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Biomedicines Oct 2023Amniotic fluid is essential for fetus wellbeing and is used to monitor pregnancy and predict fetal outcomes. Sex affects health and medicine from the beginning of life,...
Amniotic fluid is essential for fetus wellbeing and is used to monitor pregnancy and predict fetal outcomes. Sex affects health and medicine from the beginning of life, but knowledge of its influence on cell-depleted amniotic fluid (AF) and amniotic fluid cells (AFCs) is still neglected. We evaluated sex-related differences in AF and in AFCs to extend personalized medicine to prenatal life. AFCs and AF were obtained from healthy Caucasian pregnant women who underwent amniocentesis at the 16th-18th week of gestation for advanced maternal age. In the AF, inflammation biomarkers (TNFα, IL6, IL8, and IL4), malondialdehyde, nitrites, amino acids, and acylcarnitines were measured. Estrogen receptors and cell fate (autophagy, apoptosis, senescence) were measured in AFCs. TNFα, IL8, and IL4 were higher in female AF, whereas IL6, nitrites, and MDA were similar. Valine was higher in male AF, whereas several acylcarnitines were sexually different, suggesting a mitochondrial involvement in establishing sex differences. Female AFCs displayed higher expression of ERα protein and a higher ERα/ERβ ratio. The ratio of LC3II/I, an index of autophagy, was higher in female AFCs, while gene was similar in both sexes. No significant sex differences were found in the expression of the lysosomal protein LAMP1, while p62 was higher in male AFCs. gene was upregulated in male AFCs, while gene was upregulated in female ones. Finally, caspase 9 activity and senescence linked to telomeres were higher in female AFCs, while caspase 3 and β-galactosidase activities were similar. This study supports the idea that sex differences start very early in prenatal life and influence specific parameters, suggesting that it may be relevant to appreciate sex differences to cover knowledge gaps. This might lead to improving the diagnosis of risk prediction for pregnancy complications and achieving a more satisfactory monitoring of fetus health, even preventing future diseases in adulthood.
PubMed: 37893203
DOI: 10.3390/biomedicines11102830 -
Frontiers in Genetics 2023To assess the performance of diverse prenatal diagnostic approaches for nuchal translucency (NT) thickening and to investigate the optimal prenatal screening or...
To assess the performance of diverse prenatal diagnostic approaches for nuchal translucency (NT) thickening and to investigate the optimal prenatal screening or diagnostic action with a NT thickening of 95th percentile-3.50 mm. A retrospective analysis of 2,328 pregnancies with NT ≥ 95th percentile through ultrasound-guided transabdominal chorionic villus sampling (CVS), amniocentesis, or cordocentesis obtained clinical samples (chorionic villi, amniotic fluid, and cord blood), and real-time quantitative fluorescent PCR (QF-PCR), chromosome karyotyping (CS), chromosome microarray analysis (CMA), or whole exome sequencing (WES) were provided to identify genetic etiologies. In this study, the incidence of chromosomal defects increased with NT thickness. When NT ≥ 6.5 mm, 71.43% were attributed to genetic abnormalities. The 994 gravidas with fetal NT thickening underwent short tandem repeat (STR), CS, and CMA. In 804 fetuses with normal karyotypes, CMA detected 16 (1.99%) extra pathogenic or likely pathogenic copy number variations (CNVs). The incremental yield of CMA was only 1.16% (3/229) and 3.37% (10/297) in the group with NT 95th percentile-2.99 mm and NT 3.0-3.49 mm, separately. Among the 525 gravidas with fetal NT thickening who underwent STR, CMA, and WES, the incremental yield of WES was 4.09% (21/513). In the group of NT 95th percentile-2.99 mm, there were no additional single-nucleotide variations (SNVs) detected in WES, while in 143 cases with NT of 3.0-3.49 mm, the incremental yield of WES was 5.59% (8/143). In the group of NT 95th percentile-3.0 mm, since chromosomal aneuploidy and chromosomal copy number variation were the primary causes and the additional contribution of CMA and WES was not significant, we recommend NIPT-Plus for pregnant women with a NT thickening of 95th percentile-3.0 mm first. In addition, comprehensive prenatal genetic testing involving CMA and WES can benefit pregnancies with NT thickening of 3.0-3.49 mm.
PubMed: 37600658
DOI: 10.3389/fgene.2023.1227724 -
Taiwanese Journal of Obstetrics &... Sep 2023We present high-level mosaicism for 45,X in 45,X/46,X,+mar at amniocentesis in a pregnancy associated with positive non-invasive prenatal testing (NIPT) for Turner...
High-level mosaicism for 45,X in 45,X/46,X,+mar at amniocentesis in a pregnancy associated with positive non-invasive prenatal testing for Turner syndrome, normal male external genitalia and positive SRY in the fetus, a favorable fetal outcome, postnatal decrease of the 45,X cell line and...
OBJECTIVE
We present high-level mosaicism for 45,X in 45,X/46,X,+mar at amniocentesis in a pregnancy associated with positive non-invasive prenatal testing (NIPT) for Turner syndrome, normal male external genitalia and positive SRY in the fetus, a favorable fetal outcome, postnatal decrease of the 45,X cell line and cytogenetic discrepancy in various tissues.
CASE REPORT
A 35-year-old, gravida 2, para 1, woman underwent amniocentesis at 16 weeks of gestation because of positive NIPT for Turner syndrome (Z score = -11.72 for X chromosome) at 10 weeks of gestation. Amniocentesis revealed a karyotype of 45,X[13]/46,X,+mar[8]. Simultaneous molecular analysis on the DNA extracted from uncultured amniocytes revealed the results of arr (X) × 1, (Yp) × 0-1 (0.63), (Yq) × 0, (1-22) × 2 in array comparative genomic hybridization (aCGH) and rsa(X) × 1, Yp11.31 × 0-1, Yq11.21 × 0, (13, 18, 21) × 2 in multiplex ligation-dependent probe amplification (MLPA). The parental karyotypes were normal. Prenatal ultrasound revealed normal male external genitalia. She was referred for genetic counseling, and continuing pregnancy was advised. A 2875-g male baby was delivered at 38 weeks of gestation with normal male external genitalia. The karyotypes of cord blood, umbilical cord and placenta were 46,X,+mar[27]/45,X[13], 46,X,+mar[24]/45,X[16] and 45,X[22]/46,X,+mar[18], respectively. SRY testing on cord blood revealed a positive result. When follow-up at age two months, the neonate was normal in development. The karyotype of peripheral blood was 46,X,+mar[25]/45,X[13]/46,X,idic r(Y) [2]. Interphase fluorescence in situ hybridization (FISH) analysis on 103 buccal mucosal cells using Yp11.2-specific probe RP11-119E4 and Xp22.31-specific probe RP11-143E20 showed that 90 cells (90/103 = 87%) had double Yp signals, 3 cells (3/103 = 3%) had single Yp signal and 10 cells (10/103 = 10%) had no Yp signal.
CONCLUSION
High-level mosaicism for 45,X in 45,X/46,X,+mar at amniocentesis with positive Yp and SRY can be associated with a favorable fetal outcome, postnatal decrease of the 45,X cell line and cytogenetic discrepancy in various tissues.
Topics: Male; Female; Pregnancy; Humans; Mosaicism; Turner Syndrome; Comparative Genomic Hybridization; Amniocentesis; In Situ Hybridization, Fluorescence; Fetus; Karyotyping; Cell Line; Genitalia
PubMed: 37679007
DOI: 10.1016/j.tjog.2023.07.020 -
The Journal of Maternal-fetal &... Dec 2024The present study investigated the relationship between bronchopulmonary dysplasia (BPD) and intra-amniotic infection with species.
OBJECTIVES
The present study investigated the relationship between bronchopulmonary dysplasia (BPD) and intra-amniotic infection with species.
METHODS
This was a single-center, retrospective cohort study. Patients with singleton pregnancies who underwent inpatient management at our department for preterm premature rupture of membranes (PPROM), preterm labor, cervical insufficiency, and asymptomatic cervical shortening at 22-33 gestational weeks were included. Amniocentesis was indicated for patients with PPROM or an elevated maternal C-reactive protein level (≥0.58 mg/dL). Patients with an amniotic fluid IL-6 concentration ≥3.0 ng/mL were diagnosed with intra-amniotic inflammation, while those with positive aerobic, anaerobic, , and spp. cultures were diagnosed with microbial invasion of the amniotic cavity (MIAC). Patients who tested positive for both intra-amniotic inflammation and MIAC were considered to have intra-amniotic infection. An umbilical vein blood IL-6 concentration >11.0 pg/mL indicated fetal inflammatory response syndrome (FIRS). The maternal inflammatory response (MIR) and fetal inflammatory response (FIR) were staged using the Amsterdam Placental Workshop Group Consensus Statement.
RESULTS
Intra-amniotic infection with spp. was diagnosed in 37 patients, intra-amniotic infection without spp. in 28, intra-amniotic inflammation without MIAC in 58, and preterm birth without MIR/FIR and FIRS in 86 as controls. Following an adjustment for gestational age at birth, the risk of BPD was increased in patients with intra-amniotic infection with spp. (adjusted odds ratio: 10.5; 95% confidence interval: 1.55-71.2), but not in those with intra-amniotic infection without spp. or intra-amniotic inflammation without MIAC.
CONCLUSION
BPD was only associated with intra-amniotic infection with species.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Ureaplasma; Chorioamnionitis; Retrospective Studies; Bronchopulmonary Dysplasia; Prevalence; Interleukin-6; Prenatal Exposure Delayed Effects; Placenta; Premature Birth; Fetal Membranes, Premature Rupture; Amniotic Fluid; Inflammation
PubMed: 38418200
DOI: 10.1080/14767058.2024.2320670 -
Drug Discoveries & Therapeutics Nov 2023Complete chromosome 9 trisomy (T9) is a rare and fatal chromosomal disorder. We performed non-invasive prenatal testing (NIPT) in a patient with threatened abortion...
Complete chromosome 9 trisomy (T9) is a rare and fatal chromosomal disorder. We performed non-invasive prenatal testing (NIPT) in a patient with threatened abortion symptoms and found that the fetal was at risk for complete chromosome 9 trisomy. This shows that NIPT has certain accuracy in detecting trisomy of chromosome 9, which provide options for prenatal diagnosis of rare chromosomal abnormalities.
Topics: Female; Pregnancy; Humans; Amniocentesis; Trisomy; Noninvasive Prenatal Testing; Chromosomes, Human, Pair 9
PubMed: 37821384
DOI: 10.5582/ddt.2023.01051 -
American Journal of Obstetrics and... Feb 2024Idiopathic bleeding in the second trimester of pregnancy complicates <1% of all pregnancies. This pregnancy complication can be caused by alterations in local hemostasis...
BACKGROUND
Idiopathic bleeding in the second trimester of pregnancy complicates <1% of all pregnancies. This pregnancy complication can be caused by alterations in local hemostasis in the decidua due to infection/inflammation in the choriodecidual niche. This condition is associated with intraamniotic inflammatory complications. Antibiotic therapy effectively reduces the intensity of intraamniotic inflammation in certain pregnancy pathologies. However, whether antibiotic administration can reduce the intensity of the intraamniotic inflammatory response or eradicate microorganisms in patients with idiopathic bleeding during the second trimester of pregnancy remains unclear.
OBJECTIVE
This study primarily aimed to determine whether antimicrobial agents can reduce the magnitude of intraamniotic inflammation in patients with idiopathic bleeding in the second trimester of pregnancy by assessing the concentration of interleukin-6 in the amniotic fluid before and after 7 days of antibiotic treatment. The secondary aim was to determine whether treatment with a combination of antibiotics altered the microbial load of Ureaplasma species DNA in amniotic fluid.
STUDY DESIGN
This retrospective cohort study included singleton-gestation patients with idiopathic bleeding between 15+0 and 27+6 weeks who underwent transabdominal amniocentesis at the time of admission. Follow-up amniocentesis was performed in a subset of patients unless abortion or delivery occurred earlier. Concentrations of interleukin-6 were measured in the amniotic fluid samples, and the presence of microbial invasion of the amniotic cavity was assessed using culture and molecular microbiological methods. Intraamniotic inflammation was defined as an interleukin-6 concentration ≥3000 pg/mL in the amniotic fluid samples.
RESULTS
A total of 36 patients with idiopathic bleeding in the second trimester of pregnancy were included. All the patients underwent initial amniocentesis. Patients with intraamniotic inflammation (n=25) were treated using a combination of antibiotics consisting of intravenous ceftriaxone, intravenous metronidazole, and peroral clarithromycin. The patients without intraamniotic inflammation (n=11) were treated expectantly. In total, 25 patients delivered 7 days after admission. All patients with intraamniotic inflammation at the initial amniocentesis who delivered after 7 days underwent follow-up amniocentesis. Treatment with antibiotics decreased the interleukin-6 concentration in the amniotic fluid at follow-up amniocentesis compared with that at the initial amniocentesis in patients with intraamniotic inflammation (median [interquartile range]: 3457 pg/mL [2493-13,203] vs 19,812 pg/mL [11,973-34,518]; P=.0001). Amniotic fluid samples with Ureaplasma species DNA had a lower microbial load at the time of follow-up amniocentesis compared with the initial amniocentesis (median [interquartile range]: 1.5×10 copies DNA/mL [1.3×10-1.7×10] vs 8.0×10 copies DNA/mL [6.7×10-1.6×10]; P=.02).
CONCLUSION
Antibiotic therapy was associated with reduced intraamniotic inflammation in patients with idiopathic bleeding in the second trimester complicated by intraamniotic inflammation. Moreover, antibiotic treatment has been associated with a reduction in the microbial load of Ureaplasma species DNA in the amniotic fluid.
Topics: Pregnancy; Female; Humans; Pregnancy Trimester, Second; Chorioamnionitis; Interleukin-6; Retrospective Studies; Anti-Bacterial Agents; Inflammation; Amniocentesis; Amniotic Fluid; Ureaplasma; Uterine Hemorrhage; DNA; Fetal Membranes, Premature Rupture
PubMed: 37516399
DOI: 10.1016/j.ajog.2023.07.041 -
Frontiers in Genetics 2023Intellectual disability-7 (MRD7) is a subtype disorder of intellectual disability (MRD) involving feeding difficulties, hypoactivity, and febrile seizures at an age of...
Intellectual disability-7 (MRD7) is a subtype disorder of intellectual disability (MRD) involving feeding difficulties, hypoactivity, and febrile seizures at an age of early onset, then progressive intellectual and physical development deterioration. We purposed to identify the underlying causative genetic factors of three individuals in each Chinese family who presented with symptoms of intellectual disability and facial dysmorphic features. We provided prenatal diagnosis for the three families and genetic counseling for the prevention of this disease. We collected retrospective clinical diagnostic evidence for the three probands in our study, which included magnetic resonance imaging (MRI), computerized tomography (CT), electroencephalogram (EEG), and intelligence tests for the three probands in our study. Genetic investigation of the probands and their next of kin was performed by Trio-whole exome sequencing (WES). Sanger sequencing or quantitative PCR technologies were then used as the next step to verify the variants confirmed with Trio-WES for the three families. Moreover, we performed amniocentesis to explore the state of the three pathogenic variants in the fetuses by prenatal molecular genetic diagnosis at an appropriate gestational period for the three families. The three probands and one fetus were clinically diagnosed with microcephaly and exhibited intellectual developmental disability, postnatal feeding difficulties, and facial dysmorphic features. Combining probands' clinical manifestations, Trio-WES uncovered the three heterozygous variants in : a novel variant exon3_exon4del p.(Gly4_Asn109del), a novel variant c.1159C>T p.(Gln387*), and a previously presented but rare pathogenic variant c.1309C>T p.(Arg437*) (NM_001396.5) in three families, respectively. In light of the updated American College of Medical Genetic and Genomics (ACMG) criterion, the variant of exon3_exon4del and c.1159C>T were both classified as likely pathogenic (PSV1+PM6), while c1309C>T was identified as pathogenic (PVS1+PS2_Moderate+PM2). Considering clinical features and molecular testimony, the three probands were confirmed diagnosed with MRD7. These three discovered variants were considered as the three causal mutations for MRD7. Prenatal diagnosis detected the heterozygous dominant variant of c.1159C>T p.(Gln387*) in one of the fetuses, indicating a significant probability of MRD7, subsequently the gestation was intervened by the parents' determination and professional obstetrical operation. On the other side, prenatal molecular genetic testing revealed wild-type alleles in the other two fetuses, and their parents both decided to sustain the gestation. We identified two novel and one rare mutation in which has broadened the spectrum of and provided evidence for the diagnosis of MRD7 at the molecular level. Besides, this study has supported the three families with MRD7 to determine the causative genetic factors efficiently and provide concise genetic counseling for the three families by using Trio-WES technology.
PubMed: 38179410
DOI: 10.3389/fgene.2023.1290949 -
Taiwanese Journal of Obstetrics &... Nov 2023To evaluate the correlation of high levels [>2.0 multiples of median (MoM)] of amniotic fluid alpha-fetoprotein (AFAFP) in midtrimester with abnormal fetal outcome.
OBJECTIVE
To evaluate the correlation of high levels [>2.0 multiples of median (MoM)] of amniotic fluid alpha-fetoprotein (AFAFP) in midtrimester with abnormal fetal outcome.
MATERIALS AND METHODS
We retrospectively studied 6245 pregnant women with singleton pregnancy who had undergone amniocentesis between 15 and 27 weeks' gestation at Mackay Memorial Hospital between January 2014 and June 2020. Fifty-five cases had high AFAFP levels (>2.0 MoM). We investigated the abnormal fetal outcomes.
RESULTS
Among the fifty-five cases with high AFAFP levels (>2.0 MoM), thirty (54.5%) had fetal chromosomal abnormalities, major structural abnormalities, and/or adverse obstetric events. Eight cases (14.5%) had chromosomal abnormalities including trisomy 21 (3 cases), trisomy 18 (3 cases), mosaic trisomy 18 (1 cases), and mosaic ring 13 (1 case). Seventeen cases (30.9%) had major structural abnormalities including abdominal wall defect (6 cases) and central nervous system (5 cases), gastrointestinal tract (3 cases), cardiovascular (2 cases), and genitourinary tract (2 cases) abnormalities. Fifteen cases (27%) had adverse obstetric events, including preterm delivery (5 cases), intrauterine fetal demise (4 cases), small for gestational age (4 cases), preeclampsia (4 cases), gestational diabetes mellitus (2 cases), gestational hypertension (1 case), preterm prelabor rupture of membrane (1 case), prolonged labor (1 case), and preterm uterine contraction (1 case).
CONCLUSION
A high AFAFP level (>2.0 MoM) in midtrimester can be associated with abnormal fetal outcome, including chromosomal abnormalities, major structural abnormalities, and adverse obstetric events. Women with a prenatal diagnosis of high AFAFP levels (>2.0 MoM) should be alerted of the possibility of abnormal fetal outcomes, and further detailed genetic studies and serial sonographic examinations are recommended.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Amniotic Fluid; alpha-Fetoproteins; Trisomy 18 Syndrome; Retrospective Studies; Chromosome Aberrations; Pregnancy Trimester, Second
PubMed: 38008506
DOI: 10.1016/j.tjog.2022.12.013 -
Molecular Genetics & Genomic Medicine Mar 2024Chromosomal microarray (CMA) is commonly utilized in the obstetrics setting. CMA is recommended when one or more fetal structural abnormalities is identified. CMA is... (Review)
Review
BACKGROUND
Chromosomal microarray (CMA) is commonly utilized in the obstetrics setting. CMA is recommended when one or more fetal structural abnormalities is identified. CMA is also commonly used to determine genetic etiologies for miscarriages, fetal demise, and confirming positive prenatal cell-free DNA screening results.
METHODS
In this study, we retrospectively examined 523 prenatal and 319 products-of-conception (POC) CMA cases tested at Nationwide Children's Hospital from 2011 to 2020. We reviewed the referral indications, the diagnostic yield, and the reported copy number variants (CNV) findings.
RESULTS
In our cohort, the diagnostic yield of clinically significant CNV findings for prenatal testing was 7.8% (n = 41/523) compared to POC testing (16.3%, n = 52/319). Abnormal ultrasound findings were the most common indication present in 81% of prenatal samples. Intrauterine fetal demise was the common indication identified in POC samples. The most common pathogenic finding observed in all samples was isolated trisomy 21, detected in seven samples.
CONCLUSION
Our CMA study supports the clinical utility of prenatal CMA for clinical management and identifying genetic etiology in POC arrays. In addition, it provides insight to the spectrum of prenatal and POC CMA results as detected in an academic hospital clinical laboratory setting that serves as a reference laboratory.
Topics: Female; Humans; Pregnancy; Chromosome Disorders; Down Syndrome; Fetal Death; Prenatal Diagnosis; Retrospective Studies
PubMed: 38263869
DOI: 10.1002/mgg3.2349 -
Taiwanese Journal of Obstetrics &... Nov 2023
Low-level mosaic trisomy 6 at amniocentesis can be a culture artefact and associated with a favorable outcome and cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes.
Topics: Pregnancy; Female; Humans; Amniocentesis; Trisomy; Artifacts; Prenatal Diagnosis; Chromosome Disorders; Cytogenetic Analysis; Mosaicism; Comparative Genomic Hybridization
PubMed: 38008519
DOI: 10.1016/j.tjog.2023.09.008