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Human Cell Sep 2023Trisomy 13 (Patau syndrome) is a kind of congenital chromosomal abnormality disease. Trisomy 13 has high occurrence in fetuses or infants from the old aged pregnant...
Trisomy 13 (Patau syndrome) is a kind of congenital chromosomal abnormality disease. Trisomy 13 has high occurrence in fetuses or infants from the old aged pregnant women. Screening out the fetus with trisomy 13 early and avoiding the infant with trisomy 13 to be born is the main strategy in the care of delivery women with the fetus with trisomy 13. The current screening method is not perfect and has room to strengthen. In this study, we aimed to establish a method to strengthen the current screening methods, which would be cheap, fast and convenient. Technically, we obtained the commercially available genomic DNA extracted from the amniotic fluid puncture of the pregnant woman with the trisomy 13 fetus, 2 genomic DNA extracted from 2 healthy male (one adult and one teenager) and 1 genomic DNA extracted from 1 healthy adult female as the qPCR template DNAs and the commercially available Sybr green qPCR mater mix as the qPCR reaction liquid; we also designed and synthesized 5 pairs of qPCR primers, respectively, corresponding to IL-10 gene on 1# chromosome, STAT1 gene on 2# chromosome, CXCR3 gene on X chromosome, TSPY1 gene on Y chromosome and LINC00458 gene on 13# chromosome. We then performed Sybr green qPCR measurement. Further, we used the qPCR data to perform the mathematical calculation and finally formed a new algorithm. Using this new algorithm, we easily distinguished the trisomy 13 sample out of the normal samples. The method established this study could strengthen and complement the current methods. In conclusion, our study initiated a pilot study to screen the trisomy 13 and prospected some new directions for efforts.
Topics: Adult; Female; Pregnancy; Male; Humans; Middle Aged; Aged; Adolescent; Amniotic Fluid; Prenatal Diagnosis; Trisomy 13 Syndrome; Trisomy; Down Syndrome; Amniocentesis; Pilot Projects; Chromosome Disorders; DNA; Cell Cycle Proteins
PubMed: 37318693
DOI: 10.1007/s13577-023-00930-6 -
Ultrasound in Obstetrics & Gynecology :... Oct 2023To evaluate the impact of detailed late first-trimester ultrasound (LFTU) on the positive predictive value (PPV) of a high-risk non-invasive prenatal test (NIPT) result...
OBJECTIVE
To evaluate the impact of detailed late first-trimester ultrasound (LFTU) on the positive predictive value (PPV) of a high-risk non-invasive prenatal test (NIPT) result for various chromosomal abnormalities.
METHODS
This was a retrospective study of all cases undergoing invasive prenatal testing from three tertiary providers of obstetric ultrasound over 4 years, each using NIPT as a first-line screening test. Data were collected from pre-NIPT ultrasound, NIPT, LFTU, placental serology and later ultrasound examinations. Prenatal testing for chromosomal abnormalities was performed by microarray, initially using array comparative genomic hybridization and then single nucleotide polymorphism (SNP) array for the last 2 years. Uniparental disomy testing was performed by SNP array during all 4 years. The majority of NIPT tests were analyzed using the Illumina platform, initially confined to the assessment of the common autosomal trisomies, sex chromosome aneuploidies and rare autosomal trisomies (RAT), then extending to genome-wide analysis for the last 2 years.
RESULTS
Amniocentesis or chorionic villus sampling (CVS) was performed on 2657 patients, 1352 (51%) of whom had undergone prior NIPT, with 612 (45%) of these returning a high-risk result and meeting the inclusion criteria for the study. LFTU findings significantly affected the PPV of the NIPT result for trisomies 13 (T13), 18 (T18) and 21 (T21), monosomy X (MX) and RAT but not for the other sex chromosomal abnormalities or segmental imbalances (> 7 Mb). Abnormal LFTU increased the PPV close to 100% for T13, T18, T21, MX and RAT. The magnitude of the change in PPV was highest for the most severe chromosomal abnormalities. When LFTU was normal, the incidence of confined placental mosaicism (CPM) was highest in those with a high-risk NIPT result for T13, followed by T18 and T21. After normal LFTU, the PPV for T21, T18, T13 and MX decreased to 68%, 57%, 5% and 25%, respectively.
CONCLUSIONS
LFTU after a high-risk NIPT result can alter the PPV for many chromosomal abnormalities, assisting counseling regarding invasive prenatal testing and pregnancy management. The high PPVs of NIPT for T21 and T18 are not sufficiently modified by normal LFTU findings to alter management. These at-risk patients should be offered CVS for earlier diagnosis, particularly given the low rate of CPM associated with these aneuploidies. Patients with a high-risk NIPT result for T13 and normal LFTU findings often wait for amniocentesis or avoid invasive testing altogether given the low PPV and higher rate of CPM in this context. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Pregnancy; Humans; Female; Pregnancy Trimester, First; Trisomy; Retrospective Studies; Comparative Genomic Hybridization; Placenta; Prenatal Diagnosis; Aneuploidy; Sex Chromosome Aberrations; Trisomy 13 Syndrome
PubMed: 37247395
DOI: 10.1002/uog.26272 -
Pediatrics and Neonatology Sep 2023
Topics: Humans; Infant; Diazoxide; Trichlormethiazide; Trisomy 13 Syndrome; Body Water; Treatment Outcome
PubMed: 37225554
DOI: 10.1016/j.pedneo.2023.04.003 -
American Journal of Obstetrics and... Oct 2023Analysis of cell-free DNA from maternal blood provides effective screening for trisomy 21 in singleton pregnancies. Data on cell-free DNA screening in twin gestations...
BACKGROUND
Analysis of cell-free DNA from maternal blood provides effective screening for trisomy 21 in singleton pregnancies. Data on cell-free DNA screening in twin gestations are promising although limited. In previous twin studies, cell-free DNA screening was primarily performed in the second trimester and many studies did not report chorionicity.
OBJECTIVE
This study aimed to evaluate the screening performance of cell-free DNA for trisomy 21 in twin pregnancies in a large, diverse cohort. A secondary aim was to evaluate screening performance for trisomy 18 and trisomy 13.
STUDY DESIGN
This was a retrospective cohort study of twin pregnancies from 17 centers for which cell-free DNA screening was performed from December 2011 to February 2020 by one laboratory using massively parallel sequencing technology. Medical record review was conducted for all newborns and data on the birth outcome, the presence of any congenital abnormalities, phenotypic appearance at birth, and any chromosomal testing that was undertaken in the antenatal or postnatal period were extracted. Cases with a possible fetal chromosomal abnormality with no genetic test results were reviewed by a committee of maternal-fetal medicine geneticists. Cases with a vanishing twin and inadequate follow-up information were excluded. A minimum of 35 confirmed cases of trisomy 21 was required to capture a sensitivity of at least 90% with a prevalence of at least 1.9% with 80% power. Test characteristics were calculated for each outcome.
RESULTS
A total of 1764 samples were sent for twin cell-free DNA screening. Of those, 78 cases with a vanishing twin and 239 cases with inadequate follow-up were excluded, leaving a total of 1447 cases for inclusion in the analysis. The median maternal age was 35 years and the median gestational age at cell-free DNA testing was 12.3 weeks. In total, 81% of the twins were dichorionic. The median fetal fraction was 12.4%. Trisomy 21 was detected in 41 of 42 pregnancies, yielding a detection rate of 97.6% (95% confidence interval, 83.8-99.7). There was 1 false negative and no false positive cases. Trisomy 21 was detected in 38 out of 39 dichorionic twin pregnancies, yielding a detection rate of 97.4% (95% confidence interval, 82.6-99.7). Trisomy 18 was detected in 10 of the 10 affected pregnancies. There was 1 false positive case. Trisomy 13 was detected in 4 of the 5 cases, yielding a detection rate of 80% (95% confidence interval, 11.1-99.2). There was one false negative and no false positive cases. The nonreportable rate was low at 3.9 %.
CONCLUSION
Cell-free DNA testing is effective in screening for trisomy 21 in twin gestations from the first trimester of pregnancy. Detection of trisomy 21 was high in dichorionic and monochorionic twins, and the nonreportable result rates were low. This study included high numbers of cases of trisomy 18 and 13 when compared with the current literature. Although screening for these conditions in twins seems to be promising, the numbers were too small to make definitive conclusions regarding the screening efficacy for these conditions. It is possible that cell-free DNA testing performance may differ among laboratories and vary with screening methodologies.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Adult; Infant; Down Syndrome; Pregnancy, Twin; Trisomy; Prenatal Diagnosis; Trisomy 18 Syndrome; Trisomy 13 Syndrome; Cell-Free Nucleic Acids; Retrospective Studies
PubMed: 37030426
DOI: 10.1016/j.ajog.2023.04.002 -
Fetal and Pediatric Pathology Aug 2023We assessed the frequency and type of associated congenital anomalies encountered with fetal tethered spinal cord (TSC) determined prenatally.
OBJECTIVE
We assessed the frequency and type of associated congenital anomalies encountered with fetal tethered spinal cord (TSC) determined prenatally.
METHOD
A retrospective review was conducted based on the associated fetal abnormalities following diagnosis of low-lying fetal conus medullaris during the prenatal ultrasound.
RESULTS
Of the 26 fetuses with low-lying conus medullaris, four were solitary TSC and 22 had TSC combined with associated congenital malformations, including four cases with spina bifida occulta, four cases with spina bifida aperta, one case with severe hydrocephalus, and 13 cases with multisystem congenital malformations. Among all the 13 cases with combined multisystem congenital malformations, four cases had vertebral defects, anal anomalies, cardiac defects, trachea-esophageal fistula, renal anomalies, and limb anomalies (VACTERL) syndrome, two cases had combined kidney development abnormalities, one case had cloacal exstrophy (OEIS syndrome), and six cases had chromosomal abnormalities (one case of chromosome 7q deletion, two cases of trisomy 13 syndrome, one case of trisomy 18 syndrome, one case of trisomy 9 syndrome, and one case of chromosome 4p deletion).
CONCLUSIONS
Low-lying conus medullaris found during prenatal ultrasound examination were often associated with neural tube malformations or multi-systemic complex developmental malformations. The frequency of chromosomal abnormalities was 23.1%.
Topics: Pregnancy; Female; Humans; Spine; Heart Defects, Congenital; Chromosome Aberrations; Spinal Cord
PubMed: 36719707
DOI: 10.1080/15513815.2023.2172632 -
Journal of Pediatric Surgery Aug 2023Patients with Trisomy 13(T13) and 18(T18) have many comorbidities that may require surgical intervention. However, surgical care and outcomes are not well described,...
BACKGROUND
Patients with Trisomy 13(T13) and 18(T18) have many comorbidities that may require surgical intervention. However, surgical care and outcomes are not well described, making patient selection and family counseling difficult. Here the surgical history and outcomes of T13/ T18 patients are explored.
METHODS
A retrospective review of patients with T13 or T18 born between 1990 and 2020 and cared for at a tertiary children's hospital (Riley Hospital for Children, Indianapolis IN) was conducted, excluding those with insufficient records. Primary outcomes of interest were rates of mortality overall and after surgery. Factors that could predict mortality outcomes were also assessed.
RESULTS
One-hundred-seventeen patients were included, with 65% T18 and 35% T13. More than half of patients(65%) had four or more comorbidities. Most deaths occurred by three months at median 42.0 days. Variants of classic trisomies (mosaicism, translocation, partial duplication; p = 0.001), higher birth weight(p = 0.002), and higher gestational age(p = 0.01) were associated with lower overall mortality, while cardiac(p = 0.002) disease was associated with higher mortality. Over half(n = 64) underwent surgery at median age 65 days at time of first procedure. The most common surgical procedures were general surgical. Median survival times were longer in surgical rather than nonsurgical patients(p<0.001). Variant trisomy genetics(p = 0.002) was associated with lower mortality after surgery, while general surgical comorbidities(p = 0.02), particularly tracheoesophageal fistula/esophageal atresia(p = 0.02), were associated with increased mortality after surgery.
CONCLUSIONS
Trisomy 13 and 18 patients have vast surgical needs. Variant trisomy was associated with lower mortality after surgery while general surgical comorbidities were associated with increased mortality after surgery. Those who survived to undergo surgery survived longer overall.
LEVEL OF EVIDENCE
III.
Topics: Child; Humans; Infant; Trisomy 13 Syndrome; Chromosome Disorders; Trisomy; Trisomy 18 Syndrome; Retrospective Studies
PubMed: 36402594
DOI: 10.1016/j.jpedsurg.2022.10.010 -
The Cleft Palate-craniofacial Journal :... Oct 2023Patau syndrome (trisomy 13) is a severe disorder associated with multiple systemic defects. Patau syndrome is commonly associated with ocular abnormalities but rarely...
Patau syndrome (trisomy 13) is a severe disorder associated with multiple systemic defects. Patau syndrome is commonly associated with ocular abnormalities but rarely associated with congenital glaucoma. To obtain a better surgical view, palatoplasty requires neck extension during surgery. The intraocular pressure (IOP) of patients with Patau syndrome can increase owing to the neck extension position while undergoing palatoplasty, particularly in those with congenital glaucoma. Here, we describe a case with increased IOP measured using a rebound tonometer during palatoplasty in a pediatric patient with Patau syndrome and congenital glaucoma. This case shows that it may be important to reduce the degree of neck extension and shorten the operation time to minimize any increase in the IOP during palatoplasty in pediatric patients with Patau syndrome accompanied by congenital glaucoma.
Topics: Humans; Child; Intraocular Pressure; Trisomy 13 Syndrome; Tonometry, Ocular; Glaucoma; Cleft Palate
PubMed: 35473400
DOI: 10.1177/10556656221097209