Pregnancy outcomes of fetuses with congenital heart disease after a prenatal diagnosis with chromosome microarray.

OBJECTIVE: To evaluate the pregnancy outcomes of fetuses with congenital heart disease (CHD) after chromosome microarray (CMA)-based prenatal diagnosis. METHOD: Amniocentesis was performed in 1035 pregnant women carrying fetuses with CHD between September 2014 and December 2019. Chromosomal aberrations in fetuses with CHD were evaluated using CMA. The pregnancy outcomes were followed up from 6 months to 5 years. RESULTS: The overall CHD detection rate by CMA was 10.1% (105/1035; 50 fetuses: aneuploidy, 55 fetuses: pathogenic or likely pathogenic copy number variations). Among 1003 fetuses who were followed up, 4, 236, 763, and 18 cases were of miscarriages, pregnancy termination, live births, and postnatal deaths, respectively. Self-healed CHD was observed in 401 (52.6%) fetuses. The pregnancy termination rate of fetuses with chromosomal anomalies was significantly higher than that of fetuses without chromosomal anomalies (93.1% vs. 15.5%, p < 0.001). However, other pregnancy outcomes, including mortality, preterm labor, and low-weight birth rate, were similar between the two groups. CONCLUSION: The outcome of CMA is an important factor influencing parents' choice of whether to continue the pregnancy. Self-healing rate of prenatal diagnosed CHD is high. The mortality and morbidity of fetuses with CHD following prenatal CMA testing are relatively low.

Confirmation rate of cell free DNA screening for sex chromosomal abnormalities according to the method of confirmatory testing.

OBJECTIVE: To examine the positive predictive value (PPV) of cfDNA screening for sex chromosome aneuploidies (SCA) in a large series of over 90 000 patients. METHODS: Retrospective study based on samples that were sent to Cenata, a private laboratory which uses the Harmony Prenatal Test. The SCA high-risk results were stratified according to the method of diagnostic testing and according to karyotype result. RESULTS: The study population consisted of 144 cases. The CfDNA test indicated monosomy X, XXX, XXY, and XYY in 62, 37, 40, and 5 cases, respectively. The overall PPV was 38.9% (30.9-47.4), 29.0% (18.2-42.9) for monosomy X, 29.7% (15.9-47.9) for 47,XXX, 57.5% (40.9-73.0) for 47,XXY, and 80.0% (28.4-99.5) for 47,XYY). A total of 112 (77.8%) women with a high-risk result for SCAs opted for prenatal karyotyping. In this group, there were significant differences in the PPV if the karyotype was assessed by amniocentesis or by CVS: 29.5% vs 50.0%. This significant difference was driven by the monosomy X result which shows a significantly higher PPV in CVS (54.6% (23.4-83.3) vs 17.1% (6.6-33.6)). For the other SCAs, the differences were not significant. CONCLUSION: PPV of an abnormal cfDNA test for SCAs is low, particularly for monosomy X. The confirmation rate depends on the type of confirmatory test.

Should vanishing twin pregnancies be systematically excluded from cell-free fetal DNA testing?

OBJECTIVE: To demonstrate the feasibility of cell-free DNA (cfDNA) testing in vanishing twin (VT) pregnancies in routine clinical practice. METHODS: Our study included 24 874 singleton and 206 VT consecutive pregnancies. Cell-free DNA was analyzed by massively parallel sequencing. Both aneuploidy analysis (chromosomes 13,18, 21, X, and Y) and fetal fraction estimation were performed according to an Illumina algorithm. Contaminant DNA contribution from the demised co-twin was studied in detail. RESULTS: VT pregnancies exhibited a higher prevalence of screen-positive cases (5.8% vs 2.5%), sex discrepancies (10.2% vs 0.05%), and false positive rates (FPR) (2.6% vs 0.3%) than singleton pregnancies. However, their incidence was significantly lower in tests performed after the 14th week (screen-positive cases: 3.1%; sex discrepancies: 7.8%; and FPR: 0.8%). Among the 12 cases in which cfDNA was performed at two time points, fading of contaminating cfDNA was observed in four cases with a sex discrepancy and in one false positive for trisomy 18, resulting in a final correct result. CONCLUSIONS: Our data suggest VT pregnancies could be included in cfDNA testing as long as it is applied after the 14th week of pregnancy. However, future studies to validate our findings are needed before including VT cases in routine clinical practice. Once established, unnecessary invasive procedures could be avoided, mitigating negative emotional impact on future mothers.

Noninvasive detection of F8 int22h-related inversions and sequence variants in maternal plasma of hemophilia carriers.

Direct detection of F8 and F9 sequence variants in maternal plasma of hemophilia carriers has been demonstrated by microfluidics digital PCR. Noninvasive prenatal assessment of the most clinically relevant group of sequence variants among patients with hemophilia, namely, those involving int22h-related inversions disrupting the F8 gene, poses additional challenges because of its molecular complexity. We investigated the use of droplet digital PCR (ddPCR) and targeted massively parallel sequencing (MPS) for maternal plasma DNA analysis to noninvasively determine fetal mutational status in pregnancies at risk for hemophilia. We designed family-specific ddPCR assays to detect causative sequence variants scattered across the F8 and F9 genes. A haplotype-based approach coupled with targeted MPS was applied to deduce fetal genotype by capturing a 7.6-Mb region spanning the F8 gene in carriers with int22h-related inversions. The ddPCR analysis correctly determined fetal hemophilia status in 15 at-risk pregnancies in samples obtained from 8 to 42 weeks of gestation. There were 3 unclassified samples, but no misclassification. Detailed fetal haplotype maps of the F8 gene region involving int22h-related inversions obtained through targeted MPS enabled correct diagnoses of fetal mutational status in 3 hemophilia families. Our data suggest it is feasible to apply targeted MPS to interrogate maternally inherited F8 int22h-related inversions, whereas ddPCR represents an affordable approach for the identification of F8 and F9 sequence variants in maternal plasma. These advancements may bring benefits for the pregnancy management for carriers of hemophilia sequence variants; in particular, the common F8 int22h-related inversions, associated with the most severe clinical phenotype.

Fetal XCMR: a numerical phantom for fetal cardiovascular magnetic resonance imaging.

BACKGROUND: Validating new techniques for fetal cardiovascular magnetic resonance (CMR) is challenging due to random fetal movement that precludes repeat measurements. Consequently, fetal CMR development has been largely performed using physical phantoms or postnatal volunteers. In this work, we present an open-source simulation designed to aid in the development and validation of new approaches for fetal CMR. Our approach, fetal extended Cardiac-Torso cardiovascular magnetic resonance imaging (Fetal XCMR), builds on established methods for simulating CMR acquisitions but is tailored toward the dynamic physiology of the fetal heart and body. We present comparisons between the Fetal XCMR phantom and data acquired in utero, resulting in image quality, anatomy, tissue signals and contrast. METHODS: Existing extended Cardiac-Torso models are modified to create maternal and fetal anatomy, combined according to simulated motion, mapped to CMR contrast, and converted to CMR data. To provide a comparison between the proposed simulation and experimental fetal CMR images acquired in utero, images from a typical scan of a pregnant woman are included and simulated acquisitions were generated using matching CMR parameters, motion and noise levels. Three reconstruction (static, real-time, and CINE), and two motion estimation methods (translational motion, fetal heart rate) from data acquired in transverse, sagittal, coronal, and short-axis planes of the fetal heart were performed to compare to in utero acquisitions and demonstrate feasibility of the proposed simulation framework. RESULTS: Overall, CMR contrast, morphologies, and relative proportions of the maternal and fetal anatomy are well represented by the Fetal XCMR images when comparing the simulation to static images acquired in utero. Additionally, visualization of maternal respiratory and fetal cardiac motion is comparable between Fetal XCMR and in utero real-time images. Finally, high quality CINE image reconstructions provide excellent delineation of fetal cardiac anatomy and temporal dynamics for both data types. CONCLUSION: The fetal CMR phantom provides a new method for evaluating fetal CMR acquisition and reconstruction methods by simulating the underlying anatomy and physiology. As the field of fetal CMR continues to grow, new methods will become available and require careful validation. The fetal CMR phantom is therefore a powerful and convenient tool in the continued development of fetal cardiac imaging.

An efficient sequence for fetal brain imaging at 3T with enhanced T1 contrast and motion robustness.

PURPOSE: Ultrafast single-shot T2 -weighted images are common practice in fetal MR exams. However, there is limited experience with fetal T1 -weighted acquisitions. This study aims at establishing a robust framework that allows fetal T1 -weighted scans to be routinely acquired in utero at 3T. METHODS: A 2D gradient echo sequence with an adiabatic inversion was optimized to be robust to fetal motion and maternal breathing optimizing grey/white matter contrast at the same time. This was combined with slice to volume registration and super resolution methods to produce volumetric reconstructions. The sequence was tested on 22 fetuses. RESULTS: Optimized grey/white matter contrast and robustness to fetal motion and maternal breathing were achieved. Signal from cerebrospinal fluid (CSF) and amniotic fluid was nulled and 0.75 mm isotropic anatomical reconstructions of the fetal brain were obtained using slice-to-volume registration and super resolution techniques. Total acquisition time for a single stack was 56 s, all acquired during free breathing. Enhanced sensitivity to normal anatomy and pathology with respect to established methods is demonstrated. A direct comparison with a 3D spoiled gradient echo sequence and a controlled motion experiment run on an adult volunteer are also shown. CONCLUSION: This paper describes a robust framework to perform T1 -weighted acquisitions and reconstructions of the fetal brain in utero. Magn Reson Med 80:137-146, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

[Application for prenatal diagnosis using both chromosomal karyotype analysis and BACs-on-Beads assay].

OBJECTIVE: To assess the application value in prenatal diagnosis using karyotype analysis combined with BACs-on-Beads (BoBs) assay. METHODS: Nine hundred sixty five pregnant women were subjected to amniocentesis, chromosomal karyotype analysis and detection of BoBs were employed simultaneously for abnormal number of chromosomes and 9 chromosome microdeletion syndrome in prenatal diagnosis. RESULTS: Fifty cases common chromosome aneupoidies were successfully detected by both karyotype analysis and BoBs which included 31 cases of trisomy 21,10 cases of trisomy 18 and 9 cases with sex chromosome abnormality. BoBs in addition detected 1 case of DiGeorge-1 microdeletion syndrome and 1 case of 7q11.23 microduplication syndrome. All 9 fetuses with chromosome abnormalities detected by karyotyping were missed by BoBs, including 2 cases of marker chromosomes,4 cases of chromosomal translocation,1 case of chromosomal inversion, 2 cases of Sex chromosome mosaicism; 2 cases of fetal inherited from the parents,7 cases for novel mutations. CONCLUSION: Karyotype analysis combined with BoBs dedtection is a rapid, effective and highly accurate prenatal diagnosis model that may should be widely used in clinical diagnosis.

Use of radiotelemetry to assess perinatal cardiac function in the ovine fetus and newborn.

The late gestation fetal ECG (fECG) has traditionally been difficult to characterize due to the low fECG signal relative to high maternal noise. Although new technologies have improved the feasibility of its acquisition and separation, little is known about its development in late gestation, a period in which the fetal heart undergoes extensive maturational changes. Here, we describe a method for the chronic implantation of radiotelemetry devices into late gestation ovine fetuses to characterize parameters of the fECG following surgery, throughout late gestation, and in the perinatal period. We found no significant changes in mean aortic pressure (MAP), heart rate (HR), or ECG in the 5 days following implantation; however, HR decreased in the first 24 h following the end of surgery, with associated increases in RR, PR, and QRS intervals. Over the last 14 days of fetal life, fetal MAP significantly increased, and HR significantly decreased, as expected. MAP and HR increased as labor progressed. Although there were no significant changes over time in the ECG during late gestation, the duration of the PR interval initially decreased and then increased as birth approached. These results indicate that although critical maturational changes occur in the late gestation fetal myocardium, the mechanisms that control the cardiac conduction are relatively mature in late gestation. The study demonstrates that radiotelemetry can be successfully used to assess fetal cardiac function, in particular conduction, through the process of labor and delivery, and may therefore be a useful tool for study of peripartum cardiac events.

Fetal magnetocardiography using optically pumped magnetometers: a more adaptable and less expensive alternative?

Fetal magnetocardiography provides the requisite precision for diagnostic measurement of electrophysiological events in the fetal heart. Despite its significant benefits, this technique with current cryogenic based sensors has been limited to few centers, due to high cost of maintenance. In this study, we show that a less expensive non-cryogenic alternative, optically pumped magnetometers, can provide similar electrophysiological and quantitative characteristics when subjected to direct comparison with the current technology. Further research can potentially increase its clinical use for fetal magnetocardiography. © 2016 John Wiley & Sons, Ltd.

[The value of a novel prenatal diagnosis model with combination of karyotyping and BACs-on-BeadsTM technique].

OBJECTIVE: To explore the value of a novel prenatal diagnosis model using combined chromosomal karyotyping and BACs-on-BeadsTM(BoBs), a newly-developed technique. METHODS: 1048 single pregnancy pregnant women with various diagnostic indications were performed amniocentesis for prenatal diagnosis with karyotyping and BoBs simultaneously. RESULTS: Among 1047 successfully cultured specimens, 50 chromosomal abnormalities were identified with BoBs, including 43 common chromosomal trisomies, 3 chimeric chromosomes and 4 structural abnormalities, of which 3 microdeletions/microduplications were not detected with karyotyping. Except for extra yield of 1 Robertsonian translocation, the other numerical chromosomal abnormalities were detected with both karyotyping and BoBs. Ten fetal chromosome abnormalities were confirmed with karyotyping, including 8 structural abnormalities and 2 chimeric chromosomes. CONCLUSION: Combination of karyotyping and BoBs turned out to be a rapid, complementary and effective diagnostic model for fetal chromosomal abnormalities and microdeletion syndromes, which could yield a higher detection rate of fetal chromosomal abnormalities and chromosomal microdeletions/microduplications.

Development of computational pregnant female and fetus models and assessment of radiation dose from positron-emitting tracers.

PURPOSE: Molecular imaging using PET and hybrid (PET/CT and PET/MR) modalities nowadays plays a pivotal role in the clinical setting for diagnosis and staging, treatment response monitoring, and radiation therapy treatment planning of a wide range of oncologic malignancies. The developing embryo/fetus presents a high sensitivity to ionizing radiation. Therefore, estimation of the radiation dose delivered to the embryo/fetus and pregnant patients from PET examinations to assess potential radiation risks is highly praised. METHODS: We constructed eight embryo/fetus models at various gestation periods with 25 identified tissues according to reference data recommended by the ICRP publication 89 representing the anatomy of the developing embryo/fetus. The developed embryo/fetus models were integrated into realistic anthropomorphic computational phantoms of the pregnant female and used for estimating, using Monte Carlo calculations, S-values of common positron-emitting radionuclides, organ absorbed dose, and effective dose of a number of positron-emitting labeled radiotracers. RESULTS: The absorbed dose is nonuniformly distributed in the fetus. The absorbed dose of the kidney and liver of the 8-week-old fetus are about 47.45 % and 44.76 % higher than the average absorbed dose of the fetal total body for all investigated radiotracers. For 18F-FDG, the fetal effective doses are 2.90E-02, 3.09E-02, 1.79E-02, 1.59E-02, 1.47E-02, 1.40E-02, 1.37E-02, and 1.27E-02 mSv/MBq at the 8th, 10th, 15th, 20th, 25th, 30th, 35th, and 38th weeks of gestation, respectively. CONCLUSION: The developed pregnant female/fetus models matching the ICRP reference data can be exploited by dedicated software packages for internal and external dose calculations. The generated S-values will be useful to produce new standardized dose estimates to pregnant patients and embryo/fetus from a variety of positron-emitting labeled radiotracers.

[Mutation screening and prenatal diagnosis of methylmalonic academia in a Chinese pedigree by Ion Torrent semiconductor sequencing].

OBJECTIVE: To identify pathogenic mutations in a Chinese pedigree affected with methylmalonic academia for genetic counseling and prenatal diagnosis. METHODS: Molecular analysis of the MUT, MMACHC, MMAA and MMAB genes was performed for the proband with methylmalonic academia by Ion Torrent semiconductor sequencing. Candidate mutations were validated by Sanger sequencing. The couple was offered prenatal diagnosis via analyzing of the fetal DNA through amniocentesis. RESULTS: The proband was found to be compound heterozygous for c.609G>A (p.Trp203X) and c.658-660del AAG (p.Lys220del) mutations, which were inherited respectively from each of his parents. Prenatal diagnosis showed that the fetus has inherited two wild-type parental alleles. CONCLUSION: The targeted Ion Torrent PGM sequencing has detected pathogenic mutations in the Chinese pedigree affected with methylmalonic academia, which has provided molecular evidence for clinical diagnosis, genetic counseling and prenatal diagnosis for the family.

Noninvasive prenatal testing for Wilson disease by use of circulating single-molecule amplification and resequencing technology (cSMART).

BACKGROUND: Noninvasive prenatal testing (NIPT) for monogenic diseases by use of PCR-based strategies requires precise quantification of mutant fetal alleles circulating in the maternal plasma. The study describes the development and validation of a novel assay termed circulating single-molecule amplification and resequencing technology (cSMART) for counting single allelic molecules in plasma. Here we demonstrate the suitability of cSMART for NIPT, with Wilson Disease (WD) as proof of concept. METHODS: We used Sanger and whole-exome sequencing to identify familial ATP7B (ATPase, Cu(++) transporting, ß polypeptide) gene mutations. For cSMART, single molecules were tagged with unique barcodes and circularized, and alleles were targeted and replicated by inverse PCR. The unique single allelic molecules were identified by sequencing and counted, and the percentage of mutant alleles in the original maternal plasma sample was used to determine fetal genotypes. RESULTS: Four families with WD pedigrees consented to the study. Using Sanger and whole-exome sequencing, we mapped the pathogenic ATP7B mutations in each pedigree and confirmed the proband's original diagnosis of WD. After validation of cSMART with defined plasma models mimicking fetal inheritance of paternal, maternal, or both parental mutant alleles, we retrospectively showed in second pregnancies that the fetal genotypes assigned by invasive testing and NIPT were concordant. CONCLUSIONS: We developed a reliable and accurate NIPT assay that correctly diagnosed the fetal genotypes in 4 pregnancies at risk for WD. This novel technology has potential as a universal strategy for NIPT of other monogenic disorders, since it requires only knowledge of the parental pathogenic mutations.

Novel chemiluminescent imaging microtiter plates for high-throughput detection of multiple serum biomarkers related to Down's syndrome via soybean peroxidase as label enzyme.

Novel chemiluminescent (CL) imaging microtiter plates with high-throughput, low-cost, and simple operation for detection of four biomarkers related to Down's syndrome screening were developed and evaluated. To enhance the sensitivity of CL immunosensing, soybean peroxidase (SBP) was used instead of horseradish peroxide (HRP) as a label enzyme. The microtiter plates were fabricated by simultaneously immobilizing four capture monoclonal antibodies, anti-inhibin-A, anti-unconjugated oestriol (anti-uE3), anti-alpha-fetoprotein (anti-AFP), and beta anti-HCG (anti-ß-HCG), on nitrocellulose (NC) membrane to form immunosensing microtiter wells. Under a sandwiched immunoassay, the CL signals on each sensing site of the microtiter plates were collected by a charge-coupled device (CCD), presenting an array-based chemiluminescence imaging method for detection of four target antigens in a well at the same time. The linear response to the analyte concentration ranged from 0.1 to 40 ng/mL for inhibin-A, 0.075 to 40 ng/mL for uE3, 0.2 to 400 ng/mL for AFP, and 0.4 to 220 ng/mL for ß-HCG. The proposed microtiter plates possessed high-throughput, good stability, and acceptable accuracy for detection of four antigens in clinical serum samples and demonstrated potential for practical applicability of the proposed method to Down's syndrome screening. Graphical Abstract Schematic evaluation of the microtiter plater for simultaneous detection of the four biomarkers.

Use of 'non-medical' ultrasound imaging before mid-pregnancy in Copenhagen.

We have investigated prospectively how many pregnant women purchase ultrasound imaging before week 20, why they purchase scans, and which professional skills and certifications women expect the person performing the scan to have. In addition, we wanted to investigate whether the women were aware of any professional authorization procedures. Women attending the second trimester malformation scan of the Danish Prenatal Screening Program (n = 645) filled in a questionnaire about their use of non-medical ultrasound scans. Of these women, 154 (24%) had bought ultrasound scans: 50% wanted to have the fetal health and development checked and 49% wanted to find out the gender of the fetus. In addition, 68% felt that they received an evaluation of the fetal health state and 58% believed that there was legislation demanding a professional authorization needed to perform ultrasound imaging. This study shows that there is a significant demand among pregnant women for commercial ultrasound imaging of their fetus for various reasons. Knowledge of certifications and requirements for legal authorization is, however, sparse.

A transcervical amniotic fluid collector: a new medical device for the assessment of amniotic fluid in patients with ruptured membranes.

AIM: To describe a new device for the transcervical collection of amniotic fluid (AF) in patients with ruptured membranes, and to compare the concentration of proteins in fluid retrieved by transabdominal amniocentesis and the transcervical AF collector. STUDY DESIGN: Paired AF samples were collected in patients with preterm prelabor rupture of membranes (PROM) (n=11) by transabdominal amniocentesis and with the transcervical AF collector (Yoon's AF Collector™). Three proteins known to have high concentrations in AF [α-fetoprotein (AFP), ß-human chorionic gonadotrophin (ß-hCG), and prolactin] were measured. RESULTS: (1) There was a significant correlation between the concentrations of analytes in AF obtained by transabdominal amniocentesis and by the transcervical AF collector (r=0.94, P<0.001 for AFP; r=0.96, P<0.001 for ß-hCG; r=0.72, P<0.05 for prolactin); (2) Bland-Altman plots showed no evidence of heteroscedasticity between transabdominal or transcervical AF concentrations of these markers. CONCLUSIONS: There was a strong correlation between the concentrations of proteins in AF collected by amniocentesis or with the transcervical device.

Prenatal Detection of Coarctation of the Aorta in a Non-selected Population: A Prospective Analysis of 10 Years of Experience.

The objective of this study was to assess the ability of different parameters to identify fetuses requiring neonatal care for coarctation of the aorta (CoA). Between January 2003 and December 2012, 175 fetuses referred for great vessel disproportion were divided into two groups: group A (n = 51) with high risk of CoA and delivery planned in tertiary care referral center and group B (n = 124) with no increased risk of CoA. In group A, diagnosis of CoA was confirmed in 38/51 (74 %). In group B, 2/124 had CoA. Multiple logistic regression analysis identified the best combination as diffusely hypoplastic and/or angular aortic arches, ventricular septal defect and aortic valve diameter <5 mm at 36-week gestational age (GA). Positive predictive value was 75 % when vessel disproportion was noted before 28-week GA and 73 % in the third trimester. Postnatal diagnosis involved 38 cases of CoA which had not been referred. One case of CoA diagnosed after birth was referred prenatally for difficulty of screening without any defect. The results of our prospective study are in agreement with those of previous series, but our false positive rate was lower especially when the diagnosis of vascular disproportion was made at third trimester. The performance of fetal cardiac screening does not seem to be very good, but prenatal diagnosis is probably not always possible: Among our three false negative cases, two had isolated vascular disproportion and the third no risk factors.

Correlation of cord blood pH, base excess, and lactate concentration measured with a portable device for identifying fetal acidosis.

OBJECTIVE: To determine the effectiveness of portable lactate analyzers in identifying fetal acidosis by correlating arterial and venous lactate values from umbilical cord blood with lactate, pH, and base excess measurements from central laboratory analyzers. METHODS: We performed a prospective study using arterial and venous cord blood from 52 women with a singleton fetus delivered at term. We evaluated the correlation between the cord blood lactate concentration measured using two of the same portable devices (Lactate Plus, Nova Biomedical) with the result from a central laboratory analyzer. Analyses of the correlation between arterial lactate concentration measured on the portable device with arterial pH and base excess were then performed. RESULTS: We observed a median arterial pH of 7.24 (range 7.05 to 7.35) and a median arterial lactate concentration of 3.7 mmol/L (range 1.7 to 8.8 mmol/L). An excellent correlation was observed between lactate concentrations measured by the two portable devices (arterial R² = 0.98 and venous R² = 0.98), and between the portable device and the central laboratory analyzer (arterial R² = 0.94 and venous R² = 0.95). In our population, the optimal cut-offs to predict a pH < 7.20 or a base excess > -8.0 mmol/L were a lactate concentration of 4.9 mmol/L and 5.3 mmol/L, respectively, according to receiver operator characteristic analysis. With a lactate concentration > 4.9 mmol/L, the portable device had a sensitivity of 82% and a specificity of 90% to identify samples with an arterial pH < 7.20. CONCLUSION: Cord blood lactate concentration measured with a portable device is a good predictor of cord blood base excess and pH. Future studies should be designed to correlate scalp blood lactate measurements with clinical outcomes.

Objectif : Déterminer l'efficacité des analyseurs de lactate portatifs, pour ce qui est de l'identification de l'acidose fœtale, en mettant en corrélation les valeurs artérielle et veineuse du lactate constatées dans le sang de cordon ombilical et les mesures du lactate, du pH et de l'excès de bases révélées par les analyseurs du laboratoire central. Méthodes : Nous avons mené une étude prospective en utilisant le sang de cordon artériel et veineux prélevé chez 52 femmes qui ont connu une grossesse monofœtale s'étant soldée en un accouchement à terme. Nous avons évalué la corrélation entre la concentration en lactate du sang de cordon mesurée au moyen de deux exemplaires du même appareil portatif (Lactate Plus, Nova Biomedical) et le résultat obtenu au moyen d'un analyseur du laboratoire central. Nous avons par la suite procédé à des analyses de la corrélation entre la concentration artérielle en lactate mesurée au moyen de l'appareil portatif et les valeurs artérielles du pH et de l'excès de bases. Résultats : Nous avons constaté un pH artériel médian de 7,24 (plage : 7,05 - 7,35) et une concentration artérielle en lactate médiane de 3,7 mmol/l (plage : 1,7 - 8,8 mmol/l). Une excellente corrélation a été constatée entre les concentrations en lactate mesurées par les deux appareils portatifs (R2 artériel = 0,98 et R2 veineux = 0,98) et entre les concentrations mesurées par l'appareil portatif et par l'analyseur du laboratoire central (R2 artériel = 0,94 et R2 veineux = 0,95). Au sein de notre population, les seuils optimaux permettant de prédire un pH < 7,20 ou un excès de bases > −8,0 mmol/l ont été des concentrations en lactate de 4,9 mmol/l et de 5,3 mmol/l, respectivement, selon l'analyse de la fonction d'efficacité du récepteur. En présence d'une concentration en lactate > 4,9 mmol/l, l'appareil portatif comptait une sensibilité de 82 % et une spécificité de 90 % pour ce qui est de l'identification des prélèvements présentant un pH artériel < 7,20. Conclusion : La concentration en lactate du sang de cordon qui est mesurée au moyen d'un appareil portatif constitue un bon facteur prédictif pour ce qui est du pH et de l'excès de bases du sang de cordon. De futures études devraient être conçues de façon à pouvoir mettre en corrélation les concentrations en lactate dans le sang prélevé sur le cuir chevelu et les résultats cliniques.

Noninvasive prenatal diagnosis using next-generation sequencing.

Nowadays, prenatal diagnosis is necessary for pregnant women. For the parents who are expecting a child, the genetic test may provide the information whether they are carrying rare gene mutations and whether they are at risk of passing them onto their offspring. However, the ultimate determination of genetic diseases often requires invasive procedures such as amniocentesis and chorionic villus sampling, which may cause fetal miscarriage. A noninvasive type of prenatal diagnosis needs to be developed in clinical practice to dispel safety concerns. In this paper, we will review the technical advancement of using maternal circulating nucleic acids as the sample in noninvasive studies, and highlight the utilization of next-generation sequencing in the screening of genetic diseases.