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H S Cuckle

Publications and source records attributed to H S Cuckle.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1992

Antenatal maternal serum screening for Down's syndrome: results of a demonstration project.

OBJECTIVES: To assess the implementation of antenatal screening for Down's syndrome in practice, using individual risk estimates based on maternal age and the three serum markers: alpha fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin. DESIGN: Demonstration project of Down's syndrome screening; women with a risk estimate at term of 1 in 250 or greater were classified as "screen positive" and offered diagnostic amniocentesis. SETTING: Hospital and community antenatal clinics in four health districts in London. SUBJECTS: 12,603 women of all ages with singleton pregnancies seen between February 1989 and the end of May 1991, with follow up of the outcome of pregnancy completed to the end of 1991. MAIN OUTCOME MEASURES: Uptake of screening, detection rate for Down's syndrome, false positive rate, odds of being affected given a positive result, and uptake of amniocentesis in women with positive screening results, together with the costs of the screening programme. RESULTS: The uptake of screening was 74%. The detection rate was 48% (12/25), and the false positive rate was 4.1%, consistent with results expected from previous work based on observational studies. There was a loss of detection due to the selective use of ultrasound scans among women with positive screening results. One affected pregnancy occurred among 205 reclassified as negative; this illustrated the danger of false negatives occurring in this group and lends weight to the view that if an ultrasound estimate of gestational age is used it should be carried out routinely on all women rather than selectively among those with positive results. The estimated cost of avoiding the birth of a baby with Down's syndrome was about 38,000 pounds, substantially less than the lifetime costs of care. CONCLUSION: Antenatal maternal serum screening for Down's syndrome is effective in practice and can be readily integrated into routine antenatal care. It is cost effective and performs better than selection for amniocentesis on the basis of maternal age alone.

Amniocentesis↗
PubMed1992

Detection of hydatidiform mole in maternal serum screening programmes for Down's syndrome.

OBJECTIVE: To determine how frequently hydatidiform mole will be detected in a maternal serum Down's syndrome screening programme. DESIGN: Affected pregnancies were identified using a national register. Unconjugated oestriol (uE3) and human chorionic gonadotrophin (hCG) were measured in stored serum samples and alphafetoprotein (AFP) levels were available from previous neural tube defect screening at 15-20 weeks gestation. SUBJECTS: Ten pregnancies with a complete mole (i.e., hydropic placenta without a fetus), nine with stored serum samples and one with an AFP level only. RESULTS: The median values were 0.08, 0.13 and 1.83 multiples of the normal median for AFP, uE3 and hCG respectively. Six out of nine (67%) tested for all three markers had a high risk of Down's syndrome given maternal age and the marker levels. CONCLUSION: Many molar pregnancies that have not presented clinically before 15 weeks will be detected through Down's syndrome screening.

Adult↗
PubMed1992

Maternal serum unconjugated oestriol and human chorionic gonadotrophin levels in pregnancies with insulin-dependent diabetes: implications for screening for Down's syndrome.

OBJECTIVE: To investigate maternal serum unconjugated oestriol (uE3) and human chorionic gonadotrophin (hCG) levels in pregnant women with insulin-dependent diabetes mellitus and to consider the implications of the results for antenatal screening for Down's syndrome. DESIGN: Descriptive study using stored antenatal serum samples. SETTING: Stored serum samples collected from women receiving routine antenatal care in Oxford. SUBJECTS: 126 singleton pregnancies in 92 women with insulin-dependent diabetes mellitus and for each pregnancy, two pregnancies without diabetes matched for gestational age and duration of storage of the serum sample. None of the pregnancies was associated with fetal neural tube defect or Down's syndrome. MAIN STUDY MEASURES: Maternal serum uE3 and hCG levels at 15-22 weeks gestation. Alpha-fetoprotein (AFP) levels were also measured for comparison. RESULTS: The median uE3 level in the diabetic pregnancies was 0.92 multiples of the median (MoM) for pregnancies without diabetes at the same gestational age (P less than 0.05); and the hCG level was 0.95 MoM (P = 0.48). The median AFP level was also reduced to 0.77 MoM (P less than 0.001). CONCLUSION: The reduction in uE3 and AFP levels in insulin-dependent diabetic pregnancies is sufficiently great to be taken into account in maternal serum screening programmes for Down's syndrome. Dividing the uE3 and AFP levels in such pregnancies by the corresponding median for insulin-dependent diabetic pregnancies will yield a similar false-positive rate in pregnancies with and without insulin-dependent diabetes mellitus.

Chorionic Gonadotropin↗
PubMed1992

Maternal serum screening for Down's syndrome: the effect of routine ultrasound scan determination of gestational age and adjustment for maternal weight.

OBJECTIVE: To investigate the effect of using a routine ultrasound estimate of gestational age and maternal weight adjustment on maternal serum alpha-fetoprotein (AFP), unconjugated oestriol (uE3) and human chorionic gonadotrophin (hCG) levels in antenatal screening for Down's syndrome. DESIGN: Women with a singleton pregnancy without Down's syndrome were screened using the three serum markers and an estimate of gestational age based on 'dates' (time since first day of the last menstrual period) and one based on an ultrasound scan examination was recorded together with maternal weight. SETTING: Women attending the Homerton Hospital, Hackney, for their antenatal care between February 1989 and January 1990. SUBJECTS: 2113 women with a singleton pregnancy without Down's syndrome. RESULTS: The use of ultrasound to estimate gestational age (usually based on the biparietal diameter of the fetal skull) led to a significant reduction in the variance of each marker at a given week of pregnancy. The level of each marker was negatively associated with maternal weight, so that adjustment for weight also led to a reduction in variance. These data on gestational age and maternal weight, taken together with published data on pregnancies associated with Down's syndrome, indicate that the routine use of ultrasound to estimate gestational age will increase the detection rate from 58% to 67% while maintaining the false-positive rate at 5%, or reduce the false-positive rate from 5.7% to 3.1% while maintaining the detection rate at 60%. Routine maternal weight adjustment for the serum marker levels was much less useful, increasing the detection rate by about 0.5% for a given false-positive rate, or reducing the false-positive rate about 0.1% for a given detection rate. CONCLUSION: An ultrasound gestational age estimate available at the time of Down's syndrome screening confers a substantial advantage to screening performance with a further small benefit resulting from maternal weight adjustment, which is worth adopting if it can be done without difficulty or extra cost.

Biomarkers↗
PubMed1991

Second trimester amniotic fluid oestriol, dehydroepiandrosterone sulphate, and human chorionic gonadotrophin levels in Down's syndrome.

OBJECTIVE: To investigate the reason for low maternal serum unconjugated oestriol (uE3) and raised human chorionic gonadotrophin (hCG) levels in Down's syndrome pregnancies. DESIGN: Measurement of uE3, total oestriol (tE3), dehydroepiandrosterone sulphate (DHEAS), a precursor of oestriol, and hCG in 15-20 week amniotic fluid samples from pregnancies with and without Down's syndrome. SETTING: The retrieval and use of stored amniotic fluid samples collected from women who had had an amniocentesis for antenatal diagnosis. SUBJECTS: 45 women with a Down's syndrome pregnancy and 224 unaffected controls of the same gestational age. RESULTS: The median level of amniotic fluid in affected pregnancies was low for uE3, tE3 and DHEAS but high for hCG: 0.50, 0.46, 0.35 and 1.58 multiples of the normal median, respectively. CONCLUSION: These results suggest that the abnormal maternal serum levels of uE3 and hCG in affected pregnancies are due mainly to abnormal feto-placental synthesis, rather than feto-maternal transfer.

Adult↗
PubMed1990

Measurement of activity of urea resistant neutrophil alkaline phosphatase as an antenatal screening test for Down's syndrome.

OBJECTIVE: To investigate the value of measuring maternal urea resistant neutrophil alkaline phosphatase activity as an antenatal screening test for Down's syndrome. DESIGN: Case-control study of blood samples collected at nine to 27 weeks of pregnancy. SETTING: Antenatal clinics in London and Oxford. PATIENTS: 72 Women whose fetuses had been diagnosed by amniocentesis or chorionic villus sampling as having Down's syndrome and 156 women whose fetuses did not have the syndrome. Only singleton pregnancies were studied. MAIN OUTCOME MEASURE: Activity of urea resistant neutrophil alkaline phosphatase measured cytochemically. RESULTS: The median enzyme activity in the index patients was 1.65 times the expected median for the controls at the same duration of pregnancy (p less than 0.0001; 95% confidence interval 1.56 to 1.74). A cut off value that identified the 5% of control patients with the highest activities yielded a rate of detection of Down's syndrome of 79% (95% confidence interval 70 to 89%). CONCLUSION: Activity of urea resistant neutrophil alkaline phosphatase is an effective maternal blood marker for Down's syndrome. Its use in antenatal screening could lead to a substantial improvement in the detection of this disorder. Before introducing the test into routine medical practice it will have to be automated so that it can be used on a large scale and is less subjective.

Adult↗