K H Nicolaides

King's College London, Londinium, England, United Kingdom

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Publications (738)3285.91 Total impact

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    DESCRIPTION: Abstract Send to: Ultrasound Obstet Gynecol. 2008 Oct;32(5):646-51. doi: 10.1002/uog.6211. Cervical length and maternal factors in expectantly managed prolonged pregnancy: prediction of onset of labor and mode of delivery. Rao A1, Celik E, Poggi S, Poon L, Nicolaides KH; Fetal Medicine Foundation Prolonged Pregnancy Group. Collaborators (10) Gajewska K, Molina F, Granvillano O, Kaur A, Paramasivam G, Khoury O, Nikolopoulou D, Fonseca E, Palaniappan V, Raffaelli R. Author information Abstract OBJECTIVE: To examine the value of combining cervical length and maternal characteristics in a prolonged-pregnancy clinic in the prediction of the probability of firstly, spontaneous onset of labor within the subsequent 10 days and secondly, the need for Cesarean section. METHODS: This was a prospective study of women with singleton pregnancies attending an ultrasound-based prolonged-pregnancy clinic at 40 + 4 to 41 + 6 weeks of gestation. The policy was to delay induction of labor by 7-10 days unless there was evidence of a specific medical or obstetric indication or the mother wanted earlier delivery. The measurement of cervical length was not given to the obstetrician, midwife or patient. Regression analysis was used to determine which of the following factors had a significant contribution in predicting induction of labor: maternal age, body mass index (BMI), ethnic origin, parity and cervical length. Regression analysis was also used to determine which of the factors amongst the maternal characteristics, onset of labor and cervical length provided significant prediction of Cesarean section. RESULTS: We examined 2316 pregnancies but we excluded from further analysis 452 (19.5%) cases because iatrogenic delivery was carried out within the subsequent 6 days, including 427 cases of induction of labor (340 at the request of the mother and 87 for medical indications) and 25 cases of Cesarean section. In the remaining 1864 cases there was spontaneous onset of labor and delivery within 10 days in 1536 (82.4%) and induction of labor in 7-10 days in 328 (17.6%). The rate of Cesarean section was 15.2% (233 of 1536) in those with spontaneous onset of labor and 36.0% (118 of 328) in those whose labor was induced. Regression analysis demonstrated that in the prediction of induction of labor there were significant contributions from cervical length, BMI, parity and gestational age, and in the prediction of Cesarean section there were significant contributions from onset of labor, cervical length, BMI, parity and ethnicity. CONCLUSION: Ultrasonographic measurement of cervical length at 41 weeks together with maternal factors can define the patient-specific probability of spontaneous onset of labor in the subsequent week and the risk of Cesarean section.
  • R Chaoui · G Orosz · K S Heling · A Sarut-Lopez · K H Nicolaides
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    ABSTRACT: To describe a new sign of cleft lip and palate (CLP), the maxillary gap, which is visible in the mid-sagittal plane of the face used routinely for measurement of fetal nuchal translucency thickness. This was a retrospective study of stored images of the mid-sagittal view of the fetal face at 11-13 weeks' gestation from 86 cases of CLP and 86 normal controls. The images were examined to determine if a maxillary gap was present and the size was measured offline. In 37 (43.0%) cases of CLP the defect was isolated and in 49 (57.0%) there were additional fetal defects. In the isolated CLP group, the diagnosis of facial cleft was made in the first trimester in 9 (24.3%) and in the second trimester in 28 (75.7%). In the group with additional defects, the diagnosis of facial cleft was made in the first trimester in 46 (93.9%) and in the second trimester in 3 (6.1%). A maxillary gap was observed in 96% of cases of CLP with additional defects, in 65% of those with isolated CLP and in 7% of normal fetuses. There was a large gap (>1.5 mm) or complete absence of signals from the maxilla in the midline in 69% of cases of CLP with additional defects, in 35% of those with isolated CLP and in none of the normal controls. The maxillary gap is a new simple marker of possible CLP, which could increase the detection rate of CLP especially in isolated cases. This article is protected by copyright. All rights reserved.
    Ultrasound in Obstetrics and Gynecology 08/2015; DOI:10.1002/uog.15675 · 3.14 Impact Factor
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    K. O. Kagan · D. Wright · K. H. Nicolaides
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    ABSTRACT: Objective To examine performance of screening for major trisomies by a policy of first-line assessment of risk with maternal age, fetal nuchal translucency thickness (NT) and ductus venosus pulsatility index for veins (DV-PIV) followed by cell-free (cf) DNA testing, in pregnancies with an intermediate risk.Methods We estimated the distribution of risks based on maternal age, fetal NT and DV-PIV in a dataset of 86 917 unaffected and 491 trisomic pregnancies undergoing prospective screening for trisomies. Performance of screening for trisomies by cfDNA testing was derived from a meta-analysis of clinical validation studies. We estimated performance and cost of screening for trisomies by different combinations of ultrasound screening and cfDNA testing.ResultsScreening for trisomies 21, 18 and 13 by a combination of maternal age, fetal NT and DV-PIV in all pregnancies, followed by invasive testing in the high-risk group (≥1:10) and cfDNA testing in the intermediate-risk group (1:11–1:3000) can potentially detect about 96%, 95% and 91% of cases, respectively, with an FPR of 0.8%. On the assumption that the costs for ultrasound screening, cfDNA testing and invasive testing are €150, €500 €1000, respectively, the overall cost of such a policy would be about €250 per patient. The alternative policy of universal screening by cfDNA testing, can potentially detect about 99%, 97% and 92% of cases of trisomies 21, 18 and 13, but at the overall cost of more than €500 per patient.Conclusion Combined screening by first-trimester ultrasound examination and cfDNA testing can detect a high proportion of trisomies with a low FPR.
    Ultrasound in Obstetrics and Gynecology 07/2015; 45(1). DOI:10.1002/uog.14691 · 3.14 Impact Factor
  • C. Fadigas · Y. Saiid · R. Gonzalez · L. C. Poon · K. H. Nicolaides
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    ABSTRACT: Objective To investigate the value of fetal biometry at 35-37 weeks’ gestation in the prediction of delivery of small for gestational age (SGA) neonates, in the absence of preeclampsia (PE).Methods Screening study in singleton pregnancies at 35-37 weeks, including 278 that delivered SGA neonates with birth weight <5th percentile and 5,237 cases unaffected by SGA, PE or gestational hypertension. Multivariable logistic regression analysis was used to determine if screening by a combination of maternal factors and Z-scores of fetal head circumference (HC), abdominal circumference (AC) and femur length (FL) or estimated fetal weight (EFW) had significant contribution in predicting SGA neonates.ResultsMultivariable logistic regression analysis demonstrated that the likelihood of SGA<5th decreased with maternal weight and height, and in parous women the risk increased with inter-pregnancy interval. The risk was higher in women of Afro-Caribbean and South Asian racial origins, in cigarette smokers, in nulliparous women, and in those with prior history of SGA, with or without prior PE. Combined screening by maternal characteristics and history with EFW Z-scores at 35-37 weeks, predicted 85% of SGA neonates with birth weight <5th percentile delivering at <2 weeks of assessment, at 10% false positive rate. The respective detection rate for the prediction of SGA neonates delivering at ≥37 weeks’ gestation was 70%. The performance of screening by a combination of Z-scores for fetal HC, AC and FL was similar to that achieved by the EFW Z-score.Conclusion Combined testing by maternal characteristics and fetal biometry at 35-37 weeks could identify, at 10% false positive rate, about 85% of pregnancies that subsequently deliver SGA neonates within two weeks of assessment and 70% of those delivering at ≥37 weeks.
    Ultrasound in Obstetrics and Gynecology 05/2015; 45(5):559-565. DOI:10.1002/uog.14816 · 3.14 Impact Factor
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    ABSTRACT: Objectives To report clinical implementation of cell-free (cf)DNA analysis of maternal blood in screening for trisomies 21, 18 and 13 in twin pregnancies and examine variables that could influence the failure rate of the test.MethodscfDNA testing was performed in 515 twin pregnancies at 10–28 weeks’ gestation. Failure rate of the test to provide results was compared to that in 1,847 singleton pregnancies and logistic regression analysis was used to determine which factors amongst maternal and pregnancy characteristics were significant predictors of test failure rate.ResultsFailure rate of the cfDNA test at first sampling was 1.7% in singletons and 5.6% in twins. In those with a result, the median fetal fraction in twins was 8.7% (range 4.1-30.0%), which was lower than in singletons (11.7%, range 4.0-38.9%). Multivariable regression analysis demonstrated that twin pregnancy, higher maternal weight and conception by IVF provided significant independent prediction of test failure. Follow-up was available in 351 (68.2%) of the twin pregnancies and included 334 with euploid fetuses, 12 discordant for trisomy 21 and five discordant for trisomy 18. In all 323 euploid cases with a result, the risk score for each trisomy was <1:10,000. In 11 of the 12 cases with trisomy 21 and in the five with trisomy 18, the cfDNA test gave a high-risk result but in one case of trisomy 21 the score was <1:10,000.Conclusions In twins screening by cfDNA testing is feasible but failure rate is higher and detection rate may be lower than in singletons.
    Ultrasound in Obstetrics and Gynecology 01/2015; 45(1). DOI:10.1002/uog.14690 · 3.14 Impact Factor
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    Dataset: uog14691
    K. O. Kagan · D. Wright · K. H. Nicolaides
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    Dataset: uog14692
    K. O. Kagan · D. Wright · K. H. Nicolaides
  • Article: Reply.
    N Persico · K H Nicolaides
    Ultrasound in Obstetrics and Gynecology 03/2014; 43(3):356-7. DOI:10.1002/uog.13232 · 3.14 Impact Factor
  • M M Gil · R Akolekar · M S Quezada · B Bregant · K H Nicolaides
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    ABSTRACT: Objective To review clinical validation or implementation studies of maternal blood cell-free (cf) DNA analysis and define the performance of screening for fetal trisomies 21, 18 and 13 and sex chromosome aneuploidies.Methods Searches of PubMed, EMBASE and The Cochrane Library were performed to identify all peer-reviewed articles on cfDNA testing in screening for aneuploidies between January 2011, when the first such study was published, and 4 January 2015.ResultsIn total, 37 relevant studies were identified and these were used for the meta-analysis on the performance of cfDNA testing in screening for aneuploidies. These studies reported cfDNA results in relation to fetal karyotype from invasive testing or clinical outcome. Weighted pooled detection rates (DR) and false-positive rates (FPR) in singleton pregnancies were 99.2% (95% CI, 98.5-99.6%) and 0.09% (95% CI, 0.05-0.14%), respectively, for trisomy 21, 96.3% (95% CI, 94.3-97.9%) and 0.13% (95% CI, 0.07-0.20) for trisomy 18, 91.0% (95% CI, 85.0-95.6%) and 0.13% (95% CI, 0.05-0.26%) for trisomy 13, 90.3% (95% CI, 85.7-94.2%) and 0.23% (95% CI, 0.14-0.34%) for monosomy X and 93.0% (95% CI, 85.8-97.8%) and 0.14% (95% CI, 0.06-0.24%) for sex chromosome aneuploidies other than monosomy X. For twin pregnancies, the DR for trisomy 21 was 93.7% (95% CI, 83.6-99.2%) and the FPR was 0.23% (95% CI, 0.00-0.92%). Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.Conclusion Screening for trisomy 21 by analysis of cfDNA in maternal blood is superior to that of all other traditional methods of screening, with higher DR and lower FPR. The performance of screening for trisomies 18 and 13 and sex chromosome aneuploidies is considerably worse than that for trisomy 21.
    Fetal Diagnosis and Therapy 02/2014; 35(3). DOI:10.1159/000358326 · 2.30 Impact Factor
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    D Wright · A Syngelaki · I Bradbury · R Akolekar · K H Nicolaides
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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; 35(2). DOI:10.1159/000357430 · 2.30 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; 34(4):199-205. DOI:10.1159/000356170 · 2.30 Impact Factor
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    K H Nicolaides · A Syngelaki · L C Poon · M. 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; 35(3). DOI:10.1159/000356066 · 2.30 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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    L C Y Poon · G Karagiannis · A Leal · X C Romero · K H Nicolaides
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    L C Y Poon · G Karagiannis · A Leal · X C Romero · K H Nicolaides
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    Dataset: 7628 ftp
    L C Y Poon · R Akolekar · R Lachmann · J Beta · K H Nicolaides
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    M D Savvidou · R Akolekar · E Zaragoza · L C Poon · K H Nicolaides
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    N Guex · C Iseli · A Syngelaki · C Deluen · G Pescia · K H Nicolaides · I Xenarios · B Conrad
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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 07/2013; 33(7). DOI:10.1002/pd.4130 · 3.27 Impact Factor
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    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 07/2013; 42(1). DOI:10.1002/uog.12504 · 3.14 Impact Factor
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    K H Nicolaides · D Wright · L C Poon · A Syngelaki · M. 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 07/2013; 42(1). DOI:10.1002/uog.12511 · 3.14 Impact Factor

Publication Stats

28k Citations
3,285.91 Total Impact Points

Institutions

  • 1981–2014
    • King's College London
      • Division of Asthma, Allergy and Lung Biology
      Londinium, England, United Kingdom
  • 2013
    • University of Plymouth
      • School of Computing and Mathematics
      Plymouth, England, United Kingdom
  • 1985–2013
    • ICL
      Londinium, England, United Kingdom
  • 2012
    • Hospital Universitario San Cecilio
      • Department of Obstetrics and Gynaecology
      Granata, Andalusia, Spain
    • University College London Hospitals NHS Foundation Trust
      • Department of Fetal Medicine
      Londinium, England, United Kingdom
  • 2010
    • Hospital Universitario Virgen de las Nieves
      • Department of Obstetrics and Gynaecology
      Granata, Andalusia, Spain
  • 2008–2010
    • University of Tuebingen
      • Department of Gynecology and Obstetrics
      Tübingen, Baden-Württemberg, Germany
    • Hospital Clínic de Barcelona
      • Servicio de Medicina Materno Fetal
      Barcino, Catalonia, Spain
  • 1991–2010
    • King's College Hospital NHS Foundation Trust
      • Department of Obstetrics and Gynaecology
      Londinium, England, United Kingdom
    • Eppendorf Deutschland
      Hamburg, Hamburg, Germany
    • University of Zagreb
      Zagrabia, Grad Zagreb, Croatia
  • 2006
    • University Hospital Brussels
      Bruxelles, Brussels Capital Region, Belgium
    • Wright State University
      • Department of Obstetrics and Gynecology
      Dayton, Ohio, United States
    • Universitair Ziekenhuis Leuven
      • Department of Gynaecology and obstetrics
      Leuven, VLG, Belgium
  • 2002–2006
    • Medical Research Council (UK)
      • MRC Clinical Trials Unit
      Londinium, England, United Kingdom
  • 1992–2006
    • The Fetal Medicine Foundation
      Londinium, England, United Kingdom
    • Imperial College Healthcare NHS Trust
      Londinium, England, United Kingdom
  • 2005
    • Center for Prenatal Diagnosis and Human Genetics, Kudamm-199
      Berlín, Berlin, Germany
  • 1997–2005
    • University Hospital of Ioannina
      Yannina, Epirus, Greece
  • 2001
    • London School of Hygiene and Tropical Medicine
      Londinium, England, United Kingdom
  • 2000
    • The King's College
      Charlotte, North Carolina, United States
  • 1994–2000
    • Chelsea and Westminster Hospital NHS Foundation Trust
      Londinium, England, United Kingdom
  • 1990–2000
    • The Kings College
      Brooklyn, New York, United States
  • 1984–2000
    • The Peninsula College of Medicine and Dentistry
      • School of Medicine
      Plymouth, England, United Kingdom
  • 1998
    • St George's, University of London
      Londinium, England, United Kingdom
    • University of Freiburg
      • Institute of Anatomy and Cell Biology
      Freiburg, Baden-Württemberg, Germany
  • 1996
    • University of London
      Londinium, England, United Kingdom
  • 1993
    • Freie Universität Berlin
      Berlín, Berlin, Germany
    • Ipswich Hospital NHS Trust
      Ipswich, England, United Kingdom
  • 1989
    • Wayne State University
      Detroit, Michigan, United States
  • 1988
    • Western General Hospital
      Edinburgh, Scotland, United Kingdom
  • 1983–1984
    • University of Nottingham
      • Division of Obstetrics and Gynaecology
      Nottigham, England, United Kingdom