K H Nicolaides

University of Plymouth, Plymouth, England, United Kingdom

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Publications (837)3463.18 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Severe early-onset (SEO) pre-eclampsia (PE) is a leading cause of maternal and fetal morbidity in the UK and at present there is not a reliable clinical tool to predict the disease's onset. Hypertension (essential in the diagnosis of PE) has been associated with dysregulation of numerous plasma proteins, both in pregnant and non-pregnant studies. The aim of this work is to identify whether the angiotensinogen to kallikrein ratio is altered in the first trimester of pregnancies that go on to develop pre-eclampsia.
    Archives of Disease in Childhood - Fetal and Neonatal Edition 06/2014; 99(Suppl 1):A5. · 3.45 Impact Factor
  • Article: Reply.
    N Persico, K H Nicolaides
    Ultrasound in Obstetrics and Gynecology 03/2014; 43(3):356-7. · 3.56 Impact Factor
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    ABSTRACT: Objective: To review clinical validation or implementation studies of maternal blood cell-free (cf) DNA analysis in screening for aneuploidies and to explore the potential use of this method in clinical practice. Methods: Searches of PubMed and MEDLINE were performed to identify all peer-reviewed articles on cfDNA testing in screening for aneuploidies between 2011, when the first such study was published, and 20 December 2013. Results: Weighted pooled detection rates (DR) and false-positive rates (FPR) in singleton pregnancies were 99.0% (95% CI 98.2-99.6) and 0.08% (95% CI 0.03-0.14), respectively, for trisomy 21; 96.8% (95% CI 94.5-98.4) and 0.15% (95% CI 0.08-0.25) for trisomy 18; 92.1% (95% CI 85.9-96.7) and 0.20% (95% CI 0.04-0.46) for trisomy 13; 88.6% (95% CI 83.0-93.1) and 0.12% (95% CI 0.05-0.24) for monosomy X, and 93.8% (95% CI 85.9-98.7) and 0.12% (95% CI 0.02-0.28) for sex chromosome aneuploidies other than monosomy X. For twin pregnancies, the DR was 94.4% (95% 74.2-99.0) and the FPR was 0% (95% CI 0.00-1.84) for trisomy 21. Conclusion: An analysis of cfDNA in maternal blood provides effective screening for trisomies. © 2014 S. Karger AG, Basel.
    Fetal Diagnosis and Therapy 02/2014; · 1.90 Impact Factor
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    ABSTRACT: Objective: To examine the performance of screening for trisomies 21, 18 and 13 at 11-13 weeks' gestation using specific algorithms for these trisomies based on combinations of fetal nuchal translucency thickness (NT), fetal heart rate (FHR), ductus venosus pulsatility index for veins (DV PIV), and serum free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PLGF) and α-fetoprotein (AFP). Methods: Model-based estimates of screening performance were produced for the distribution of maternal ages in England and Wales in 2011, and prospectively collected data on fetal NT, FHR, DV PIV, β-hCG, PAPP-A, PLGF and AFP from singleton pregnancies undergoing aneuploidy screening. Results: In screening by NT, FHR, free β-hCG and PAPP-A, using specific algorithms for trisomy 21 and trisomies 18 and 13 at the risk cutoff of 1:100, the estimated detection rate (DR) was 87.0% for trisomy 21 and 91.8% for trisomies 18 and 13, at a false-positive rate (FPR) of 2.2%. Addition of PLGF, AFP and DV PIV increased the DR to 93.3% for trisomy 21 and 95.4% for trisomies 18 and 13 and reduced the FPR to 1.3%. Conclusions: Effective screening for trisomies can be achieved using specific algorithms based on NT, FHR, DV PIV, β-hCG, PAPP-A, PLGF and AFP. © 2013 S. Karger AG, Basel.
    Fetal Diagnosis and Therapy 12/2013; · 1.90 Impact Factor
  • P Chaveeva, P Kosinski, D Puglia, L C Poon, K H Nicolaides
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    ABSTRACT: Objective: To compare the outcome of trichorionic triplet (TCT) and dichorionic triplet (DCT) pregnancies managed expectantly and those with embryo reduction (ER) at 10-14 weeks to twins or singletons. Methods: This was a retrospective study of triplet pregnancies with 3 live fetuses managed expectantly or by ER. Data were combined with the results of previous studies that used similar entry criteria and outcome measures. The management options were compared for rates of miscarriage and preterm birth <33 weeks. Results: In TCTs managed expectantly (n = 358), the rates of miscarriage and preterm birth were 3.1 and 35.1%. Compared to the expectantly managed TCTs, the rate of miscarriage was higher and preterm birth lower in TCTs with ER to 2 fetuses (n = 833, 7.3 and 13.1%, respectively) and TCTs with ER to 1 fetus (n = 78, 11.5 and 8.7%). In DCTs managed expectantly (n = 136), the rates of miscarriage and preterm birth were 8.8 and 46.0%. In DCTs with ER to 2 fetuses (n = 15) or ER to 1 fetus (n = 42), there was a non-significant increase in miscarriage (13.3 and 16.7%, respectively) and decrease in preterm birth (23.1 and 8%, respectively). Conclusions: In TCT and DCT pregnancies, ER increases the rate of miscarriage but reduces the rate of preterm birth. © 2013 S. Karger AG, Basel.
    Fetal Diagnosis and Therapy 11/2013; · 1.90 Impact Factor
  • K H Nicolaides, A Syngelaki, L C Poon, M Gil, D Wright
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    ABSTRACT: Objective: To examine potential performance of screening for trisomies by cell-free (cf) DNA testing in maternal blood contingent on results of first-line testing by combinations of fetal translucency thickness (NT), fetal heart rate (FHR), ductus venosus pulsatility index (DV PIV), and serum-free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PLGF) and α-fetoprotein (AFP). Methods: Performance was estimated for firstly, screening by cfDNA in all pregnancies and secondly, cfDNA testing contingent on results of first-line testing by combinations of ultrasound and biochemical markers. Results: In first-line screening by cfDNA testing, the detection rate for trisomy 21 and trisomies 18 or 13 would be 99 and 96%, respectively, after invasive testing in 1% of the population. In contingent screening, a detection rate of 98% for trisomy 21 and 96% for trisomy 18 or 13, at an invasive testing rate of 0.7%, can be achieved by carrying out cfDNA testing in about 35, 20 and 11% of cases identified by first-line screening with the combined test alone (age, NT, FHR, β-hCG, PAPP-A), the combined test plus PLGF and AFP and the combined test plus PLGF, AFP and DV PIV, respectively. Conclusions: Effective first-trimester screening for trisomies can be achieved by contingent screening incorporating biomarkers and cfDNA testing. © 2013 S. Karger AG, Basel.
    Fetal Diagnosis and Therapy 10/2013; · 1.90 Impact Factor
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    Dataset: 7628 ftp
    L C Y Poon, R Akolekar, R Lachmann, J Beta, K H Nicolaides
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    Dataset: 7628 ftp
    L C Y Poon, R Akolekar, R Lachmann, J Beta, K H Nicolaides
  • M M Gil, M S Quezada, B Bregant, M Ferraro, K H Nicolaides
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    ABSTRACT: OBJECTIVE: To explore the feasibility of routine maternal blood cell-free (cf) DNA testing in screening for trisomies 21, 18 and 13 at 10 weeks' gestation. METHOD: In this prospective study, women attending The Fetal Medicine Centre in London, UK, between October 2012 and April 2013, with singleton pregnancy and live fetus with CRL 32-45 mm, were screened for trisomies 21, 18 and 13 by cfDNA testing at 10 weeks and the combined test at 12 weeks. RESULTS: cfDNA testing was performed in 1005 singleton pregnancies with a median maternal age of 37 (range, 20-49) years. Risks for trisomies were provided for 957 (95.2%) cases and in 98.0% these were available within 14 days from sampling. In 48 (4.8%) cases no result was provided due to problems with delivery to the laboratory, low fetal fraction or assay failure. Repeat sampling was performed in 40 cases and a result obtained in 27 (67.5%) of these. In 11 cases the risk score for trisomy 21 and in five cases that for trisomy 18 was > 99%, in one the risk for trisomy 13 was 34% and in 968 the risk for each of the three trisomies was < 0.01%. The suspected trisomies were confirmed by karyotyping after chorionic villus sampling (CVS), except in one case of trisomy 18 in which the karyotype was normal. On the basis of the maternal age distribution of the study population, the expected and observed numbers for each of the three trisomies were similar. Both cfDNA and combined testing detected all trisomies, but the estimated false-positive rates (FPR) were 0.1% and 3.4%, respectively. CONCLUSION: Routine screening for trisomies 21, 18 and 13 by cfDNA testing at 10 weeks is feasible and has a lower FPR than does combined testing, but abnormal results require confirmation by CVS. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.
    Ultrasound in Obstetrics and Gynecology 06/2013; · 3.56 Impact Factor
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    K H Nicolaides, D Wright, L C Poon, A Syngelaki, M Gil
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    ABSTRACT: OBJECTIVE: To define risk cut-offs with corresponding detection rates (DR) and false-positive rates (FPR) in screening for trisomy 21 using maternal age and combinations of first-trimester biomarkers in order to determine which women should undergo contingent maternal blood cell-free (cf) DNA testing. METHODS: From singleton pregnancies undergoing screening for aneuploidies at three UK hospitals between March 2006 and May 2012, we analyzed prospectively collected data on the following biomarkers: fetal nuchal translucency thickness (NT) and ductus venosus pulsatility index for veins (DV-PIV) at 11 + 0 to 13 + 6 weeks' gestation and serum free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PlGF) and alpha-fetoprotein (AFP) at 8 + 0 to 13 + 6 weeks. Estimates of risk cut-offs, DRs and FPRs were derived for combinations of biomarkers and these were used to define the best strategy for contingent cfDNA testing. RESULTS: In contingent screening, detection of 98% of fetuses with trisomy 21 at an overall invasive testing rate < 0.5% can be potentially achieved by offering cfDNA testing to about 36%, 21% and 11% of cases identified by first-line screening using the combined test alone, using the combined test with the addition of serum PlGF and AFP and using the combined test with the addition of PlGF, AFP and DV-PIV, respectively. CONCLUSIONS: Effective first-trimester screening for trisomy 21, with DR of 98% and invasive testing rate < 0.5%, can be potentially achieved by contingent screening incorporating biomarkers and cfDNA testing. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.
    Ultrasound in Obstetrics and Gynecology 06/2013; · 3.56 Impact Factor
  • Source
    A Khalil, K H Nicolaides
    Ultrasound in Obstetrics and Gynecology 05/2013; · 3.56 Impact Factor
  • K H Nicolaides, A Syngelaki, M Gil, V Atanasova, D Markova
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    ABSTRACT: OBJECTIVE: To assess the performance of cell-free DNA (cfDNA) testing in maternal blood for detection of fetal aneuploidy of chromosomes 13, 18, 21, X, and Y using targeted sequencing of single-nucleotide polymorphisms. METHODS: Prospective study in 242 singleton pregnancies undergoing chorionic villus sampling at 11 to 13 weeks. Maternal blood was collected before chorionic villus sampling and sent to Natera (San Carlos, CA, USA). cfDNA was isolated from maternal plasma, and targeted multiplex PCR amplification followed by sequencing of 19 488 polymorphic loci covering chromosomes 13, 18, 21, X, and Y was performed. Sequencing data were analyzed using the NATUS algorithm that determines the copy number and calculates a sample-specific accuracy for each of the five chromosomes tested. Laboratory personnel were blinded to fetal karyotype. RESULTS: Results were provided for 229 (94.6%) of the 242 cases. Thirty-two cases were correctly identified as aneuploid, including trisomy 21 [n = 25; sensitivity = 100% (CI: 86.3-100%), specificity = 100% (CI: 98.2-100%)], trisomy 18 (n = 3), trisomy 13 (n = 1), Turner syndrome (n = 2), and triploidy (n = 1), with no false positive or false negative results. Median accuracy was 99.9% (range: 96.0-100%). CONCLUSIONS: cfDNA testing in maternal blood using targeted sequencing of polymorphic loci at chromosomes 13, 18, 21, X, and Y holds promise for accurate detection of fetal autosomal trisomies, sex chromosome aneuploidies, and triploidy. © 2013 John Wiley & Sons, Ltd.
    Prenatal Diagnosis 04/2013; · 2.68 Impact Factor
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    ABSTRACT: The proof-of-principle of diagnosing fetal aneuploidy by shotgun sequencing cell-free DNA from maternal blood was demonstrated independently by two groups in 2008.(1,2) The strength of the initial approach was the fact that it was genome-wide by design, yet it was exclusively or mainly limited in scope to the detection of trisomy 21 (T21). Follow-up studies then substantiated the lower sensitivity of the approach for autosomal trisomies other than T21. This article is protected by copyright. All rights reserved.
    Prenatal Diagnosis 04/2013; · 2.68 Impact Factor
  • L C Y Poon, T Musci, K Song, A Syngelaki, K H Nicolaides
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    ABSTRACT: Objective: To examine the possible relationship between maternal and fetal characteristics and pregnancy outcomes on fetal and maternal cell-free (cf) DNA in maternal plasma at 11-13 weeks' gestation. Methods: cfDNA was extracted from maternal plasma of 1,949 singleton pregnancies and chromosome-selective sequencing was used to determine the proportion of cfDNA and total cfDNA counts which was of fetal and maternal origin. Multivariate regression analysis was used to determine whether specific maternal and fetal characteristics and pregnancy complications, such as preeclampsia (PE), early spontaneous preterm birth (SPB) and delivery of small for gestational age (SGA) neonates, were significant predictors of fetal and maternal cfDNA in maternal plasma. Results: The fetal and maternal cfDNA plasma concentration increased with serum pregnancy-associated plasma protein-A and free β-human chorionic gonadotropin level, was higher in women of Afro-Caribbean and East-Asian racial origin than in Caucasians, and lower in smokers, but it was not significantly altered in pregnancies complicated by PE, SPB or SGA. The fetal cfDNA level was inversely related to maternal weight and uterine artery pulsatility index, and maternal cfDNA increased with maternal weight. Conclusions: The fetal and maternal cfDNA level in maternal plasma is affected by maternal and fetal characteristics, but it is not altered in pregnancy complications.
    Fetal Diagnosis and Therapy 03/2013; · 1.90 Impact Factor
  • Article: Reply.
    F S Molina, G Rus, L F Gómez, J Florido, K H Nicolaides
    Ultrasound in Obstetrics and Gynecology 11/2012; 40(5):612-3. · 3.56 Impact Factor
  • A Khalil, D Sodre, A Syngelaki, R Akolekar, K H Nicolaides
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    ABSTRACT: Objective: To examine aortic systolic blood pressure (SBP(Ao)), pulse wave velocity (PWV) and augmentation index (adjusted to a heart rate of 75 beats per minute, AIx-75) at 11-13 weeks' gestation in pregnancies delivering small for gestational age (SGA) neonates with and without preeclampsia (PE). Methods: At 11+0 to 13+6 weeks' gestation, maternal history was recorded and PWV, AIx-75, SBP(Ao), uterine artery pulsatility index (PI) and maternal serum pregnancy-associated plasma protein-A (PAPP-A) were measured. We compared women with (n = 337) and without (n = 48) PE that delivered SGA neonates with unaffected controls (n = 6,429). Results: In the SGA group without PE, compared to unaffected controls, there was no significant difference in AIx-75 (1.03 vs. 1.00 multiple of the median, MoM), PWV (0.98 vs. 1.00 MoM) or SBP(Ao) (1.01 vs. 1.00 MoM), but uterine artery PI was increased (1.10 vs. 1.00 MoM) and PAPP-A decreased (0.85 vs. 1.00 MoM). In SGA with PE, compared to unaffected controls, there was increased AIx-75 (1.13 vs. 1.00 MoM), SBP(Ao) (1.09 vs. 1.00 MoM), uterine artery PI (1.40 vs. 1.00 MoM) and decreased PAPP-A (0.72 vs. 1.00 MoM), but no significant difference in PWV (1.05 vs. 1.00 MoM). Conclusion: In pregnancies with SGA neonates, impaired placentation is reflected in low PAPP-A and high uterine artery PI at 11-13 weeks' gestation. In the SGA group with PE, but not in those without PE, there is increased SBP(Ao) and AIx-75.
    Fetal Diagnosis and Therapy 09/2012; · 1.90 Impact Factor
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    ABSTRACT: To examine the possible association between aneuploidies and fetal lateral cerebral ventriculomegaly in the first trimester of pregnancy. Three-dimensional brain volumes were acquired by transvaginal ultrasound examination at 11-13 weeks' gestation in 410 euploid fetuses and 63 fetuses with trisomy 21, 34 with trisomy 18 and seven with trisomy 13. Lateral ventricles were assessed in a transverse view, just above the roof of the third ventricle and measurements of the areas of the lateral ventricles and choroid plexuses were obtained. The ratio between choroid plexus and lateral ventricle areas (CLR) was calculated. Measurements in aneuploid fetuses were compared to those in euploid fetuses. In euploid fetuses the lateral ventricle and choroid plexus areas increased, whereas the CLR decreased with fetal biparietal diameter. In fetuses with trisomy 21, lateral ventricle and choroid plexus areas were smaller but CLR was not significantly different from that in euploid fetuses. In trisomy 18 and 13 fetuses, CLR was significantly smaller than in euploid fetuses. The CLR was below the 5(th) centile of normal range in 11 (32.4%) fetuses with trisomy 18 and in six (85.7%) with trisomy 13. There is evidence of ventriculomegaly at 11-13 weeks' gestation in most fetuses with trisomy 13 and one third of fetuses with trisomy 18.
    Ultrasound in Obstetrics and Gynecology 05/2012; 40(3):282-7. · 3.56 Impact Factor

Publication Stats

23k Citations
3,463.18 Total Impact Points

Institutions

  • 2008–2013
    • University of Plymouth
      • School of Computing and Mathematics
      Plymouth, England, United Kingdom
    • Centre Hospitalier Régional Universitaire de Lille
      Lille, Nord-Pas-de-Calais, France
    • University of Tuebingen
      Tübingen, Baden-Württemberg, Germany
    • The Chinese University of Hong Kong
      • Department of Obstetrics and Gynaecology
      Hong Kong, Hong Kong
  • 2002–2013
    • University College London
      • Institute for Women's Health
      London, ENG, United Kingdom
    • Royal College Of Paediatrics and Child Health
      Londinium, England, United Kingdom
  • 1993–2013
    • Chelsea and Westminster Hospital NHS Foundation Trust
      Londinium, England, United Kingdom
    • McMaster University
      • Department of Surgery
      Hamilton, Ontario, Canada
  • 1981–2013
    • King's College London
      • • Department of Medical and Molecular Genetics
      • • Division of Asthma, Allergy and Lung Biology
      Londinium, England, United Kingdom
  • 2011–2012
    • University-Hospital Brugmann UVC
      Bruxelles, Brussels Capital Region, Belgium
    • Hospital Universitario San Cecilio
      • Department of Obstetrics and Gynaecology
      Granata, Andalusia, Spain
    • University of Porto
      Oporto, Porto, Portugal
    • University Hospital of Heraklion
      Irákleio, Attica, Greece
    • Medizinische Universität Innsbruck
      • Univ.-Klinik für Gynäkologie und Geburtshilfe
      Innsbruck, Tyrol, Austria
  • 2006–2012
    • Center for Prenatal Diagnosis and Human Genetics, Kudamm-199
      Berlín, Berlin, Germany
    • University Hospital Brussels
      Bruxelles, Brussels Capital Region, Belgium
    • The Ohio State University
      • Department of Obstetrics and Gynecology
      Columbus, OH, United States
    • Wright State University
      • Department of Obstetrics and Gynecology
      Dayton, Ohio, United States
  • 1992–2012
    • The Fetal Medicine Foundation
      Londinium, England, United Kingdom
  • 2008–2011
    • University of Maryland, Baltimore
      • Department of Obstetrics, Gynecology and Reproductive Sciences
      Baltimore, MD, United States
  • 2010
    • Hannover Medical School
      Hanover, Lower Saxony, Germany
    • Hospital Universitario Virgen de las Nieves
      • Department of Obstetrics and Gynaecology
      Granata, Andalusia, Spain
    • University of Liège
      • Department of Obstetrics and Gynecology
      Liège, WAL, Belgium
  • 1986–2010
    • King's College Hospital NHS Foundation Trust
      • • Department of Obstetrics and Gynaecology
      • • Department of Child Health
      Londinium, England, United Kingdom
  • 2004–2009
    • Universitair Ziekenhuis Leuven
      • Department of Gynaecology and obstetrics
      Leuven, VLG, Belgium
    • Charité Universitätsmedizin Berlin
      Berlín, Berlin, Germany
    • University Medical Center Schleswig-Holstein
      Kiel, Schleswig-Holstein, Germany
  • 2005
    • University of Leeds
      Leeds, England, United Kingdom
  • 1997–2005
    • University Hospital of Ioannina
      Yannina, Epirus, Greece
  • 2001
    • London School of Hygiene and Tropical Medicine
      Londinium, England, United Kingdom
  • 1998–2001
    • St. George's School
      • • Department of Medical Genetics
      • • Medical Genetics Unit
      Middletown, Rhode Island, United States
  • 2000
    • Imperial College Healthcare NHS Trust
      Londinium, England, United Kingdom
  • 1998–2000
    • University of Freiburg
      • Institute of Anatomy and Cell Biology
      Freiburg, Lower Saxony, Germany
  • 1990–2000
    • The Kings College
      Denmark, South Carolina, United States
    • ICL
      Londinium, England, United Kingdom
  • 1985–2000
    • The Peninsula College of Medicine and Dentistry
      • School of Medicine
      Plymouth, England, United Kingdom
  • 1996–1997
    • University of London
      Londinium, England, United Kingdom
  • 1995
    • University of Bristol
      Bristol, England, United Kingdom
  • 1990–1993
    • University of Groningen
      • Department of Obstetrics and Gynaecology
      Groningen, Province of Groningen, Netherlands
  • 1991
    • Eppendorf Deutschland
      Hamburg, Hamburg, Germany
    • University of Zagreb
      • School of Medicine (MEF)
      Zagreb, Grad Zagreb, Croatia
  • 1989
    • The University of Edinburgh
      • Section of Obstetrics and Gynaecology
      Edinburgh, SCT, United Kingdom
  • 1988
    • Western General Hospital
      Edinburgh, Scotland, United Kingdom
  • 1983
    • University of Nottingham
      • Division of Obstetrics and Gynaecology
      Nottigham, England, United Kingdom