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Birth Defects Research May 2024Absent or hypoplastic nasal bone (AHNB) on first or second-trimester ultrasonography (USG) is an important soft marker of Down syndrome. However, due to its varied... (Observational Study)
Observational Study
BACKGROUND
Absent or hypoplastic nasal bone (AHNB) on first or second-trimester ultrasonography (USG) is an important soft marker of Down syndrome. However, due to its varied incidence in euploid and aneuploid fetuses, there is always a dilemma of whether to go for invasive fetal testing for isolated AHNB. This study aims to assess outcomes specifically within the context of Indian ethnicity women.
MATERIALS AND METHODS
This was a prospective observational study. All patients who reported with AHNB in the first- or second-trimester USG were included. Genetic counseling was done, and noninvasive and invasive testing was offered. Chromosomal anomalies were meticulously recorded, and pregnancy was monitored.
RESULTS
The incidence of AHNB in our study was 1.16% (47/4051). Out of 47 women with AHNB, the isolated condition was seen in 32 (0.78%) cases, while AHNB with structural anomalies was seen in nine cases (0.22%). Thirty-nine women opted for invasive testing. Six out of 47 had aneuploidy (12.7%), while two euploid cases (4.25%) developed nonimmune hydrops. The prevalence of Down syndrome in fetuses with AHNB was 8.5% (4/47) and 0.42% (17/4004) in fetuses with nasal bone present. This difference was statistically significant (p = .001).
CONCLUSION
The results indicate that isolated AHNB cases should be followed by a comprehensive anomaly scan rather than immediately recommending invasive testing. However, invasive testing is required when AHNB is associated with other soft markers or abnormalities. As chromosomal microarray is more sensitive than standard karyotype in detecting chromosomal aberrations, it should be chosen over karyotype.
Topics: Humans; Female; Nasal Bone; Pregnancy; Prospective Studies; Down Syndrome; Adult; Ultrasonography, Prenatal; Aneuploidy; India; Genetic Counseling; Prenatal Diagnosis; Parents; Pregnancy Trimester, Second; Chromosome Aberrations
PubMed: 38801241
DOI: 10.1002/bdr2.2348 -
Placenta Jul 2024Confined placental mosaicism (CPM) is thought to be one of the main sources of false-positive prenatal cell-free DNA (cfDNA) screening results, but extensive and...
INTRODUCTION
Confined placental mosaicism (CPM) is thought to be one of the main sources of false-positive prenatal cell-free DNA (cfDNA) screening results, but extensive and systematic studies to prove this statement are limited. We evaluate the contribution of CPM to false-positive prenatal cfDNA screening results in the largest cohort published to date.
METHOD
We systematically offered postnatal analysis on placenta and umbilical cord to women who had a negative amniocentesis following a positive prenatal cfDNA screening result. A standardized protocol was used in which (when available) biopsies were taken at five locations in the placenta and umbilical cord.
RESULTS
We analyzed a series of 99 placentas. CPM could be confirmed in 32.3 % of cases (32/99). CPM was detected across all subtypes of chromosomal aberrations (common and rare autosomal trisomies, sex chromosome abnormalities, copy number variations and autosomal monosomies). A lower detection rate was present in umbilical cord biopsies in comparison with placental biopsies. When comparing different sections of the placenta, no clear difference could be observed with regard to the probability of CPM being present nor to the grade of mosaicism.
DISCUSSION
We confirm an important role for CPM in explaining false-positive prenatal cfDNA screening results. Placental regional differences are common. Given its limited clinical relevance, we do however not advocate placental studies in a diagnostic setting.
Topics: Humans; Female; Mosaicism; Pregnancy; Cell-Free Nucleic Acids; Placenta; Adult; Noninvasive Prenatal Testing; False Positive Reactions
PubMed: 38744036
DOI: 10.1016/j.placenta.2024.04.012 -
The Journal of Maternal-fetal &... Dec 2024To explore the prenatal clinical utility of chromosome microarray analysis (CMA) for polyhydramnios and evaluate the short and long-term prognosis of fetuses with...
OBJECTIVES
To explore the prenatal clinical utility of chromosome microarray analysis (CMA) for polyhydramnios and evaluate the short and long-term prognosis of fetuses with polyhydramnios.
METHODS
A total of 600 singleton pregnancies with persistent polyhydramnios from 2014 to 2020 were retrospectively enrolled in this study. All cases received amniocentesis and were subjected to CMA results. All cases were categorized into two groups: isolated polyhydramnios and non-isolated polyhydramnios [with soft marker(s) or with sonographic structural anomalies]. All fetuses were followed up from 6 months to five years after amniocentesis to acquire short and long-term prognosis.
RESULTS
The detection rates of either aneuploidy or pathogenic copy number variants in fetuses with non-isolated polyhydramnios were significantly higher than those with isolated polyhydramnios (5.0 1.5%, = 0.0243; 3.6 0.8%, = 0.0288). The detection rate of total chromosomal abnormalities in the structural abnormality group was significantly higher than that in the isolated group (10.0 2.3%, = 0.0003). In the CMA-negative cases, the incidence of termination of pregnancy, neonatal and childhood death, and non-neurodevelopmental disorders in fetuses combined with structural anomalies was significantly higher than that in fetuses with isolated polyhydramnios ( < 0.05). We did not observe any difference in the prognosis between the isolated group and the combined group of ultrasound soft markers. In addition, the risk of postnatal neurodevelopmental disorders was also consistent among the three groups (1.6 1.3 1.8%).
CONCLUSION
For low-risk pregnancies, invasive prenatal diagnosis of isolated polyhydramnios might be unnecessary. CMA should be considered for fetuses with structural anomalies. In CMA-negative cases, the prognosis of fetuses with isolated polyhydramnios was good, and polyhydramnios itself did not increase the risk of postnatal neurological development disorders. The worse prognosis mainly depends on the combination of polyhydramnios with structural abnormalities.
Topics: Humans; Female; Pregnancy; Polyhydramnios; Adult; Retrospective Studies; Chromosome Aberrations; Microarray Analysis; Pregnancy Outcome; Prenatal Diagnosis; Prognosis; Amniocentesis; Ultrasonography, Prenatal
PubMed: 38710614
DOI: 10.1080/14767058.2024.2344089 -
Ultrasound in Obstetrics & Gynecology :... May 2024Hemoglobin (Hb) Bart's disease is a severe manifestation of alpha thalassemia, resulting in fetal tissue hypoxia and severe anemia. There is limited research available...
OBJECTIVE
Hemoglobin (Hb) Bart's disease is a severe manifestation of alpha thalassemia, resulting in fetal tissue hypoxia and severe anemia. There is limited research available on assessing fetal speckle tracking analysis as a response to fetal anemia caused by Hb Bart's disease and its utility as a sonographic predictor for Hb Bart's disease. This study aimed to assess the diagnostic performance of fetal cardiac parameters derived from speckle tracking echocardiography for distinguishing between affected and unaffected fetuses in pregnancies at risk of Hb Bart's disease during the 17-24 gestational weeks.
METHODS
A total of 115 pregnant women at risk for fetal Hb Bart's disease, who underwent either amniocentesis or cordocentesis at Siriraj Hospital, Bangkok Thailand, were included. Speckle tracking analysis was performed on the 4-chamber view (4CV) of the fetal heart, assessing heart size, shape, ventricular contractility, and left ventricular function prior to invasive prenatal testing. Logistic regression analysis determined significant cardiac predictors and calculated the probability of a fetus having Hb Bart's disease.
RESULTS
Among the cohort, 38 fetuses (33%) were diagnosed with Hb Bart's disease, and 9 cases (7.8%) exhibited frank hydropic signs. In comparison to the control group, affected fetuses displayed a notable enlargement of the 4CV and a more globular shape specifically in the right ventricular chamber. Additionally, there were significant differences in the left global and longitudinal contractility between affected and unaffected fetuses. However, at mid-gestation, no significant distinctions were observed in terms of transverse contractility and left ventricular function between the two groups. Based on logistic regression analysis, combined cardiac parameters derived from speckle tracking analysis as a function of head circumference, could differentiate non-hydropic fetuses with Hb Bart's disease from unaffected fetuses, achieving a maximum sensitivity of 100%, specificity of 98.7%, and overall accuracy of 99.06%.
CONCLUSIONS
Speckle tracking echocardiography has the potential to accurately identify early fetal heart changes in individuals at risk of developing Bart's anemia during the second trimester. This not only offers a novel predictive marker for Hb Bart's disease but also helps address the question of the underlying mechanisms of heart failure associated with anemia. This article is protected by copyright. All rights reserved.
PubMed: 38706423
DOI: 10.1002/uog.27676 -
American Journal of Perinatology Apr 2024This study aimed to determine the diagnostic yield of chromosomal microarray analysis (CMA) performed in cases of fetal abnormalities detected during the third...
OBJECTIVE
This study aimed to determine the diagnostic yield of chromosomal microarray analysis (CMA) performed in cases of fetal abnormalities detected during the third trimester of pregnancy.
STUDY DESIGN
A retrospective review of medical records was conducted for women who underwent amniocentesis at or beyond 28 weeks of gestation between January 2017 and February 2023. CMA results of pregnancies with abnormal sonographic findings not detected before 28 weeks were included.
RESULTS
A total of 482 fetuses met the inclusion criteria. The average maternal age was 31.3 years, and the average gestational age at amniocentesis was 32.3 weeks. The overall diagnostic yield of CMA was 6.2% (30 clinically significant copy number variations [CNVs]). The yield was 16.4% in cases with two or more fetal malformations, while cases with a single anomaly revealed a diagnostic yield of 7.3%. Cases presenting isolated polyhydramnios or isolated fetal growth restriction had a lower yield of 9.3 and 5.4%, respectively. Of the 30 clinically significant cases, 19 (or 63.4%) exhibited recurrent CNVs. The remaining 11 cases (or 36.6%) presented unique CNVs. The theoretical yield of Noninvasive Prenatal Testing (NIPT) in our cohort is 2% for aneuploidy, which implies that it could potentially miss up to 70% of the significant findings that could be identified by CMA. In 80% of the fetuses (or 24 out of 30) with clinically significant CNVs, the structural abnormalities detected on fetal ultrasound examinations corresponded with the CMA results.
CONCLUSION
The 6.2% detection rate of significant CNVs in late-onset fetal anomalies confirms the value of CMA in third-trimester amniocentesis. The findings underscore the necessity of CMA for detecting CNVs potentially overlooked by NIPT and emphasize the importance of thorough genetic counseling.
KEY POINTS
· CMA yields 6.2% for third-trimester anomalies.. · NIPT may miss 70% of CMA findings.. · Ultrasound matched 80% of CMA results..
PubMed: 38688298
DOI: 10.1055/s-0044-1786514 -
American Journal of Obstetrics and... Apr 2024Brain injury and poor neurodevelopment have been consistently reported in infants and adults born before term. These changes occur, at least in part, prenatally and are...
BACKGROUND
Brain injury and poor neurodevelopment have been consistently reported in infants and adults born before term. These changes occur, at least in part, prenatally and are associated with intra-amniotic inflammation. The pattern of brain changes has been partially documented by magnetic resonance imaging but not by neurosonography along with amniotic fluid brain injury biomarkers.
OBJECTIVE
This study aimed to evaluate the prenatal features of brain remodeling and injury in fetuses from patients with preterm labor with intact membranes or preterm premature rupture of membranes and to investigate the potential influence of intra-amniotic inflammation as a risk mediator.
STUDY DESIGN
In this prospective cohort study, fetal brain remodeling and injury were evaluated using neurosonography and amniocentesis in singleton pregnant patients with preterm labor with intact membranes or preterm premature rupture of membranes between 24.0 and 34.0 weeks of gestation, with (n=41) and without (n=54) intra-amniotic inflammation. The controls for neurosonography were outpatient pregnant patients without preterm labor or preterm premature rupture of membranes matched 2:1 by gestational age at ultrasound. Amniotic fluid controls were patients with an amniocentesis performed for indications other than preterm labor or preterm premature rupture of membranes without brain or genetic defects whose amniotic fluid was collected in our biobank for research purposes matched by gestational age at amniocentesis. The group with intra-amniotic inflammation included those with intra-amniotic infection (microbial invasion of the amniotic cavity and intra-amniotic inflammation) and those with sterile inflammation. Microbial invasion of the amniotic cavity was defined as a positive amniotic fluid culture and/or positive 16S ribosomal RNA gene. Inflammation was defined by amniotic fluid interleukin 6 concentrations of >13.4 ng/mL in preterm labor and >1.43 ng/mL in preterm premature rupture of membranes. Neurosonography included the evaluation of brain structure biometric parameters and cortical development. Neuron-specific enolase, protein S100B, and glial fibrillary acidic protein were selected as amniotic fluid brain injury biomarkers. Data were adjusted for cephalic biometrics, fetal growth percentile, fetal sex, noncephalic presentation, and preterm premature rupture of membranes at admission.
RESULTS
Fetuses from mothers with preterm labor with intact membranes or preterm premature rupture of membranes showed signs of brain remodeling and injury. First, they had a smaller cerebellum. Thus, in the intra-amniotic inflammation, non-intra-amniotic inflammation, and control groups, the transcerebellar diameter measurements were 32.7 mm (interquartile range, 29.8-37.6), 35.3 mm (interquartile range, 31.2-39.6), and 35.0 mm (interquartile range, 31.3-38.3), respectively (P=.019), and the vermian height measurements were 16.9 mm (interquartile range, 15.5-19.6), 17.2 mm (interquartile range, 16.0-18.9), and 17.1 mm (interquartile range, 15.7-19.0), respectively (P=.041). Second, they presented a lower corpus callosum area (0.72 mm [interquartile range, 0.59-0.81], 0.71 mm [interquartile range, 0.63-0.82], and 0.78 mm [interquartile range, 0.71-0.91], respectively; P=.006). Third, they showed delayed cortical maturation (the Sylvian fissure depth-to-biparietal diameter ratios were 0.14 [interquartile range, 0.12-0.16], 0.14 [interquartile range, 0.13-0.16], and 0.16 [interquartile range, 0.15-0.17], respectively [P<.001], and the right parieto-occipital sulci depth ratios were 0.09 [interquartile range, 0.07-0.12], 0.11 [interquartile range, 0.09-0.14], and 0.11 [interquartile range, 0.09-0.14], respectively [P=.012]). Finally, regarding amniotic fluid brain injury biomarkers, fetuses from mothers with preterm labor with intact membranes or preterm premature rupture of membranes had higher concentrations of neuron-specific enolase (11,804.6 pg/mL [interquartile range, 6213.4-21,098.8], 8397.7 pg/mL [interquartile range, 3682.1-17,398.3], and 2393.7 pg/mL [interquartile range, 1717.1-3209.3], respectively; P<.001), protein S100B (2030.6 pg/mL [interquartile range, 993.0-4883.5], 1070.3 pg/mL [interquartile range, 365.1-1463.2], and 74.8 pg/mL [interquartile range, 44.7-93.7], respectively; P<.001), and glial fibrillary acidic protein (1.01 ng/mL [interquartile range, 0.54-3.88], 0.965 ng/mL [interquartile range, 0.59-2.07], and 0.24 mg/mL [interquartile range, 0.20-0.28], respectively; P=.002).
CONCLUSION
Fetuses with preterm labor with intact membranes or preterm premature rupture of membranes had prenatal signs of brain remodeling and injury at the time of clinical presentation. These changes were more pronounced in fetuses with intra-amniotic inflammation.
PubMed: 38685550
DOI: 10.1016/j.ajog.2024.04.025 -
AJOG Global Reports May 2024Preterm birth accounts for 60% to 80% of neonatal mortality. Approximately one-third of preterm births are caused by the spontaneous onset of preterm labor....
BACKGROUND
Preterm birth accounts for 60% to 80% of neonatal mortality. Approximately one-third of preterm births are caused by the spontaneous onset of preterm labor. Nevertheless, 70% to 90% of women diagnosed with preterm labor will not deliver within 7 days. Thus, many women will be unnecessarily treated by preterm labor with risk medications. Better tools are needed to categorize women in preterm labor into high or low risk of preterm delivery.
OBJECTIVE
This study aimed to evaluate the amino-terminal pro-brain natriuretic peptide concentration in the amniotic fluid as a prognostic test to predict the risk of delivery within 48 hours or 7 days and before 34 0/7 or 37 0/7 weeks of gestation in women in preterm labor.
STUDY DESIGN
A total of 102 pregnant women presenting signs and symptoms of spontaneous preterm birth (22 0/7 to 34 0/7 weeks of gestation) were included. Amniotic fluid was obtained by amniocentesis, and amino-terminal pro-brain natriuretic peptide concentration was measured. Below normal concentration was defined as <0.5 multiples of the median of the standard curve according to gestational age. The risk of preterm delivery was estimated according to normal or lower-than-normal amino-terminal pro-brain natriuretic peptide concentrations. The predictive capacity of the test (below normal amino-terminal pro-brain natriuretic peptide concentration) was evaluated to identify spontaneous preterm birth at 48 hours or 7 days from amniocentesis and less than 34 0/7 or 37 0/7 weeks at delivery.
RESULTS
For the outcome delivery within 48 hours, lower-than-normal amino-terminal pro-brain natriuretic peptide concentration had 94.6% sensitivity, 73.8% specificity, 96.0% negative predictive value, 3.61 positive likelihood ratio, and 0.07 negative likelihood ratio. For the outcome delivery within 7 days, the test had 93.9% sensitivity, 88.7% specificity, 94.0% negative predictive value, 8.31 positive likelihood ratio, and 0.07 negative likelihood ratio. For the outcomes of spontaneous preterm birth before 34 0/7 and 37 0/7 weeks of gestation, below normal amino-terminal pro-brain natriuretic peptide concentrations had 80.0% sensitivity, 83.0% specificity, 78.0% negative predictive value, 4.70 positive likelihood ratio, and 0.24 negative likelihood ratio and 64.1% sensitivity, 91.7% specificity, 44.0% negative predictive value, 7.70 positive likelihood ratio, and 0.39 negative likelihood ratio, respectively.
CONCLUSION
Among patients in spontaneous preterm labor, the detection of lower-than-normal amino-terminal pro-brain natriuretic peptide concentrations (<0.5 multiples of the median) in amniotic fluid has an excellent predictive capacity to identify those patients at low risk of preterm delivery within 48 hours or 7 days.
PubMed: 38681954
DOI: 10.1016/j.xagr.2024.100345 -
Journal of Personalized Medicine Mar 2024This study represents our second investigation into NIPT, involving a more extensive patient cohort with a specific emphasis on the high-risk group. The high-risk group...
This study represents our second investigation into NIPT, involving a more extensive patient cohort with a specific emphasis on the high-risk group. The high-risk group was subsequently divided into two further groups to compare confirmed cases versus unconfirmed via direct methods. The methodology encompassed the analysis of 1400 consecutive cases from a single genetic center in western Romania, where NIPT was used to assess the risk of specific fetal chromosomal abnormalities. All high-risk cases underwent validation through direct analysis of fetal cells obtained via invasive methods, including chorionic villus sampling and amniocentesis. The confirmation process utilized QF-PCR, karyotyping, and SNP-Array methods customized to each case. Results: A high risk of aneuploidy at NIPT was identified in 36 out of 1400 (2.57%) cases and confirmed in 28 cases. The study also detected an increased risk for copy number variations (CNVs) in 1% of cases, confirmed in two instances involving one large microdeletion and one large microduplication. Trisomy 21 was the exclusive anomaly where NIPT confirmed all cases with identified risk. High-risk NIPT results which were not validated by invasive methods, were classified as false positives; parents in these cases determined to continue the pregnancy. In conclusion, NIPT can serve as a screening method for all pregnancies; however, in high-risk cases, an invasive confirmation test is strongly recommended.
PubMed: 38672993
DOI: 10.3390/jpm14040366 -
American Journal of Perinatology May 2024Recent advances in genetics and imaging have ushered substantial breakthroughs in screening and diagnosis for chromosomal and structural abnormalities. Thus, it is...
Recent advances in genetics and imaging have ushered substantial breakthroughs in screening and diagnosis for chromosomal and structural abnormalities. Thus, it is imperative that health care providers caring for pregnant individuals should reexamine established practices in prenatal screening and diagnosis. In the past, screening for chromosomal abnormalities was based almost entirely on Down syndrome. Pregnant individuals aged > 35 years were considered at "high risk" or of "advanced maternal age" based on age alone; however, the advent of tests with high sensitivity for prenatal detection of chromosomal abnormalities should lead to abandoning that concept, at least from the perspective of chromosomal abnormalities. Given that first-trimester and second-trimester screenings will fail to detect between 5 and 20% of Down syndrome, in most situations, noninvasive testing with cell-free DNA should be the first-line screen for Down syndrome. The fact that over 99% of fetuses with Down syndrome will be detected prenatally with cell-free DNA gives other fetal chromosomal and structural abnormalities increasing prominence. Chromosomal microarray analysis (CMA) permits prenatal detection of several clinically important chromosomal aberrations that cannot be detected by karyotype and may exist in structurally normal fetuses with low-risk cell-free DNA screening. As such, CMA should be more readily conducted when invasive testing is performed, regardless of the presence of a structural abnormality. Isolated sonographic "soft markers" have no clinical significance in patients who have normal cell-free DNA screening, can cause unwarranted anxiety and a negative impact on pregnancy, and perhaps it is time to stop discussing them. Detailed first-trimester ultrasound allows early detection of several severe fetal anomalies and, therefore, in settings with adequately trained personnel and resources, should be used more frequently. This opinion traces the evolution of prenatal screening and diagnosis and advocates for a paradigm shift that aligns with recent developments in prenatal screening and diagnostic capabilities. KEY POINTS: · Noninvasive prenatal testing with cell-free DNA should be available to all pregnant individuals.. · Chromosomal microarray should be available to all pregnant individuals undergoing amniocentesis.. · Patients >35 years with low-risk screening are not at "high risk" for chromosomal abnormalities..
PubMed: 38657662
DOI: 10.1055/a-2312-8824 -
Cureus Apr 2024Invasive prenatal testing, amniocentesis, and chorionic villus sampling offer insights into fetal genetic integrity and health, but carry inevitable minor risks of... (Review)
Review
Invasive prenatal testing, amniocentesis, and chorionic villus sampling offer insights into fetal genetic integrity and health, but carry inevitable minor risks of miscarriage and infection, thus complicating the decision-making process for parents. Previous research has revealed several factors that influence the decision to undergo invasive prenatal testing, including demographic, clinical, and psychological aspects, and attitudes towards testing. Informed choice, involving understanding options and aligning them with personal values, is crucial, with healthcare providers playing a key role in offering unbiased information. This systematic review aims to gather and synthesize literature data on the above factors to draw conclusions to aid antenatal care providers in supporting couples to make more informed decisions about their prenatal care. A systematic search was performed in PubMed and PsycInfo databases using the appropriate keywords and an in-depth evaluation of the studies retrieved followed. Finally, 17 articles were eligible for our review investigating the decision-making process of invasive prenatal testing. Factors like maternal age, education, and ethnicity are pivotal during the decision-making process. Clinical characteristics also influence decisions and women with pregnancies categorized as high-risk or those who have undergone fertility treatment display a preference for invasive testing. There seems to be a direct correlation between a woman's willingness to consider pregnancy termination, deeply rooted in psychological and moral stances, and the inclination to undergo invasive testing. In the patient decision-making process, the provision and depth of knowledge are of paramount importance. A comprehensive understanding facilitates more informed decisions. Finally, attitudes towards termination of pregnancy, as another factor influencing the decision-making process, reveal a nuanced landscape where personal beliefs, religious considerations, legal restrictions, and perspectives on disability converge. Within this complex context, religion emerges as an important determinant, shaping individuals' views on the morality of abortion. This review sheds light on the most important factors influencing the couples' consent for invasive prenatal testing. Healthcare professionals must identify which factors are critical in every specific case among several sociodemographic, clinical, emotional, and religious factors. Thus, they will be able to provide balanced and comprehensive information to help couples under this stressful procedure. We advocate for a patient-centered multidisciplinary approach while navigating couples through the intricate landscape of decision-making concerning invasive prenatal testing.
PubMed: 38654958
DOI: 10.7759/cureus.58803