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Howard S Cuckle

Publications and source records attributed to Howard S Cuckle.

7 recordsLinked to original sources
PubMed2007

Serum müllerian-inhibiting substance in Down's syndrome pregnancies.

BACKGROUND: To examine whether maternal serum levels of müllerian-inhibiting substance (MIS) differ in Down's syndrome and unaffected pregnancies. METHODS: Case-control study was conducted using stored serum from an antenatal screening programme. Sera from 25 Down's syndrome pregnancies were retrieved from -20 degrees C storage together with 125 unaffected controls individually matched for maternal age, weeks of gestation and duration of storage. Results were expressed in multiples of the gestation-specific median value (MoM) in controls. RESULTS: The median value in Down's syndrome pregnancies was 0.83 MoM (P = 0.77, two-tail Wilcoxon rank sum test). Among unaffected pregnancies, there was a statistically significant correlation between MIS and pregnancy-associated plasma protein-A (P < 0.05). MIS levels were elevated in pregnancies where assisted reproduction techniques had been used. CONCLUSION: There is no evidence for a substantial reduction in maternal serum MIS levels in Down's syndrome pregnancies. This study provides useful information regarding serum MIS levels in pregnancy.

Adult↗
PubMed2006

Aneuploidy screening: what test should I use?

Screening for the risk of fetal aneuploidy can be effectively performed in either the first or second trimester. When obtained independently, the interpretation of those data is straightforward. However, the effectiveness of screening can be enhanced by combining studies performed in each trimester in a variety of ways. In this commentary we will define and discuss both the advantages and disadvantages of using integrated, stepwise, sequential or contingency screening for risk assessment of fetal aneuploidy.

Adult↗
PubMed2005

Primary prevention of Down's syndrome.

BACKGROUND: Antenatal screening has the capacity to detect more than 90% of Down's syndrome pregnancies leading to therapeutic abortion. Successes in recent years with such so-called 'secondary' prevention have not been matched with progress in primary prevention. Despite considerable research over many decades the principle cause of the disorder is unknown. METHODS: This paper considers three potential primary prevention strategies, (1) avoiding reproduction at advanced maternal age, (2) pre-implantation genetic diagnosis for couples who are at high risk of Down's syndrome, and (3) folic acid supplementation. The principle aetiological hypotheses are also reviewed. INTERPRETATION: A strategy of completing the family before a maternal age of 30 could more than halve the birth prevalence of this disorder. Women with a high a priori risk should have access to pre-implantation genetic diagnosis, which can lead to a reasonably high pregnancy rate with an extremely low risk of a Down's syndrome. The evidence suggesting an aetiological role for defective folate and methyl metabolism is not sufficient to justify an active preventative strategy of folic acid supplementation without performing a large clinical trial. Current supplementation policies designed to prevent neural tube defects may incidentally prevent Down's syndrome, provided a sufficiently high dose of folic acid is used. Further progress in primary prevention is hampered by limited aetiological knowledge and there is an urgent need to refocus research in that direction.

Journal Article↗
PubMed2005

Down syndrome screening marker levels in women with a previous aneuploidy pregnancy.

BACKGROUND: In Down syndrome screening programmes, women with a previous affected pregnancy are assumed to have the same marker distribution as those without a family history. This assumption needs to be tested. METHODS: Information on previous aneuploidy pregnancies was routinely sought on the test request forms in three centres, Leeds, Romford and the Fetal Medicine Centre, London. For each woman with a previous aneuploidy (case), five unaffected pregnancies to women without a history were selected as controls. The markers tested included maternal serum free beta-human chorionic gonadotrophin (hCG), pregnancy-associated plasma protein A (PAPP-A), alpha-fetoprotein, unconjugated estriol and ultrasound nuchal translucency thickness. RESULTS: There were 375 cases: 303 with previous Down syndrome, 63 with Edwards syndrome and 9 with Patau's syndrome. There was a statistically significant difference between cases and controls, in the distribution of free beta-hCG and PAPP-A levels, adjusted for gestation. On average, free beta-hCG was increased by 10% in a subsequent pregnancy after aneuploidy (p < 0.005, Wilcoxon rank sum test) and for PAPP-A the increase was 15% (p < 0.0001). No other marker was significantly different. CONCLUSION: Risk calculation algorithms need to be modified to take account of the increased marker levels. Until data from sufficient affected pregnancies are available for study, it would be prudent to assume that the same increase as in unaffected pregnancies applies.

Adult↗
PubMed2005

Assessment of risk for the development of pre-eclampsia by maternal characteristics and uterine artery Doppler.

OBJECTIVE: To develop a method for the estimation of patient-specific risk for the development of pre-eclampsia by combining maternal history and uterine artery Doppler. DESIGN: Prospective multicentre observational study. SETTING: Antenatal clinics in seven hospitals in the UK and three overseas centres. POPULATION: Unselected women with singleton pregnancies attending for routine antenatal care. METHODS: Doppler studies of the uterine arteries were performed using colour flow mapping and pulsed wave Doppler at 23 weeks of gestation. The mean pulsatility index (PI) of the two uterine arteries was calculated. Doppler and maternal history variables were combined to develop a model for risk assessment. The incidence of pre-eclampsia was used to derive the prior risk for this complication. The posterior risk was derived by multiplying the prior odds with likelihood ratios (LRs) derived from independent risk factors identified from the maternal history, and the LR estimated from the heights of the frequency distributions of mean PI in affected and unaffected pregnancies. MAIN OUTCOME MEASURE: Pre-eclampsia. RESULTS: There were 17,480 women recruited to the study, in which 17,319 (99.1%) of these Doppler examination of both uterine arteries were completed, and outcome data were available in 16,806 (97.0%). Pre-eclampsia occurred in 369 (2.20%) cases. Significant independent prediction of pre-eclampsia was provided by mean PI, ethnic origin, body mass index (BMI), parity, cigarette smoking, history of hypertension and family or personal history of pre-eclampsia. Models were derived allowing calculation of patient-specific risk for development of pre-eclampsia. For a false-positive rate of 25%, the detection rate of pre-eclampsia by screening using maternal history was 45.3%, with uterine artery Doppler it was 63.1% and with combined assessment it was 67.5%. CONCLUSIONS: Combining risk factors in the mother's history with Doppler of the uterine arteries allows calculation of patient-specific risk for the development of pre-eclampsia.

Arteries↗
PubMed2002

Screening for chromosomal anomalies in the first trimester: does repeat maternal serum screening improve detection rates?

OBJECTIVE: To assess the within person biological variability of first trimester maternal serum biochemical markers of trisomy 21 across the 10-14 week gestational period. To evaluate whether repeat sampling and testing of free beta-hCG and PAPP-A during this period would result in an improved detection rate. METHODS: Women presenting at the first trimester OSCAR clinic have blood collected prior to ultrasound dating and nuchal translucency measurement. All samples are analysed for free beta-hCG and PAPP-A before an accurate estimate of gestation is available. In 10% of cases the gestation is prior to the minimum time for NT measurement (11 weeks) and these women are rebooked for a repeat visit to the clinic at the appropriate time. Our fetal database was interrogated to obtain cases in which two maternal blood samples had been collected and analysed in the 10-14 week period. Using data from the marker correlations and statistical modelling, the impact of repeat testing on detection rate for trisomy 21 at a fixed 5% false positive rate, was assessed. RESULTS: 261 pairs of data were available for analysis collected over a 3 year period. The correlation between free beta-hCG in sample 1 and sample 2 was 0.890 and that for PAPP-A was 0.827. The average within person biological variation for free beta-hCG was 21% and 32% for PAPP-A. The increase in detection rate when using both sets of marker data was 3.5% when using serum biochemistry and maternal age, and 1.3% when using nuchal translucency, serum biochemistry and maternal age. CONCLUSION: Repeat sampling and testing of maternal serum biochemical markers is unlikely to substantially improve first trimester screening performance.

Chorionic Gonadotropin, beta Subunit, Human↗