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Objective To determine the feasibility of rescue cerclage and amnioreduction at advanced cervical dilation or gestational age. Methods We present a retrospective case series of women who underwent rescue cerclage at either an advanced gestational age (24 + 0 to 24 + 6 weeks) or cervical dilation (≥4 cm), with a subset undergoing amnioreduction prior to cerclage placement. Results Nine women were included and amnioreduction was performed in 7 (78%). A bi-modal distribution of obstetric outcomes was observed, with 5 (56%) women delivering ≥34 weeks gestation, 3 (33%) of which delivered at term. Two (22%) women experienced intra-operative rupture of membranes and subsequent perinatal deaths. Two (22%) women delivered extremely premature, with one resulting in infant death. Discussion Our data show that rescue cerclage with amnioreduction may be successful at advanced gestational ages or cervical dilations, suggesting that these women should be included in prospective studies to better establish the efficacy and safety of this procedure. [ABSTRACT FROM AUTHOR]

Objective: Our goal was to evaluate the approach to the increased risk of fetal chromosomal anomaly in pregnant women over thirty-five years of age. Methods: We retrospectively examined pregnant women over the age of 35 who underwent interventional procedures for fetal karyotype analysis in the Perinatology Clinic of University of Health Sciences Turkey Kanuni Sultan Süleyman Training and Research Hospital. Regardless of the indication for karyotype analysis, pregnant women over the age of 35 who underwent karyotype analysis were included in the study. Results: Abnormal karyotype was detected in 76 (8.7%) of a total of 867 pregnant women examined in the study. Of 76 abnormal karyotypes, 51 were found as trisomy 21 (67.7%), 15 as trisomy 18 (21%), and 3 as trisomy 13 (4%). Three fetal karyotype analyzes revealed Turner syndrome (4%), 1 Klinefelter syndrome (1.3%), 2 mosaic trisomy 21 (2.6%) and 1 mosaic Turner syndrome (1.3%). In the patients who underwent interventional procedures primarily because of advanced maternal age, abnormal karyotype was detected in 6 (1.9%) of them. The rates of abnormal karyotype results for double, triple and quadruple tests were 6.4%, 1.9% and 5.8%, respectively. Conclusion: The use of a triple test has no definite impact on the results of pregnant women of older age. When there is no fetal abnormality in the ultrasound, double and quadruple tests may be requested or since the fetal death rate is minimal in amniocentesis, it can be recommended directly without performing any screening tests in pregnant women with older age. [ABSTRACT FROM AUTHOR]

Objective: Jacobsen syndrome is an infrequent contiguous gene syndrome that involves the deletion of the long arm of chromosome 11. It is mostly accompanied by intellectual disability and other abnormalities. The majority of the patients are hospitalized or lost within the first two years of life. Case: We report a case of a fetus at 21 weeks of gestation with Jacobsen syndrome who presented with a conotruncal cardiac defect. Amniocentesis was performed, and karyotype analysis revealed that there was a de novo deletion of chromosome 11. The family decided to terminate the pregnancy. Conclusion: Prenatal diagnosis of Jacobsen syndrome is not always possible, since the characteristic ultrasound findings vary greatly between patients. Additionally, existing symptoms and signs may not always be found with imaging techniques. However, if present, certain ultrasonographic findings should lead clinicians to consider the syndrome. The study aims to present a rare case of Jacobsen syndrome, inform the clinicians, and guide on this syndrome and its possible outcomes. [ABSTRACT FROM AUTHOR]

Objective: To investigate the importance of prenatal ultrasound in the detection of Down syndrome by evaluating ultrasonographic and minor ultrasonographic findings in fetuses with this aneuploidy. Methods: Patients who were reported to have trisomy 21 as a result of karyotype analysis performed by cordocentesis, amniocentesis, or chorionic villus biopsy materials and who underwent ultrasound scan before diagnosis between 18 and 26 weeks of gestation by the Maternal Fetal Medicine Department between 2013 and 2020 were included in the study group. Results: The results of 132 of 4525 (2.9%) invasive procedures were reported to have trisomy 21 and ultrasound scans of each fetus were performed in our department. The mean gestational age at the ultrasound scans was 19.2±3.8 (SD) weeks. At least one major structural anomaly or minor ultrasonographic finding was detected in 99.2% of all fetuses. Major structural anomalies were present in 80 (60.6%) fetuses. In fetuses with major structural anomalies, cardiac defects (53.7%) were the most detected anomalies. No ultrasound findings could be detected in one (0.8%) of the remaining 52 patients, and only isolated minor findings were detected in 51 (38.6%) fetuses. More than half (60.7%) of these fetuses had a single minor finding. The most common isolated single minor finding was nuchal fold thickness in 13 (41.9%) fetuses followed by aberrant right subclavian artery in six (19.3%) fetuses. Conclusion: Down syndrome displays a large variety of different sonographic findings on fetal ultrasound. Although major structural anomalies and multiple minor findings are generally considered more important, the presence of any isolated minor marker may be the only detectable finding of Down syndrome. [ABSTRACT FROM AUTHOR]

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Background. Karyotyping and genome copy number variation sequencing (CNV-seq) are two techniques frequently used in prenatal diagnosis. This study aimed to explore the diagnostic potential of using a combination of these two methods in order to provide a more accurate clinical basis for prenatal diagnosis. Methods. We selected 822 pregnant women undergoing amniocentesis and separated them into six groups according to different risk indicators. Karyotyping and CNV-seq were performed simultaneously to compare the diagnostic performance of the two methods. Results. Among the different amniocentesis indicators, abnormal fetal ultrasounds accounted for 39.29% of the total number of examinees and made up the largest group. The abnormal detection rate of non-invasive prenatal testing (NIPT) high risk was 37.93% and significantly higher than the other five groups (P < 0:05). The abnormal detection rate of mixed indicators was significantly higher than the history of the adverse reproductive outcomes group (P = 0.0151). The two methods combined found a total of 119 abnormal cases (14.48%). Karyotyping detected 57 cases (6.93%) of abnormal karyotypes, 30 numerical aberrations, and 27 structural aberrations. CNV-seq identified 99 cases (12.04%) with altered CNVs, 30 cases of chromosome aneuploidies, and 69 structural aberrations (28 pathogenic, eight that were likely pathogenic, and 33 microdeletion/duplication variants of uncertain significance (VUS)). Thirty-seven cases were found abnormal by both methods, 20 cases were detected abnormally by karyotyping (mainly mutual translocation and mostly balanced), and 62 cases of microdeletion/duplication were detected by CNV-seq. Steroid sulfatase gene (STS) deletion was identified at chromosome Xp22.31 in three cases. Postnatal follow-up confirmed that babies manifested skin abnormalities one week after birth. Six fetuses had Xp22.31 duplications ranging from 1.5 Kb to 1.7 Mb that were detected by CNV-seq. Follow-up showed that five babies presented no abnormalities during follow-up, except for one terminated pregnancy due to a history of adverse reproductive outcomes. Conclusion. The combination of using CNV-seq and karyotyping significantly im-proved the detection rate of fetal pathogenic chromosomal abnormalities. CNV-seq is an effective complement to karyotyping and improves the accuracy of prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Background: MCPH1 is known as the microcephalin gene (OMIM: *607117), of which the encoding protein is a basic regulator of chromosome condensation (BCRT-BRCA1 C-terminus). The microcephalin protein is made up of three BCRT domains and conserved tandem repeats of interacting phospho-peptides. There is a strong connection between mutations of the MCPH1 gene and reduced brain growth. Specifically, individuals with such mutations have underdeveloped brains, varying levels of mental retardation, delayed speech and poor language skills. Methods: In this article, a family with two affected fetuses presenting a mutation of the MCPH1 gene is reported. During the first trimester ultrasound of the second pregnancy, the measure of nuchal translucency was increased (NT = 3.1 mm) and, therefore, the risk for chromosomal abnormalities was high. Chorionic villi sampling (CVS) was then performed. Afterwards, fetal karyotyping and Next Generation Sequencing were carried out. Afterwards, NGS was also performed in a preserved sample of the first fetus which was terminated due to microcephaly. Results: In this case, the fetuses had a novel homozygous mutation of the MCPH1 gene (c.348del). Their parents were heterozygous for the mutation. The fetuses showed severe microcephaly. Because of the splice sites in introns, this mutation causes the forming of dysfunctional proteins which lack crucial domains of the C-terminus. Conclusion: Our findings portray an association between the new MCPH1 mutation (c.348del) and the clinical features of autosomal recessive primary microcephaly (MCPH), contributing to a broader spectrum related to these pathologies. To our knowledge, this is the first prenatal diagnosis of MCPH due to a novel MCPH1 mutation. [ABSTRACT FROM AUTHOR]

Objective: We present detection of mosaicism for 46,X,i(Y) (q10) in the blood lymphocytes in a phenotypically normal male neonate with prenatally detected 45,X/46, XY at amniocentesis and cytogenetic discrepancy in various tissues. Case report: A 35-year-old, gravida 2, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,X [8]/46,XY [15]. Simultaneous array comparative genomic hybridization (aCGH) on uncultured amniocytes revealed the result of arr (Y) × 0–1 with 25.493-Mb mosaic deletion of chromosome Yp11.31-q11.23. Prenatal ultrasound findings were unremarkable. The fetus had normal male external genitalia on fetal ultrasound. Following genetic counseling, the pregnancy was carried to 38 weeks of gestation, and a phenotypically normal male baby was delivered without any abnormalities of the male external genitalia. The cord blood had a karyotypes of 46,X,i(Y) (q10)[8]/45,X[3]/46,XY [29], and placenta had a karyotypes of 45,X [25]/46,X,i(Y) (q10)[7]/46,XY [8]. When follow-up at age two months, the neonate was normal in development. The peripheral blood had a karyotypes of 46,X,i(Y) (q10)[8]/45,X[5]/46,XY [27]. Interphase fluorescence in situ hybridization (FISH) analysis on 101 buccal mucosal cells showed normal X and Y signals in 101/101 cells. Conclusion: Fetuses with 45,X/46, XY at amniocentesis can be associated with mosaicism for 46,X,i(Y) (q10) in the blood lymphocytes, cytogenetic discrepancy in various tissues and a favorable outcome.

Introduction: Most pregnant women are concerned about fetal abnormalities and screening tests. Pharmacological and non-pharmacological methods are used to control anxiety in pregnancy. But, there is still no suitable and ideal strategy to reduce anxiety in pregnancy and childbirth. Therefore, this study was performed with aim to compare the effect of foot reflexology and H7 point acupressure on anxiety in women undergoing amniocentesis. Methods: This clinical trial study was performed in 2020on 84 pregnant women candidates for amniocentesis in sonography clinic in Birjand. Individuals were assigned to three groups: foot reflexology, H7 point acupressure and control. In the intervention groups, foot reflexology in the solar plexus and H7 point acupressure were performed by the researcher once 30 minutes before amniocentesis. Reflexology and acupressure were also performed by mothers during the waiting period for amniocentesis. The control group did not receive any intervention. Data collection tools were demographic and pregnancy questionnaires and Spielberger State Anxiety Scale. The Spielberger state questionnaire was completed before the intervention, immediately after and 10 days after amniocentesis and trait anxiety before the intervention and ten days after amniocentesis. Data were analyzed using SPSS software (version 16) and ANOVA, chi-square, analysis of variance with Bonferroni post hoc test and paired t-test. P

Objective: We present prenatal diagnosis of high-level mosaicism for 45,X in 45,X/46,X,idic(Y)(q11.2) at amniocentesis in a pregnancy with a favorable outcome and postnatal progressive decrease of the 45,X cell line. Case report: A 36-year-old, gravida 4, para 3, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,X[22]/46,X,idic(Y)(q11.2)[4]. Prenatal ultrasound was unremarkable, and the fetus had normal male external genitalia. Repeat amniocentesis was performed at 20 weeks of gestation, and the second amniocentesis revealed a karyotype of 45,X[24]/46,X,idic(Y)(q11.2)[3]. Simultaneous interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes revealed that 60% (62/103 cells) were Y-deleted cells. After genetic counseling, the parents decided to continue the pregnancy, and a 3020-g male baby was delivered with a body length of 52 cm, normal male genital organs and no phenotypic abnormalities. The karyotypes of cord blood, umbilical cord and placenta were 45,X[20]/46,X,idic(Y)(q11.2)[20], 45,X[31]/46,X,idic(Y)(q11.2)[9] and 45,X[40], respectively. At age one month, FISH analysis on urinary cells and buccal mucosal cells revealed 11.5% (7/61 cells) and 13.6% (16/118 cells), respectively for mosaicism for the Y-deleted cells. At age five month, the karyotype of peripheral blood was 45,X[9]/46,X,idic(Y)(q11.2)[31]. FISH analysis on buccal mucosal cells showed no abnormal Y-deleted cell (0/101 cells). At age 11 month, the karyotype of peripheral blood was 45,X[5]/46,X,idic(Y)(q11.2)[35]. FISH analysis on 102 buccal mucosal cells showed no abnormal signals. The infant was doing well with normal physical and psychomotor development. Conclusion: High-level mosaicism for 45,X in 45,X/46,X,idic(Y)(q11.2) at amniocentesis can be associated with a favorable outcome and progressive decrease of the 45,X cell line.

Background and Objective: Zinc deficiency has been suggested as a risk factor for adverse pregnancy outcomes. Since dealing with zinc deficiency is an easy and inexpensive method, this study was conducted with the aim of investigating the relationship between adverse pregnancy outcomes and zinc concentration of amniotic fluid and maternal plasma in the second trimester and biomarkers of the first and second trimester. Methods: This cross-sectional study was conducted on 102 pregnant mothers who were candidates for amniocentesis in Mousavi Hospital in Zanjan in 2018 through convenience sampling. Women with normal amniocentesis results were followed up until delivery in terms of adverse pregnancy outcomes (incidence of preeclampsia, intrauterine growth retardation, premature delivery, fetal death, and low birth weight) and were divided into two groups with adverse pregnancy outcomes (first group) and without adverse pregnancy outcomes (second group) and were compared in terms of zinc concentration in plasma and amniotic fluid. Findings: The concentration of zinc in the plasma of the mothers of the first group (59.53±15.88 µg/dl) was significantly lower than that of the mothers of the second group (71.44±19.25 µg/dl) (p=0.02). However, there was no significant difference in the concentration of zinc in the amniotic fluid of the two study groups. In this study, the best cutoff point to determine people at risk of adverse pregnancy outcomes was determined to be 60.5 µg/dl. Conclusion: Based on the results of this study, there seems to be a relationship between low zinc concentration of plasma in pregnant women and adverse outcomes.

This correction notice is for an article titled "Results of mother-to-child transmission in hepatitis B-positive mothers who underwent amniocentesis" published in BMC Infectious Diseases. The correction addresses an error in the equal contribution note. The original note incorrectly stated that Zhenyan Han and Yuzhu Yin were the co-first authors, while the correct note states that Jin Zhou and Peizhen Zhang are the co-first authors who contributed equally to the work. The correction has been made to the original article. The publisher, Springer Nature, remains neutral regarding jurisdictional claims and institutional affiliations. The authors of the article are Jin Zhou, Peizhen Zhang, Zhangmin Tan, Chuo Li, Lin Yao, Zhenyan Han, and Yuzhu Yin. [Extracted from the article]

This article, titled "EP17.20: Amniocentesis and therapeutic amnioreduction prior to 'Rescue Cerclage' (AARC Protocol)," discusses a study conducted between December 2021 and 2023 to determine if amniotic fluid tests could identify patients who would benefit from rescue cerclage. The study included 26 patients with pregnancies involving singleton and twins, gestational age between 14-24 weeks, cervical dilation less than 4cm, and no signs of labor. The primary outcome measured was the amniocentesis to delivery interval (ADI), and secondary outcomes included gestational age at delivery and perinatal survival. The study found that patients with low-risk amniotic fluid tests who underwent rescue cerclage had a longer ADI and higher perinatal survival rate compared to those with high-risk amniotic fluid tests. The authors conclude that their AARC protocol effectively identifies low-risk patients for intra-amniotic inflammation or infection (IAI) who would benefit from rescue cerclage. [Extracted from the article]

This article discusses a study that aimed to determine whether a quantitative cervicovaginal fluid fetal fibronectin (fFN) test can be used to identify the presence of intra-amniotic inflammation in women with spontaneous preterm labor and intact membranes. The study included 78 patients who underwent transabdominal amniocentesis, and the diagnostic indices of the cervicovaginal fluid fFN test were calculated. The results showed that a cervicovaginal fluid fFN concentration of ≥125 ng/mL had high sensitivity, specificity, and positive likelihood ratio for identifying intra-amniotic inflammation. The authors conclude that this test can serve as a non-invasive liquid biopsy for intra-amniotic inflammation. [Extracted from the article]

Objective: We present 45,X/46,XX at amniocentesis associated with cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes and in different amniocenteses and a favorable fetal outcome with a normal karyotype at birth. Case report: A 35-year-old, gravida 3, para 2, woman underwent amniocentesis at 20 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,X[11]/46,XX[108], consistent with 9.2% mosaicism for 45,X. Prenatal ultrasound findings were unremarkable. She was referred for genetic counseling at 25 weeks of gestation, and repeat amniocentesis at 26 weeks of gestation revealed a karyotype of 45,X[4]/46,XX[16], consistent with 20% mosaicism for 45,X. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes using SurePrint G3 Unrestricted CGH ISCA v2, 8 × 60K (Agilent Technologies, Santa Clara, CA, USA) revealed arr (1–22, X) × 2, Y × 0 with no genomic imbalance. The woman was advised to continue pregnancy, and at 38 weeks of gestation, a healthy 3140-g female baby was delivered with no phenotypic abnormalities. The cord blood had a karyotype of 46,XX (40/40 cells). When follow-up at age two months, the neonate had normal development and a normal karyotype. Conclusion: Confirmation of 45,X/46,XX at amniocentesis should include conventional cytogenetic analysis and karyotyping on cultured amniocytes, and sole molecular analysis on uncultured amniocytes may miss the diagnosis of 45,X/46,XX.

Abstract Background Mucopolysaccharidosis VI (MPS VI) or Maroteaux–Lamy syndrome is an autosomal recessive lysosomal storage disorder. Clinical manifestations are related to progressive accumulation of dermatan sulfate (DS). Two-dimensional electrophoresis has traditionally been used for the diagnosis of MPS disorders. The method is only qualitative and is time consuming. For prenatal diagnosis of MPS, 6–8 ml of amniotic fluid is required and 5 working days to complete. It needs personal experience to do the test and to interpret the results. Mass spectrometry (MS) is now available as a quantitative method and for prenatal diagnosis of MPS it needs less amniotic fluid and takes only 2 working days. It is more accurate, less person dependent, but it costs more. Our aim was to introduce quantitative determination of dermatan sulfate using mass spectrometry in the prenatal diagnosis of MPS VI in Egypt and to compare this technique to the classical qualitative diagnosis using two-dimensional electrophoresis (2-DEP) of the glycosaminoglycans (GAGs) in amniotic fluid. Thirty pregnant females each with single fetus were subjected to amniocentesis at 16 weeks gestation. Ten with a previously affected MPS VI infant and twenty served as controls. Prenatal diagnosis (PD) was done by both MS and 2-DEP. Results MS verified 2-DEP results which showed 5 affected and 5 non-affected fetuses with MPS VI. Conclusion Two-dimensional electrophoresis of the GAGs in amniotic fluid is a good qualitative method and MS was an accurate quantitative method for prenatal diagnosis of MPS type VI. Quantitative determination of GAGs in AF by mass spectrometry is quicker. Where prenatal diagnosis is recommended for at risk pregnancies, mass spectrometry could be used more in the future as it gives rapid and accurate results.

Objective: We present prenatal diagnosis of maternal uniparental disomy (UPD) 21 in association with low-level mosaic trisomy 21 at amniocentesis in a pregnancy associated with intrauterine growth restriction (IUGR) and a favorable outcome. Case report: A 42-year-old, gravida 2, para 0, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis initially revealed a karyotype of 46,XX in 20/20 colonies of cultured amniocytes. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed a result of arr [GRCh37] (21) × 3 [0.16], (X) × 2, compatible with mosaic trisomy 21. After extensive investigation, the final result of conventional cytogenetic analysis of cultured amniocytes was 47,XX,+21[1]/46,XX[40]. The parental karyotypes were normal. Repeat amniocentesis was performed at 21 weeks of gestation. The cultured amniocytes had a karyotype of 47,XX,+21[3]/46,XX[27] and the uncultured amniocytes had a mosaic trisomy 21 level of 8.8% (10/114 cells) by interphase fluorescence in situ hybridization (FISH), a mosaic trisomy 21 level of 10% (log2 ratio = 0.08) by aCGH, and maternal UPD 21 by polymorphic DNA marker analysis. Prenatal ultrasound revealed IUGR. At 38 weeks of gestation, a phenotypically normal 2695-g baby was delivered. The cord blood and umbilical cord had the karyotype of 46,XX and maternal UPD 21. The placenta had a karyotype of 47,XX,+21[8]/46,XX[32] and a maternal origin of trisomy 21. Postnatal FISH analysis on 101 buccal mucosal cells showed 6.9% (7/101 cells) mosaicism compared with 2% (2/100 cells) in the normal control. The baby was doing well at age four months. Conclusion: Pregnancy with low-level mosaic trisomy 21 and maternal UPD 21 at amniocentesis can be associated with IUGR and a favorable outcome. Fetuses with maternal UPD 21 can be associated with mosaic trisomy 21 at amniocentesis.

Objective: We present detection of maternal uniparental disomy (UPD) 9 in association with low-level mosaic trisomy 9 at amniocentesis in a pregnancy associated with intrauterine growth restriction (IUGR), an abnormal first-trimester maternal serum screening result, abnormal non-invasive prenatal testing (NIPT), maternal preeclampsia and a favorable outcome. Case report: A 37-year-old, primigravid woman underwent first-trimester maternal serum screening and NIPT at 11 weeks of gestation, which revealed a gene dosage increase in chromosome 9 and low levels of plasma protein-A (PAPP-A) and placental growth factor (PlGF) in maternal blood. The woman underwent amniocentesis at 16 weeks of gestation, which revealed a karyotype of 47,XX,+9[4]/46,XX[35] in cultured amniocytes. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed a result of arr [GRCh37] (9) × 3 [0.14] (X) × 2, compatible with mosaic trisomy 9. The parental karyotypes were normal. Repeat amniocentesis was performed at 20 weeks of gestation. The cultured amniocytes had a karyotype of 47,XX,+9[1]/46,XX[23]. The uncultured amniocytes had a mosaic trisomy 9 level of 10.7% (12/112 cells) by interphase fluorescence in situ hybridization (FISH), a mosaic trisomy 9 level of 10–14% (log2 ratio = 0.1) by aCGH, and maternal uniparental isodisomy 9 by polymorphic DNA marker analysis. Prenatal ultrasound revealed IUGR, and the mother had preeclampsia. At 29 weeks of gestation, a 1054-g phenotypically normal baby was delivered because of preterm labor. The cord blood and umbilical cord had the karyotype of 46, XX and maternal UPD 9 and isodisomy 9, while the placenta had trisomy 9 of maternal origin. Postnatal FISH anlaysis on 101 buccal mucosal cells and 100 urinary cells at age three months detected no trisomy 9 signals. The baby was doing well at age six months. Conclusion: Pregnancy with low-level mosaic trisomy 9 and maternal UPD 9 at amniocentesis can be associated with IUGR, maternal preeclampsia and a favorable outcome. Fetuses with maternal UPD 9 can be associated with an abnormal NIPT result concerning chromosome 9, an abnormal first-trimester maternal serum screening result (low PAPP-A and low PlGF) and mosaic trisomy 9 at amniocentesis.

Objective  The aim of this study is to evaluate high-risk pregnant females' offspring as regard the presence of any medical condition, hereditary disorder, or major anomaly as well as to document parental sociodemographic characteristics and compliance with follow-up schedules of fetal medicine and clinical genetic clinics. Study Design  This prospective 2-year cohort study of neonates and infants reported the referral indications, investigations, and diagnoses obtained through prenatal and postnatal examinations. It also reported their parental follow-up vigilance. Results  Of the 811 infants of high risk females referred 460 (56.7%) came for assessment. Mean parental consanguinity and endogamy were 67 and 71.3%, respectively. All pregnant mothers underwent first-trimester biochemical testing (plasma protein-A, α-fetoprotein [AFP], human chorionic gonadotropin [hCG]) and serial ultrasound examinations. Seventy mothers needed second-trimester biochemical testing (AFP, hCG, and estriol). Sixty-two mothers underwent amniocentesis where G-banding karyotype, fluorescence in situ hybridization and targeted molecular testing for the specific gene mutation of single gene disorders were conducted according to suspected disorders. High quality fetal ultrasound was performed when brain malformations were suspected, while 16 fetuses required brain MRI examination. Mean age of newborns at first examination was 26.5 days. They were grouped according to the maternal indication for referral. Upon examination, 18 neonates had confirmed congenital malformations/genetic disorders. Five of them were diagnosed prenatally. In four other fetuses with single gene disorder, the molecular diagnosis of their affected siblings was not established prior to this pregnancy; thus, prenatal diagnosis was not possible. The remaining nine cases were diagnosed postnatally. Conclusion  Parental consanguinity and endogamy were increased among high-risk pregnancies. Public awareness about potential adverse effects of consanguineous marriages and the importance of genetic testing are imperative. A structured multidisciplinary team of specialists in fetal medicine, clinical genetics, and neonatology provides good genetic services. Expansion and financial support of these services are urgently required. Key Points A multidisciplinary team provides good genetic services in high-risk pregnancies. Parental consanguinity and endogamy are increased among high-risk pregnancies. Increased public awareness about genetic testing importance and financial support are imperative. [ABSTRACT FROM AUTHOR]

To evaluate the rate of mid-trimester microbial invasion of the amniotic cavity (MIAC) in asymptomatic women and its association with preterm birth. This is a prospective cohort study of asymptomatic women undergoing mid-trimester amniocentesis for genetic testing between 14 and 24 weeks of gestation. For each participant, a sample of amniotic fluid was incubated in an aerobic and anaerobic facultative culture media and another sample was tested for the presence of specific Mycoplasma species (Ureaplasma urealyticum, Ureaplasma parvum, and Mycoplasma hominis) using quantitative-PCR. Results were not revealed to the participants or their health care providers. All participants were followed until delivery. MIAC was defined by a positive culture or a positive PCR for Mycoplasma species. The primary outcome was a spontaneous preterm birth or preterm premature rupture of membranes before 35 weeks of gestation. We included 812 women at a median gestational age of 16 5/7 (interquartile: 15 6/7–17 4/7) weeks. Twenty-six (3.2%) had a spontaneous delivery before 35 weeks. We observed no case of positive PCR for Mycoplasma species and 4 (0.5%) cases of positive culture that were all considered to be skin contaminants. None of those four cases was associated with preterm birth. Nulliparity, low family income and history of preterm birth were associated with spontaneous delivery before 35 weeks. We found no case of mid-trimester MIAC using a combination of culture and Mycoplasma-specific PCR techniques in a large cohort of low-risk asymptomatic pregnant women. We estimate that mid-trimester MIAC is rare in low-risk population but more sensitive and broad-range microbiologic techniques, such as 16S DNA detection by PCR, could be further evaluated. [ABSTRACT FROM AUTHOR]

To investigate the amino acid (AA)-related metabolic characteristics of amniotic fluid (AF) obtained by ultrasound-guided amniocentesis from fetuses with isolated choroid plexus cysts of the central nervous system. Ultrasound-guided amniocentesis was performed on 17 fetuses with isolated choroid plexus cysts (ICPCs) and 17 normal fetuses. The AF samples from normal pregnancies were matched with the case samples in a 1:1 ratio based upon gestational age. The AF samples from the 34 fetuses were analyzed by liquid chromatography–mass spectrometry (LC–MS). Then, the peak areas of the metabolites were analyzed by principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and univariate statistical analysis. This study ultimately identified 31 AAs. Seven differentially abundant AAs were screened out, including citrulline, ethanolamine, aspartic acid, valine, 5-hydroxylysine, proline, and isoleucine (p-value<0.05). A total of 4 metabolic pathways were significantly altered in the ICPC group: valine, leucine and isoleucine biosynthesis; valine, leucine and isoleucine degradation; pantothenate and coenzyme A (CoA) biosynthesis; and arginine biosynthesis. The results of this study indicate that fetuses with ICPC have disrupted levels of citrulline, ethanolamine, aspartic acid, valine, 5-hydroxylysine, proline, and isoleucine, which may ultimately affect fetal glucose and lipid metabolism. [ABSTRACT FROM AUTHOR]

In a partial molar pregnancy, the level of β-Human chorionic gonadotropin (β-HCG) is often within a large spectrum. An extremely high level of β-HCG levels (>1.000.000) is only 2-3% of partial moles. Partial molar pregnancy commonly presented with mildly elevated HCG (<100,000), vaginal bleeding, abortion and rarely complicated with medical complications and theca lutein cysts. We present a case with extremely high HCG levels (1.861.011 IU / L) in the early second trimester and complicated by maternal anemia, hyperthyroidism, proteinuric hypertension, hirsutism, and enlarged bilateral theca lutein cysts. During follow-up, the patient's HCG level returned to normal after 27 weeks. Clinicians should keep in mind that partial mole hydatidiform may be presented with very high HCG levels. They should be aware of the medical conditions that may complicate this disease and adopt a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

Sophisticated screening protocols for genetic abnormalities constitute an important component of current prenatal care, aiming to identify high-risk pregnancies and offer appropriate counseling to parents regarding their options. Definite prenatal diagnosis is only possible by invasive prenatal diagnostic testing (IPDT), mainly including amniocentesis and chorionic villous sampling (CVS). The aim of this comparative review was to summarize and compare the existing recommendations on IPDT from the most influential guidelines. All the reviewed guidelines highlight that IPDT is indicated based on a positive screening test rather than maternal age alone. Other indications arise from medical history and sonography, with significant variations identified between the guidelines. The earlier time for amniocentesis is unequivocally set at ≥15 gestational weeks, whereas for CVS, the earlier limit varies from ≥10 to ≥11 weeks. Certain technical aspects and the overall approach demonstrate significant differences. Periprocedural management regarding Rhesus alloimmunization, virologic status and use of anesthesia or antibiotics are either inconsistent or insufficiently addressed. The synthesis of an evidence-based algorithm for IPDT is of crucial importance to healthcare professionals implicated in prenatal care to avoid unnecessary interventions without compromising optimal prenatal care. [ABSTRACT FROM AUTHOR]

Objective: Tetrasomy 9p and trisomy 9p are rare chromosomal aberrations. The phenotypes of tetrasomy 9p and trisomy 9p are variable. Most cases are diagnosed in the postnatal period. The study aims to analyze the prenatal phenotype of tetrasomy 9p and trisomy 9p in terms of ultrasound and screening tests. Methods: A set of 1573 prenatal tests performed from 2016 to 2021 was reviewed to identify all cases with trisomy 9p and tetrasomy 9p. In four cases with 9p gain, non-invasive and invasive test results were analyzed. Results: Four cases with the 9p gain were diagnosed in the prenatal period: two cases with tetrasomy 9p and two cases with trisomy 9p. Nasal bone hypoplasia and ventriculomegaly are common features of 9p gain. In two out of four cases with the 9p gain, an increased risk of trisomy 21 was found in the combined firsttrimester screening test. Conclusion: Trisomy 9p and tetrasomy 9p are characterized by a variable phenotype in the prenatal period, manifesting in genetically abnormal fetuses. The tetrasomy 9p and trisomy 9p may suggest trisomy 21 in the first trimester. [ABSTRACT FROM AUTHOR]

Can preimplantation genetic testing for structural rearrangement (PGT-SR) based on low-coverage next-generation sequencing (NGS) accurately discriminate between normal and carrier embryos of reciprocal translocation (RecT) and Robertsonian translocation (RobT)? A total of 109 couples with RecT or RobT were included in this study. The ages, bad obsteric histories (BOH), blood karyotype and IVF cycle information, including the number of cumulus–oocyte complexes, metaphase II oocytes, two pronuclei oocytes and blastocysts were recorded. 0.1 × whole genome sequencing (WGS) of embryos followed by copy number variation (identifying unbalanced/balanced) and 2 × WGS of parents and embryos followed by haplotype analysis (discriminating between normal and carrier) were carried out in PGT-SR cycles. The embryos without translocation were transferred and clinical outcomes evaluated. Among all the couples in this study, 67 patients had RecT and 42 had RobT. After unbalanced and balanced detection, 103 balanced embryos underwent a further normal and carrier discrimination procedure, and 53 normal embryos were identified. Finally, 32 normal embryos were transferred, with an ongoing pregnancy rate of 46.88% (15/32). All ongoing pregnancies underwent amniocentesis, and the amninocentesis karyotyping results showed 100% concordance with PGT-SR diagnosis. Our low-coverage NGS-based PGT-SR method can accurately discriminate between normal and carrier status of balanced embryos. The method is cost-effective and has broad clinical applicability. [ABSTRACT FROM AUTHOR]

Backgrounds: Toxoplasmosis, a prevalent parasitic infection, is primarily caused by Toxoplasma gondii (T. gondii). This infection poses a significant threat to neonates during pregnancy and individuals with compromised immune systems. Consequently, it is imperative to develop a novel diagnostic approach that combines high sensitivity with low-risk sampling to effectively manage patients. The aim of this study is to utilize serological and molecular techniques for the diagnosis of T. gondii infection in 100 pregnant women who were under the care of a gynecologist and were candidates for amniocentesis., Methods: During the 15-19th weeks of pregnancy, a total of 100 samples each of amniotic fluid, buffy coat, plasma, and urine simultaneously were collected from pregnant women candidates for amniocentesis in Mazandaran province, northern Iran. This study involved various assessments: (1) detecting anti-T. gondii IgM and IgG in plasma through chemiluminescence assay (2) determining IgG avidity in plasma using the Enzyme-linked immunosorbent assay technique (3) identifying of T. gondii DNA in amniotic fluid, buffy coat and urine by nested PCR (nPCR) and quantitative real-time PCR (qPCR) methods targeting the REP-529 gene, as well as genotyping using GRA6 target genes, and (4) assessing the sensitivity and specificity of the nPCR and qPCR tests., Results: Out of 100 pregnant women screened, 70 were between the ages of 31 to 40 years old. Among them, 23 and 44 had one and two previous pregnancies. Additionally, 13 and 8 women had one and two history of abortions, respectively. Following serologic testing, 52% of the individuals were positive for T. gondii antibodies. Of these, 52 samples were positive for IgG antibodies, and one sample was positive for both IgG and IgM antibodies. Notably, all 52 cases with IgG positivity exhibited a high level of IgG avidity. Regarding the molecular testing of amniotic fluid samples, two pregnant women tested positive in the nPCR assay, while three tested positive in the qPCR assay. Furthermore, genotyping revealed that all positive samples belonged to type I of the T. gondii genotype. Moreover, none of the 100 buffy coat and urine samples tested positive for T. gondii using the nPCR and qPCR techniques., Conclusion: The findings of the current study suggest that serological methods alone may not be reliable in diagnosing congenital toxoplasmosis and cannot rule out the diagnosis of toxoplasmosis and must be approved by molecular tests., Competing Interests: Declarations. Ethics approval and consent to participate: This study was ethically approved by the Ethics Committee of Mazandaran University of Medical Sciences (IR.MAZUMS.REC.1400.11546), and all procedures adhered to ethical rules and principles set forth in the Declaration of Helsinki. Also, Informed consent was obtained from all the participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: To explore the value of applying multiple genetic testing techniques for the prenatal diagnosis of Turner syndrome fetuses with complex mosaic small supernumerary marker chromosomes (sSMC)., Methods: Chromosomal karyotypes of amniotic fluid samples from 5 030 pregnant women who had undergone amniocentesis at the Prenatal Diagnosis Center of the Third Affiliated Hospital of Zhengzhou University from January to December 2022 were retrospectively reviewed. Three fetuses with complex mosaicism fetuses (carrying 2 types of sSMC) were selected as the study subjects. Genetic tests including G-banded chromosomal karyotyping analysis, fluorescence in situ hybridization (FISH), chromosomal microarray analysis (CMA), and copy number variation sequencing (CNV-seq) were used to clarify the origin and mosaic status of the sSMC. This study has been approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (No. 2023-159-01)., Results: G-banded chromosomal analysis of fetus 1 showed a karyotype of 45,X[64]/46,X,+mar1[13]/46,X,+mar2[3]. FISH results showed that 52% of of its cells had contained one X chromosome signal, whilst 48% contained two X chromosome signals. CMA results revealed the fetus had harbored a 32.32 Mb and a 50.93 Mb deletion in Xp22.33p21.1 and Xq22.2q28 regions, respectively, in addition with mosaic deletions of approximately 1.43 copies, 1.78 copies and 1.43 copies in the Xp21.1p11.1, Xq11.1q21.1 and Xq21.2q22.2 regions, respectively. The fetus 2 had a karyotype of 45,X[27]/46,X,+mar1[14]/46,X,+mar2[12]. FISH results indicated that 88% of its cells contained one X chromosomes signal and two Y chromosome signals, and 12% contained signals for one X chromosomes signal and one Y chromosome signal. CNV-seq results revealed a deletion of 7.74 Mb in the Yq11.222q11.23 region and a mosaic duplication of approximately 1.738 copies in the Yp11.31q11.221 region. The fetus 3 had a karyotype of 45,X[60]/46,X,+mar1[11]/46,X,+mar2[6]. FISH results showed that 28% of its cells contained one X chromosome signal, and 72% contained tow X chromosome signals. CNV-seq results revealed deletions of 55.60 Mb and 53.50 Mb in the Xp22.33p11.1 and Xq22.1q28 regions, respectively, along with a mosaic deletion of approximately 1.85 copies in the Xp11.1q13.2 region and a mosaic repeats of approximately 2.66 copies in the Xq13.2q22.1 region. The sSMCs in the 3 fetuses had all originated from sex chromosomes and were of complex mosaic type. After genetic counseling, the three couples had all opted to terminate the pregnancy., Conclusion: The combined use of multiple genetic testing techniques has determined the origin and structure of complex mosaic sSMCs and provided a basis for prenantal diagnosis and genetic counseling.

Background: To assess the effectiveness of rescue cerclage concerning pregnancy and neonatal outcomes in women with acute cervical insufficiency (CI) complicated with intra-amniotic inflammation (IAI) compared with those managed expectantly., Methods: This retrospective cohort study included 87 consecutive singleton pregnant women (17-25 weeks) with acute CI who underwent amniocentesis to assess IAI. Amniotic fluid (AF) samples were assayed for interleukin-6 to define IAI (≥ 2.6 ng/mL). Primary and secondary outcomes were assessed in a subset of CI patients with IAI. The primary outcome measures were spontaneous preterm birth (SPTB) at < 28 and < 34 weeks, and the secondary outcomes were interval from sampling to delivery, neonatal survival, neonatal birth weight, and histologic and clinical chorioamnionitis. Macrolide antibiotics were prescribed depending on the type of microorganism isolated from the AF, clinically suspected IAI, and the discretion of the attending clinician., Results: IAI was identified in 65.5% (57/87) of patients with CI, of whom 73.6% (42/57) were treated with macrolide antibiotics. Among the CI patients with IAI (n = 57), 40 underwent rescue cerclage and 17 were expectantly managed. The rates of SPTBs at < 28 and < 34 weeks were significantly lower and the latency period was significantly longer in the cerclage group than in the group that was managed expectantly. The median birth weight and neonatal survival rate were significantly higher in the cerclage group than in the group that was managed expectantly. However, the rates of histologic and clinical chorioamnionitis did not differ between the groups. Multivariable analyses revealed that rescue cerclage placement and administration of macrolide antibiotics were significantly associated with a decrease in SPTBs at < 28 and < 34 weeks, prolonged gestational latency, and increased likelihood of neonatal survival, after adjusting for possible confounding parameters; however, macrolide antibiotic administration did not reach statistical significance with respect to SPTB at < 34 weeks and neonatal survival ( P = 0.076 and 0.063, respectively)., Conclusion: Rescue cerclage along with macrolide antibiotic treatment may positively impact pregnancy and neonatal outcomes in women with CI complicated by IAI, compared with expectant management. These findings suggest the benefit of cerclage placement even in patients with CI complicated by IAI., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Objective: We present low-level mosaic trisomy 21 at amniocentesis and cordocentesis in a pregnancy associated with a favorable fetal outcome and perinatal progressive decrease of the trisomy 21 cell line., Case Report: A 36-year-old, primigravid woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. This pregnancy was conceived by in vitro fertilization and embryo transfer (IVF-ET). Amniocentesis revealed a karyotype of 47,XY,+21 [3]/46,XY [17] (15% mosaicism) and simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (21) × 2∼3 (X,Y) × 1, consistent with 24.5% mosaicism for trisomy 21. Cordocentesis performed at 21 weeks of gestation revealed a karyotype of 47,XY,+21 [3]/46,XY [37] (6% mosaicism). She was referred for genetic counseling at 31 weeks of gestation, and continuing the pregnancy was advised. The parental karyotypes and prenatal ultrasound were normal. At 37 weeks of gestation, a phenotypically normal baby was delivered with a body weight of 2900-g. The karyotypes of cord blood, umbilical cord and placenta were 47,XY,+21 [1]/46,XY [39] (2.5% mosaicism), 47,XY,+21 [10]/46,XY [30] (25% mosaicism) and 47,XY,+21 [22]/46,XY [18] (55% mosaicism), respectively. Quantitative fluorescent polymerase chain reaction (QF-PCR) analysis on the DNA extracted from umbilical cord and parental bloods excluded uniparental disomy (UPD) 21 and revealed a maternal origin of the extra chromosome 21. When follow-up at the age of 2 months, the neonate was normal in phenotype and development. The peripheral blood had a karyotype of 47,XY,+21 [1]/46,XY [39] (2.5% mosaicism), and interphase fluorescence in situ hybridization (FISH) analysis on uncultured buccal mucosal cells revealed 4.7% (5/105 cells) mosaicism for trisomy 21, compared with 0% (5/100 cells) in the normal control., Conclusion: Low-level mosaic trisomy 21 at amniocentesis and cordocentesis can be associated with favorable fetal outcome and perinatal progressive decrease of the trisomy 21 cell line., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2024. Published by Elsevier B.V.)

Objective: We present first-trimester application of expanded non-invasive prenatal testing (NIPT) in the genetic investigation of fetal 1p36 deletion syndrome associated with a familial unbalanced reciprocal translocation of 46,XX,der(1)t(1;2) (p36.2;q37.3)dmat., Case Report: A 37-year-old, gravida 2, para 0, woman underwent expanded NIPT at 13 weeks of gestation because of advanced maternal age and the fear of complications of invasive procedures of prenatal diagnosis. She had experienced one spontaneous abortion. The pregnancy was conceived by in vitro fertilization and embryo transfer (IVF-ET) because of tubal occlusion. NIPT was positive for 1p36 deletion. At 17 weeks of gestation, she underwent amniocentesis but intrauterine fetal death occurred after amniocentesis and the pregnancy was terminated. Amniocentesis revealed a derivative chromosome 1 with an aberrant short arm terminal segment of chromosome 1. Subsequent cytogenetic analysis of parental bloods showed a karyotype of 46,XY in the father and a karyotype of 46,XX,t(1;2) (p36.2;q37.3) in the mother. The karyotype of amniocytes was 46,XX,der(1)t(1;2) (p36.2;q37.3)dmat, consistent with partial monosomy 1p (1p36.2→pter) and partial trisomy 2q (2q37.3→qter). Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes revealed the result of arr 1p36.33p36.22 (852,863-11,303,452) × 1.0 and arr 2q37.3 (242,785,405-243,068,396) × 3.0 [GRCh 37] with a 10.451-Mb deletion of 1p36.33-p36.22 encompassing 116 OMIM genes including RERE and a 283-kb duplication of 2q37.3 encompassing one OMIM gene of PDCD1., Conclusion: Expanded NIPT has the advantage of early detection of familial unbalanced reciprocal translocation in the fetus., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2024. Published by Elsevier B.V.)

Objective: We present prenatal diagnosis of a 14-Mb 11p11.2-p13 deletion by chromosome microarray analysis (CMA) in a pregnancy with fetal recombinant chromosome 11 syndrome of rec(11)del(11) (p11.2p13)ins(11) (q21p11.2p13) and maternal intrachromosomal insertion of ins(11) (q21p11.2p13)., Case Report: A 25-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of a family history of psychiatric disorders in her two brothers and one maternal uncle. Array comparative genomic hybridization (aCGH) analysis of amniocentesis revealed a 14-Mb 11p13p11.2 deletion. The pregnancy was terminated at 19 weeks of gestation, and a 252-g fetus was delivered. Cytogenetic analysis of the parental bloods and cord blood revealed a karyotype of 46,XX,ins(11) (q21p11.2p13) in the mother, 46,XY in the father and 46,XY,rec(11)del(11) (p11.2p13)ins(11) (q21p11.2p13) in the fetus. aCGH analysis on the DNA extracted from cord blood revealed the result of arr 11p13q11.2 (32,697,424-46,712,173) × 1.0 [GRCh37] with a 14-Mb deletion of 11p13-p11.2 encompassing 54 OMIM genes including PHF21A, ALX4, EXT2 and SLC1A2. Polymorphic DNA marker analysis showed a maternal origin of the 11p deletion. The present case had an 11p13-p11.2 deletion encompassing 11p12-p11.3 which is associated with Potocki-Shaffer syndrome (PSS) or chromosome 11p11.2 deletion syndrome., Conclusion: CMA is useful for prenatal detection of fetal genomic imbalance in case of familial intrachromosomal insertion., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2024. Published by Elsevier B.V.)

Objective: We present prenatal diagnosis of mosaic trisomy 21 at amniocentesis associated with unbalanced Robertsonian translocation in the fetus and a favorable fetal outcome., Case Report: A 41-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Her husband was 41 years old. Amniocentesis revealed a karyotype of 46,XX,+21,der(21;21) (q10;q10)[8]/46,XX[18], consistent with 30.8% (8/26 colonies) mosaicism for trisomy 21. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (1-22,X) × 2 with no genomic imbalance. Repeat amniocentesis at 21 weeks of gestation revealed a karyotype of 46,XX,+21,der(21;21) (q10;q10)[2]/46,XX[25], consistent with 7.4% (2/27 colonies) mosaicism for trisomy 21. Cord blood sampling revealed the result of 46,XX and rsa X(P095) × 2, 13,18,21(P095) × 2. Prenatal ultrasound findings were normal. At 23 weeks of gestation, she underwent cord blood sampling which revealed a karyotype of 46,XX. At 26 weeks of gestation, she was referred for genetic counseling. No repeat amniocentesis and continuing the pregnancy were advised. The mother had a karyotype of 46,XX, and the father had a karyotype of 46,XY. At 38 weeks of gestation, a 3476-g, phenotypically normal baby was delivered. The cord blood had a karyotype of 46,XX,+21,der(21;21) (q10;q10)[1]/46,XX[39] (2.5% mosaicism). The placenta had a karyotype of 46,XX,+21,der(21;21) (q10;q10) (40/40 cells). When follow-up at age two months, the neonate was normal in phenotype and development. The peripheral blood had a karyotype of 46,XX (40/40 cells), and aCGH analysis on buccal mucosal cells resulted no genomic imbalance., Conclusion: Low-level mosaic trisomy 21 at amniocentesis due to mosaic unbalanced Robertsonian translocation with a normal cell line can be associated with a favorable fetal outcome, cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, cytogenetic discrepancy among various tissues and perinatal progressive decrease of the trisomy 21 cell line., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2024. Published by Elsevier B.V.)

Objective: We present prenatal diagnosis of Jacobsen syndrome associated with a distal 11q deletion and a distal 8q duplication by chromosome microarray analysis (CMA) in a fetus with multiple congenital anomalies on fetal ultrasound., Case Report: A 41-year-old, gravida 2, para 1, woman underwent amniocentesis at 25 weeks of gestation because of intrauterine growth restriction, endocardial cushion defect, clenched hands, arthrogryposis, rocker bottom feet and craniosynostosis on fetal ultrasound. Amniocentesis revealed a karyotype of 46,XX,add(11)(q23.3). Array comparative genomic hybridization (aCGH) analysis of the DNA extracted from the uncultured amniocytes revealed the result of arr 8q24.13q24.3 × 3, 11q23.3q25 × 1. Analysis of FGFR2 revealed no mutation. The karyotype was 46,XX,der(11)t(8;11)(q24.13;q23.3). The parental karyotypes were normal. The pregnancy was subsequently terminated, and a dead malformed fetus was delivered with craniofacial dysmorphism of low-set malformed ears, depressed nasal bridge, hypertelorism, small mouth, clenched hands and rocker bottom feet. Cytogenetic analysis of the placenta revealed a karyotype of 46,XX,der(11)t(8;11)(q24.13;q23.3). aCGH analysis of the DNA extracted from the umbilical cord showed the result of arr 8q24.13q24.3 (126,302,369-146,280,020) × 3.0, arr 11q23.3q25 (120,469,928-134,868,407) × 1.0 [GRCh37] with a 19.978-Mb duplication of 8q24.13-q24.3 and a 14.398-Mb deletion of 11q23.3-q25 encompassing the genes of BSX, ETS1, FLI1 and ARHGAP32., Conclusion: CMA is useful for detection of de novo chromosomal rearrangement in the fetus with multiple congenital anomalies on fetal ultrasound., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2024. Published by Elsevier B.V.)

Aim: We aimed to assess the amniotic fluid glucose concentration cut-off as an indicator of fetal chromosomal abnormalities, such as trisomy 13, 18, and 21., Methods: This prospective observational study included pregnant females who underwent amniocentesis. Participants were divided into two groups on the border of 22 weeks of gestational age (<22 and ≥22-week groups)., Results: In total, 224 pregnant females were included in the analysis. In the <22 week group, 15 females had trisomies 13/18/21 and 174 females had no trisomies. In the ≥22 week group, 18 females had trisomies 13/18/21 and 17 had no trisomies. In each group, there was a difference in amniotic fluid glucose concentration between fetuses with trisomies 13, 18, and 21 and other fetuses with normal karyotype or minor chromosomal abnormalities. In both groups, the amniotic glucose concentration was noticeably lower in trisomies 13/18/21 (p = 0.002 in the <22 week group; p = 0.039 in the ≥22 week group). According to receiver operating characteristic curves, the optimal cut-off point of glucose concentration was 46 mg/dL in the <22 week group (odds ratio 6.55; 95% confidence interval 1.78-24.1) and 24 mg/dL in the ≥22 week group (odds ratio 8.40; 95% confidence interval 1.83-38.6)., Conclusions: Our study suggested that glucose concentration in amniotic fluid is an indicator of trisomy 13, 18, and 21. Amniotic fluid glucose concentration itself does not diagnose fetal trisomy, but this may be helpful in selecting treatment facilities., (© 2024 Japan Society of Obstetrics and Gynecology.)

Introduction: Intra-amniotic inflammation is causally linked to spontaneous preterm labor. The gold standard for the diagnosis of intra-amniotic inflammation is the determination of an amniotic fluid profile obtained from transabdominal amniocentesis, which is invasive. Cervicovaginal fluid fetal fibronectin (fFN) is a widely-used predictive biomarker for spontaneous preterm labor. The aims of this study are to determine (1) whether a quantitative cervicovaginal fluid fFN test can be used to identify the presence of intra-amniotic inflammation; and (2) an appropriate cut-off value of a cervicovaginal fluid fFN concentration for the identification of intra-amniotic inflammation., Material and Methods: This prospective cohort study included 78 patients with preterm labor and intact membranes who had a sample collected for quantitative cervicovaginal fluid fFN measurement and underwent transabdominal amniocentesis. Intra-amniotic inflammation was defined as an amniotic fluid interleukin-6 concentration ≥2.6 ng/mL. Clinicians were masked from the results of cervicovaginal fluid fFN and amniotic fluid interleukin-6 concentrations. Logistic regression analysis was used to determine which factors were significant predictors of intra-amniotic inflammation. The diagnostic indices of the cervicovaginal fluid fFN test for the identification of intra-amniotic inflammation were calculated., Results: (1) Frequency of intra-amniotic inflammation was 26.9% (21/78); (2) the higher the cervicovaginal fluid fFN concentration, the greater the risk of intra-amniotic inflammation (p < 0.001); (3) cervicovaginal fluid fFN concentration ≥125 ng/mL had an area under the curve of 0.91 (95% confidence interval: 0.83-0.96) for the identification of intra-amniotic inflammation with 100% sensitivity, 100% negative predictive value, 82.46% specificity and a positive likelihood ratio of 5.7; and (4) cervicovaginal fluid fFN cut-off of 125 ng/mL had a significant higher predictive performance than the traditional cut-off (50 ng/mL) for the identification of intra-amniotic inflammation., Conclusions: Quantitative cervicovaginal fluid fFN with a cut-off of 125 ng/mL had a high sensitivity and a negative predictive value as well as a positive likelihood ratio for the identification of intra-amniotic inflammation. Its high sensitivity and negative predictive value can be used to decrease an index of suspicion of intra-amniotic inflammation. This test may be useful as an initial assessment test to select appropriate patients for amniocentesis to determine intra-amniotic inflammation., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Purpose: In some cases of prenatal genetic testing, an ample amount of fetal DNA is needed, to allow for parallel testing (conducting several genetic tests simultaneously). This study investigated the association between amniotic fluid DNA concentration and various factors. We aimed to define the required amount of amniotic fluid to be extracted in amniocentesis, to allow parallel testing throughout gestational weeks., Methods: DNA concentration was analyzed from amniocentesis samples taken during the years 2016-2022. Sex association was also analyzed in postnatal whole blood samples from a separate cohort. Theoretical minimum volume of amniotic fluid needed to ensure enough DNA for chromosomal microarray analysis and exome sequencing was calculated., Results: We focused our analysis on 2573 samples, which were taken during weeks 17-23 and 30-35. DNA concentrations increased from weeks 17 to 21, with relatively stable concentrations thereafter. Significantly higher DNA concentrations were seen in pregnancies of female fetuses. DNA concentrations in postnatal whole blood samples did not show this association. Across most weeks, the volume needed to extract 2 µg of DNA from 95% of the samples was about 34 ml., Conclusion: DNA concentrations in amniotic fluid vary according to gestational age and are higher in pregnancies of female fetuses. This should be considered when determining the volume of fluid extracted and the timing of amniocentesis, with greater volumes needed in earlier stages of pregnancy., (© 2024. The Author(s).)

Purpose: This study aims to analyze whether undergoing amniocentesis during pregnancy in women diagnosed with hepatitis B virus (HBV) infection leads to HBV transmission to newborns., Methods: Retrospective data collection was conducted from June 2019 to November 2022 on expectant mothers positive for hepatitis B surface antigen (HBsAg) who underwent amniocentesis at The Third Affiliated Hospital of Sun Yat-sen University, along with data on their newborns. The study summarized the HBV infection status of newborns born to mothers with different expressions of hepatitis B e antigen (HBeAg), antiviral treatment versus no treatment, and different HBV DNA viral loads before delivery., Results: In this study, 346 expectant mothers tested positive for HBsAg, along with 351 newborns (including 5 sets of twins, with 8 infants (2.28%) testing HBsAg-positive at birth. All newborns received dual immunotherapy and were followed up. At 7-12 months, retesting for HBsAg positivity and HBV DNA positivity among infants revealed that out of the infants born with HBsAg positivity, 7 cases had seroconverted to negative, while the remaining infant, who was positive for both HBsAg and HBeAg at birth, tested positive for both HBsAg and HBV DNA at 7-12 months. Thus, one case of vertical transmission of hepatitis B from mother to child occurred in this study. The proportion of infants born with HBsAg + among newborns born to HBeAg-positive mothers (4 cases, 6.06%) was significantly higher than that among newborns born to HBeAg-negative mothers (4 cases, 1.41%) (P < 0.05). The proportion of infants born with HBsAg + showed no significant difference between newborns born to mothers receiving antiviral therapy (2 cases, 2.90%) and those born to mothers not receiving antiviral therapy (6 cases, 2.13%) (P > 0.05). Among expectant mothers with viral load ≥ 6 log 10 IU/mL before delivery, 3 newborns (30.00%) were manifesting HBsAg positivity at birth, significantly higher than the group with viral load < 6 log 10 IU/mL before delivery (5 cases, 1.47%) (P < 0.05)., Conclusion: Among HBsAg-positive expectant mothers, only a small number of infants are infected with the hepatitis B virus at birth, the proportion of which is relatively low. Infants born to mothers who are HBeAg-positive or have a viral load ≥ 6 log10 IU/mL have a higher risk of being born positive., (© 2024. The Author(s).)

Objective: To document the course of neonatal and short-term outcomes in pregnancies after first trimester CMV (cytomegalovirus) seroconversion and negative amniotic fluid (AF) CMV PCR., Methods: We included 375 patients with a first-trimester CMV seroconversion and amniocentesis at ≥21 weeks. Termination of pregnancy (TOP) was offered in case antenatally severe CMV-related fetopathy was documented either by ultrasound or by MRI. AF CMV PCR-negative fetuses underwent a PCR CMV on neonatal urine (NU). Perinatal and short-term infant outcomes were investigated by a questionnaire, sent to parents., Results: AF CMV PCR was positive in 118/375 cases (31.4%). TOP was performed in 46/118 (38.9%) and fetal demise occurred twice. Questionnaires were sent to 327 patients with an overall response rate of 77%. Three groups were considered: Group 1: the early infected group (AF CMV PCR positive; N=62), group 2: the late infected group (AF CMV PCR negative, NU CMV PCR positive; N=7) and group 3: the control group (AF+NU CMV PCR negative; N=160). Compared with group 3, group 1 was more frequently symptomatic at birth (6.2% vs 19.4%; p=0.006). In short-term follow-up, hearing impairment (23.5%; p<0.001), mild motor deficit - defined as abnormal early motor development or the need for physiotherapy in later life (21.6%; p=0.005) - and subnormal vision (15.7%; p=0.02) were significantly more frequent. Compared with group 3, group 2 showed more often jaundice (57.1%; p=0.04) and petechiae (28.6%; p=0.04) at birth, but other short-term symptoms were lacking., Conclusion: Although neonates may screen positive on urine for CMV after an AF CMV negative PCR, they show rarely and only mild sequelae in early life., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We present low-level mosaic trisomy 14 at amniocentesis., Case Report: A 37-year-old, gravida 2, para 1, woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. This pregnancy was conceived by in vitro fertilization and embryo transfer (IVF-ET). Amniocentesis revealed a karyotype of 47,XX,+14 [4]/46,XX [27], consistent with 12.9% mosaicism for trisomy 14. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (1-22, X) × 2 with no genomic imbalance. Prenatal ultrasound findings were unremarkable. She was referred for genetic counseling at 21 weeks of gestation and was offered expanded non-invasive prenatal testing (NIPT) which was positive for trisomy 14. At 24 weeks of gestation, she underwent repeat amniocentesis which revealed a karyotype of 47,XX,+14 [2]/46,XX [26], consistent with 7% mosaicism for trisomy 14. The parental karyotypes were normal. Simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes revealed no genomic imbalance. Polymorphic marker analysis excluded uniparental disomy (UPD) 14. Interphase fluorescence in situ hybridization (FISH) analysis on 104 uncultured amniocytes detected no trisomy 14 cell. At 35 weeks of gestation, a 2315-g phenotypically normal baby was delivered. The umbilical cord and placenta had the karyotype of 46, XX (40/40 cells). aCGH analysis on the DNA extracted from peripheral blood and buccal mucosal cells at the age of three months revealed no genomic imbalance. The neonate was normal in phenotype and development during postnatal follow-ups., Conclusions: Low-level mosaic trisomy 14 at amniocentesis can be associated with cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, perinatal progressive decrease of the trisomy 14 cell line and a favorable fetal outcome., Competing Interests: Declaration of competing interest The author has no conflicts of interest relevant to this article., (Copyright © 2024. Published by Elsevier B.V.)

Genetic counseling of mosaic and non-mosaic tetrasomy 9p remains difficult because of the possible associated congenital abnormalities, cytogenetic discrepancy in various tissues, true-positive and false-positive diagnosis in non-invasive prenatal testing (NIPT), uniparental disomy (UPD) 9, tissue-limited mosaicism, perinatal progressive decrease of the aneuploid cell line, phenotypic normal carriers and possible favorable fetal outcome in the cases with mosaic tetrasomy 9p at amniocentesis. This article presents a comprehensive review of various counseling issues concerning mosaic and non-mosaic tetrasomy 9p at prenatal diagnosis, and the information provided is very useful for genetic counseling under such circumstances., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2024. Published by Elsevier B.V.)

Genetic counseling of mosaicism for a deletion due to partial monosomy in a cell line with 46 chromosomes associated with a normal cell line at amniocentesis remains difficult because mosaic deletion due to partial monosomy has been reported to be associated with either normal or abnormal phenotype in prenatal diagnosis. This article makes a comprehensive review of the reported cases of mosaicism for a deletion due to partial monosomy in a cell line with 46 chromosomes associated with a normal cell line at amniocentesis and various counseling issues such as culture artefact, cytogenetic discrepancy between cultured and uncultured amniocytes and among various tissues, perinatal progressive decrease of the abnormal cell line and a possible favorable fetal outcome. The information provided is useful for obstetricians and genetic counselors during genetic counseling of the parents who wish to keep the babies under such a circumstance., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2024. Published by Elsevier B.V.)

Genetic counseling of mosaicism for balanced translocation with a normal cell line at amniocentesis is not difficult because most of the reported cases have normal phenotypes. However, genetic counseling of mosaicism for unbalanced translocation with a normal cell line at amniocentesis remains difficult because cases with mosaic unbalanced translocation with a normal cell line at prenatal diagnosis have been reported to be associated with either normal or abnormal phenotype. This article makes a comprehensive review of the reported cases of de novo or familial mosaic unbalanced translocation with a normal cell line and various counseling issues such as meiotic event, post-zygotic mitotic event, culture artefact, chimerism, uniparental disomy (UPD), jumping translocation, cytogenetic discrepancy between cultured and uncultured amniocytes and among various tissues, perinatal progressive decrease of the unbalanced translocation cell line and a possible favorable fetal outcome. The information provided is useful for obstetricians and genetic counselors during genetic counseling of the parents who wish to keep the babies under such a circumstance., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2024. Published by Elsevier B.V.)

Competing Interests: Declaration of competing interest The author has no conflicts of interest relevant to this article.

Objective: We present mosaic distal 13q duplication due to mosaic unbalanced translocation 46,XY,der(14)t(13;14)(q32.2;p13)/46,XY at amniocentesis in a pregnancy associated with a favorable fetal outcome., Case Report: A 37-year-old, gravida 2, para 0, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY, add(14) (p13)[17]/46,XY[13] (56.6% mosaicism). Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes revealed arr 13q32.2q34 × 2∼3, consistent with 45% mosaicism for distal 13q duplication. Repeat amniocentesis at 24 weeks of gestation revealed a karyotype of 46,XY,der(14)t(13;14)(q32.2;p13)[14]/46,XY[16] (46.6% mosaicism). The parental karyotypes were normal. aCGH analysis on the DNA extracted from uncultured amniocytes revealed arr 13q32.2q34 × 2.38, consistent with 30-40% mosaicism for distal 13q duplication. Interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes detected 22.8% (23/101 cells) mosaicism for distal 13q duplication. Prenatal ultrasound findings were unremarkable. At 39 weeks of gestation, a 3616-g phenotypically normal baby was delivered. The karyotypes of cord blood, umbilical cord and placenta were 46,XY,der(14)t(13;14)(q32.2;p13)[20]/46,XY[20] (50% mosaicism), 46,XY,der(14)t(13;14)(q32.2;p13)[14]/46,XY[26] (35% mosaicism) and 46,XY (40/40 cells) (0% mosaicism), respectively. When follow-ups at the age of 4½ months and the age of one year, the peripheral blood had the karyotype of 46,XY,der(14)t(13;14)(q32.2;p13)[18]/46,XY[22] (45% mosaicism). Interphase FISH analysis on buccal mucosal cells at the age of 4½ months revealed 2.7% (3/110 cells) mosaicism for distal 13q duplication, compared with 1% (1/100 cells) in the normal control. The neonate was normal in phenotype and development., Conclusions: Mosaic unbalanced translocation at amniocentesis can be associated with a favorable fetal outcome, perinatal progressive decrease of the aneuploid cell line and cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes., Competing Interests: Declaration of competing interest The author has no conflicts of interest relevant to this article., (Copyright © 2024. Published by Elsevier B.V.)

Genetic counseling of mosaicism for a duplication due to partial trisomy in a cell line with 46 chromosomes associated with a normal cell line at amniocentesis remains difficult because mosaic duplication due to partial trisomy has been reported to be associated with either normal or abnormal phenotype in prenatal diagnosis. This article makes a comprehensive review of the reported cases of mosaicism for a duplication due to partial trisomy in a cell line with 46 chromosomes associated with a normal cell line at amniocentesis and various counseling issues such as culture artefact, cytogenetic discrepancy between cultured and uncultured amniocytes and among various tissues, perinatal progressive decrease of the abnormal cell line and a possible favorable fetal outcome. The information provided is useful for obstetricians and genetic counselors during genetic counseling of the parents who wish to keep the babies under such a circumstance., Competing Interests: Conflicts of interest statement The authors have no conflicts of interest relevant to this article., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: This is a retrospective comparative study. We aimed to analyze the results of karyotype and chromosomal microarray analysis (CMA) of amniotic fluid across different gestational weeks and evaluate the clinical value in prenatal diagnosis, particularly in the late pregnancies., Methods: Samples from 580 pregnant women of 18-23 weeks of gestation (mid-gestation group) and 196 pregnant women of 24-32 weeks of gestation (late group) were performed both standard G-band karyotype analysis and CMA., Results: Among the 580 pregnant women in the routine group, the most common indications were positive Down's screening (213/580, 36.7%), followed by advanced maternal age (196/580, 33.8%); while fetal structural anomalies on ultrasonography were the top reason for amniocentesis in the late group (56/196, 28.6%). In the routine group, the total detection rate was 12.1% (70/580), of which 4.1% (24/580) were identified by karyotype analysis and 11.2% (65/580) by CMA. The total detection rate was 15.3% (30/196) in the late group, of which 5.1% (10/196) were detected by karyotype analysis, and 14.3% (28/196) by CMA., Conclusion: Karyotype analysis and CMA are complementary in detecting chromosomal abnormalities. Amniotic cavity puncture in the karyotype analysis in 18-23 weeks of gestation and 24-32 weeks of gestation is safe and effective, more obvious effect on the latter., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)