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H S Cuckle

Publications and source records attributed to H S Cuckle.

At least 19 recordsLinked to original sources
PubMed1998

Measures of urine concentration in maternal urine screening for Down syndrome.

A study was carried out to assess eight methods of normalizing the level of urinary beta-core human chorionic gonadotropin (hCG) for variable urine concentration. We compared the standard approach--creatinine determination by the Jaffe method--with high performance liquid chromatography (HPLC) measurement of creatinine, osmolarity and optical density at five wavelengths. Urine samples were included from a total of 472 women with unaffected singleton pregnancies at 15 weeks' gestation. The median beta-core hCG value was determined for each decile group when the results were ranked in turn according to the different measures of urine concentration. Creatinine using the Jaffe method had a much stronger relationship with median beta-core hCG than the other measures. Linear regression across the decile groups gave an R2 value for Jaffe of 0.85 compared with HPLC of 0.53, osmolarity of 0.52, optical density at 405 nm of 0.72, at 450 nm of 0.57, at 490 nm of 0.33, at 570 nm of 0.34 and at 630 nm of 0.33. We conclude that when screening with urinary beta-core hCG measuring creatinine appears to be an adequate method of allowing for variable urine concentration.

Chorionic Gonadotropin, beta Subunit, Human↗
PubMed1998

Effect of maternal age curve on the predicted detection rate in maternal serum screening for Down syndrome.

The effect of the choice of maternal age-specific prevalence curve on the model predicted Down syndrome detection rate was examined. All 19 published regression curves from 11 birth prevalence series in four meta-analyses were included. The detection rate for a five per cent false-positive rate was estimated for three combinations of markers. For free beta human chorionic gonadotropin and alpha-fetoprotein the lowest predicted detection rate was 62.3 per cent and the highest 64.1 per cent, a range of 1.8 per cent. When unconjugated oestriol was added as a third marker it was 65.6-67.3 per cent, a 1.7 per cent range, and when inhibin A was the fourth marker the detection rate was 72.0-73.4 per cent, a 1.4 per cent range. The number of series included in the regression had the biggest effect: when the authors had used a subset thought to have the highest ascertainment the predicted detection rate generally increased. The type of regression equation used and restrictions on the age range over which the regression was performed were less important factors. The effect of the choice of curve on the predicted increase in detection achieved by incorporating additional markers was relatively small: 3.1-3.3 per cent for unconjugated oestriol and a further 6.1-6.5 per cent for inhibin A. This analysis shows that the model inaccuracy caused by the maternal age curve is not small but is unlikely to be large enough to influence Down syndrome screening policy decisions.

Chorionic Gonadotropin, beta Subunit, Human↗
PubMed1996

Combining inhibin A with existing second-trimester markers in maternal serum screening for Down's syndrome.

To assess the value of inhibin A as an additional second-trimester maternal serum marker of Down's syndrome we studied 56 affected and 280 unaffected pregnancies matched for gestational age. The median level in the cases was 1.62 multiples of the gestation-specific median (MOM) in the controls, with 95 per cent confidence limits of 1.34-1.96. The distribution of inhibin levels in affected and unaffected pregnancies was approximately log Gaussian, with means about 1 standard deviation apart. This degree of separation was similar to that for human chorionic gonadotropin (hCG), free beta-hCG, and unconjugated oestriol (uE3), but about double that of alpha-fetoprotein (AFP) measured in the same samples. Inhibin was largely uncorrelated with AFP and uE3, whereas the log correlation coefficient with hCG was 0.29 (P = 0.19) for Down's syndrome and 0.41 (P < 0.0001) for unaffected pregnancies; with free beta-hCG, it was 0.18 (P = 0.38) and 0.38 (P < 0.0001), respectively. On the basis of these results and other published studies, we estimate that measuring inhibin A in addition to AFP and hCG or free beta-hCG (with or without uE3) will increase the detection rate for a fixed 5 per cent false-positive rate by about 7 per cent.

Biomarkers↗
PubMed1996

Nomograms to help inform women considering Down's syndrome screening.

OBJECTIVE: To derive graphical information for use in counselling women considering whether or not to have maternal serum screening for Down's syndrome. DESIGN: Statistical modelling of the frequency distribution of estimated Down's syndrome risk for four marker combinations. RESULTS: Nomograms are provided showing for each maternal age: (a) the detection and false-positive rates, and (b) the proportion of pregnancies with different estimated risks. CONCLUSION: When screening is offered, clinicians need to have information readily available on test accuracy and the likely result, which is specific to the individual.

Chorionic Gonadotropin↗
PubMed1995

Cost effectiveness of antenatal screening for cystic fibrosis.

OBJECTIVE: To estimate the cost effectiveness of different antenatal screening programmes for cystic fibrosis. SETTING: Antenatal clinics and general practices in the United Kingdom. DESIGN: Four components of the screening process were identified: information giving, DNA testing, genetic counselling, and prenatal diagnosis. The component costs were derived from the literature and from a pilot screening study in Yorkshire. The cost of a given screening programme was then obtained by summing the components according to the specific screening strategy adopted (sequential and couple), the proportion of carriers detected by the DNA test, and the uptake of screening. Baseline assumptions were made about the proportion with missing information on carrier status from previous pregnancies (20%), the proportion changing partners between pregnancies (20%), and the uptake of prenatal diagnosis (100%). Sensitivity analysis was performed by varying these assumptions. MAIN OUTCOME MEASURE: Cost per affected pregnancy detected. RESULTS: Under the baseline assumptions sequential screening costs between pounds 40,000 and pounds 90,000 per affected pregnancy detected, depending on the carrier detection rate and uptake. Couple screening was more expensive, ranging from pounds 46,000 to pounds 104,000. From the sensitivity analysis a 10% change in the assumed proportion with missing information from a previous pregnancy alters the cost by pounds 4000; a 10% change in the proportion with new partners has a similar effect but only for couple screening; and cost will change directly in proportion to the uptake of prenatal diagnosis. CONCLUSIONS: While economic analysis cannot determine screening policy, the paper provides the NHS with the information on cost effectiveness needed to inform decisions on the introduction of a screening service for cystic fibrosis.

Cost-Benefit Analysis↗
PubMed1995

Urinary multiple marker screening for Down's syndrome.

We have examined the possibility of using multiple markers in maternal urine rather than serum in order to screen for Down's syndrome. Urine samples were available from 36 cases (24 Down's syndrome, five Edwards' syndrome, three Turner's syndrome, one Klinefelter's syndrome, one triploidy, one triple-X, one twin discordant for Down's syndrome) and 294 controls, including three twins. Three markers were tested: the beta-core fragment of human chorionic gonadotrophin (hCG), total oestrogen (tE) and the free alpha subunit of hCG. Levels were corrected for creatinine excretion and expressed as multiples of the gestation-specific median (MOM) level from the singleton controls. The median value for the singleton Down's syndrome cases was 6.02, 0.74, and 1.08 MOM for beta-core-hCG, tE, and alpha-hCG, respectively. The increases in beta-core-hCG and the reduction in tE levels were highly significant (P < 0.0001 and 0.005, respectively; Wilcoxon rank sum test) but the increase in free alpha-hCG was not (P = 0.40). On the basis of a mathematical model, the expected detection rate for a 5 per cent false-positive rate was 79.6 per cent for beta-core-hCG alone, which increased to 82.3 per cent when combined with tE. Aneuploidies other than Down's syndrome were characterized by low levels of tE and either low or high beta-core-hCG.

Adult↗
PubMed1994

Screening for neural tube defects.

The birth prevalence of neural tube defects fell by 95% in England and Wales between 1970 and 1990 largely as a result of antenatal screening, subsequent diagnosis and selective abortion of affected pregnancies. Anencephaly can be diagnosed using ultrasound, whereas both amniotic fluid biochemistry and ultrasound are required for the diagnosis of spina bifida. Both methods have a false-positive rate of about two per 1000 when carried out in high-risk pregnancies. The diagnostic results are likely to be better if the two methods are used in parallel. Maternal serum alpha-fetoprotein screening at 16-18 weeks gestation can detect about 75% of pregnancies affected by spina bifida. Routine ultrasound anomaly screening, usually performed at 18-20 weeks gestation, can detect a similar proportion. New developments indicate that earlier, more accurate detection may be possible but more research will be needed before this can be established.

Biochemistry↗
PubMed1994

Maternal serum inhibin levels in second-trimester Down's syndrome pregnancies.

Maternal serum inhibin levels were measured in 19 second-trimester pregnancies affected by fetal Down's syndrome and 95 unaffected control pregnancies matched for gestational age. A statistically significant elevation was found in the affected pregnancies compared with the controls (Wilcoxon rank sum test: one-tail P = 0.02). The median level in the cases was 1.3 times that in the controls, with 95 per cent confidence limits of 0.9-1.9. Although the inhibin levels were unrelated to those of alpha-fetoprotein and unconjugated oestriol in the same samples, there was a statistically significant correlation with human chorionic gonadotropin. This together with the relatively small elevation in cases suggests that inhibin would be of limited value in maternal screening for Down's syndrome.

Chorionic Gonadotropin↗
PubMed1994

Urinary beta-core human chorionic gonadotrophin: a new approach to Down's syndrome screening.

Human chorionic gonadotrophin (hCG) is the most discriminatory maternal serum marker of Down's syndrome. We have carried out a study to establish whether urinary beta-core-hCG, a major metabolic product of hCG, might be an even better marker. Urine samples were available from seven singleton pregnancies with Down's syndrome, and one each of Edwards' syndrome, triploidy, and twins discordant for Down's syndrome. beta-Core-hCG levels were corrected for creatinine and expressed as multiples of the normal gestation-specific median (MOM) level derived from 67 singleton controls. There was a highly statistically significant elevation in level among the singleton Down's syndrome cases (P < 0.0005; Wilcoxon rank sum test). All had levels exceeding 2 MOM with a median of 6.11 MOM (95 per cent confidence interval 3.7-10.0). The levels were extremely low in Edwards' syndrome (0.08 MOM) and triploidy (0.02 MOM), but the twin pregnancy discordant for Down's syndrome did not have a raised beta-core-hCG level (0.64 MOM). The findings are sufficiently encouraging to investigate the possibility of urinalysis as a routine modality in the prenatal screening for Down's syndrome and other common serious aneuploidies.

Adolescent↗