Maternal serum alpha-fetoprotein and ethnic origin.
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Biomedical subjects
Publications and source records attributed to H S Cuckle.
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The risk of an individual woman having a pregnancy associated with Down's syndrome was estimated from her age and her serum alpha-fetoprotein (AFP) level at 14-20 weeks gestation. The estimates were made using published data on the risk of Down's syndrome in relation to maternal age from 4528 affected and over 5 million unaffected pregnancies, and on the risk in relation to serum AFP from 68 affected and 36,645 unaffected pregnancies. Separate estimates were derived for AFP levels using gestational age based on the time since the first day of the last menstrual period and on an ultrasound biparietal diameter measurement. In each case this was done with and without adjusting AFP levels to take account of maternal weight. The same sources of data were also used to construct six Down's syndrome screening policies, each combining information on maternal age and serum AFP. For example with one policy the detection rate would be 28% and would involve selecting 2.8% of unaffected pregnancies for amniocentesis; using age alone the same detection rate could only be achieved by selecting 4.3% of unaffected pregnancies for amniocentesis--an increase of 50%. In general, screening for Down's syndrome using both maternal age and serum AFP is more efficient than either alone.
The available epidemiological studies of lung cancer and exposure to other people's tobacco smoke, in which exposure was assessed by whether or not a person classified as a non-smoker lived with a smoker, were identified and the results combined. There were 10 case-control studies and three prospective studies. Overall, there was a highly significant 35% increase in the risk of lung cancer among non-smokers living with smokers compared with non-smokers living with non-smokers (relative risk 1.35, 95% confidence interval 1.19 to 1.54). Part of this increase was almost certainly caused by the misclassification of some smokers as non-smokers. As smokers, who are more likely to get lung cancer than non-smokers, tend to live with smokers this misclassification probably exaggerated the estimated increase in risk. Adjustment for this error reduced the estimate to 30% (relative risk 1.30), but as people who live with non-smokers may still be exposed to other people's smoke this estimate was revised again to allow for the fact that a truly unexposed reference group was not used. The increase in risk among non-smokers living with smokers compared with a completely unexposed group was thus estimated as 53% (relative risk of 1.53). This analysis, and the fact that non-smokers breathe environmental tobacco smoke, which contains carcinogens, into their lungs and that the generally accepted view is that there is no safe threshold for the effect of carcinogens, leads to the conclusion that breathing other people's tobacco smoke is a cause of lung cancer. About a third of the cases of lung cancer in non-smokers who live with smokers, and about a quarter of the cases in non-smokers in general, may be attributed to such exposure.
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An enzyme-linked immunosorbent assay (ELISA) was evaluated for serum alpha-fetoprotein determination in the antenatal screening for fetal open neural tube defects. The ELISA was used concurrently with an existing radioimmunoassay (RIA) method until serum specimens from 5000 pregnant women, between 15 and 20 weeks gestation, had been tested. The accuracy of the ELISA was similar to that of the RIA; the median AFP values by gestational week obtained with the ELISA were, on average, 2 KIU/L higher than the corresponding RIA values; the 10th and 90th percentiles, in terms of multiples of the median (MoM), were very similar. The precision of the two methods was also similar. The ELISA method yielded 1.8% results from unaffected pregnancies above 2.5 MoM compared with 1.4% by RIA, a small but statistically significant difference (P = 0.03). Both methods detected the same affected pregnancies identified during this period; five open neural tube defects, three with exomphalos and three intra-uterine deaths. The ELISA method was simple, required about one quarter less operator time than the RIA and enabled results to be generated in one day rather than the two days required by RIA. The ELISA method is a suitable alternative to RIA for routine use in screening for fetal neural tube defects.
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A randomised double blind controlled trial was conducted to see whether vitamin A supplementation in the form of retinyl palmitate would increase the concentrations of serum retinol and retinol binding protein. A total of 376 people were studied and were allocated to one of 7 regimens covering doses of vitamin A from O (placebo) to 36,000 IU daily. Supplementation continued for 6 months and blood samples were collected immediately before the start of supplementation, after 3 months and after 6 months. There was a small but statistically significant increase in serum retinol levels associated with supplementation, but no significant increase in serum retinol binding protein. The extent of the increase in serum retinol was related to the extent of the supplementation. On average, for every 10,000 IU of retinyl palmitate per day, the serum retinol concentration increased by 13 micrograms/l after 3 months (an increase of 2%) and 12 micrograms/l after 6 months of supplementation (2% increase). All the regimens used showed no evidence of toxicity other than minor symptomatic and physical changes affecting the skin and mucous membranes.
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Four hundred forty-seven women attending a breast clinic because of either suspicious lesions, anxiety about breast cancer, follow-up after the removal of a benign breast lesion, or a family history of breast cancer had a routine test for percentage of ferritin-bearing lymphocytes ( FBL ) in their peripheral blood. Among patients who received surgery following physical examination in the clinic and/or mammography, the test was positive in 40 of the 45 (89%) with Stage I;II carcinoma, 3 of 3 with Stage IV carcinoma, and only in 29 of the 97 (37%) with benign breast disease. The possible reasons for the poorer detection rate in Stage III carcinoma are discussed. The test, however, identified 2 cases of Stage I carcinoma, 1 of breast lymphoma, and 12 with premalignant lesions in those who were found normal on physical examination and mammography. Ferritin-bearing lymphocyte results tended to become negative after surgical removal of the lesion, and became positive on recurrence of the tumor and appearance of metastases. The detection rate was maximized by combining the FBL test with the clinical modes of detection.
The median maternal serum alpha-fetoprotein (AFP) level at 14-20 weeks' gestation in 61 pregnancies associated with Down syndrome was 0.72 multiples of the median (MoM) value for a series of 36 652 singleton pregnancies unaffected by Down syndrome or neural-tube defect--a statistically significant reduction. The difference is great enough to form the basis of a screening test. By selecting for amniocentesis women with serum AFP levels less than or equal to 0.5 MoM at 14-20 weeks' gestation (excluding any of these that ultrasound cephalometry shows to have been due to the overestimation of gestational age) 21% of pregnancies with Down syndrome would be identified as well as 5% of unaffected pregnancies. If amniocentesis were offered to all women aged 38 years or more and, in addition, to younger women with serum AFP below specified maternal age-dependent cut-off levels (less than or equal to 1.0 MoM at 37 years, less than or equal to 0.9 at 36, less than or equal to 0.8 at 35, less than or equal to 0.7 at 34, less than or equal to 0.6 at 32-33, less than or equal to 0.5 at 25-31) 40% of pregnancies with Down syndrome and 6.8% unaffected pregnancies would be selected.
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All 103 amniotic fluids with positive gel-acetylcholinesterase (AChE) test results, obtained in Oxford between July 1980 and March 1983, were tested for the presence of fetal calf serum using a counter-immunoelectrophoresis test for bovine serum albumin. None of the samples from pregnancies associated with neural-tube defect (85), exomphalos (nine) and intrauterine death (four) had a positive fetal calf serum test, suggesting little or no immunological cross-reaction between the antiserum used in the test and amniotic fluid proteins. Among the remaining five samples, from unaffected pregnancies (two bloodstained and three clear), two had positive fetal calf serum test results (both were clear samples). The fetal calf serum test is therefore a useful technique capable of identifying false-positive AChE test results, without mis-classifying true-positive results as false-positive.
Amniotic fluid samples from eight pregnancies associated with exomphalos or gastroschisis and 24 with open spina bifida were used to confirm the hypothesis that when the alpha-fetoprotein and gel acetylcholinesterase tests are positive in an amniotic fluid not visibly contaminated with blood, the two defects can be distinguished by scanning densitometry of the electrophoretic gel. The ratio of the density for the acetylcholinesterase band in the gel to that of the pseudocholinesterase band was less than or equal to 0.10 for the open abdominal wall defects and 0.27 or more for open spina bifida. Based on this and a previously reported series, a cut-off level of about 0.15 is suggested.
The estimation of gestational age by "dates" (time since the first day of the last menstrual period) and by means of an ultrasound scan examination (measurement of fetal biparietal diameter) lead to different results when screening for open spina bifida by maternal serum alphafetoprotein (A.F.P.) measurement. This paper provides estimates of the detection rate for open spina bifida, the false positive rate, and the odds of being affected given a positive A.F.P. result when gestational age is estimated according to the two methods. Estimates are also given on the odds of being affected for individuals with a particular serum A.F.P. result. The estimates may be useful to those concerned with the development and design of screening programmes for open spina bifida as well as to clinicians concerned with providing risk estimates for individual patients.