first affected child, a 5-year-old boy, exhibited neurodevelopmental delay, while the second, a fetus, presented with hydrops fetalis. SNP-genotype analysis revealed a recombination event during gamete formation in the father that may have contributed to the deletion in his offspring. Meanwhile, the couple's haplotypes will facilitate the selection of normal gametes in the setting of assisted reproduction. Our study demonstrated the potential of OGM in identifying CCRs and its ability to work with current methodologies to refine precise breakpoints and construct accurate haplotypes for couples with a CCR.
Asunto(s)
Cromosomas Humanos Par 6 , Translocación Genética , Preescolar , Femenino , Humanos , Recién Nacido , Masculino , Embarazo , Aberraciones Cromosómicas , Cromosomas Humanos Par 6/genética , Análisis Citogenético , GenómicaRESUMEN
OBJECTIVE: To carry out genetic analysis for a fetus with confined placental mosaicism (CPM) for trisomy 2 (T2) in conjunct with fetal uniparental disomy (UPD). METHODS: Amniocentesis and chromosomal karyotyping was carried out for a pregnant woman with a high risk for chromosome 2 anomalies indicated by non-invasive prenatal testing (NIPT). Single nucleotide polymorphism array (SNP-array) and trio-whole exome sequencing (Trio-WES) were carried out. Ultrasonography was used to closely monitor the fetal growth. Multifocal sampling of the placenta was performed after delivery for copy number variation sequencing (CNV-seq). RESULTS: The fetus was found to have a normal chromosomal karyotype. SNP-array has revealed multiple regions with loss of heterozygosity (LOH) on chromosome 2. Trio-WES confirmed the presence of maternal UPD for chromosome 2. Ultrasonography has revealed intrauterine growth restriction and oligohydramnios. Intrauterine fetal demise had occurred at 23+4 weeks of gestation. Pathological examination had failed to find salient visceral abnormality. The placenta was proved to contain complete T2 by CNV-seq. CONCLUSION: T2 CPM can cause false positive result for NIPT and may be complicated with fetal UPD, leading to adverse obstetric outcomes such as intrauterine growth restriction, oligohydramnios and intrauterine fetal demise.
Asunto(s)
Oligohidramnios , Placenta , Femenino , Humanos , Embarazo , Amniocentesis , Cromosomas Humanos Par 2/genética , Variaciones en el Número de Copia de ADN , Muerte Fetal , Retardo del Crecimiento Fetal/genética , Feto , Mosaicismo , Trisomía/genética , Disomía Uniparental/genéticaRESUMEN
PURPOSE: To investigate the impact of COVID-19 on the treatment of children with congenital diaphragmatic hernia (CDH). METHODS: We retrospectively collected and compared the data of patients with CDH admitted between January 1, 2020 and December 31, 2021(study group) with the CDH patients admitted before the pandemic between January 1, 2018 and December 31, 2019 (control group). RESULTS: During the pandemic, 41 patients with CDH diagnosed prenatally were transferred to our hospital, and 40 underwent surgical repair. The number of patients treated in our hospital increased by 24.2% compared with the 33 patients before the pandemic. During the pandemic, the overall survival rate, postoperative survival rate and recurrence rate were 85.4%, 87.5% and 7.3%, respectively, and there were no significant differences compared with the control group (75.8%, 83.3% and 9.1%, respectively). The average length of hospital stay in patients admitted during the pandemic was longer than that in the control group (31 days vs. 16 days, P < 0.001), and the incidence of nosocomial infection was higher than that in the control group (19.5% vs. 3%, P = 0.037). CONCLUSIONS: CDH patients confirmed to be SARS-CoV-2 infection-free can receive routine treatment. Our data indicate that the implementation of protective measures during the COVID-19 pandemic, along with appropriate screening and case evaluation, do not have a negative impact on the prognosis of children.
Asunto(s)
COVID-19 , Hernias Diafragmáticas Congénitas , COVID-19/epidemiología , Niño , Hernias Diafragmáticas Congénitas/epidemiología , Hernias Diafragmáticas Congénitas/cirugía , Humanos , Pandemias , Estudios Retrospectivos , SARS-CoV-2RESUMEN
Electrohysterogram (EHG) is a promising method for noninvasive monitoring of uterine electrical activity. The main purpose of this study was to characterize the multichannel EHG signals to distinguish between term delivery and preterm birth, as well as deliveries within and beyond 24 h. A total of 219 pregnant women were grouped in two ways: (1) term delivery (TD), threatened preterm labor (TPL) with the outcome of preterm birth (TPL_PB), and TPL with the outcome of term delivery (TPL_TD); (2) EHG recording time to delivery (TTD) ≤ 24 h and TTD > 24 h. Three bipolar EHG signals were analyzed for the 30 min recording. Six EHG features between multiple channels, including multivariate sample entropy, mutual information, correlation coefficient, coherence, direct partial Granger causality, and direct transfer entropy, were extracted to characterize the coupling and information flow between channels. Significant differences were found for these six features between TPL and TD, and between TTD ≤ 24 h and TTD > 24 h. No significant difference was found between TPL_PB and TPL_TD. The results indicated that EHG signals of TD were more regular and synchronized than TPL, and stronger coupling between multichannel EHG signals was exhibited as delivery approaches. In addition, EHG signals propagate downward for the majority of pregnant women regardless of different labors. In conclusion, the coupling and propagation features extracted from multichannel EHG signals could be used to differentiate term delivery and preterm birth and may predict delivery within and beyond 24 h.
Asunto(s)
Trabajo de Parto , Trabajo de Parto Prematuro , Nacimiento Prematuro , Electromiografía/métodos , Femenino , Humanos , Recién Nacido , Trabajo de Parto Prematuro/diagnóstico , Embarazo , Contracción UterinaRESUMEN
OBJECTIVE: To estimate the association of unicornuate uterus (UU) with adverse obstetric outcomes. METHODS: Using data from 26 737 singleton childbirths from a tertiary hospital from 1999 to 2019, we identified 44 births from women with a UU. A total of 367 births from women with a normal uterus were randomly selected as controls. The outcome measures were preterm birth (PTB), breech presentation, and cesarean delivery. The subdivisions of PTB and indications for cesarean delivery were described. RESULTS: The presence of UU was associated with an increased risk of PTB (adjusted risk ratio [aRR], 2.3; 95% confidence interval [CI], 1.1-4.9), breech presentation (aRR, 6.2; 95% CI, 2.9-13.2), and cesarean delivery (aRR, 2.1; 95% CI, 1.8-2.7). For women with a UU, most PTBs (7/9) were moderate to late PTBs, and approximately half of the PTBs (4/9) were iatrogenic due to preeclampsia (PE). Breech presentation, PE, and prior surgery for rudimentary horn resection were UU-related indications for cesarean delivery. CONCLUSIONS: Women with a UU have a higher risk of PTB, breech presentation, and cesarean delivery. Understanding of the subdivisions of PTBs and indications for cesarean delivery might help clinicians when counseling women with pregnancy complicated by a UU.
Asunto(s)
Presentación de Nalgas , Nacimiento Prematuro , Presentación de Nalgas/epidemiología , Parto Obstétrico , Femenino , Humanos , Recién Nacido , Embarazo , Resultado del Embarazo/epidemiología , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Estudios Retrospectivos , ÚteroRESUMEN
Preeclampsia (PE) is one of the most significant pregnancy-related hypertensive disorders. Currently, there are no useful markers to predict the onset of the condition in pregnant women. To provide further insights into the pathogenesis of PE and identify biomarkers of the condition, we used isobaric tags for relative and absolute quantitation (iTRAQ) proteomics coupled with 2-D LC-MS/MS, to analyze urinary protein profiles from 7 PE patients and 7 normotensive pregnant women. A total of 294 proteins were abnormally expressed in PE patients. Of these, 233 were significantly down-regulated and 61 proteins were significantly up-regulated. Bioinformatics analysis using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database, found that the most differentially expressed proteins (DEPs) were involved in coagulation and complement pathways, the renin-angiotensin system and cell adhesion molecules (CAMs) pathways. We further validated three of the DEPs, including serotransferrin (TF) and complement factor B (CFB) by immunoblottingand serum paraoxonase/arylesterase 1 (PON1) by ELISA using 14 pairs of urine samples from PE patients and normal pregnant women. Taken together, our results provide the basis for further understanding the pathogenesis of PE and identifying predictive biomarkers.
Asunto(s)
Preeclampsia/orina , Proteínas/metabolismo , Proteómica/métodos , Femenino , Humanos , Embarazo , Proteoma/metabolismo , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: High levels of circulating cell-free DNA (cfDNA) have been reported in patients with inflammatory conditions. The aim of the study was to investigate the levels of cfDNA in patients with systemic lupus erythematosus (SLE). MATERIALS AND METHODS: Comparative groups comprised 22 nonpregnant and 36 pregnant women with SLE (test groups) and 60 nonpregnant and 199 pregnant women with no history of SLE (control groups). The levels of cfDNA in plasma were quantitated by a fluorometric dsDNA assay. RESULTS: Compared to controls, the median levels of cfDNA were significantly higher in nonpregnant SLE patients (7.38 ng/mL vs 4.6 ng/mL, P = 0.033) and in pregnant SLE patients (7.65 ng/mL vs 5.25 ng/mL, P = 0.003). Based on SLE disease activity index (SLEDAI) scores, the median cfDNA levels were significantly higher in patients with active disease (4 < SLEDAI < 15) compared with patients with inactive disease (SLEDAI < 4) (13.58 ng/mL vs 6.72 ng/mL, P = 0.01). While there was a trend of increased cfDNA levels with higher SLEDAI scores (R2 = 0.3, P < 0.001), we found no association of increased cfDNA levels with nephritis, skin manifestations, multiorgan inflammations or with other inflammatory markers such as decreased C3 and C4 levels or increased anti-ds DNA antibodies. CONCLUSIONS: Our results suggest that in addition to classical SLE serological markers, measurement of circulating plasma cfDNA levels has potential as a useful biomarker for assessing SLE disease activity in patients and monitoring treatment.
Asunto(s)
Ácidos Nucleicos Libres de Células/metabolismo , Lupus Eritematoso Sistémico/diagnóstico , Complicaciones del Embarazo/diagnóstico , Adulto , Biomarcadores/metabolismo , Estudios de Casos y Controles , Femenino , Humanos , Persona de Mediana Edad , Embarazo , Diagnóstico Prenatal/métodosRESUMEN
OBJECTIVE: The aim of the study was to determine the contribution and significance of maternal copy number variations (CNVs) to false-positive noninvasive prenatal testing (NIPT) trisomy results. METHODS: A total of 112 021 patients were referred for NIPT. Fetal aneuploidy testing was performed using low coverage massively parallel sequencing, and results reported as chromosome Z-scores. Copy number variation sequencing (CNV-Seq) was used to detect maternal DNA CNVs. RESULTS: Confirmatory amniocentesis and karyotyping of 563 of 781 patients (72%) receiving a positive trisomy result revealed 489 true and 74 false positives. In 6 of these 74 patients (8.1%), CNV-Seq revealed non-pathogenic maternal duplications (1.76-10.90 megabases) on the chromosome associated with the fetal trisomy. There was a strong correlation of higher Z-scores with increasing size of the maternal CNVs (R2 = 0.94). When the contribution of the maternal CNV-Seq reads to chromosome Z-scores were removed, all original Z-scores shifted to the normal range. CONCLUSIONS: Maternal CNVs can potentially contribute to a small but significant number of false-positive fetal trisomies detected by NIPT. To avoid unnecessary invasive procedures and better manage patients, we recommend that confirmatory maternal DNA sequencing is performed when the NIPT methodology used indicates a high risk of a maternal CNV. © 2017 John Wiley & Sons, Ltd.
Asunto(s)
Variaciones en el Número de Copia de ADN/genética , Enfermedades Fetales/diagnóstico , Diagnóstico Prenatal/métodos , Trisomía/diagnóstico , Adulto , Errores Diagnósticos , Reacciones Falso Positivas , Femenino , Enfermedades Fetales/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Cariotipificación/métodos , Madres , Embarazo , Análisis de Secuencia de ADN/métodos , Trisomía/genéticaRESUMEN
OBJECTIVE: The study aimed to determine whether cell-free fetal DNA (cffDNA) present in amniotic fluid supernatant can be used as a surrogate for amniocyte-based diagnosis of fetal chromosomal abnormalities. METHOD: Amniocentesis was performed on 28 high-risk pregnancies. Amniocytes and the cffDNA fraction were prepared from the amniotic fluid samples. Chromosomal analysis of amniocytes was performed by either karyotyping or single nucleotide polymorphism (SNP) arrays. The corresponding cffDNA samples were blindly analyzed by copy number variation (CNV) sequencing in an independent laboratory. RESULTS: In the 28 matching amniocyte and cffDNA samples, there was a high diagnostic concordance for detection of euploidy, aneuploidy and CNVs. From ten samples referred for karyotyping, two aneuploidies (20%) were identified. From 18 samples referred for SNP array analysis, three pathogenic CNVs (16.7%) were identified. CNV sequencing of the 28 cffDNA samples also detected the two aneuploidies and the three pathogenic CNVs, giving an overall concordance rate of 100% for detection of pathogenic chromosome abnormalities. Compared with SNP array analysis, CNV sequencing returned a higher yield of benign or variants of unknown significance. CONCLUSION: Copy number variation sequencing of cffDNA represents an alternative approach to conventional prenatal diagnostic methods for reliable and accurate detection of clinically significant chromosomal abnormalities. © 2016 John Wiley & Sons, Ltd.
Asunto(s)
Líquido Amniótico/metabolismo , Trastornos de los Cromosomas/diagnóstico , Variaciones en el Número de Copia de ADN/genética , ADN/genética , Amniocentesis , Amnios/citología , Aneuploidia , Aberraciones Cromosómicas , Trastornos de los Cromosomas/diagnóstico por imagen , Trastornos de los Cromosomas/genética , Síndrome de Down/diagnóstico , Femenino , Humanos , Cariotipificación , Polimorfismo de Nucleótido Simple , Embarazo , Embarazo de Alto Riesgo , Diagnóstico Prenatal , Análisis de Secuencia de ADN , Síndrome de Turner/diagnósticoRESUMEN
OBJECTIVE: To study the value of second trimester maternal serum soluble Fms-like tyrosine kinase 1 (sFlt-1), placenta grouth factor (PlGF) and their ratio in the prediction of preeclampsia. METHODS: In this nested case-control study, we collected second trimester maternal serum samples at 15-20 weeks and 24-28 weeks of gestation from those who developed gestational hypertensive disorders. Maternal serum sFlt-1 and PlGF were measured by electrochemiluminescence immunoassay on an automated platform. The value of sFlt-1, PlGF and their ratio were compared between gestational hypertensive group and the control group. RESULTS: Totally 41 patients with preeclampsia, 44 patients with gestational hypertension and 88 women with normal pregnancy outcomes were included in this study. There was no difference of age, gravidity, parity and preconception body mass index (BMI) between these three groups (P > 0.05) .Gestational week at delivery and neonatal birth weight were different between preeclampsia group and the control group (P < 0.01). The mean value of sFlt-1, PlGF and sFlt-1/PlGF ratio was (1 658 ± 488) µg/L, (141 ± 80) µg/L and 17 ± 9 in preeclampsia group, (1 945 ± 575) µg/L, (143 ± 52) µg/L and 15 ± 6 in gestational hypertension group, and (2 084 ± 741) µg/L, (65 ± 58) µg/L and 16 ± 9 in the control group at 15-20 weeks of gestation. There was no difference of sFlt-1, PlGF value and their ratio among the three groups at 15-20 weeks of gestation (P > 0.05) . The median value of sFlt-1, PlGF and sFlt-1/PlGF ratio were 8 525 µg/L, 35 µg/L and 398.0 in preeclampsia group, 905 µg/L, 336 µg/L and 2.7 in gestational hypertension group, 1 028 µg/L, 477 µg/L and 2.3 in the control group at 24-28 weeks of gestation. The value of sFlt-1, PlGF and their ratio was significantly different between preeclampsia group and the control group at 24-28 weeks of gestation (P < 0.01) . PlGF value was different between gestational hypertension group and the control group (P < 0.01) . The sensitivity and specificity of serum sFlt-1, PlGF and sFlt-1/PlGF ratio at 24-28 weeks of gestation to predict preeclampsia were 93% and 99% for sFlt-1 (cut off value 2 500 µg/L), 92% and 77% for PlGF (cut off value 270 µg/L) , 89% and 99% for sFlt-1/PlGF ratio (cut off value 11) . CONCLUSION: The value of sFlt-1, PlGF and their ratio at 24-28 weeks of gestation was significantly changed before clinical onset of preeclampsia.Use these serum indicators to predict preeclampsia will hopefully provide objective evidence for the management of patients who will develop preeclampsia later.
Asunto(s)
Preeclampsia/sangre , Preeclampsia/diagnóstico , Proteínas Gestacionales/sangre , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre , Adolescente , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Humanos , Hipertensión Inducida en el Embarazo/sangre , Hipertensión Inducida en el Embarazo/diagnóstico , Persona de Mediana Edad , Factor de Crecimiento Placentario , Valor Predictivo de las Pruebas , Embarazo , Resultado del Embarazo , Segundo Trimestre del Embarazo , Curva ROC , Factores de Riesgo , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND: High brain-derived neurotrophic factor (BDNF) concentrations have been found to be associated with a decreased risk of Alzheimer's disease (AD) in observational studies, but the causality for this association remains unclear. Therefore, we aimed to examine the association between genetically determined plasma BDNF levels and AD using a two-sample Mendelian randomization (MR) method. METHODS: Twenty single-nucleotide polymorphisms associated with plasma BDNF concentrations were identified as genetic instruments based on a genome-wide association study with 3301 European individuals. Summary-level data on AD were obtained from the International Genomics of Alzheimer's Project, involving 21,982 AD cases and 41,944 controls of European ancestry. To evaluate the relationship between plasma BDNF concentrations and AD, we employed the inverse-variance weighted method along with a series of sensitivity analyses. RESULTS: The inverse-variance weighted MR analysis showed that genetically determined BDNF concentrations were associated with a decreased risk of AD (odds ratio per SD increase, 0.91; 95% confidence interval, 0.86-0.96; p =0.001). The association between plasma BDNF concentrations and AD was further confirmed through sensitivity analyses using different MR methods, and MR-Egger regression suggested no directional pleiotropy for this association. CONCLUSION: Genetically determined BDNF levels were associated with a decreased risk of AD, suggesting that BDNF was implicated in the development of AD and might be a promising target for the prevention of AD.
Asunto(s)
Enfermedad de Alzheimer , Factor Neurotrófico Derivado del Encéfalo , Femenino , Humanos , Masculino , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/epidemiología , Factor Neurotrófico Derivado del Encéfalo/sangre , Factor Neurotrófico Derivado del Encéfalo/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido SimpleRESUMEN
Fetal growth restriction (FGR), a leading cause of perinatal morbidity and mortality, is caused by fetal, maternal, and placental factors. Uniparental disomy (UPD) is a rare condition that leads to imprinting effects, low-level mosaic aneuploidies and homozygosity for pathogenic variants. In the present study, UPD events were detected in 5 women with FGR by trio exome sequencing (trio-WES) of a cohort of 150 FGR cases. Furthermore, noninvasive prenatal testing results of the 5 patients revealed a high risk of rare autosomal trisomy. Trio-WES showed no copy-number variations (CNVs) or nondisease-causing mutations associated with FGR. Among the 5 women with FGR, two showed gene imprinting, and two exhibited confined placental mosaicism (CPM) by copy number variant sequencing (CNV-seq). The present study showed that in FGR patients with UPD, the detection of imprinted genes and CPM could enhance the genetic diagnosis of FGR.
Asunto(s)
Placenta , Disomía Uniparental , Humanos , Embarazo , Femenino , Disomía Uniparental/genética , Secuenciación del Exoma , Retardo del Crecimiento Fetal/genética , Trisomía , MosaicismoRESUMEN
BACKGROUND: Infantile myofibromatosis (IM) is a rare disorder characterized by the formation of nodules in the skin, muscle, bone, and, more rarely, visceral organs. Very few cases are detected prenatally, and the final diagnosis cannot be made until pathology is completed after birth. Here, we present a case of disseminated form IM (DFIM) with a diagnosis established on prenatal genetic grounds. CASE PRESENTATION: A woman at 23 weeks of gestation was referred for ultrasound evaluation of fetal kidney abnormality. Generalized masses in the skin and muscle of the fetus developed at 28 weeks. Prenatal genetic testing identified the pathogenic heterozygous variant c.1681C > T (p.R561C) of the PDGFRB gene inherited from the asymptomatic father. Intrauterine demise occurred at 31 weeks. Autopsy confirmed DFIM with involvement of the heart and kidney. All cases of prenatally detected IM were reviewed, revealing an association of high mortality with DFIM. CONCLUSIONS: Prenatal IM diagnosis is difficult. Initial detection is always based on ultrasound. DFIM has high mortality. The germline p.R561C mutation in PDGFRB may cause fetal demise due to severe visceral involvement of IM. Prenatal genetic testing provides a diagnosis before pathological results are available, leading to better counseling and management of pregnancy with a fetus with IM.
Asunto(s)
Miofibromatosis , Embarazo , Femenino , Humanos , Miofibromatosis/diagnóstico por imagen , Miofibromatosis/genética , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/genética , Mutación de Línea Germinal , Diagnóstico PrenatalRESUMEN
OBJECTIVE: Absence of homozygosity (AOH) is a genetic characteristic known to cause human diseases mainly through autosomal recessive or imprinting mechanisms. The importance and necessity of accurate AOH detection has become more clinically significant in recent years. However, it remains a challenging task for sequencing-based methods thus far. METHODS: In this study, we developed and optimized a new bioinformatic algorithm based on the assessment of minimum sequencing coverage, optimal bin size, the Z-score threshold of four types of allele count and the frequency for accurate genotyping using 28 AOH negative samples, and redefined the AOH detection cutoff value. We showed the performance of chromosome analysis by five-fold coverage whole genome sequencing (CMA-seq) for AOH identification in 27 typical prenatal/postnatal AOH positive samples, which were previously confirmed by chromosomal microarray analysis with single nucleotide polymorphism array (CMA/SNP array). RESULTS: The blinded study indicated that for all three forms of AOH, including whole genomic AOH, single chromosomal AOH and segmental AOH, and all kinds of sample types, including chorionic villus sampling, amniotic fluid, cord blood, peripheral blood and abortive tissue, CMA-seq showed equivalent detection power to that of routine CMA/SNP arrays (750K). The subtle difference between the two methods is that CMA-seq is prone to detect small inconsecutive AOHs, while CMA/SNP array reports it as a whole. CONCLUSION: Based on our newly developed bioinformatic algorithm, it is feasible to detect clinically significant AOH using CMA-seq in prenatal diagnosis.
RESUMEN
Objective: Mosaicism is a common biological phenomenon in organisms and has been reported in many types of chromosome abnormalities, including the absence of heterozygosity (AOH). Due to the detection limitations of the sequencing approach, mosaic AOH events are rarely assessed in clinical cases. Herein, we report the performance of mosaic AOH identification using a low-pass (5~8-fold) WGS method (termed 'CMA-seq', an abbreviation for 'Chromosome Analysis by Sequencing') in fetal genetic diagnosis. Methods: Thirty AOH-negative, eleven constitutional AOH, and three mosaic AOH samples were collected as training data sets to develop the algorithm and evaluate the suitable thresholds for distinguishing mosaic AOH. Twenty-four new chromosomal aberrant cases, along with sixteen constitutional AOH samples, which were previously ascertained via the SNP-array-based method, were used as a validation data set to measure the performance in terms of sensitivity and specificity of this algorithm. Results: A new statistic, 'D-value', was implemented to identify and distinguish constitutional and mosaic AOH events. The reporting thresholds for constitutional and mosaic AOH were also established. In the validation set consisting of 24 new cases, seven constitutional AOH cases and 1 mosaic AOH case were successfully identified, indicating that the results were consistent with those of the SNP-array-based method. The results of all sixteen constitutional AOH validation samples also met the threshold requirements. Conclusions: In this study, we developed a new bioinformatic algorithm to accurately distinguish mosaic AOH from constitutional AOH by low-pass WGS. However, due to the small sample size of the training data set, the algorithm proposed in this manuscript still needs further refinements.
RESUMEN
BACKGROUND: As an essential indicator of labour and delivery, uterine contraction (UC) can be detected by manual palpation, external tocodynamometry and internal uterine pressure catheter. However, these methods are not applicable for long-term monitoring. OBJECTIVE: This paper aims to recognize UCs with electrohysterogram (EHG) and find the best electrode combination with fewer electrodes. METHODS: 112 EHG recordings were collected by our bespoke device in our study. Thirteen features were extracted from EHG segments of UC and non-UC. Four classifiers of the decision tree, support vector machine (SVM), artificial neural network, and convolutional neural network were established to identify UCs. The optimal classifier among them was determined by comparing their classification results. The optimal classifier was applied to evaluate all the possible electrode combinations with one to eight electrodes. RESULTS: The results showed that SVM achieved the best classification capability. With SVM, the combination of electrodes on the right part of the uterine fundus and around the uterine body's median axis achieved the overall best performance. CONCLUSIONS: The optimal electrode combination with fewer electrodes was confirmed to improve the clinical application for long-term monitoring of UCs.
Asunto(s)
Contracción Uterina , Monitoreo Uterino , Adolescente , Electrodos , Electromiografía/métodos , Femenino , Humanos , Embarazo , Monitoreo Uterino/métodos , ÚteroRESUMEN
Objective: Previous studies have shown that ex utero intrapartum therapy (EXIT) is safe and feasible for newborns with congenital diaphragmatic hernia (CDH). This study reports our experience with EXIT in fetuses with CDH in an attempt to explore the efficacy of EXIT on the survival rate of this population. Methods: A retrospective analysis of the clinical data of 116 children with CDH was conducted. The children were assigned to EXIT and non-EXIT groups. Propensity score matching (PSM) toward clinical data was performed, and the clinical characteristics and outcomes were compared. Taking survival at discharge as the main outcome, logistic regression analysis was carried out to explore the efficacy of EXIT on survival. Results: During the study period, 30 of 116 children received EXIT. After PSM, the survival rates of the EXIT group and the non-EXIT group were 82.76% (24/29) and 48.28% (14/29), respectively (p=0.006). EXIT (OR=0.083, 95% CI=0.013to 0.525, p=0.008), liver herniation (OR=16.955, 95% CI=2.342 to 122.767, p=0.005), and gestational age at diagnosis (OR=0.662, 95% CI=0.497 to 0.881, p=0.005) were independent mortality-related risk factors of all children with CDH. Ninety-nine of 116 children underwent surgery. After PSM, the postoperative survival rates of the EXIT group and non-EXIT group were 84.6% (22/26) and 76.9% (20/26), respectively (p=0.754). Liver herniation (OR=10.451, 95% CI=1.641 to 66.544, p=0.013) and gestational age at diagnosis (OR=0.736, 95% CI=0.577 to 0.938, p=0.013) were independent mortality-related risk factors of children after surgery. Conclusion: EXIT can be performed safely for selected prenatally diagnosed CDH neonates with potentially better survival and does not cause more maternal complications compared with traditional cesarean section.
RESUMEN
OBJECTIVE: To investigate the factors associated with cell-free DNA test failure, and the optimal subsequent management of these pregnancies. METHODS: This was a retrospective study of 27,363 singleton pregnancies undergoing cell-free DNA testing. Women with cell-free DNA test failure were divided into a high-risk group and a low-risk group according to their indications. The subsequent management and pregnancy outcomes of these women were followed up. RESULTS: The rate of cell-free DNA test failure at the first sampling was 1.49%, and 78.4% of failures were due to a low fetal fraction. Of the 66 women who refused any subsequent management, an adverse pregnancy outcome was seen in 5 cases, all belonging to the high-risk group. Of the 13 low-risk women who chose second-trimester maternal serum screening, all obtained a low-risk maternal serum screening result and an unaffected pregnancy outcome. A redraw was chosen by 171 women, which yielded a result in 75.4% and their pregnancy outcomes were unaffected; 42 women had an uninformative result again and received an amniocentesis. As 158 women had an amniocentesis after the first sampling, this procedure was offered in 200 cases altogether. Abnormal genetic testing results were shown in six (3%, 6/200) cases, all in the high-risk group. CONCLUSIONS: High-risk pregnant women with cell-free DNA test failure are at increased risk of adverse pregnancy outcomes. A second sampling for cell-free DNA test or maternal serum screening might be suggested to low-risk women. Invasive prenatal diagnosis should be offered to the high-risk patients, especially those with a second cell-free DNA test failure.
Asunto(s)
Ácidos Nucleicos Libres de Células , Trisomía , Femenino , Humanos , Embarazo , Resultado del Embarazo , Mujeres Embarazadas , Diagnóstico Prenatal , Estudios Retrospectivos , Síndrome de la Trisomía 18RESUMEN
Uterine contraction (UC) is an essential clinical indicator in the progress of labour and delivery. Electrohysterogram (EHG) signals recorded on the abdomen of pregnant women reflect the uterine electrical activity. This study proposes a novel algorithm for automatic recognition of UCs with EHG signals to improve the accuracy of detecting UCs. EHG signals by electrodes, the tension of the abdominal wall by tocodynamometry (TOCO) and maternal perception were recorded simultaneously in 54 pregnant women. The zero-crossing rate (ZCR) of the EHG signal and its power were calculated to modulate the raw EHG signal and highlight the EHG bursts. Then the envelope was extracted from the modulated EHG for UC recognition. Besides, UC was also detected by the conventional TOCO signal. Taking maternal perception as a reference, the UCs recognized by EHG and TOCO were evaluated with the sensitivity, positive predictive value (PPV), and UC parameters. The results show that the sensitivity and PPV are 87.8% and 93.18% for EHG, and 84.04% and 90.89% for TOCO. EHG detected a larger number of UCs than TOCO, which is closer to maternal perception. The duration and frequency of UC obtained from EHG and TOCO were not significantly different (p > 0.05). In conclusion, the proposed UC recognition algorithm has high accuracy and simple calculation which could be used for real-time analysis of EHG signals and long-term monitoring of UCs.
Asunto(s)
Electromiografía/métodos , Contracción Uterina , Monitoreo Uterino/métodos , Pared Abdominal , Algoritmos , Automatización , Femenino , Humanos , EmbarazoRESUMEN
Next-generation sequencing (NGS) is emerging as a new method for the detection of clinically significant copy number variants (CNVs). In this study, we developed and validated rapid CNV-sequencing (rCNV-seq) for clinical application in prenatal diagnosis. Low-pass whole-genome sequencing was performed on PCR libraries prepared from amniocyte genomic DNA. From 10-40 ng of input DNA, PCR-free libraries consistently produced sequencing data with high unique read mapping ratios, low read redundancy, low coefficient of variation for all chromosomes and high genomic coverage. In validation studies, reliable and accurate CNV detection using PCR-free-based rCNV-seq was demonstrated for a range of common trisomies and sex chromosome aneuploidies as well as microdeletion and duplication syndromes. In reproducibility studies, CNV copy number and genomic intervals closely matched those defined by chromosome microarray analysis. Clinical testing of genomic DNA samples from 217 women referred for prenatal diagnosis identified eight samples (3.7%) with known chromosome disorders. We conclude that PCR-free-based rCNV-seq is a sensitive, specific, reproducible and efficient method that can be used in any NGS-based diagnostic laboratory for detection of clinically significant CNVs.