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H C Watt

Publications and source records attributed to H C Watt.

29 records · Page 2Linked to original sources
PubMed1997

The effect of differences in the distribution of maternal age in England and Wales on the performance of prenatal screening for Down's syndrome.

We aimed to determine how differences in the age at which women had their pregnancies influenced the expected detection and false-positive rates of serum screening for Down's syndrome (i) between 1970 and 1993 in England and Wales, and (ii) between regions and districts of England and Wales in 1991. We applied published estimates of Down's syndrome screening to regional and district data on the age distribution of maternities and changes in the age distribution over time in England and Wales obtained from the Office of Population Censuses and Surveys. From 1970 to 1993 women, on average, became pregnant at an older age; the percentage of maternities among women aged 35 or more increased from 7 to 9.2 per cent. This was not a great enough change to have had a material effect on the performance of Down's syndrome screening. In 1991, the percentage of maternities among women aged 35 or more varied from 5 to 20 per cent among Health Districts, a difference that would influence the performance of screening; for example, using the triple test and a risk cut-off of 1 in 250, the detection rates would have varied from about 55 to 70 per cent and the false-positive rates from 4.4 to 8.8 per cent across different districts. The tendency for women to have their pregnancies at an older age would have had a negligible impact on the performance of serum screening for Down's syndrome, but differences in the age when women had their pregnancies in different parts of the country would lead to twice as many women being referred for amniocentesis in some districts than in others when offered the same method of serum screening and at the same risk cut-off level. The results will have important implications for the local purchasers of Down's syndrome screening services.

Adult↗
PubMed1997

The dose-response relationship between cigarette consumption, biochemical markers and risk of lung cancer.

The relationship between the number of cigarettes smoked per day and the incidence of lung cancer is linear but, from the multistage model of carcinogenesis, it should be quadratic (upwards curving). We investigated this anomaly in a study of 11,403 male never smokers and current smokers in whom carboxyhaemoglobin (COHb) was measured in all and serum cotinine in 1175. The relationship between the biochemical markers and the reported number of cigarettes per day was approximately linear up to 20 cigarettes per day as expected. But above 20 cigarettes per day the marker levels increased less steeply and were 35% lower than expected in men who smoked more than 40 cigarettes per day. Less smoke is inhaled from each cigarette by men with high daily cigarette consumption than by men with lower consumption. Allowance for this transforms the observed linear dose-response relationship into one consistent with the expected quadratic relationship. The anomaly is explained by the observation that heavier smokers inhale less smoke from each cigarette.

Adult↗
PubMed1997

Reliability of statistics on Down's syndrome notifications.

OBJECTIVES: To evaluate the completeness of notifications of Down's syndrome live births and terminations to the Office for National Statistics (ONS) using data from the National Down Syndrome Cytogenetic Register (NDSCR). To examine the agreement of observed birth prevalence of Down's syndrome with the expected birth prevalence derived from published maternal age specific rates. METHODS: The number of live births (adjusted to allow for the estimated underascertainment) and the number of terminations due to fetal Down's syndrome from NDSCR were compared with those figures reported to the ONS. Subsequently, using the NDSCR figures, the live birth prevalence of Down's syndrome that would have occurred in the absence of antenatal diagnosis and selective termination was calculated in England and Wales in the years 1990-1993. These figures were compared with those derived by applying published age specific prevalences to the maternal age distribution in England and Wales. RESULTS: It is estimated that only 48% and 46% respectively of Down's syndrome live births and terminations of pregnancy were notified to ONS between 1990 and 1993. The annual expected birth prevalences of Down's syndrome obtained by applying maternal age specific prevalences to the maternal age distribution were in close agreement with observed rates from NDSCR. CONCLUSIONS: There is considerable underreporting of Down's syndrome births and terminations to ONS. The NDSCR data are more complete and therefore the effects of screening should be monitored using data from this source, or using estimates derived from the age specific rates of Down's syndrome.

Abortion, Induced↗
PubMed1996

Effect of allowing for ethnic group in prenatal screening for Down's syndrome.

We conducted a study to investigate ethnic group differences in levels of serum markers used in screening for Down's syndrome [serum alpha-fetoprotein (AFP), unconjugated oestriol (uE3), total human chorionic gonadotrophin (hCG), free alpha- and free beta-hCG, and dimeric inhibin-A], to estimate the extent to which maternal weight differences between ethnic groups explain these differences, and to estimate the effect of adjusting for ethnic group and maternal weight on screening performance. Serum measurements were taken from women who were screened prenatally for Down's syndrome. AFP, uE3, and hCG concentrations were available from 9462 white, 4215 black, and 4392 South Asian women with singleton pregnancies without Down's syndrome or neural tube defects between 15 and 22 weeks' gestational age. Frozen serum samples were available from a subset of 922 white, 449 black, and 135 South Asian women and were used for measurement of free alpha-hCG, free beta-hCG, and inhibin. Values were expressed as multiples of the median (MOM) for women of the same gestational age. There were statistically significant differences in the serum marker levels between ethnic groups that were not explained by differences in maternal weight. The main differences were found in black women compared with white women; black women had serum AFP levels 22 per cent higher (95 per cent confidence interval 20-24 per cent), total hCG levels 19 per cent higher (16-22 per cent), and free beta-hCG levels 12 per cent (3-21 per cent) higher. The other differences were less than 10 per cent. Adjusting for ethnic group only had a small estimated effect on screening performance: a maximum of about 0.5 per cent extra detection at a 5 per cent false-positive rate. At a fixed risk cut-off level, the false-positive rate will not be materially different between different ethnic groups. Adjusting serum markers for ethnic groups improves Down's syndrome screening performance to a very small extent. It is worthwhile because of its established value in AFP screening for open neural tube defects.

Asian People↗
PubMed1996

Serum markers for Down's syndrome in relation to number of previous births and maternal age.

We conducted a study to investigate the effect of parity on the following six serum markers used in screening for Down's syndrome, after adjusting them for ethnic group and maternal weight: alpha-fetoprotein (AFP), unconjugated oestriol (uE3), total human chorionic gonadotrophin (hCG), free alpha-hCG, free beta-hCG, and dimeric inhibin A. We aimed to estimate the effect of adjusting for any differences found on the screening performance. AFP, uE3, and hCG concentrations were available from 16,666 women with singleton pregnancies without Down's syndrome or neural tube defects and without insulin-dependent diabetes mellitus, who were screened between 15 and 22 weeks' gestational age. Stored serum samples were available on a subset of 1347 women and these were used to measure free alpha-hCG, free beta-hCG, and inhibin A. Serum concentrations were expressed as multiples of the median (MOM) for women of the same gestational age, weight, and ethnic group. Of the six markers, only hCG levels were affected by parity; hCG levels decreased by 3.1 per cent per previous birth (95 per cent confidence interval 2.2-4.0 per cent); there was no significant relationship between the number of previous abortions and hCG level after adjustment for the number of previous births. The effect of previous births on hCG was not due to maternal age. Only AFP was affected by maternal age, but the effect was small; levels increased by 4.4 per cent per 10 years of age (3.2-5.7 per cent). It is not worthwhile adjusting serum markers for parity or for maternal age in prenatal screening for Down's syndrome because their effect on the performance of screening is negligible.

Adolescent↗
PubMed1996

Maternal serum inhibin-A in pregnancies with insulin-dependent diabetes mellitus: implications for screening for Down's syndrome.

A nested case-control study using stored serum samples collected as part of a prospective study of the outcome of pregnancy was performed to investigate concentrations of (dimeric) inhibin-A in maternal serum between 15 and 22 weeks of pregnancy in 126 pregnancies among 92 women with insulin-dependent diabetes mellitus (IDDM). Each IDDM pregnancy was matched with two control singleton pregnancies for gestational age (same completed week) and duration of sample storage (same calendar quarter). The median inhibin-A level in the IDDM pregnancies was 0.88 multiples of the median (MOM) for pregnancies without IDDM at the same gestational age (P = 0.05) (95 per cent confidence interval 0.78-1.00) or 0.91 MOM after adjustment for maternal weight. These results enable inhibin-A values to be adjusted so that prenatal screening for Down's syndrome can be performed using this marker in IDDM pregnancies as well as in non-diabetic pregnancies.

Chorionic Gonadotropin↗
PubMed1996

Maternal serum inhibin-A levels in twin pregnancies: implications for screening for Down's syndrome.

A nested case-control study using stored serum samples collected as part of a prospective study of the outcome of pregnancy was performed to investigate concentrations of (dimeric) inhibin-A in maternal serum between 15 and 22 weeks of pregnancy in 200 twin pregnancies and 600 singleton control pregnancies. Each twin pregnancy was matched with three singleton pregnancies for gestational age (same completed week) and duration of sample storage (same calendar year), although for one twin there was insufficient serum. The median inhibin-A level in the twin pregnancies was 1.99 multiples of the median (MOM) for singleton pregnancies (P < 0.001) [95 per cent confidence interval (CI) 1.83-2.16]. These results enable inhibin-A values to be adjusted so that prenatal screening for Down's syndrome can be performed using this marker in twin pregnancies as well as in singleton pregnancies.

Chorionic Gonadotropin↗
PubMed1995

Prospective observational study to assess value of prostate specific antigen as screening test for prostate cancer.

OBJECTIVE: To evaluate measurement of serum prostate specific antigen as a potential screening test for future clinical prostate cancer among healthy men. DESIGN: Nested case-control study with stored serum samples collected from 49,261 men with follow up using national death and cancer registration systems. SUBJECTS: 265 asymptomatic men who subsequently developed clinical prostate cancer and 1055 controls matched for age, study centre, and duration of storage of samples. MAIN OUTCOME MEASURES: Distribution of concentrations of the antigen in men who developed prostate cancer and in controls. RESULTS: Prostate specific antigen concentrations were significantly higher in men who subsequently developed prostate cancer than in controls. In the first three years after blood collection the median concentration was 23 times greater in cases than in controls of the same age at the same centre (that is, 23 multiples of the median). A smaller difference persisted thereafter; 4.0 multiples of the median 3-6 years after blood collection, 3.6 6-10 years, and 1.8 after 10 years. In the first three years the proportion of men who developed prostate cancer and had raised levels of the antigen (> or = 12 multiples of the median) (detection rate or sensitivity) was 81% (95% confidence interval 54% to 96%). The proportion of men who did not develop prostate cancer but had levels this high (false positive rate) was only 0.5%. CONCLUSION: Prostate specific antigen measurement is a highly discriminatory screening test for prostate cancer among healthy men. In the general population, 60-74 year old men who had > or = 12 times the normal median level would have about a 50% chance of developing clinical prostate cancer in the next three years. Measurement of this antigen is a good enough screening test to justify a randomised controlled trial to determine any reduction in mortality from prostate cancer.

Aged↗
PubMed1994

Apolipoproteins and ischaemic heart disease: implications for screening.

Apolipoproteins and lipids are established risk factors of ischaemic heart disease (IHD) but their efficacy as screening tests is not known. We therefore examined the mortality from IHD and serum concentrations of lipids and apolipoproteins in a prospective study of 21,520 men aged 35-64 years. Serum apo B was the apolipoprotein most strongly associated with IHD risk; a decrease in apo B of 10% was associated with 22% lower risk of IHD. However, measurement of apo B alone detected only 17% of all IHD deaths at the cost of a 5% false-positive rate. Combining apo B with apo AI and apo (a) increased the detection rate to 19%. With systolic blood pressure, smoking, and family history of IHD the detection rate increased to 28%. We conclude that screening for IHD by measuring apo B alone or with apo AI and apo (a) is too poor to discriminate between recommending drug therapy or lifestyle change for some and not others. It is not advisable to screen for IHD by measuring any combination of cholesterol, apo B, apo AI, apo (a) and the other risk factors. The primary aim in prevention of ischaemic heart disease should be to lower the risk factors in the population.

Adult↗
PubMed1994

Value of maternal serum unconjugated oestriol measurement in prenatal screening for Down's syndrome.

We compared the medical and financial cost-effectiveness of prenatal serum screening for Down's syndrome using maternal age, serum alpha-fetoprotein and human chorionic gonadotrophin with and without the use of unconjugated oestriol. The use of unconjugated oestriol is medically more cost-effective than screening without it at all levels of detection. The actual performance depends on whether gestational age is estimated using 'dates' or an ultrasound scan. At a detection rate of 60 per cent, the proportion of unaffected fetal losses per case diagnosed at amniocentesis is about 22 per cent less if gestational age is estimated using dates (time since the first day of the last menstrual period) and about 47 per cent less if it is based on an ultrasound scan examination. At this detection rate, the inclusion of unconjugated oestriol increases costs by about 2k pounds per case diagnosed (36k pounds instead of 34k pounds) if gestational age is estimated using dates, but it is no more expensive if gestational age is measured from an ultrasound scan examination (indeed, it is more cost-effective at detection rates above 60 per cent). Since there is little change in the financial cost with the inclusion of unconjugated oestriol, for the improved medical performance of screening, it is worthwhile including it in the screening test.

Amniocentesis↗