PubMed Health⌕ Search

Biomedical subjects

J Densem

Publications and source records attributed to J Densem.

12 recordsLinked to original sources
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↗
PubMed1995

Repeat maternal serum testing for Down's syndrome screening using multiple markers with special reference to free alpha and free beta-hCG.

To determine the effect of routine repeat testing in serum screening for Down's syndrome, we compared estimates of the detection and false-positive rates. Five serum markers were measured--alpha-fetoprotein (AFP), unconjugated oestriol (uE3), human chorionic gonadotrophin (hCG), and its two subunits, free alpha and free beta-hCG. First and repeat test marker levels were available from 142 women whose samples had been routinely collected and stored in an antenatal serum bank. Different repeat testing policies were compared for various combinations of the markers. If all women had repeat tests using the four markers AFP, uE3, and free alpha and free beta-hCG, the detection rate for a 5 per cent false-positive rate was 69 per cent compared with 65 per cent if no women were repeated. Policies of repeating selected women gave similar results. The small gain in screening performance with repeat testing performed routinely is not worthwhile. If a woman does happen to have a repeat test, her risk estimate should, however, be based on both results, not just the second.

Biomarkers↗
PubMed1995

The tar reduction study: randomised trial of the effect of cigarette tar yield reduction on compensatory smoking.

BACKGROUND: Observational and short term intervention studies have reported that smokers of low tar cigarettes inhale more deeply (that is, compensate) than those who smoke high tar cigarettes. To quantify this effect a long term randomised trial was conducted on the effects of switching to low tar cigarettes. METHODS: The trial was carried out between April 1985 and March 1988 among cigarette smokers in the British Civil Service, measuring blood carboxyhaemoglobin (COHb) levels and serum cotinine levels as markers of tobacco smoke intake. Volunteers first switched to a cigarette brand yielding around 10% less tar than their usual brand to identify smokers able to change brand. The 434 subjects who successfully switched were then randomly allocated to one of three groups: (a) "fast reduction" group which changed to a brand of cigarettes with a tar yield of about half that of their usual brand; (b) "slow reduction" group which reduced to the same level in steps over several months; and (c) a control group which continued smoking cigarettes with a tar yield 10% lower than their usual brand. RESULTS: Over the course of the trial cigarette consumption declined slightly in all three groups. In both the "fast reduction" and the "slow reduction" groups, intake of COHb and cotinine was reduced, though not to the same extent as the yield reduction. Comparison of the results before randomisation with those at the end of the trial showed that a reduction in carbon monoxide yield of 45% was associated with a decrease in carbon monoxide intake of 19% (95% confidence interval 14% to 24%) and that a reduction in nicotine yield of 40% was associated with an 11% (6% to 16%) reduction in nicotine intake, reflecting relative intakes of about 1.5 for both carbon monoxide and nicotine in the "fast reduction" group. Results were similar in the "slow reduction" group with a 42% reduction in carbon monoxide yield, a 16% (11% to 22%) reduction in carbon monoxide intake, a 37% reduction in nicotine yield, and a 6% (0% to 13%) reduction in nicotine intake. Estimates of compensation derived from these results were 65% for carbon monoxide, 79% for nicotine, and 62% for tar. CONCLUSIONS: Compensation, demonstrated when switching from a high tar cigarette to a low tar one, was incomplete. Advising people who have failed to give up smoking to switch to low tar cigarettes will reduce the intake of smoke constituents to a small extent. This would be expected to decrease their risk of smoking-related diseases, although by a smaller amount than would be achieved by giving up smoking altogether.

Adaptation, Psychological↗
PubMed1994

Repeat maternal serum testing in multiple marker Down's syndrome screening programmes.

The effect of repeat testing in maternal serum multiple marker screening for Down's syndrome was estimated using samples stored in an antenatal serum bank. Human chorionic gonadotropin (hCG) and unconjugated oestriol (uE3) levels were determined in 142 pairs of routinely collected samples which had already been tested for alpha-fetoprotein (AFP). For each marker, about two-thirds of the pairs of values were within 20 per cent of each other and most were within 40 per cent. A multivariate Gaussian model was used to estimate the detection and false-positive rates for different repeat testing policies. A policy of repeat testing those with a high risk of a Down's syndrome term pregnancy given age and marker levels would reduce the false-positive rate but there would also be a reduction in the detection rate. For example, using all three markers and a 1 in 250 cut-off risk, the estimated false-positive rate would fall from 5.3 to 3.8 per cent but the detection rate would decrease from 58 to 55 per cent. A policy of repeating those with either high or borderline risks would produce a modest improvement in screening efficiency. Repeating the 11 per cent with a risk exceeding 1 in 500 yields an estimated false-positive rate of 5.0 per cent and a detection rate of 60 per cent. A policy of selective repeat testing is not recommended as it would not substantially improve screening efficiency. Nonetheless, if a repeat test has been performed, the parameters given in this paper will enable an unbiased estimate of the Down's syndrome risk to be calculated for individual women.

Chorionic Gonadotropin↗
PubMed1993

Serum alpha-fetoprotein and neural tube defects in the first trimester of pregnancy. MRC Vitamin Study Research Group.

As part of the Medical Research Council randomized trial of vitamin supplementation in the prevention of neural tube defects (NTDs), maternal serum alpha-fetoprotein (AFP) was available for 19 NTD pregnancies. Each of these was matched with four unaffected controls, by maternal age, participating centre, and duration of sample storage. The samples came from women whose gestational age ranged from 6 to 14 completed weeks. The median AFP level in the affected pregnancies was 1.2 multiples of the median value in unaffected pregnancies of the same gestational age (95 per cent confidence interval (CI) 0.83-1.59). This confirmed the view that serum AFP measurement is of no practical value in the detection of NTDs in the first trimester of pregnancy. The study also showed that folic acid supplementation, used as a method of preventing NTDs, had no effect on the concentrations of maternal serum AFP up to 14 weeks of pregnancy.

Female↗
PubMed1993

The use of free beta-hCG in antenatal screening for Down's syndrome.

OBJECTIVE: To investigate the value of the measurement of free beta human chorionic gonadotrophin (hCG) as a serum marker of Down's syndrome in the second trimester of pregnancy. DESIGN: A prospective observational study using stored antenatal serum samples. SETTING: Serum samples collected from women receiving routine antenatal care in Oxford. SUBJECTS: Seventy-five singleton pregnancies with fetal Down's syndrome and 367 unaffected singleton pregnancies. Each affected pregnancy was matched with five control pregnancies for maternal age, gestational age, and duration of storage of the serum sample. None of the pregnancies were associated with neural tube defects. MAIN STUDY MEASURES: Maternal serum free beta-hCG levels. These were compared with total hCG levels in the same pregnancies. The performance of screening using free beta-hCG was compared with that using the principal markers, namely alpha-fetoprotein (AFP), unconjugated oestriol (uE3), and total hCG together with maternal age. RESULTS: The median free beta-hCG level in the affected pregnancies was 2.22 multiples of the normal median (MoM), significantly higher than in the unaffected pregnancies (95% confidence interval, 1.84-2.68 MoM). The discriminatory performances of free beta-hCG and total hCG, each considered separately, were similar; with a cut-off level of 2.5 MoM the detection rate was 43% and 5.7 of unaffected pregnancies had raised free beta-hCG levels (likelihood ratio of 7.5 (43/5.7)), somewhat better discrimination than the 32% and 4.6% respectively using total hCG (likelihood ratio of 7.0 (32/4.6)). With a higher cut-off level of 3.5 MoM, the rates were 19% and 2.7% respectively (likelihood ratio of 7.0), using free beta-hCG, worse than the 19% and 1.4% using total hCG (likelihood ratio of 13.6). Screening using maternal age, AFP, uE3 and free beta-hCG (instead of total hCG) yielded a detection rate of 62% (instead of 58%) at a screening risk cut-off level corresponding to a 5% false-positive rated). CONCLUSION: The main advantage in using free beta-hCG instead of total hCG is that there is a small increase in the detection rate (4%) for a given false-positive rate when used with maternal age, AFP and uE3. The main disadvantage is that there is less practical experience with free beta-hCG measurement and insufficient data to screen in certain categories of pregnancy (e.g. twins). The best practical advice is to use total hCG for the present but consider changing to free beta-hCG either (i) after further data are available that will permit the interpretation of screening results in the same way as is currently available with total hCG, or (ii) if its use with another marker confers a worthwhile increase in the detection rate for a given false-positive rate.

Adult↗
PubMed1989

Repeat maternal serum alpha-fetoprotein testing in antenatal screening programmes for Down's syndrome.

The risk of having a Down's syndrome term pregnancy was estimated using maternal age and the results of two maternal serum alpha-fetoprotein (AFP) tests carried out between 14 and 20 weeks gestation. The estimates of risk were derived from published data and the AFP results from nine affected and 145 unaffected pregnancies in which repeat testing had been carried out. Repeat AFP testing is unjustified in antenatal screening programmes for Down's syndrome, but if a second test happens to have been done, the appropriate estimate of risk that would be applicable when counselling individual patients depends on both results. For example a woman aged 35 years and 6 months with a first AFP level of 0.50 multiples of the normal median (MoM) was estimated to have a risk of 1:172. If a second test were done on a fresh sample and the AFP level were 0.80 MoM then the estimated risk would be 1:216 which is higher than the estimated risk of 1:353 obtained if the second test were regarded as the only result. Estimates of risk are given for maternal serum AFP results in first and second tests ranging from 0.40 to 2.50 MoM.

Adult↗
PubMed1988

Maternal serum thyroid antibodies in early pregnancy and fetal Down's syndrome.

Thyroid antibodies were measured in mid-trimester antenatal serum samples from 77 pregnancies affected by fetal Down's syndrome and 385 unaffected control pregnancies. Using a haemagglutination technique, thyroglobulin antibodies were detected in 5.2 per cent of cases (4) and 2.9 per cent of controls (11), and thyroid microsomal antibodies were detected in 22 per cent (17) and 15 per cent (59), respectively. Using an enzyme-linked immunosorbent assay (ELISA) for thyroglobulin antibodies and a cut-off level of 50 KIU/l, positive results were found in 25 per cent of cases (19) and 22 per cent of controls (84). Using an ELISA for thyroid microsomal antibodies and the same cut-off level, the proportions were 52 per cent (40) and 39 per cent (149), respectively. While not statistically significant, the differences were consistent with the previously reported increased levels of thyroid antibody found in non-pregnant women who had had pregnancies associated with Down's syndrome.

Antibodies↗