Prenatal Test Results Research Articles

Pregnancy Outcome following Prenatal Diagnosis of Chromosomal Anomaly: A Record Linkage Study of 26,261 Pregnancies.

Previous studies have demonstrated the influence of changes in the age at which women give birth, and of developments in prenatal screening and diagnosis on the number of pregnancies diagnosed and terminated with chromosomal anomalies. However, we are unaware of any population studies examining pregnancy terminations after diagnosis of chromosomal anomalies that has included all aneuploidies and the influence of maternal factors. The aims of this study were to examine the association between results of prenatal tests and pregnancy termination, and the proportion of foetuses with and without chromosomal anomalies referred for invasive diagnostic tests over time. Diagnostic information of 26,261 prenatal invasive tests from all genetic service laboratories in Scotland from 2000 to 2011 was linked to Scottish Morbidity Records to obtain details on pregnancy outcome. Binary logistic regression was carried out to test the associations of year and type of diagnosis with pregnancy termination, while controlling for maternal age, neighbourhood deprivation and parity. There were 24,155 (92.0%) with no chromosomal anomalies, 1,483 (5.6%) aneuploidy diagnoses, and 623 (2.4%) diagnoses of anomaly that was not aneuploidy (including translocations and single chromosome deletions). In comparison with negative test results, pregnancies diagnosed with trisomy were most likely to be terminated (adjusted OR 437.40, 95% CI 348.19–549.46) followed by other aneuploid anomalies (adjusted OR 95.94, 95% CI 69.21–133.01). During the study period, fewer pregnancies that were diagnosed with aneuploidy were terminated, including trisomy diagnoses (adjusted OR 0.44, 95% CI 0.26–0.73). Older women were less likely to terminate (OR 0.35, 95% CI 0.28, 0.42), and parity was also an independent predictor of termination. In keeping with previous findings, while the number of invasive diagnostic tests declined, the proportion of abnormal results increased from 6.09% to 10.88%. Systematic advances in prenatal screening have improved detection rates for aneuploidy. This has been accompanied by a reduction in the rate of termination for aneuploidy. This may reflect societal changes with acceptance of greater diversity, but this is speculation, and further research would be needed to test this.

NIPTRIC: an online tool for clinical interpretation of non-invasive prenatal testing (NIPT) results

To properly interpret the result of a pregnant woman’s non-invasive prenatal test (NIPT), her a priori risk must be taken into account in order to obtain her personalised a posteriori risk (PPR), which more accurately expresses her true likelihood of carrying a foetus with trisomy. Our aim was to develop a tool for laboratories and clinicians to calculate easily the PPR for genome-wide NIPT results, using diploid samples as a control group. The tool takes the a priori risk and Z-score into account. Foetal DNA percentage and coefficient of variation can be given default settings, but actual values should be used if known. We tested the tool on 209 samples from pregnant women undergoing NIPT. For Z-scores < 5, the PPR is considerably higher at a high a priori risk than at a low a priori risk, for NIPT results with the same Z-score, foetal DNA percentage and coefficient of variation. However, the PPR is effectively independent under all conditions for Z-scores above 6. A high PPR for low a priori risks can only be reached at Z-scores > 5. Our online tool can assist clinicians in understanding NIPT results and conveying their true clinical implication to pregnant women, because the PPR is crucial for individual counselling and decision-making.

Couple's Narratives of Communion and Isolation Following Abnormal Prenatal Microarray Testing Results.

In 2% to 3% of cases, prenatal microarray testing detects deletions and duplications in a fetus' genome that are undetected by conventional cytogenetics. Many of these changes are associated with variable or uncertain symptomatology. Little is known about how couples experience uncertain results. This study analyzed 24 interviews with members of 12 heterosexual U.S. couples who received pathogenic or uncertain microarray prenatal testing results. Researchers used narrative analysis to examine couples' understanding and incorporation of findings into decision making regarding pregnancy termination. Couples felt unprepared for these findings and frustrated because scant information was available to aid interpretation. Women sought information and made decisions, and men marginalized their distress to support their wives. A shift in voice from first to second person indicated attempts to normalize emotional responses by making the process "common" to all couples. Families pursuing highly sensitive prenatal testing may need expert guidance to support decision making.

Does progesterone therapy increase nuchal translucency in women with threatened miscarriage?

The effect of exogenous progesterone on fetal nuchal translucency (NT) has been proposed recently. In this study, we aimed to compare the thickness of NT of patients receiving and not receiving progesterone for threatened miscarriage. This study was designed as a retrospective comparative study. Ninety five women treated with progesterone constituted the study group whereas 97 women who were not treated with progesterone constituted the control group. An ultrasonographic examination was performed on all of the women to measure NT. All patients were treated with oral micronized progesterone in the study group. The main parameters recorded for each woman were; age, body mass index (BMI), obstetrical characteristics, and gestational age at first examination, treatment duration of progesterone therapy, and results of combined and triple tests. A total of 192 pregnant women with threatened miscarriage were included in this study. The mean NT thickness was statistically significantly higher in the study group (p < 0.001), and mean serum level of human chorionic gonadotropin (hCG) was also higher in this group (p < 0.05). There was no statistically significant difference between groups in terms of age, BMI, and gestational age at first examination. ROC curve analysis demonstrated that only increased NT (area under the curve: 0.634, p = 0.005, 95% CI: 0.541-0.727) was a discriminative factor for women receiving progesterone for threatened miscarriage. Also there was a positive correlation between NT and treatment duration (r = 0.269; p < 0.001). We think that oral progesterone therapy may increase NT depending on treatment duration without causing abnormal prenatal screening test results.

The Psychological Impact of Prenatal Diagnosis and Disclosure of Susceptibility Loci: First Impressions of Parents' Experiences.

Genomic microarray may detect susceptibility loci (SL) for neurodevelopmental disorders such as autism and epilepsy, with a yet unquantifiable risk for the fetus. The prenatal disclosure of susceptibility loci is a topic of much debate. Many health care professionals fear that reporting susceptibility loci may put a psychological burden on pregnant couples. It is our policy to disclose prenatal susceptibility loci as we recognize them as actionable for prospective parents. The aim of this report was to evaluate the psychological impact of disclosing a prenatal diagnosis of susceptibility loci. The psychological impact of disclosing susceptibility loci was evaluated in the first patients who received such results. Eight out of 15 women who had a susceptibility locus disclosed and four of their partners consented to share their experiences through a telephonic evaluation (n = 12). Follow-up time ranged from 3 to 15 months after their prenatal test result. The reporting of susceptibility loci was initially ‘shocking’ for five parents while the other seven felt ‘worried’. Ten out of 12 participants indicated they would like to be informed about the susceptibility locus again, two were unsure. Most had no enduring worries. Participants unanimously indicated that pregnant couples should have an individualized pre-test choice about susceptibility loci (non)disclosure. We observed no negative psychological impact with the prenatal diagnosis and disclosure of SL on participants. A key factor in mitigating parental anxiety with SL disclosure appears to be post-test genetic counseling. Our report confirms that pregnant women and their partners prefer an individualized choice regarding the scope of prenatal testing.

51 - Triploidy in a Live-Born Female With Normal Non-Invasive Prenatal Testing Results

Non-invasive prenatal testing (NIPT) has become an increasingly popular option for pregnancies with abnormal ultrasound (U/S) findings. Although it has high clinical sensitivity and specificity for trisomy 21, some other, rarer cytogenetic conditions are less likely to be detected with certain NIPT methods. Triploidy is a rare genetic condition that usually results in miscarriage or stillbirth. Very few triploid pregnancies result in a live birth. We present a case of a female neonate with multiple anomalies and normal non-invasive testing who was diagnosed with dygynic triploidy after birth. Fetal U/S at 19 weeks was abnormal for a two-vessel cord, a cardiac defect and intrauterine growth restriction (IUGR). NIPT at 20w indicated a normal female result. Due to the abnormal U/S findings, further diagnostic testing was recommended but parents declined amniocentesis due to normal NIPT. Subsequent U/S at 30w identified anomalies including IUGR, a congenital heart defect, cerebellar hypoplasia, thoracic hemivertebrae, absent right kidney, absent left hand, right hand syndactyly and abnormal posturing of the hands and feet. The patient was born at 33 weeks gestation by C-section due to severe IUGR and fetal distress. She had additional anomalies including small posterior fossa, atrial septal defect, pulmonary hypoplasia, toe syndactyly, cutis aplasia and cleft palate. She had respiratory distress requiring mechanical ventilation. She developed bilateral pneumothoraces and progressive respiratory failure and died after 3 days. Direct FISH and cytogenetic analysis revealed a female triploid karyotype. The NIPT method used (InformaSeq) is used by many laboratories and is unable detect triploidy. This case highlights the need for more sensitive NIPT methods for detecting non-trisomic abnormal cytogenetic findings. In the context of MCA and normal NIPT, amniocentesis and karyotype and/or CMA should be recommended for families that desire diagnostic testing.

Second-generation non-invasive high-throughput DNA sequencing technology in the screening of Down's syndrome in advanced maternal age women.

The aim of the present study was to evaluate the efficacy of using non-invasive DNA testing technology in screening Down's syndrome among women of advanced maternal age (AMA) and to provide evidence for prenatal screening of Down's syndrome. With a double-blind design, 8 ml of peripheral venous blood samples were collected from 87 women aged ≥35 years after 12 weeks of pregnancy. All cases were recorded with unique identification cards with clinical details and followed up until delivery. All the non-invasive prenatal testing results were confirmed by amniotic fluid fetal karyotyping (the gold standard of aneuploidy test), follow-up examination by neonatologists or neonatal blood karyotyping. The sensitivity, specificity and other indicators of non-invasive DNA testing technology were calculated based on the data of 87 women of AMA. Among the 87 women of AMA, 5 were cases with abnormal numbers of chromosomes (3 cases of trisomy 21, 1 case of trisomy 18 and 1 case of 47, XXX). The sensitivity and specificity reached 100% for trisomy 21, trisomy 18 and 47, XXX. The present study supports that non-invasive DNA testing is a useful method of AMA screening of Down's syndrome with 100% accuracy. Therefore, it can be used as an important alternative screening method for Down's syndrome in women of AMA.

Follow-up of multiple aneuploidies and single monosomies detected by noninvasive prenatal testing: implications for management and counseling.

ObjectivesTo determine the underlying biological basis for noninvasive prenatal testing (NIPT) results of multiple aneuploidies or autosomal monosomies.MethodsRetrospective analysis of 113,415 tests to determine the study cohort, consisting of 138 (0.12%) cases reported as a single autosomal monosomy (n = 65), single trisomy with a sex chromosome aneuploidy (n = 36), or with multiple aneuploidies (n = 37). Clinical outcome information was reviewed and stratified into eight categories according to whether the karyotype or sonographic information agreed or disagreed with sequencing results.ResultsOf 67 cases with fetal or neonatal karyotypes available, 16 (24%) were partially or fully concordant with the NIPT result, 4 (6%) had aneuploidy on a reference chromosome, and 47 (70%) had normal fetal chromosomes, in which 5/47 had maternal malignancies reported. One case of maternal mosaic trisomy 8 was also detected. Of cases with no fetal karyotype information, ten had an abnormal clinical outcome, one was a normal live birth, and one reported maternal malignancy.ConclusionsNoninvasive prenatal test results of autosomal monosomy or multiple aneuploidies are rare but have a diversity of underlying biologic causes. Some reflect the fetal karyotype; some reflect the presence of other maternal or fetal chromosome abnormalities, and a small number are linked to maternal disease. © 2016 Illumina. Prenatal Diagnosis published by John Wiley & Sons, Ltd.

Case 1: Hypertension and Hyponatremia in a Neonate

A 1,695-g, 3-week-old male infant is transferred to the neonatal intensive care unit (NICU) for further evaluation of acute-onset hypertension and hyponatremia. He was born at 322/7 weeks’ gestation by cesarean delivery because of preeclampsia to a 24-year-old, gravida 3, para 2 mother with unremarkable prenatal laboratory test results. Apgar scores are 8 and 8 at 1 and 5 minutes, respectively. He develops respiratory distress after birth and is admitted to the NICU, where he has an umbilical artery catheter placed 1 day after birth for blood pressure and laboratory test monitoring. He is intubated and remains intubated for the first week. His course is subsequently unremarkable until 3 weeks, when he becomes hypertensive with systolic blood pressures in the 90s and is found to have a sodium level of 127 mEq/L (127 mmol/L) with normal prior electrolyte levels. On admission to the referral center at age 3 weeks, the patient’s blood pressure is 121/84 mm Hg, and his sodium level is 124 mEq/L (124 mmol/L). Physical examination findings are consistent with dehydration because he is found to have poor skin turgor and mottling. He is started on an infusion of 10% dextrose in half amount of normal saline, transitioned to 10% dextrose in two-third amount of normal saline, and then eventually to 10% dextrose in normal saline. During this time, electrolytes are monitored frequently to avoid an overly rapid correction of hyponatremia. Sodium improves and normalizes within 2 days of admission. A nephrologist is consulted for blood pressure management. The patient initially receives hydralazine as …

Noninvasive Prenatal Testing and Incidental Detection of Occult Maternal Malignancies

Importance Understanding the relationship between aneuploidy detection on noninvasive prenatal testing (NIPT) and occult maternal malignancies may explain results that are discordant with the fetal karyotype and improve maternal clinical care. Objective To evaluate massively parallel sequencing data for patterns of copy-number variations that might prospectively identify occult maternal malignancies. Design, Setting, and Participants Case series identified from 125 426 samples submitted between February 15, 2012, and September 30, 2014, from asymptomatic pregnant women who underwent plasma cell-free DNA sequencing for clinical prenatal aneuploidy screening. Analyses were conducted in a clinical laboratory that performs DNA sequencing. Among the clinical samples, abnormal results were detected in 3757 (3%); these were reported to the ordering physician with recommendations for further evaluation. Exposures NIPT for fetal aneuploidy screening (chromosomes 13, 18, 21, X, and Y). Main Outcomes and Measures Detailed genome-wide bioinformatics analysis was performed on available sequencing data from 8 of 10 women with known cancers. Genome-wide copy-number changes in the original NIPT samples and in subsequent serial samples from individual patients when available are reported. Copy-number changes detected in NIPT sequencing data in the known cancer cases were compared with the types of aneuploidies detected in the overall cohort. Results From a cohort of 125 426 NIPT results, 3757 (3%) were positive for 1 or more aneuploidies involving chromosomes 13, 18, 21, X, or Y. From this set of 3757 samples, 10 cases of maternal cancer were identified. Detailed clinical and sequencing data were obtained in 8. Maternal cancers most frequently occurred with the rare NIPT finding of more than 1 aneuploidy detected (7 known cancers among 39 cases of multiple aneuploidies by NIPT, 18% [95% CI, 7.5%-33.5%]). All 8 cases that underwent further bioinformatics analysis showed unique patterns of nonspecific copy-number gains and losses across multiple chromosomes. In 1 case, blood was sampled after completion of treatment for colorectal cancer and the abnormal pattern was no longer evident. Conclusions and Relevance In this preliminary study, a small number of cases of occult malignancy were subsequently diagnosed among pregnant women whose noninvasive prenatal testing results showed discordance with the fetal karyotype. The clinical importance of these findings will require further research.

Case 3: Hyperbilirubinemia Without Jaundice in a Neonate

A female infant was born at 39 weeks’ gestation at term appropriate for gestational age to a 21-year-old gravida 1, para 1 mother. Spontaneous rupture of membranes occurred 19 hours after delivery, and labor was complicated by chorioamnionitis. The prenatal history and maternal laboratory test results were unremarkable. The mother had not been tested for group B Streptococcus status but received adequate antibiotic prophylaxis before delivery. The infant was delivered via spontaneous vaginal delivery with Apgar scores of 9 and 9 at 1 and 5 minutes, respectively. She was admitted to the newborn nursery, where she received 48 hours of empiric antibiotics with ampicillin and gentamicin. The infant was discharged on the second day after birth with a transcutaneous bilirubin level of 13.3 mg/dL (227.5 μmol/L) at age 47 hours (zone 4, high risk). The mother, who was exclusively breastfeeding, was instructed to bring the infant the next day to the outpatient clinic for a bilirubin check. The serum total bilirubin was 24.4 mg/dL (417.3 μmol/L). The infant was immediately transferred to the neonatal intensive care unit and given phototherapy on admission. The infant …

Noninvasive Prenatal Testing and Incidental Detection of Occult Maternal Malignancies

ImportanceUnderstanding the relationship between aneuploidy detection on noninvasive prenatal testing (NIPT) and occult maternal malignancies may explain results that are discordant with the fetal karyotype and improve maternal clinical care.ObjectiveTo evaluate massively parallel sequencing data for patterns of copy-number variations that might prospectively identify occult maternal malignancies.Design, Setting, and ParticipantsCase series identified from 125 426 samples submitted between February 15, 2012, and September 30, 2014, from asymptomatic pregnant women who underwent plasma cell-free DNA sequencing for clinical prenatal aneuploidy screening. Analyses were conducted in a clinical laboratory that performs DNA sequencing. Among the clinical samples, abnormal results were detected in 3757 (3%); these were reported to the ordering physician with recommendations for further evaluation.ExposuresNIPT for fetal aneuploidy screening (chromosomes 13, 18, 21, X, and Y).Main Outcomes and MeasuresDetailed genome-wide bioinformatics analysis was performed on available sequencing data from 8 of 10 women with known cancers. Genome-wide copy-number changes in the original NIPT samples and in subsequent serial samples from individual patients when available are reported. Copy-number changes detected in NIPT sequencing data in the known cancer cases were compared with the types of aneuploidies detected in the overall cohort.ResultsFrom a cohort of 125 426 NIPT results, 3757 (3%) were positive for 1 or more aneuploidies involving chromosomes 13, 18, 21, X, or Y. From this set of 3757 samples, 10 cases of maternal cancer were identified. Detailed clinical and sequencing data were obtained in 8. Maternal cancers most frequently occurred with the rare NIPT finding of more than 1 aneuploidy detected (7 known cancers among 39 cases of multiple aneuploidies by NIPT, 18% [95% CI, 7.5%-33.5%]). All 8 cases that underwent further bioinformatics analysis showed unique patterns of nonspecific copy-number gains and losses across multiple chromosomes. In 1 case, blood was sampled after completion of treatment for colorectal cancer and the abnormal pattern was no longer evident.Conclusions and RelevanceIn this preliminary study, a small number of cases of occult malignancy were subsequently diagnosed among pregnant women whose noninvasive prenatal testing results showed discordance with the fetal karyotype. The clinical importance of these findings will require further research.

Discordant Noninvasive Prenatal Testing and Cytogenetic Results

Recent published studies have demonstrated the incremental value of the use of cell-free DNA for noninvasive prenatal testing with 100% sensitivity for trisomies 21 and 18 and a specificity of ≥99.7% for both. Data presented by two independent groups suggesting positive results by noninvasive prenatal testing were not confirmed by cytogenetic studies. Concordance of results among cases with noninvasive prenatal testing referred for cytogenetic prenatal and/or postnatal studies by karyotyping, fluorescence in situ hybridization, and/or oligo–single-nucleotide polymorphism microarray was evaluated for 109 consecutive specimens. Cytogenetic results were positive for trisomy 21 in 38 of the 41 noninvasive prenatal testing–positive cases (true-positive rate: 93%) and for trisomy 18 in 16 of the 25 noninvasive prenatal testing–positive cases (true-positive rate: 64%). The true-positive rate was only 44% (7/16 cases) for trisomy 13 and 38% (6/16 cases) for sex chromosome aneuploidy. These findings raise concerns about the limitations of noninvasive prenatal testing and the need for analysis of a larger number of false-positive cases to provide true positive predictive values for noninvasive testing and to search for potential biological or technical causes. Our data suggest the need for a careful interpretation of noninvasive prenatal testing results and cautious transmission of the same to providers and patients. Genet Med 17 3, 234–236.

Case 2: Premature Infant With a Fontanelle Bruit

During routine weekend rounds, the nurse practitioner notes that an 11-day fontanelle of an infant born at 33 weeks’ gestation is pulsating. She listens with her stethoscope and auscultates a bruit. On examination, the infant is not tachypneic, and there is a soft systolic ejection murmur heard at the left sternal border radiating to the axilla without a gallop. Of note, there is also no hepatomegaly apparent on examination. The remainder of her examination findings are normal. ### History The infant is a twin female born at 331/7 weeks’ gestational age who is being managed in the neonatal intensive care unit (NICU) for prematurity and feeding difficulties. She was born to a 35-year-old, gravida 2, para 0010 woman whose pregnancy was complicated by preeclampsia, preterm premature rupture of membranes, and twin gestation. At birth, the infant weighed 2,285 g (77th percentile), her head circumference was 32 cm (86th percentile), and her Apgar scores were 9 and 9 at 1 and 5 minutes, respectively. Maternal prenatal test results were unremarkable, including a first trimester screen, ultrasonography, and glucose tolerance test. Prenatal medications included prenatal vitamins and one course of betamethasone. The mother denied smoking, alcohol, or drug use during the pregnancy. The infant is breathing comfortably in room air since birth. She is not anemic and is tolerating enteral feeds since they were initiated shortly after birth. She is not yet able to use a nipple for all her feeds, so she is being fed by gavage tube. Her history does not …

Pregnancy: Prepare for unexpected prenatal test results.

Women are learning about their own health problems through fetal screening. Revise consent forms and raise awareness, urges Diana W. Bianchi.

Copy-Number Variation and False Positive Prenatal Aneuploidy Screening Results

Investigations of noninvasive prenatal screening for aneuploidy by analysis of circulating cell-free DNA (cfDNA) have shown high sensitivity and specificity in both high-risk and low-risk cohorts. However, the overall low incidence of aneuploidy limits the positive predictive value of these tests. Currently, the causes of false positive results are poorly understood. We investigated four pregnancies with discordant prenatal test results and found in two cases that maternal duplications on chromosome 18 were the likely cause of the discordant results. Modeling based on population-level copy-number variation supports the possibility that some false positive results of noninvasive prenatal screening may be attributable to large maternal copy-number variants. (Funded by the National Institutes of Health and others.)

Unjustified: The Imbalance of Information and Funding With Noninvasive Prenatal Screening

Background: Noninvasive prenatal screening (NIPS) is the latest in prenatal testing technologies for Down syndrome and other aneuploidies. It joins existing traditional screening and invasive testing. The administration and funding of prenatal testing for aneuploidy has been the subject of several studies evaluating whether women are making informed choices and whether prenatal testing is cost-effective. Methods: A review of professional medical guidelines, studies on informed consent and cost-effectiveness, and how NIPS is currently being administered and covered by private and public insurance was conducted. Results: Since the major medical organizations have recognized NIPS, particularly for women considered high risk, NIPS is being offered to expectant mothers. Increasingly, public and private insurance are covering NIPS based on the medical guidelines, with cost-effectiveness studies justifying its coverage. The same guidelines recommend pre-test counseling and post-test counseling along with providing patient educational materials with each prenatal test result. Consistent with past practice with traditional screening and invasive testing, these patient educational resources are not being provided or covered at the same rate as the testing itself. Conclusions: The administration of prenatal testing continues to only provide one part of the information recommended by medical guidelines: the testing itself. Patients are not receiving the recommended pre- and post-test counseling and educational materials, nor are these being covered to the same extent as the cost of the NIPS test itself. Unless all of the information recommended by the medical guidelines is both provided and covered to the same extent as the testing itself, offering and covering the costs of NIPS is unjustified.

Index of Suspicion in the Nursery

A male infant was born at 38-4/7-weeks’ gestation to a 39-year-old gravida 6, para 4012 mother, who presented for induction of labor because of oligohydramnios. The mother’s previous deliveries included a now healthy 18-year-old woman born at term (different father from the subsequent 3 children), 2 term neonatal demises that occurred at 4 days after birth, a healthy 5-year-old boy, and the current fetus, all reported to be from the same father. All except the last living child were born on the island of Jamaica. Both infants who died presented with early respiratory distress and succumbed in the neonatal period. Autopsies revealed hyaline membrane disease in those infants. Prenatal ultrasonography of the current fetus revealed normal development. At 34 weeks’ gestation, a course of betamethasone was administered. All prenatal serologic test results were unremarkable except for group B Streptococcus, which was unknown at the time of delivery. She received adequate penicillin prophylaxis. The infant was born by induced vaginal delivery because of oligohydramnios. The infant had spontaneous cry at delivery but became apneic at 5 minutes after birth and required positive pressure ventilation and endotracheal intubation. Apgar scores were 8 and 4 at 1 and 5 minutes, respectively. Birth weight was in the 11th percentile (2.62 kg), length in the 30th percentile (48 cm), and head circumference in the second percentile (30.5 cm). On admission to the neonatal intensive care unit, the infant had physical examination findings significant only for respiratory distress and pallor. Radiography revealed clear lung fields. The infant receives conventional ventilation and requires a fraction of inspired oxygen of 0.3 to 0.35 to maintain oxygen saturations …

735: Perinatal outcomes in pregnancies with a low fetal fraction on noninvasive prenatal testing results

735: Perinatal outcomes in pregnancies with a low fetal fraction on noninvasive prenatal testing results

Potential of syncytiotrophoblasts isolated from the cervical mucus for early non-invasive prenatal diagnosis: Evidence of a vanishing twin

BackgroundNon-invasive methods to assess the foetal genome during pregnancy will provide new opportunities to offer pregnant women a more comprehensive genetic diagnosis of their established foetus. The aim of this study was to determine the presence and frequency of foetal cells in transcervical cell (TCC) mucus samples from pregnant women and determine their suitability for early prenatal diagnosis. MethodsSyncytiotrophoblasts in aspirated TCC mucus samples were identified by immunostaining with the foetal-specific antibody NDOG1. Genetic analysis of foetal cells was performed by laser capture microdissection and quantitative fluorescent PCR (QF-PCR). ResultsIn 116 of 207 (56%) TCC samples, abundant syncytiotrophoblasts were retrieved. However, when TCC samples were stratified for the presence of chorionic villous fragments, syncytiotrophoblasts were identified in 85 of 109 (78%) samples. Significant numbers of syncytiotrophoblasts were found in TCC samples collected between 6 and 9weeks of gestation (mean 741, range 25–2884). QF-PCR analysis of NDOG1 positive syncytiotrophoblasts and matching maternal DNA confirmed their foetal origin and correct foetal cell sexing was achieved in 97% of TCC samples. The one discordant sex diagnosis was associated with a dizygotic dichorionic twin pregnancy resulting from the implantation of a female T21 embryo and a normal male embryo, where the female T21 foetus had succumbed at 6weeks of gestation and was vanishing. ConclusionsSyncytiotrophoblasts can be successfully isolated from TCC samples and represent a suitable source of cells for genetic analysis of the established foetus in early pregnancy. The study highlights a vanishing twin as a potential cause for discordant non-invasive prenatal test results.