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H Cuckle

Publications and source records attributed to H Cuckle.

At least 19 recordsLinked to original sources
PubMed2006

A model for second-trimester Down syndrome sonographic screening based on facial landmarks and digit length measurement.

OBJECTIVE: To determine whether Down syndrome can be detected by combining measurements of fetal nasal bone (NB) length, prenasal thickness (PT) and digits 2 and 3 of the hand. METHODS: Two hundred and fifty-four normal and 25 Down-syndrome fetuses were scanned between 15 and 33 weeks' gestation. Physicians performing the scans were not blinded to the fetal karyotype. Both PT and NB were measured in a mid-sagittal plane. For PT measurement calipers were placed between the frontonasal angle and the outer skin edge. Digits 2 and 3 of one hand were also measured. The results (except for PT/NB ratio) were expressed in multiples of the normal gestation-specific median (MoM). A logistic regression model was used to estimate the odds of the fetus having Down syndrome given different combinations of NB, PT, PT/NB ratio, and digits 2 and 3 measurements. The odds were used to calculate the risk of Down syndrome for each pregnant woman from her age and measurements. RESULTS: The median PT MoM for unaffected fetuses and Down-syndrome fetuses was 1.12 vs. 1.35 (P < 0.0001). The median NB MoM for unaffected and Down-syndrome fetuses was 1.03 vs. 0.81 (P < 0.001) and the PT/NB ratio MoM for unaffected and Down-syndrome fetuses was 0.63 vs. 0.96 (P < 0.001). The respective median MoM values for digits 2 and 3 of the Down-syndrome fetuses were significantly smaller (0.81 vs. 0.93 and 0.89 vs. 0.95, respectively, P = 0.003). Only the PT/NB ratio and digit 2 were finally included in the logistic regression equation. Using a 1 in 200 risk cut-off, the observed sensitivity and false-positive rate were 76% and 6.7%, respectively. CONCLUSION: Combining the PT/NB ratio and digit 2 measurements yielded a promising screening detection rate. Confirmation of our findings in a prospective study is needed before the method can be used clinically.

Adult↗
PubMed2005

Randomised controlled trial of mammographic screening in women from age 40: predicted mortality based on surrogate outcome measures.

A trial in the UK to study the effect on mortality from breast cancer of invitation for annual mammography from the age of 40-41, has randomised a total of 160 921 women in the ratio 1 : 2 to the intervention and control arms. All breast cancers diagnosed in the two arms have been identified, and the histology reviewed. This paper presents the results of an interim analysis using surrogate outcome measures to compare predicted breast cancer mortality in the two arms based on 1287 cases diagnosed to 31.12.1999. Due to earlier diagnosis, there is currently an 8% excess of invasive breast cancers in the intervention arm. The ratio of predicted deaths at 10 years in the intervention arm relative to the control arm, adjusted for this excess diagnosis, ranges from 0.89 (95% confidence interval (CI) 0.78-1.01) to 0.90 (95% CI 0.80-1.01). Screening from age 40 may result in a lower reduction in breast cancer mortality than that observed in other trials including women below age 50. This analysis based on surrogate outcome measures suggests that a reduction in breast cancer mortality may be observed in this trial. However, a number of assumptions have been necessary and firm conclusions must await the analysis of observed mortality from breast cancer.

Adult↗
PubMed2003

Centre-specific ultrasound nuchal translucency medians needed for Down syndrome screening.

Nuchal translucency (NT) measurements were compared between 13 centres participating in a multi-marker Down syndrome screening program. Results from 4765 women were analysed, and there were highly statistically significant between-centre differences after allowing for gestation (P < 0.0001). Examination of maternal serum marker levels, expressed in multiples of the median (MoM) for gestation, showed that this was not due to gestational errors. Regression analysis was carried out to derive an equation with a centre-specific component that could be used to express NT in MoMs. Use of this equation reduced the variance of logNT by 15% compared to a published equation. The equation can be readily modified for use in other centres.

Adult↗
PubMed2003

Frequency and clinical consequences of extremely high maternal serum PAPP-A levels.

A multicentre study was carried out to determine the frequency and clinical consequences of extremely high maternal serum pregnancy-associated plasma protein (PAPP)-A. There was a total of 79 pregnancies with PAPP-A exceeding 5.0 multiples of the gestation-specific median in a series of 46 776 pregnancies tested (0.2%) at the 7 collaborating centres. Five pregnancies were lost to follow-up, one miscarried and one with Noonan's syndrome was terminated. Of the remaining 72 that ended in a live birth, one infant had gastroschisis and five pregnancies had obstetric complications: pre-eclampsia, pregnancy-induced hypertension, gestational diabetes and two with growth retardation. Among women with high PAPP-A and no complications or adverse outcomes, there was no evidence of a substantial change in the levels of other Down syndrome markers or the extent of nuchal translucency. Three analytical methods were used to assay PAPP-A and yielded different frequencies of extremely high levels (0.05%, 0.4% and 0.6%) possibly owing to cross-reaction with another substance. We conclude that women with high PAPP-A can be reassured that there is no reason to suppose that the outcome of pregnancy will differ from those with normal levels, provided other markers are normal. If, as more centres move their Down syndrome screening practice to the first trimester, additional cases emerge with Noonan's syndrome or gastroschisis and raised PAPP-A, this advice will need to be modified.

Adult↗
PubMed2002

Down's syndrome screening with nuchal translucency at 12(+0)-14(+0) weeks and maternal serum markers at 14(+1)-17(+0) weeks: a prospective study.

BACKGROUND: Sonographic and biochemical methods for Down's syndrome screening have developed simultaneously, but independently. As a consequence, the rate of invasive procedures for fetal karyotyping has dramatically increased and become an important public health issue which needs to be controlled. One approach is to combine sonographic and biochemical results into a single risk assessment. METHODS: In a multicentre interventional study, nuchal translucency (NT) was measured between 12(+0) and 14(+0) weeks of gestation. Maternal serum markers (MSM) were measured between 14(+1) and 17(+0) weeks of gestation. Karyotyping was advised when: (i) NT was > or =3 mm; or (ii) the MSM-related risk was > or =1 in 250 at term. Karyotyping was delayed until after a maternal blood sample had been taken. NT and MSM were expressed as multiples of the medians (MoMs), and risks were calculated and tailored to the study population. A combined risk for NT and MSM was estimated retrospectively. Costs per case diagnosed, and the cost per case averted were calculated for the three screening strategies. RESULTS: A total of 9444 women was screened. Twenty-one fetuses (0.22%) had Down's syndrome, whilst 326 women (3.4%) were lost to follow-up. Among 9118 women followed up, 5506 had both NT and MSM, 821 had only NT, and 2791 had only MSM. Median maternal age was 30.5 years. False-positive rates for NT, MSM and NT combined with MSM were 3.0, 5.8 and 0.23% respectively. The false-positive rate generated by a sequential two-stage screening was 8.6%. Detection rates of Down's syndrome were 62 and 55% for NT and MSM respectively. Seven cases with Down's syndrome (35%) had raised NT and MSM, and 17 (81%) had either raised NT, MSM, or both. For a 5% false-positive rate, detection rates were 55 and 80% for NT alone and for combined NT and MSM respectively. Ultrasound alone appears to be more cost-effective ( pound50 per case diagnosed) than both tests ( pound61 per case diagnosed). CONCLUSIONS: The study results suggest a 25% increase in the detection rate of Down's syndrome using a combination of NT measurement at 12(+0)-14(+0) weeks and MSM at 14(+1)-17(+0) weeks for a 5% false-positive rate, with modest increase in cost.

Biomarkers↗
PubMed2001

Quality of written information used in Down syndrome screening.

A qualitative assessment was performed on 81 leaflets used in maternal serum Down syndrome screening from National Health Service (NHS) obstetric units and private screening services. Quality was assessed by factual content, presentation and reading ease and this was amalgamated into a single overall score expressed as a percentage of the maximum possible score. Eleven (14%) leaflets included all eight factual items recommended by the Royal College of Obstetricians and Gynaecologists (RCOG); only one included these and a further nine items recognised as important to the consumer. Three (4%) leaflets contained information that was incorrect and 17 (21%) that was misleading or inconsistent. Using published criteria six (7%) leaflets were well presented and ten (12%) were fairly easy to read. The average reading age was 13-14 years. The overall quality score showed that five leaflets had 80% or more of the total possible score. However a substantial number, 15 (19%), were totally unacceptable having scores of 40% or less. In general the quality of leaflets used in the UK is considered poor. A national peer-reviewed leaflet should be prepared which can be modified to suit local policy.

Down Syndrome↗
PubMed2001

Maternal serum human chorionic gonadotrophin levels in systemic lupus erythematosus and antiphospholipid syndrome.

Maternal serum human chorionic gonadotrophin (hCG) levels were measured during the second and the third trimesters of pregnancy in patients with either systemic lupus erythematosus (SLE) or primary antiphospholipid syndrome (APS). All results were expressed in multiples of the gestation-specific normal medians (MoM). The median MoM level in 17 samples from SLE patients was 1.48 compared with 0.79 MoM in 99 controls of similar gestation (p < 0.002, Wilcoxon Rank sum test). In contrast the median MoM level in 19 samples from primary APS patients was only 1.14. These preliminary findings should be further studied to evaluate the implications for Down syndrome screening, detection of SLE cases during pregnancy and the prediction of adverse outcome in SLE gestations.

Antiphospholipid Syndrome↗
PubMed2001

Use of videotapes for viewing at home to inform choice in Down syndrome screening: a randomised controlled trial.

A randomised trial was carried out to assess the effect of a Down syndrome screening video on test uptake, knowledge and psychological stress. A total of 2000 women referred for antenatal care were allocated to two equal groups: one to be sent a video to their home, before their hospital booking visit, and a control group. All women also received screening information in the form of a leaflet before booking and from a midwife at booking. The video had no effect on the screening uptake rate: 638/993 (64.2%) and 652/1007 (64.7%) in the video and control groups, respectively. Women were requested to return the video for reuse in other pregnancies and 612 (62%) did so. A subset of 1200 women were selected to be posted at 17-19 weeks' gestation a self-completed questionnaire to assess the psychological endpoints. Knowledge of screening was increased in the video group with a mean score of 7.3 compared with 6.7 in the controls, a statistically significant difference (t=3.24, p=0.0005). There were no significant differences between the groups in specific worries about abnormalities in the baby, and general anxiety. We conclude that a video can increase knowledge without affecting the uptake of the test, or psychological stress.

Anxiety↗
PubMed2001

Familial Down syndrome: evidence supporting cytoplasmic inheritance.

The frequently observed familial aggregation of Down syndrome (DS) 47,+21 and other aneuploidies and the phenomenon of double aneuploidy involving DS cannot be accounted for by chance alone. To clarify possible aetiological factors, pedigrees from all 7 affected families with repeated marriages referred to two regional genetics centres were examined. In each case the recurrence of aneuploidy was on the mother's side (p<0.01). Such a pattern suggests cytoplasmic inheritance of a risk factor. The hypothesis that mitochondrial DNA mutations have a role in the aetiology of DS is supported by other observations as well as by theoretical considerations.

DNA, Mitochondrial↗
PubMed2001

Integrating antenatal Down's syndrome screening.

Statistical modelling is used to predict screening detection and false-positive rates for policies using different marker combinations and screening modalities. Parameters are derived wherever possible from meta-analyses. Screening with four serum markers yields a similar detection rate in the first trimester as it does in the second, and both have a similar detection rate to that of ultrasound nuchal translucency screening. Ultrasound anomaly screening has a low detection rate. The integration of the different screening modalities can yield very high detection rates. Some methods of integration are preferable to others. The concurrent use of first trimester serum markers and ultrasound nuchal translucency is the most practical. The combination of three modalities with nondisclosure of the intermediate results is more efficient, but the gain in detection is too small to warrant the wait for up to 4 weeks for results. The sequential use of modalities with intermediate disclosure is more practical but will generate higher false-positive rates.

Biomarkers↗
PubMed2001

Cystic fibrosis and fragile X syndrome: the arguments for antenatal screening.

The ultimate public health aim of genetic screening is prevention. This can be achieved by reducing birth prevalence through primary or secondary methods such as pre-conceptional or antenatal screening. Tertiary prevention by neonatal screening is also an option where there is direct unbiased evidence for a substantial improvement in prognosis. In addition to this, the information provided during screening is also of value, enabling individuals to make choices that otherwise would not have been available. Having elucidated the natural histories and genetic defects underlying two common, serious genetic disorders, cystic fibrosis and fragile X syndrome, considerable efforts have been channelled into ascertaining the most efficacious method of prevention. To date there is only indirect evidence to suggest that neonatal screening improves prognosis in cystic fibrosis. Similarly, treatment for fragile X syndrome is limited and therefore early identification of the disorder by neonatal screening is unlikely to improve long term outlook. Thus the focus of this review is on primary and secondary preventive methods.

Animals↗
PubMed2000

Screening for fragile X syndrome in women of reproductive age.

We conducted a prospective intervention study of screening for fragile X syndrome in the general population. Antenatal and preconceptional screening were carried out in 9459 women aged between 19 and 44 with no known family history of fragile X syndrome. 80% were tested antenatally. 134 carriers were detected (a frequency of 1 in 70); 130 had a premutation (PM) and 4 had a full mutation (FM). Prenatal diagnosis was carried out in 108 concurrent or subsequent pregnancies among carriers involving 111 fetuses. Nine had an FM, a rate of 1 in 12; two of the affected embryos received the FM directly from the mother and in seven it was the result of expansion from a PM. In all cases with an FM the pregnancy was terminated. In PM carriers there was evidence of a selection against the mutated chromosome with a segregation ratio of 0.40. Owing to the high rate of premutated chromosomes in our population we conclude that screening for fragile X syndrome among women of reproductive age should be more widely available.

Adult↗
PubMed2000

Biochemical screening for Down syndrome.

Maternal serum screening for Down syndrome is an established practise in many countries. In the second trimester human chorionic gonadotrophin (hCG) or free beta-hCG is the marker of first choice, with alpha-fetoprotein (AFP) as the second marker and unconjugated oestriol (uE(3)) the third. Statistical models with parameters derived by meta-analysis predict that a three marker combination will yield a 67% detection rate for a 5% false-positive rate. The model prediction have been confirmed in 21 large prospective intervention studies. A fourth marker, inhibin A, increases the detection rate by 7% for the same false-positive rate. In the first trimester, similar models predict that a combination of pregnancy associated plasma protein A, free beta-hCG, AFP and uE(3) will yield a 70% detection rate. This is increased to 88% if ultrasound nuchal translucency is used as an additional marker. Screening can also be extended to Edwards' syndrome, yielding high detection rates with little increase in the false-positive rate. Abnormal marker levels are also associated with a variety of adverse outcomes of pregnancy. High quality information and decision aids are needed to minimise anxiety among screenees.

Biomarkers↗