H S Cuckle

Columbia University, New York City, New York, United States

Are you H S Cuckle?

Claim your profile

Publications (243)1456.59 Total impact

  • Source
    J. D. Sonek, H. S. Cuckle
    Ultrasound in Obstetrics and Gynecology 12/2014; 44(6). · 3.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To estimate performance of a single-nucleotide polymorphism-based noninvasive prenatal screen for fetal aneuploidy in high-risk and low-risk populations on single venopuncture.
    Obstetrics and Gynecology 07/2014; · 4.37 Impact Factor
  • Carla Davis, Howard Cuckle, Yuval Yaron
    [Show abstract] [Hide abstract]
    ABSTRACT: Down syndrome screening programs lead to the prenatal diagnosis of other chromosomal abnormalities, some of which would not be detected by the secondary use of cell-free (cf)DNA testing in screen positives. This study aims to assess the number of these incidental diagnoses.
    Prenatal Diagnosis 05/2014; · 2.51 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective To evaluate performance of first trimester nuchal translucency (NT) measurement among providers (physician-sonologists and sonographers) within the Nuchal Translucency Quality Review (NTQR) program.Methods After training and credentialing, NTQR monitored NT performance by the extent to which the median multiple of the normal median (MM) for crown-rump length (CRL), , was within the range 0.9-1.1 MoM of a published referent curve. The standard deviation (SD) of log10 MoM and slope of NT on CRL were also evaluated. We report the distribution between providers of these performance indicators and evaluate potential sources of variation.ResultsAmong the first 1.5 million scans between 2005 and 2011 there were 1,485,944 with CRL in the range 41–84 mm, from 4710 providers at 2150 sites. Among the 3463 providers with at least 30 scans, the median of the providers NT median MoMs was 0.913. Only 1901 (55%) had an NT median MoM within the expected range: 89 above 1.1 MoM, 1046 at 0.8-0.9 MoM, 344 at 0.7-0.8 MoM and 83 below 0.7 MoM. There was a small increase in the NT median MoM with the length of time in NTQR and the number of scans entered annually. On average, physician-sonologists had a higher NT median MoM than sonographers, as did those already credentialed before NTQR. The median provider SD was 0.093 and slope 13.5%. SD correlated negatively with the median MoM (r=−0.34) and positively with slope (r=0.22).Conclusion Even with extensive training, credentialing and monitoring, there remains considerable variability between NT providers. Those with more experience had performance closer to that expected.
    Ultrasound in Obstetrics and Gynecology 04/2014; · 3.56 Impact Factor
  • Peter Benn, Howard Cuckle
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective To calculate the theoretical performance of non-invasive prenatal testing based on counting methods.Methods The calculations were based on Gaussian distributions of the percent cell-free DNA from selected chromosome regions in affected and normal pregnancies. The means were derived from the relative genomic size of the chromosome region and the fetal fraction. The standard deviations were derived from the bivariate distributions of proportional counts. Depth of sequencing was varied from 10,000,000 to 100,000 and fetal fraction from 20% to 3%. Detection rate was estimated for a fixed 0.13% false-positive rate.ResultsWhen either depth or fetal fraction is high, expected Down syndrome screening detection rates are high. However, when fetal fraction is low, deeper sequencing is required to obtain high detection rates. For micro-deletion and micro-duplication screening, deeper sequencing is routinely required to consistently achieve high detection rates. There are small differences in the ability to detect a micro-deletion compared with a duplication of the same size.Conclusion While the theoretical calculations do not necessarily reflect the performance of currently available NIPT tests, it confirms that fetal fraction is a key factor. Efficacy can be substantially altered depending on the abnormality under investigation and the depth of sequencing. This article is protected by copyright. All rights reserved.
    Prenatal Diagnosis 03/2014; · 2.68 Impact Factor
  • David A. Krantz, Howard S. Cuckle
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective To determine the impact on the risk calculation of various ways of handling maternal weight when this data is provided in the first part but not the second part of a sequential screening protocol.Method Retrospective analysis of 38,986 sequential screens in which weight was provided in both the first and second trimester. Three potential strategies for calculating MoM values when the weight is not recorded at the time of second trimester risk evaluation were evaluated. First, perform no weight adjustment. Second, use the first trimester weight. Third, use the predicted second trimester weight based on the first trimester weight. To predict the second trimester weight we used a random-effects multi-level model.ResultsThe screen positive rate for Down syndrome was 3.0% (1,151/38,986) and trisomy 18 alone 0.12% (47/38,986). The 3 strategies resulted in 196(0.50%), 41(0.11%) and 23(0.06%) patients switching risk categories with the no adjustment, first trimester weight and predicted weight strategies, respectively.Conclusion Utilizing the first trimester weight or the predicted second trimester weight in sequential screening when second trimester weight is not provided offers an affordable alternative for laboratories to provide robust risk calculations and interpretations without requiring excessive use of resources. This article is protected by copyright. All rights reserved.
    Prenatal Diagnosis 03/2014; · 2.68 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In 2004, leaders in first-trimester aneuploidy screening and a multidisciplinary group of experts established the Nuchal Translucency Quality Review Program, a national program to standardize education, credentialing, and quality monitoring of nuchal translucency. Since its inception, the program has credentialed more than 6,600 physician and ultrasonographer participants and collected more than 2.4 million nuchal translucency measurements. Ongoing quality monitoring is conducted through statistical analysis comparing the distribution and standard deviation of participants' nuchal translucency measurements against those obtained from a standard referent curve. Results of these analyses are distributed to participants quarterly and are used to track each participant's performance and to trigger performance improvement activities or mandatory remediation. This program could serve as a template for future education and credentialing programs that include partnerships with academic leaders, national professional organizations, and industry.
    Obstetrics and Gynecology 01/2014; 123(1):149-54. · 4.37 Impact Factor
  • Source
    Prenatal Diagnosis 12/2013; 33(12):1218-9. · 2.68 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: The objective of this study was to provide a critical analysis of the impact of assisted conception on prenatal screening for Down syndrome (DS) in twin pregnancies and the value of various screening modalities for early detection of anomalies. Methods: The literature was searched using PubMed and the Cochrane Library focusing on prenatal screening and antenatal care of assisted-conception twin pregnancies. Results: Serum screening alone is of limited value in detecting aneuploid twins, because the unaffected cotwin can "mask" the abnormal serum results of an affected one. In addition, this test can designate the pregnancy as at high risk but not identify the affected fetus. Nuchal translucency (NT) screening is the best available modality and a highly effective screening method for twin pregnancies. Among twins, NT alone has a 69% DS detection rate, first-trimester combined NT and serum biochemistry has a 72% DS detection rate, and an integrated screen will have an 80% DS detection rate at a 5% FPR. The data in the literature concerning the effect of assisted conception on maternal serum screening markers in twin pregnancies are scarce. Conclusions: Down syndrome screening in assisted-conception twins presents clinical and technical challenges. Therefore, assisted-conception twins need close monitoring from conception to delivery, by a practitioner familiar with the available screening modalities and their relative accuracy.
    Obstetrical & gynecological survey 11/2013; 68(11):764-73. · 3.10 Impact Factor
  • American journal of obstetrics and gynecology 08/2013; · 3.97 Impact Factor
  • Howard Cuckle, Peter Benn, Eugene Pergament
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 07/2013; · 1.36 Impact Factor
  • Source
    Peter Benn, Howard Cuckle, Eugene Pergament
    [Show abstract] [Hide abstract]
    ABSTRACT: Non-invasive prenatal testing (NIPT) for aneuploidy using cell-free DNA in maternal plasma is revolutionizing prenatal screening and diagnosis. We review NIPT in the context of established screening and invasive technologies, range of cytogenetic abnormalities detectable, costs, counseling, and ethical issues. Current NIPT approaches involve whole genome sequencing, targeted sequencing, and assessment of single nucleotide polymorphism (SNP) differences between mother and fetus. Clinical trials have demonstrated the efficacy of NIPT for Down and Edwards syndromes, and possibly Patau syndrome, in high risk women. Universal NIPT screening is not cost-effective, but when used contingently in women found at moderate risk or higher by conventional screening it is effective. Positive NIPT results must be confirmed using invasive techniques. Established screening, fetal ultrasound, and invasive procedures with microarray testing, allow the detection of a broad range of additional abnormalities not yet detectable by NIPT. NIPT approaches that take advantage of SNP information potentially allow the identification of parent of origin for imbalances, triploidy, uniparental disomy, consanguinity and separately evaluate dizygotic twins. Fetal fraction enrichment, improved sequencing, and selected analysis of the most informative sequences, should result in tests for additional chromosome abnormalities. The provision of adequate pre-test counseling poses a substantial challenge.
    Ultrasound in Obstetrics and Gynecology 05/2013; · 3.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Aims: To determine first trimester maternal serum placental protein 13 (PP13) in singletons vs. twins with and without severe preeclampsia (PE). Methods: Serum samples were prospectively collected at 8-14 weeks of gestation. PP13 was determined by solid-phase immunoassay. Patients were recruited in community clinics throughout the country, and from the twin antenatal assessment clinic in Assaf Harofeh Medical Center, Zerifin, Israel. Demographics, medical, and pregnancy history were obtained at enrollment. Pregnancy outcome was collected after delivery. PP13 was compared by the Wilcoxon rank sum test. Results: In singletons, PP13 declined with maternal weight and was lower in in vitro fertilization. Levels were converted into multiples of the median (MoMs) accordingly. In twins, the median was 1.74 MoM (n=76) vs. 1.00 in singletons (n=676, P<0.0001). Among twins with severe PE (n=10), the median was 1.53 MoM vs. 1.74 in unaffected twins (P=0.10), and 2.26 (n=6) for mild PE (P=0.30). Among singletons with severe PE, the median was 0.44 MoM (n=26, P<0.0001), and for mild PE 0.62 (n=17, P<0.001). Conclusion: PP13 is higher in twins than singletons, corresponding to the larger placental mass. Among singletons with severe PE, levels were significantly reduced, however, among twins, only a non-significant tendency for a reduction was recorded, and warrants further investigation in a larger series.
    Journal of Perinatal Medicine 05/2013; · 1.43 Impact Factor
  • Howard Cuckle, Peter Benn, Eugene Pergament
    [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE: To determine the principal factors contributing to the cost of avoiding a birth with Down syndrome, using cell free (cf)DNA to replace conventional screening. METHODS: A range of unit costs were assigned to each item in the screening process. Detection rates were estimated by meta-analysis and modeling. The marginal cost associated with the detection of additional cases using cfDNA was estimated from the difference in average costs divided by the difference in detection. RESULTS: The main factor was the unit cost of cfDNA testing. For example, replacing a Combined test costing $150 with 3% false-positive rate and invasive testing at $1000, by cfDNA tests at $2000, $1500, $1000 and $500, the marginal cost is $8.0, $5.8, $3.6 and $1.4 million, respectively. Costs were lower when replacing a Quadruple test and higher for a 5% false-positive rate, but the relative importance of cfDNA unit cost was unchanged. A contingent policy whereby 10-20% women were selected for cfDNA testing by conventional screening was considerably more cost-efficient. Costs were sensitive to cfDNA uptake. CONCLUSION: Universal cfDNA screening for Down syndrome will only become affordable by public health purchasers if costs falls substantially. Until this happens, the contingent use of cfDNA is recommended. This article is protected by copyright. All rights reserved.
    Prenatal Diagnosis 05/2013; · 2.68 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Screening at 11-13 weeks with ultrasound biparietal diameter (BPD) can detect half of open spina bifida cases. Maternal serum α-fetoprotein (AFP) levels at 15-19 weeks are increased 3-4 fold, in open spina bifida. We assessed whether combined screening using BPD, AFP and other serum markers at 11-13 weeks would increase detection. POPULATION AND METHODS: Maternal AFP levels were measured on serum stored at 11-13 weeks' in 44 open spina bifida and 182 unaffected pregnancies, and results were expressed in multiples of the median for gestational age (MoM). All samples had been measured for free β-human chorionic gonadotropin (hCG) and pregnancy associated plasma protein (PAPP)-A. A multivariate Gaussian model was used to predict screening performance from the serum data and BPD measurements on 80 cases, including 36 previously published. RESULTS: The median AFP level in cases was 1.201 MoM, significantly higher than in unaffected pregnancies (P<0.01, 1-tail). The median free β-hCG was significantly reduced to 0.820 MoM (P<0.02) but the median PAPP-A was similar in cases and controls. Modelling predicted that: BPD alone would detect 50% of cases for a 5% false-positive rate or 63% for 10%; adding AFP increases detection by 2%; a combined test with BPD, AFP and free β-hCG detects 58% for 5% or 70% for 10%. DISCUSSION: Combining AFP and BPD with free β-hCG as part of first trimester aneuploidy screening would also allow early detection about two-thirds of cases with open spina bifida.
    American journal of obstetrics and gynecology 05/2013; · 3.97 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE: The aim of this research was to evaluate the addition of first trimester maternal serum placental growth factor (PlGF) and α-fetoprotein (AFP) to the combined test for Down syndrome and a serum only protocol of PlGF, AFP, free β-human chorionic gonadotropin and pregnancy-associated plasma protein-A. METHODS: Samples were from 92 Down syndrome cases with 552 matched controls. All women had a combined test at 11-14 weeks gestation. PlGF and AFP were measured and expressed in multiples of the gestation-specific median (MoM), adjusting for maternal weight and smoking status. Multivariate Gaussian modeling was used to predict detection and false-positive rates. RESULTS: The median PlGF level in the cases was 0.694 MoM and controls 1.000 MoM (p = <0.0001). The corresponding values for AFP were 0.764 MoM and 0.990 MoM (p < 0.0001). Statistical modeling predicted that for a given false-positive rate, the addition of PlGF to the combined test increases the detection rate by 4-7%. For a given detection rate, the false-positive rate could be almost halved. When both PlGF and AFP are used, the detection rate increase is 5-8%. A serum only protocol had a predicted a detection rate of 71% for a false-positive rate of 5%. CONCLUSIONS: Results suggest a substantial benefit of adding PlGF to the combined test. © 2013 John Wiley & Sons, Ltd.
    Prenatal Diagnosis 03/2013; · 2.68 Impact Factor
  • Source
    Prenatal Diagnosis 11/2012; · 2.68 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: The aim of this study was to assess the best method of combining the fetal nuchal translucency (NT) and ductus venosus (DV) blood flow in the detection of cardiac defects in chromosomally normal fetuses, during the first trimester scan. Study Design: During an 8-year period NT and the DV blood flow were routinely assessed at 11-14 weeks. Only chromosomally normal singleton pregnancies were included in the study. When a cardiac defect was suspected, or when an increased fetal NT or/and an abnormal DV blood flow were observed, early fetal echocardiogram was offered. Data on routine second and third trimester scans, neonatal follow-up or post-mortem examination were obtained from hospital records. The detection rate and false-positive rate were calculated for all major cardiac defects, considering several screening strategies: NT, Ductus Venosus Pulsatility Index (DVPI), or both above a fixed normal centile; abnormal DV A-wave; risk based on NT and DVPI or A-wave above a fixed normal centile; and combinations of these. Results: The study population included 37 chromosomally normal fetuses with a major cardiac defect and 12,799 unaffected pregnancies. Fetal NT above the 95(th) or the 99(th) centile and abnormal DV flow was observed in 40%, 27%, and 39% of the major cardiac defects, respectively. A 47% detection rate with a 2.7% false positive rate were obtained when an abnormal DV or NT above 99(th) centile were used as the selection criteria. Conclusions: Half of major fetal cardiac defects can be detected in the first trimester if NT and DV are used to select 2.7% of the normal pregnant population for fetal extended echocardiogram. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.
    Ultrasound in Obstetrics and Gynecology 11/2012; · 3.56 Impact Factor
  • Yuval Yaron, Thomas Musci, Howard Cuckle
    Prenatal Diagnosis 10/2012; · 2.68 Impact Factor
  • Article: Reply.
    P Benn, H Cuckle, E Pergament
    Ultrasound in Obstetrics and Gynecology 10/2012; 40(4):485-6. · 3.56 Impact Factor

Publication Stats

5k Citations
1,456.59 Total Impact Points


  • 2006–2014
    • Columbia University
      • Department of Obstetrics and Gynecology
      New York City, New York, United States
  • 2012
    • Tel Aviv Sourasky Medical Center
      • Institute of Genetics
      Tell Afif, Tel Aviv, Israel
    • Hospital Clínic de Barcelona
      Barcino, Catalonia, Spain
  • 2011–2012
    • UConn Health Center
      • Department of Genetics and Developmental Biology
      Farmington, CT, United States
    • Icahn School of Medicine at Mount Sinai
      Manhattan, New York, United States
  • 2007–2012
    • CUNY Graduate Center
      New York City, New York, United States
    • Royal College of Surgeons in Ireland
      • Department of Obstetrics & Gynaecology
      Dublin, Leinster, Ireland
    • Albert Einstein College of Medicine
      • Department of Obstetrics & Gynecology & Women's Health
      New York City, New York, United States
    • Maimonides Medical Center
      Brooklyn, New York, United States
  • 2006–2011
    • King's College London
      Londinium, England, United Kingdom
  • 2003–2011
    • Tel Aviv University
      • Department of Obstetrics and Gynecology
      Tel Aviv, Tel Aviv, Israel
  • 2010
    • University of São Paulo
      • Departamento de Obstetrícia e Ginecologia (FM) (São Paulo)
      Ribeirão Preto, Estado de Sao Paulo, Brazil
  • 2009
    • University of Utah
      • Department of Obstetrics and Gynecology
      Salt Lake City, UT, United States
    • Meir Medical Center
      • Department of Obstetrics and Gynecology
      Kafr Saba, Central District, Israel
  • 1994–2009
    • University of Leeds
      • • School of Medicine
      • • Division of Reproduction and Early Development
      • • Leeds Institute of Medical Education
      Leeds, England, United Kingdom
  • 2008
    • University of Colorado
      • Department of Obstetrics and Gynecology
      Denver, CO, United States
    • Wayne State University
      • Department of Obstetrics and Gynecology
      Detroit, MI, United States
  • 2000–2007
    • Sheba Medical Center
      • Department of Pathology
      Gan, Tel Aviv, Israel
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Clinical Genetics
      Amsterdam, North Holland, Netherlands
  • 2005
    • University of Connecticut
      • Department of Genetics and Developmental Biology
      Mansfield City, CT, United States
    • King's College Hospital NHS Foundation Trust
      Londinium, England, United Kingdom
    • Ministry of Health (Israel)
      Yerushalayim, Jerusalem District, Israel
  • 2004
    • University of Plymouth
      Plymouth, England, United Kingdom
  • 1999
    • Alpert Medical School - Brown University
      • Department of Pathology and Laboratory Medicine
      Providence, RI, United States
  • 1997
    • Yale University
      New Haven, Connecticut, United States
  • 1993
    • The University of Edinburgh
      • Medical Genetics Unit
      Edinburgh, SCT, United Kingdom
  • 1987
    • Westmead Hospital
      Sydney, New South Wales, Australia
  • 1982–1985
    • Oxford University Hospitals NHS Trust
      Oxford, England, United Kingdom