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N J Wald

Publications and source records attributed to N J Wald.

At least 109 records · Page 6Linked to original sources
PubMed1996

Blood folic acid and vitamin B12 in relation to neural tube defects.

OBJECTIVE: To determine the relation between blood folic acid and serum vitamin B12 in neural tube defect pregnancies using data from the MRC Vitamin Study and a literature review of all studies. DESIGN: Stored blood samples collected as part of a randomised trial of vitamin supplementation in the prevention of neural tube defects were retrieved from affected pregnancies (cases) and unaffected pregnancies (controls). Four controls were matched with each case by centre, maternal age and duration of storage of the blood sample. The samples had been collected from women at entry to the trial, immediately before the women became pregnant, and at around 12 weeks of pregnancy. Our results were combined with those already published from other studies to obtain an overall assessment of blood folic acid and vitamin B12 in relation to neural tube defects. SETTING: Blood samples were collected as part of the MRC Vitamin Study. The collaborating centres were in the United Kingdom, Hungary, Israel, Australia, Canada and Russia. PARTICIPANTS: Twenty-seven women with neural tube defect pregnancies and 108 matched controls with unaffected pregnancies. RESULTS: Serum and red cell folic acid and serum vitamin B12 levels were lower in the cases than in controls at each of the three occasions when blood samples were collected, but no comparison was significant (P > 0.05). A systematic review of all studies from the literature showed that on average, during the 1st trimester of pregnancy, serum folic acid was 0.6 ng/ml lower in neural tube defect pregnancies (P < 0.01), red cell folic acid was 77 ng/ml lower (P < 0.001) and serum vitamin B12 was 38 ng/l lower (P < 0.001). A logistic regression showed no association between serum B12 and neural tube defects after allowing for serum folic acid. CONCLUSION: our results are consistent with other evidence that folic acid and vitamin B12 levels are lower in women with neural tube defect pregnancies and consistent with evidence from randomised trials which showed that folic acid is protective.

Female↗
PubMed1996

Serum screening for Down's syndrome between 8 and 14 weeks of pregnancy. International Prenatal Screening Research Group.

OBJECTIVE: To determine the value of serum screening for Down's syndrome at 8-14 weeks of pregnancy using seven potential serum markers (alpha-fetoprotein, unconjugated oestriol, total human chorionic gonadotrophin (hCG), free alpha-hCG, free beta-hCG, pregnancy associated plasma protein A (PAPP-A), and dimeric inhibin A). DESIGN: Stored blood samples collected from women at about 10 weeks of pregnancy, prior to having chorionic villus sampling procedure on account of advanced maternal age, were retrieved from pregnancies associated with Down's syndrome and from matched unaffected pregnancies. SETTING: Twenty-one obstetric centres in nine countries. SUBJECTS: Seventy-seven pregnancies associated with Down's syndrome each matched with five controls (except in two cases that were matched with four controls) for maternal age (same five year age groups), duration of storage of the serum sample (same calendar year), and gestational age (usually same week of pregnancy). RESULTS: The levels of two potential markers differed between affected and unaffected pregnancies sufficiently to be of value in screening--free beta-hCG and PAPP-A. The median free beta-hCG level in affected pregnancies was 1.79 times the median level for unaffected pregnancies, and the median PAPP-A level was 0.43 times the normal median. These two markers were combined with maternal age to estimate a woman's risk of having a fetus with Down's syndrome. A screening programme that used a risk cutoff level of 1:300 would detect 63% of affected pregnancies and also classify 5.5% of unaffected pregnancies as screen positive. None of the other five markers added more than 2% detection for the same false-positive rate. CONCLUSION: The performance of screening using maternal age and serum-free beta-hCG and PAPP-A at 10 weeks of pregnancy was better than the double test (alpha-fetoprotein and hCG with maternal age) and similar to the triple test (alpha-fetoprotein, unconjugated oestriol and hCG with maternal age) at 15-22 weeks.

Adult↗
PubMed1996

Empirical validation of risk screening for Down's syndrome.

OBJECTIVE: To validate individual risk estimates in antenatal serum screening for Down's syndrome. METHODS: Women screened for Down's syndrome using maternal serum alpha fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic gonadotrophin (hCG) with maternal age (the triple test) or AFP, uE3, free beta subunit and free alpha subunit of hCG with maternal age (the quadruple test) were grouped according to their predicted risk of having an affected pregnancy. The mean predicted risk in each category was then compared with the observed prevalence based on the number of affected and unaffected pregnancies in each category. SUBJECTS: About 100,000 pregnant women screened for Down's syndrome from 1989 to 1995. RESULTS: There was close agreement between the predicted term risk and the prevalence at birth for both the triple test and the quadruple test. For example, with the quadruple test the predicted risk in the highest risk group was 1 in 3.3 and the prevalence was 1 in 2.6; in the lowest risk group these were 1 in 3000 and 1 in 2300 respectively. CONCLUSION: Risk estimates based on multiple marker screening for Down's syndrome are accurate. The technique used to demonstrate this is simple and offers a useful empirical check on screening performance.

Adult↗
PubMed1995

Mortality in relation to tar yield of cigarettes: a prospective study of four cohorts.

OBJECTIVE: To investigate relation between tar yield of manufactured cigarettes and mortality from smoking related diseases. DESIGN: Prospective epidemiological study of four cohorts of men studied between 1967 and 1982. SETTING: Combined data from British United Provident Association (BUPA) study (London), Whitehall study (London), Paisley-Renfrew study (Scotland), and United Kingdom heart disease prevention project (England and Wales). SUBJECTS: Of the 56,255 men aged over 35 who were included in the studies, 2742 deaths occurred among 12,400 smokers. Average follow up was 13 years. MAIN OUTCOME MEASURES: Relative mortality from smoking related diseases according to tar yields of cigarettes smoked. RESULTS: Age adjusted mortality from smoking related diseases in smokers of filter cigarettes was 9% lower (95% confidence interval 1% to 17%) than in smokers related diseases consistently decreased with decreasing tar yield. Relative mortality in cigarette smokers for a 15 mg decrease in tar yield per cigarette was 0.75 (0.52 to 1.09) for lung cancer, 0.77 (0.61 to 0.97) for coronary heart disease, 0.86 (0.50 to 1.50) for stroke, 0.78 (0.40 to 1.48) for chronic obstructive lung diseases, 0.78 (0.65 to 0.93) for these smoking related diseases combined, and 0.77 (0.65 to 0.90) for all smoking related diseases. CONCLUSION: About a quarter of deaths from lung cancer, coronary heart disease, and possibly other smoking related diseases would have been avoided by lowering tar yield from 30 mg per cigarette to 15 mg. Reducing cigarette tar yields in Britain has had a modest effect in reducing smoking related mortality.

Adult↗
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↗
PubMed1995

UKCCCR multicentre randomised controlled trial of one and two view mammography in breast cancer screening.

OBJECTIVE: To compare one view (oblique) and two view (oblique and craniocaudal) mammography in breast cancer screening. DESIGN: Randomised controlled trial. SETTING: Nine breast screening centres in England. SUBJECTS: 40,163 women aged 50-64 attending their first breast screening examination. INTERVENTIONS: Women were randomised to have one view mammography, two view mammography, or two view mammography in which one view was read by one reader and both views were read by another. MAIN OUTCOME MEASURES: Prevalence of cancer detected, recall rates, cost per cancer detected, and marginal cost per extra cancer detected. RESULTS: Two view mammography detected 24% more women with breast cancer (95% confidence interval 16% to 31%) than one view mammography. Prevalence of detected cancer was 6.84 with two view mammography and 5.52 per 1000 women with one view. The proportion of women recalled for assessment was 15% lower (95% confidence interval 6% to 23%) with two view (6.97%) than with one view (8.16%) mammography. The cost of two view screening was higher (26.46 pounds compared with 22.00 pounds per examination) but the average cost per cancer detected was similar (5330 pounds compared with 5310 pounds) and the marginal cost per extra cancer detected with two views was similar to the average cost (5400 pounds). CONCLUSION: Two view mammography is medically more effective than one view; it detects more cancers and reduces recall rates; it is also similarly cost effective financially.

Breast Neoplasms↗