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Biomedical subjects

N J Wald

Publications and source records attributed to N J Wald.

At least 19 recordsLinked to original sources
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

Serum alpha-tocopherol concentration in relation to subsequent colorectal cancer: pooled data from five cohorts.

BACKGROUND: Vitamin E is an antioxidant that inhibits mutagenesis and cell transformation. Previous findings in five prospective epidemiologic studies suggested that the level of serum alpha-tocopherol, the predominant form of vitamin E in the blood, was lower in subjects who subsequently developed colorectal cancer than in control subjects. However, the difference was neither obvious nor statistically significant in any one of these five studies. PURPOSE: To evaluate in greater detail the association between serum alpha-tocopherol concentration and risk of colorectal cancer, we pooled and analyzed the original data from the five studies. Our analyses were designed to (a) test the hypothesis with greater statistical power, (b) examine the association after adjustment for serum cholesterol levels, and (c) evaluate the association after uniform exclusion of cases diagnosed shortly after blood specimens were drawn. METHODS: Data for individual subjects were analyzed. To make the design of the component investigations uniformly nested case-control studies with individual matching, we matched controls to cases in two of the cohorts. Subjects were categorized according to study-specific quartile of serum alpha-tocopherol level within the study. The pooled analysis included 289 cases of colorectal cancer and 1267 matched controls. RESULTS: For cancers of the colon and rectum combined, the matched odds ratio (OR) for the highest quartile of serum alpha-tocopherol concentration compared with the lowest was 0.6 (95% confidence interval [CI] = 0.4-1.0). Adjustment for serum cholesterol level attenuated the OR to 0.7 (95% CI = 0.4-1.1). CONCLUSION: The results suggest that serum alpha-tocopherol concentration may be inversely related to risk of colorectal cancer. It is unclear whether an association exists, however, because the association between serum alpha-tocopherol level and decreased risk of colorectal cancer was modest, the CIs were wide, and, overall, the tests for trend in effect were not significant. IMPLICATIONS: Larger observational studies with concurrent dietary data are needed to determine whether vitamin E has a modest but potentially important protective effect against colorectal cancer.

Adolescent↗
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↗
PubMed1992

Prenatal biochemical screening for Down's syndrome and neural tube defects.

Antenatal serum screening for Down's syndrome is now becoming established in many centers throughout the world. The screening method is based on the measurement of alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin between 15 and 22 weeks of pregnancy. These measurements, used in conjunction with a woman's age, provide risk estimates of having a pregnancy with Down's syndrome for every woman screened. By identifying the 5% of women with highest risk and offering them an amniocentesis, about 60% of Down's syndrome pregnancies can be identified. If an ultrasound scan examination is used routinely to estimate gestational age, the detection rate can be increased by 5% to 10%. Recent information on the distribution of the three serum markers in twin pregnancies and pregnancies with insulin-dependent diabetes mellitus now means that screening can be carried out in such pregnancies. Various other serum markers of Down's syndrome have been reported, but at present they do not have a place in routine antenatal screening for Down's syndrome. The role of amniotic fluid acetylcholinesterase measurement, alone and in combination with amniotic fluid alpha-fetoprotein measurement, in the antenatal diagnosis of open neural tube defects has recently been clarified. The best policy is to perform an amniotic fluid alpha-fetoprotein measurement as the primary test and an acetylcholinesterase determination for those women who have an amniotic fluid alpha-fetoprotein measurement of two times the normal median or greater. The acetylcholinesterase can be measured either by the standard method (gel electrophoresis) or by a new quantitative monoclonal antibody method.

Acetylcholinesterase↗
PubMed1992

Effect of sample storage on the assay of lipoprotein(a) by commercially available radial immunodiffusion and enzyme-linked immunosorbent assay kits.

Lipoprotein(a) [Lp(a)] was measured by both a radial immunodiffusion (RID) kit from Immuno AG (Zurich, Switzerland) and a Tint Elize enzyme-linked immunosorbent assay (ELISA) kit from CytRx Biopool Ltd. (Umeå, Sweden) in serum samples that had been stored at -20 and -70 degrees C for six months. Storage temperature had no significant effect on the Lp(a) concentrations obtained by either method. After six months, mean Lp(a) degradation was 46% (95% confidence interval, 34-58%) with the RID kit; the ELISA data could not be compared between time points. In fresh sera, Lp(a) concentrations obtained by RID were 41% higher than by ELISA (because of differences in assay calibration materials), but in paired measurements of a set of 215 samples stored at -40 degrees C for an average of 10 years, Lp(a) concentrations were 62% lower by RID. This suggests that RID is more sensitive to the effects of long-term storage than is ELISA.

Drug Stability↗
PubMed1991

By how much does dietary salt reduction lower blood pressure? I--Analysis of observational data among populations.

OBJECTIVE: To estimate the quantitative relation between blood pressure and sodium intake. DESIGN: Data were analysed from published reports of blood pressure and sodium intake for 24 different communities (47 000 people) throughout the world. MAIN OUTCOME MEASURE: Difference in blood pressure for a 100 mmol/24 h difference in sodium intake. Allowance was made for differences in blood pressure between economically developed and undeveloped communities to minimise overestimation of the association through confounding with other determinants of blood pressure. RESULTS: Blood pressure was higher on average in the developed communities, but the association with sodium intake was similar in both types of community. A difference in sodium intake of 100 mmol/24 h was associated with an average difference in systolic blood pressure that ranged from 5 mm Hg at age 15-19 years to 10 mm Hg at age 60-69. The differences in diastolic blood pressure were about half as great. The standard deviation of blood pressure increased with sodium intake implying that the association of blood pressure with sodium intake in individuals was related to the initial blood pressure--the higher the blood pressure the greater the expected reduction in blood pressure for the same reduction in sodium intake. For example, at age 60-69 the estimated systolic blood pressure reduction in response to a 100 mmol/24 h reduction in sodium intake was on average 10 mm Hg but varied from 6 mm Hg for those on the fifth blood pressure centile to 15 mm Hg for those on the 95th centile. CONCLUSIONS: The association of blood pressure with sodium intake is substantially larger than is generally appreciated and increases with age and initial blood pressure.

Adolescent↗
PubMed1991

By how much does dietary salt reduction lower blood pressure? II--Analysis of observational data within populations.

OBJECTIVE: To determine whether the estimates of the size of the association between blood pressure and sodium intake derived from studies of individuals within populations can be quantitatively reconciled with our estimates derived from comparisons of the average blood pressure and sodium intake between different populations. DESIGN: Examination of data from 14 published studies that correlated blood pressure recordings in individuals against measurements of their 24 hour sodium intake (within population studies). MAIN OUTCOME MEASURE: Comparison of observed differences in blood pressure per 100 mmol/24 h difference in sodium intake in each within population study with predicted differences calculated from the between population data, after allowing for the underestimation of the true association of blood pressure with sodium intake caused by the large day to day variation in 24 hour sodium intake within individuals. RESULTS: The underestimation bias inherent in the within populations studies reduced the regression slope of blood pressure on single measures of 24 hour sodium intake to between a half and a quarter of the true value (for example, in one study from 6.0 to 2.4 mm Hg/100 mmol/24 h). Estimates from between population comparisons of the regression slope of blood pressure on sodium intake, after adjustment to take this underestimation bias into account, were similar to the values actually observed in the within population studies. CONCLUSION: The within population studies confirm our estimates from between population comparisons of the magnitude of the association between blood pressure and sodium intake.

Adolescent↗
PubMed1991

By how much does dietary salt reduction lower blood pressure? III--Analysis of data from trials of salt reduction.

OBJECTIVE: To determine whether the reduction in blood pressure achieved in trials of dietary salt reduction is quantitatively consistent with estimates derived from blood pressure and sodium intake in different populations, and, if so, to estimate the impact of reducing dietary salt on mortality from stroke and ischaemic heart disease. DESIGN: Analysis of the results of 68 crossover trials and 10 randomised controlled trials of dietary salt reduction. MAIN OUTCOME MEASURE: Comparison of observed reductions in systolic blood pressure for each trial with predicted values calculated from between population analysis. RESULTS: In the 45 trials in which salt reduction lasted four weeks or less the observed reductions in blood pressure were less than those predicted, with the difference between observed and predicted reductions being greatest in the trials of shortest duration. In the 33 trials lasting five weeks or longer the predicted reductions in individual trials closely matched a wide range of observed reductions. This applied for all age groups and for people with both high and normal levels of blood pressure. In people aged 50-59 years a reduction in daily sodium intake of 50 mmol (about 3 g of salt), attainable by moderate dietary salt reduction would, after a few weeks, lower systolic blood pressure by an average of 5 mm Hg, and by 7 mm Hg in those with high blood pressure (170 mm Hg); diastolic blood pressure would be lowered by about half as much. It is estimated that such a reduction in salt intake by a whole Western population would reduce the incidence of stroke by 22% and of ischaemic heart disease by 16% [corrected]. CONCLUSIONS: The results from the trials support the estimates from the observational data in the accompanying two papers. The effect of universal moderate dietary salt reduction on mortality from stroke and ischaemic heart disease would be substantial--larger, indeed, than could be achieved by fully implementing recommended policy for treating high blood pressure with drugs. However, reduction also in the amount of salt added to processed foods would lower blood pressure by at least twice as much and prevent some 75,000 [corrected] deaths a year in Britain as well as much disability.

Adult↗
PubMed1991

A case-control study of dietary carotene in men with lung cancer and in men with other epithelial cancers.

Dietary carotene intake during the year before diagnosis was estimated for 96 men with lung cancer, 75 men with other epithelial cancers, and 97 hospital controls. Relative to those of men in the lowest third of carotene intake (less than 1,683 micrograms/day), the smoking-adjusted odds ratios for men in the middle (1,683-2,698 micrograms/day) and upper (greater than 2,698 micrograms/day) thirds of carotene intake were 0.67 and 0.45, respectively, for lung cancer (one-sided test for trend, p = 0.048) and 0.63 and 0.65, respectively, for other epithelial cancers (one-sided test for trend p = 0.074). The protective effect of estimated dietary carotene intake was considerably stronger than was the effect of total intake of carotene-rich vegetables and fruits (grams per day), providing some evidence that the protective factor is carotene itself rather than another component of vegetables and fruits.

Aged↗
PubMed1991

Cotinine-assisted intervention in pregnancy to reduce smoking and low birthweight delivery.

OBJECTIVE: To investigate the feasibility and impact of integrating a cotinine-assisted smoking intervention programme with an existing antenatal maternal serum alpha-fetoprotein (AFP) screening service for open neural tube defects. DESIGN: A multisite randomized controlled trial. SETTING: 139 physician offices and clinic sites in Maine providing antenatal care. SUBJECTS: 2848 pregnant women who smoked 10 or more cigarettes daily, enrolled at between 15 and 20 weeks gestation, from a population base of approximately 18,000 pregnancies. INTERVENTIONS: The women were individually allocated at random to intervention or control groups within each centre at the time the serum sample was received for AFP measurement. The intervention group received an interpreted measurement of the serum cotinine, reported through the physician to the woman, along with a self-help smoking cessation booklet and a repeat serum cotinine measurement one month later, again interpreted and reported through the physician to the woman. Women in the control group received the usual anti-smoking advice provided by the antenatal care site and were not told of the study. MAIN OUTCOME MEASURES: Birthweight, physician cooperation with study protocol (as measured by effectiveness in obtaining repeat serum samples for cotinine measurements). RESULTS: Pregnancy outcome data were available for 97% of the study population, including birthweight for 2700 singleton viable pregnancies. The smoking intervention programme led to a significant 66 g increase in mean birthweight (P = 0.03; 95% CI+9 to +123 g) and to a 30% reduction in the rate of low birthweight in pregnancies managed by the 70 physicians who secured the highest rate of obtaining repeat serum samples for cotinine measurements in their intervention group. Among the remaining 69 physicians, intervention had no detectable effect on birthweight. CONCLUSION: A cotinine-assisted smoking intervention programme managed from a central location as an adjunct to a maternal serum AFP screening service can, with the cooperation of physicians responsible for antenatal care, lead to a significant and cost-effective reduction in the number of low birthweight babies. This programme is inexpensive, requires little extra effort, and does not need specially trained personnel.

Adult↗
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↗
PubMed1991

Dietary salt and blood pressure.

We have previously shown that the association between salt intake and blood pressure is large and of substantial public health importance. Analysis of the average blood pressure and average sodium intake in different communities yielded estimates of the decrease in blood pressure for a given reduction in dietary sodium according to age and blood pressure centile that successfully predicted both the association between sodium and blood pressure in observational studies and the reduction in blood pressure obtained in trials of dietary salt reduction. Here we consider the validity of criticisms of the appraisal. The fact that the observed blood pressure reductions in individual trials closely mirrored predicted values for individuals trials that varied widely (from 2.6 to 25.2 mmHg systolic according to age, existing blood pressure and the extent of salt restriction) renders bias implausible since it would be too great a coincidence for a source of error to reproduce such close matching. If the analysis is restricted to trials that avoided possible bias because (1) the high- and low-salt diets were otherwise identical, (2) the order of the diet avoided regression to the mean or (3) the trials were double-blind with diets that were otherwise identical and the order was random, the matching between observed and predicted blood pressure reductions is equally close. Our results are consistent with the Intersalt study. A reduction in dietary salt could be a simple change, yet the reduction in mortality would be large.

Adolescent↗
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↗