Prenatal Diagnosis

Cover image for Vol. 33 Issue 5

May 2013

Volume 33, Issue 5

Pages 409–508

  1. Original Articles

    1. Top of page
    2. Original Articles
    1. Non-invasive prenatal testing of fetal whole chromosome aneuploidy by massively parallel sequencing (pages 409–415)

      Desheng Liang, Weigang Lv, Hua Wang, Liangpu Xu, Jing Liu, Haoxian Li, Liang Hu, Ying Peng and Lingqian Wu

      Version of Record online: 9 JAN 2013 | DOI: 10.1002/pd.4033

      What's already known about this topic?

      • The existence of cell-free fetal DNA in maternal circulation and the advent of massive parallel sequencing (MPS) technologies have enabled non-invasive prenatal testing (NIPT) of fetal chromosome aneuploidies.

      What does this study add?

      • We discovered that the genome representation of each of the 24 chromosomes obeyed a linear relationship to its GC content. Applying this relationship, we analysed the copy number of each of the 24 chromosomes from 435 clinical samples, including a case of trisomy 9, with 100% detection sensitivity and 99.71% specificity. The sequencing was conducted using a 12-plex protocol, demonstrating that the MPS-based NIPT is scalable.
    2. You have full text access to this OnlineOpen article
      Safe, accurate, prenatal diagnosis of thanatophoric dysplasia using ultrasound and free fetal DNA (pages 416–423)

      Lyn S. Chitty, Asma Khalil, Angela N. Barrett, Eva Pajkrt, David R. Griffin and Tim J. Cole

      Version of Record online: 14 FEB 2013 | DOI: 10.1002/pd.4066

      What's already known about this topic?

      • Thanatophoric dysplasia is a lethal skeletal dysplasia amenable to prenatal diagnosis using fetal ultrasound with molecular confirmation following an invasive procedure.

      What does this study add?

      • This study provides data to help distinguish thanatophoric dysplasia from other skeletal dysplasias and demonstrates the potential for safe, definitive molecular confirmation using cell-free fetal DNA in maternal plasma.
    3. Non-invasive prenatal testing with cell-free DNA: US physician attitudes toward implementation in clinical practice (pages 424–428)

      Thomas J. Musci, Genevieve Fairbrother, Annette Batey, Jennifer Bruursema, Craig Struble and Ken Song

      Version of Record online: 22 MAR 2013 | DOI: 10.1002/pd.4091

      What's already known about this topic?

      • A previous survey study prior to the clinical availability of cell-free DNA analysis for aneuploidy detection indicated uncertainty among providers about the implementation of this technology.

      What does this study add?

      • This study indicates that within a year of clinical availability of NIPT in the United States, obstetricians have a high awareness about the technology, have used the testing clinically, and are optimistic about its use in the future.
    4. Impact of observed versus hypothesized service utilization on the incremental cost of first trimester screening and prenatal diagnosis for trisomy 21 in a Canadian province (pages 429–435)

      Amy Metcalfe, Gillian Currie, Jo-Ann Johnson, Francois Bernier, Lisa M. Lix, Andrew W. Lyon and Suzanne C. Tough

      Version of Record online: 21 MAR 2013 | DOI: 10.1002/pd.4082

      What's already known about this topic?

      • Multiple studies have been conducted to determine the cost-effectiveness of various forms of prenatal screening with conflicting results as to what form of prenatal screening is most cost-effective.
      • Studies consistently show that prenatal screening for trisomy 21 is more cost-effective than screening based on maternal age alone.

      What does this study add?

      • This study shows that the assumptions made in existing economic evaluations may not accurately reflect patient decision making and clinical practice, thus impacting the purported costs associated with various forms of prenatal screening.
      • Additionally, it provides per unit costs that permit extrapolation of costs to local centers based on their local utilization patterns.
    5. Three-dimensional ultrasound demonstration of the fetal palate in high-risk patients: the accuracy of prenatal visualization (pages 436–441)

      Liat Gindes, Alina Weissmann-Brenner, Michal Zajicek, Boaz Weisz, Alon Shrim, Keren Tzadikevitch Geffen, David Mendes, Jaacov Kuint, Michal Berkenstadt and Reuven Achiron

      Version of Record online: 12 MAR 2013 | DOI: 10.1002/pd.4083

      What's already known about this topic?

      • It is well-known that fetal palate can be demonstrated by three-dimensional ultrasound and that detection rate of cleft palate has improved over the years.

      What does this study add?

      • This study investigates the accuracy of prenatal evaluation of palate in high-risk fetuses by three-dimensional ultrasound. It shows that cleft palate can be diagnosed in 83% of the cases. Awareness should be taken to artifacts that may cause false-positive and false-negative results.
    6. Indications and pregnancy outcomes when multidisciplinary centers for prenatal diagnosis refuse request for termination of pregnancy: a retrospective French study (pages 442–448)

      M. L. Nguyen, H. Roman, M. Dommergues and E. Verspyck

      Version of Record online: 20 MAR 2013 | DOI: 10.1002/pd.4085

      What's already known about this topic?

      • In France, termination of pregnancy (TOP) must be attested by at least two physicians who are members of a Multidisciplinary Center for Prenatal Diagnosis (MCPD), which is authorized by the Ministry of Health.
      • MCPD can refuse a woman's TOP request, most often when prognosis is uncertain or severity debatable. The outcomes of such pregnancies may be variable and are poorly investigated to date.

      What does this study add?

      • The refusal rate of TOP by MCPD has remained stable and rare in France in recent years. However, the rate of effective TOP is high (36.3%) and particularly when requested during the first trimester and in cases of structural anomalies of the fetus. The rate of lost to follow-up is particularly high (23.2%) and reflects conflict between physicians and parents wishing to terminate their pregnancy.
    7. Women and their partners' preferences for Down's syndrome screening tests: a discrete choice experiment (pages 449–456)

      Fran E. Carroll, Hareth Al-Janabi, Terry Flynn and Alan A. Montgomery

      Version of Record online: 27 MAR 2013 | DOI: 10.1002/pd.4086

      What's already known about this topic?

      • Decision making about Down's syndrome screening can be difficult, and there are different tests available should screening be chosen.

      What does this study add?

      • This research offers important insight into the test attributes that are valued most by both pregnant women and their partners.
      • This provides important information to policymakers seeking to understand more about the preferences for and relative value of screening test attributes according to those who use them. The findings will also be of interest to providers and those who help women make decisions about screening tests.
    8. Maternal serum placental growth factor and α-fetoprotein testing in first trimester screening for Down syndrome (pages 457–461)

      Kim Donalson, Steve Turner, Lesley Morrison, Päivi Liitti, Christel Nilsson and Howard Cuckle

      Version of Record online: 26 MAR 2013 | DOI: 10.1002/pd.4087

      What's already known about this topic?

      • PLGF and AFP are first trimester Down syndrome markers, albeit fairly weak ones. Both markers are informative for other conditions in early pregnancy.

      What does this study add?

      • This is a case–control study that demonstrates the benefit of adding new markers, in particular PLGF, to both combined and serum-only screening protocols in the first trimester. Performance of a serum-only first trimester quad test is comparable with the second trimester quad test.
    9. Detection of the fetal conotruncal anomalies using real-time three-dimensional echocardiography with live xPlane imaging of the fetal ductal arch view (pages 462–466)

      Yi Xiong, Tao Liu, Han Jing Gan, Ying Wu, Jin Feng Xu, Yuen Ha Ting, Tak Yeung Leung and Tze Kin Lau

      Version of Record online: 15 MAR 2013 | DOI: 10.1002/pd.4088

      What's already known about this topic?

      • Many techniques, including 2D and STIC, were already used to screen and diagnose the fetal conotruncal anomalies, but not real-time 3D ultrasound.

      What does this study add?

      • Real-time 3D ultrasound enables detection of conotruncal anomalies.
    10. First-trimester Down syndrome screening in renal-transplanted pregnant women: a model for adjusting the false-positives rates (pages 467–470)

      Maribel Grande, Vicenç Cararach, Elena Casals and Antoni Borrell

      Version of Record online: 18 MAR 2013 | DOI: 10.1002/pd.4089

      What's already known about this topic?

      • Renal-transplanted women present an increased false-positive rate at first-trimester maternal serum screening for Down's syndrome as compared with control women.

      What does this study add?

      • A method for adjusting fβ-hCG levels during first trimester according to serum creatinine to lower the elevated false-positive and invasive procedure rates in this group of patients should be confirmed.
    11. The impact of maternal weight discrepancies on prenatal screening results for Down syndrome (pages 471–476)

      Tianhua Huang, Wendy S. Meschino, Nan Okun, Alan Dennis, Barry Hoffman, Nathalie Lepage, Shamim Rashid, Ritu Aul and Sandra A. Farrell

      Version of Record online: 19 MAR 2013 | DOI: 10.1002/pd.4090

      What's already known about this topic?

      • The concentrations of maternal serum markers change with maternal weight.
      • The MoM values of serum markers should be adjusted for maternal weight to improve the accuracy of screening tests.

      What does this study add?

      • The importance of obtaining accurate maternal weight for improving screening accuracy.
      • The magnitude of the effect of relatively small differences between the actual weight and reported weight on the calculated risk of Down syndrome.
      • The weight discrepancy that warrants revision of a screening result when screening for Down syndrome.
    12. Effectiveness of the model for prenatal control of severe thalassemia (pages 477–483)

      Theera Tongsong, Pimlak Charoenkwan, Pannee Sirivatanapa, Chanane Wanapirak, Wirawit Piyamongkol, Supatra Sirichotiyakul, Kasemsri Srisupundit, Fuanglada Tongprasert, Suchaya Luewan, Thawalwong Ratanasiri, Ratana Komwilaisak, Piyamas Saksiriwuttho, Chutawadi Vuthiwong, Peerapun Punpuckdeekoon, Prisana Panichkul, Wibool Rueangchainikhom, Jirawat Choowong, Nawaporn Orungrote, Sravuth Sarapak, Ekachai Kovavisarach, Prapon Jaruyawongs, Thitinan Tansathit, Podjanee Phadungkiatwattana, Jittima Rujiwetpongstorn, Ounjai Kor-anantakul, Chitkasaem Suwanrath, Tharangrut Hanprasertpong and Savitree Pranpanus

      Version of Record online: 31 MAR 2013 | DOI: 10.1002/pd.4095

      What's already known about this topic?

      • Several screening systems have been proposed in the literature.

      What does this study add?

      • Effectiveness of the screening system, in term of sensitivity, specificity, positive and predictive value, is first determined.
    13. DNA methylation of the p66Shc promoter is decreased in placental tissue from women delivering intrauterine growth restricted neonates (pages 484–491)

      Anja Tzschoppe, Helmuth Doerr, Wolfgang Rascher, Tamme Goecke, Matthias Beckmann, Ralf Schild, Ellen Struwe, Jürgen Geisel, Heike Jung and Jörg Dötsch

      Version of Record online: 26 MAR 2013 | DOI: 10.1002/pd.4096

      What's already known about this topic?

      • Previous studies assessed epigenetic dysregulation as potential mechanism in the developmental programming of disease after intrauterine growth restriction (IUGR).

      What does this study add?

      • We analyzed promoter methylation and gene expression of the mitochondrial adaptor protein p66Shc and found decreased p66Shc promoter methylation in placental tissue of IUGR versus appropriate for gestational age and small for gestational age neonates.
      • Whether this plays a role in the pathophysiology of disease after IUGR remains speculative.
    14. Long-term outcomes of children with umbilical vein varix diagnosed prenatally (pages 492–496)

      Y. Melcer, I. Ben-Ami, Y. Wiener, A. Livne, A. Herman and R. Maymon

      Version of Record online: 25 MAR 2013 | DOI: 10.1002/pd.4098

      What's already known about this topic?

      • Umbilical vein varix is defined as a focal enlargement of the umbilical vein and represents about 4% of fetal umbilical cord malformations.
      • This rare anomaly has been related to stillborn infants.
      • Studies have reported on the correlation between UVV and fetal anomalies, aneuploidies, fetal hydrops, and other adverse pregnancy outcomes.

      What does this study add?

      • This is a first study to suggest a possible association between UVV diagnosed prenatally and child developmental delay
    15. Omphalocele in the first trimester: prediction of perinatal outcome (pages 497–501)

      Mikaël Tassin, Céline Descriaud, Caroline Elie, Véronique Houfflin Debarge, Yves Dumez, Franck Perrotin and Alexandra Benachi

      Version of Record online: 25 MAR 2013 | DOI: 10.1002/pd.4102

      What's already known about this topic?

      • The size of the omphalocele, especially in cases of giant omphaloceles, is associated with neonatal morbidity, such as respiratory insufficiency, feeding difficulties and prolonged hospitalizations.
      • Recent studies have evaluated standardized measurement of omphalocele, using omphalocele sac diameter relative to fetal biometries: The omphalocele circumference/abdominal circumference ratio was found to be predictive of herniation of the liver, respiratory insufficiency and type of surgical management.

      What does this study add?

      • This study evaluates a new standardized measurement of omphalocele in the first trimester, using the mean diameter of the omphalocele instead of its circumference because the variability in omphalocele shape can alter the circumference measurements.
      • This study relates to a large number of cases of omphaloceles in the first trimester with prenatal and postnatal follow-up.
    16. QF-PCR as a substitute for karyotyping of cytotrophoblast for the analysis of chorionic villi: advantages and limitations from a cytogenetic retrospective audit of 44,727 first-trimester prenatal diagnoses (pages 502–508)

      Francesca R. Grati, Francesca Malvestiti, Beatrice Grimi, Elisa Gaetani, Anna Maria Di Meco, Anna Trotta, Rosaria Liuti, Sara Chinetti, Francesca Dulcetti, Anna Maria Ruggeri, Cristina Agrati, Giuditta Frascoli, Silvia Milani, Simona De Toffol, Lorenza Martinoni, Silvia Paganini, Livia Marcato, Federico Maggi and Giuseppe Simoni

      Version of Record online: 21 APR 2013 | DOI: 10.1002/pd.4099

      What's already known about this topic?

      • The gold standard analysis of CVS includes the cytogenetic analysis of cytotrophoblast (STC) and mesenchyme (LTC).
      • QF-PCR is a widely used method for rapid aneuploidy detection in prenatal samples.
      • The application of QF-PCR on CVS is problematic because discrepant results with karyotype have been reported.
      • A combined approach QF-PCR +; LTC was proposed instead of STC +; LTC to minimize the risk of discrepant results and achieve a simplification of cytogenetic methods and procedures for the analysis of CVS.

      What does this study add?

      • Compared with the STC + LTC combined method, QF-PCR + LTC is associated with a cumulative risk of false-negative result ranging from ~1/3100 to 1/4400 (depending on the sex chromosome investigation), similar cost/sample (considering a high throughput cytogenetic lab organization and a CE-IVD marked QF-PCR assay) and identical reporting time because preliminary result communications based on only QF-PCR test are generally discouraged as routine practice.

SEARCH

SEARCH BY CITATION