{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T05:40:20Z","timestamp":1760766020687,"version":"build-2065373602"},"reference-count":34,"publisher":"BMJ","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1979,4]]},"abstract":"<jats:p>A review of the data supports the suggestion of Knox (1974) that the sex ratio and incidence of anencephalics vary together within populations, as they are known to do between populations. There seems some doubts, though, whether Knox was correct in hypothesising that the sex ratio of anencephalics varies with their incidence in relation to the dizygotic twinning rate. The pattern of variation seems to suggest that there are two sorts of cause of anencephaly, one of which is environmental and affects predominantly female embryos. The other may be environmental or genetic, and seems to attack the sexes in roughly equal numbers. If this hypothesis were correct, it would carry implications for the testing of specific teratogens.<\/jats:p>","DOI":"10.1136\/jmg.16.2.129","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T14:50:51Z","timestamp":1226328651000},"page":"129-133","source":"Crossref","is-referenced-by-count":32,"title":["The sex ratio in anencephaly."],"prefix":"10.1136","volume":"16","author":[{"given":"W H","family":"James","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1979,4,1]]},"reference":[{"year":"1966","author":"Stevenson","key":"ref_1","unstructured":"Stevenson et al. (1966)"},{"year":"1972","author":"Emanuel","key":"ref_2","unstructured":"Emanuel et al. (1972)"},{"key":"ref_3","unstructured":"The most obvious explanation of such a phenomenon is that some environmental factor causes predominantly female anencephalics, and that another factor affects the sexes almost equally. This latter factor might be genetic or environmental, but, to judge from Fig. 6 of Leck (1972), it seems to be rather evenly distributed across populations. The same Fig. suggests that the environmental factor only operates substantially within Caucasian populations. This presumably is the explanation of the general failure to find environmental variation of anencephaly rates (for example, by season and class) in those populations in which the incidence is low. It is not, I suggest, that low incidence populations can only provide small samples in which, for reasons of statistical power, such variation is not detectable, but that the variation does not exist to a comparable extent in those populations anyway.","article-title":"The most obvious explanation of such a phenomenon is that some environmental factor causes predominantly female anencephalics, and that another factor affects the sexes almost equally. This latter factor might be genetic or environmental, but, to judge from Fig. 6 of Leck (1972), it seems to be rather evenly distributed across populations. The same Fig. suggests that the environmental factor only operates substantially within Caucasian populations. This presumably is the explanation of the general failure to find environmental variation of anencephaly rates (for example, by season and class) in those populations in which the incidence is low. It is not, I suggest, that low incidence populations can only provide small samples in which, for reasons of statistical power, such variation is not detectable, but that the variation does not exist to a comparable extent in those populations anyway"},{"key":"ref_4","article-title":"suggested that the sex ratio of anencephalics is dependent jointly on the incidence of anencephaly and the dizygotic twinning rate. In contrast, I have suggested","volume-title":"that the sex ratio of anencephalics is dependent on the incidence of anencephaly, regardless of the dizygotic twinning rate. The data reviewed above in relation to race and parity seem to favour my formulation rather than Knox's. However, the point could scarcely be regarded as a serious indictment of his hypothesis: doubtless that may be adjusted to accommodate such epidemiological detail. Indeed, I suppose that hypothesis will be tested, not by amassing epidemiological data (which sometimes seem interpretable by a skilled advocate to support any hypothesis), but by work in a pathology laboratory","author":"Knox","year":"1974","unstructured":"Knox (1974) suggested that the sex ratio of anencephalics is dependent jointly on the incidence of anencephaly and the dizygotic twinning rate. In contrast, I have suggested (James, 1979) that the sex ratio of anencephalics is dependent on the incidence of anencephaly, regardless of the dizygotic twinning rate. The data reviewed above in relation to race and parity seem to favour my formulation rather than Knox's. However, the point could scarcely be regarded as a serious indictment of his hypothesis: doubtless that may be adjusted to accommodate such epidemiological detail. Indeed, I suppose that hypothesis will be tested, not by amassing epidemiological data (which sometimes seem interpretable by a skilled advocate to support any hypothesis), but by work in a pathology laboratory."},{"key":"ref_5","article-title":"At present, a woman may avoid a second neural tube defect by the process of amniocentesis and selective abortion, but the fact that defective fetuses can be identified is no reason for relaxing efforts to diminish their incidence. An abortion can never be regarded more favourably than as the lesser of two evils. It seems unlikely that the unfortunate wisdomafter-the-event that followed the potato trials (Lemire","author":"(Knox,","year":"1978","unstructured":"At present, a woman may avoid a second neural tube defect by the process of amniocentesis and selective abortion, but the fact that defective fetuses can be identified is no reason for relaxing efforts to diminish their incidence. An abortion can never be regarded more favourably than as the lesser of two evils. It seems unlikely that the unfortunate wisdomafter-the-event that followed the potato trials (Lemire et al., 1978) will indefinitely deter clinicians from further work in this field. So one may expect, and welcome the possibility, that clinical trials will sooner or later be initiated to test tea (Fedrick, 1974) and tinned meat (Knox, 1972). This being so, there seem two points worth making about the power of trials in this context.","journal-title":"et al; will indefinitely deter clinicians from further work in this field. So one may expect, and welcome the possibility, that clinical trials will sooner or later be initiated to test tea"},{"article-title":"If it were true that only a proportion of anencephalics are caused by environmental agents, then we must recognise the limited power of trials to implicate them, even if they are correctly suspected. It would seem optimistic to expect any identifiable environmental teratogen to cause more than 2 of cases. Let us assume that women are chosen in whom the probability of bearing a case of ASB is 0 05, and that half of them are assigned to an untreated control group, and that the other half are treated, so that their probability of yielding a case is 0-017. The size of each sample, experimental and control, required to stand an 80% chance of detecting this difference at a one-tailed significance level of 5%","year":"1967","key":"ref_6","unstructured":"If it were true that only a proportion of anencephalics are caused by environmental agents, then we must recognise the limited power of trials to implicate them, even if they are correctly suspected. It would seem optimistic to expect any identifiable environmental teratogen to cause more than 2 of cases. Let us assume that women are chosen in whom the probability of bearing a case of ASB is 0 05, and that half of them are assigned to an untreated control group, and that the other half are treated, so that their probability of yielding a case is 0-017. The size of each sample, experimental and control, required to stand an 80% chance of detecting this difference at a one-tailed significance level of 5% is 357 (Snedecor and Cochran, 1967)."},{"key":"ref_7","unstructured":"It might be more realistic to suppose that anencephaly is caused not by one environmental agent but several. Let us assume, for example, that tea caused 1 anencephalic in 5, and tinned meat caused another 1 in 5. It would require experimental and control samples each numbering 5326 to stand an 80 % chance of detecting, at the one-tailed 5 % level of significance, the expected diminution in rate from 5% to 4% after proscribing one of those items. However, it would only require samples of 1187 to detect the expected diminution in rate from 5 % to 3 % after proscribing both. So for practical purposes, it might be more politic to devise, if mothers were willing, a trial in which both items were proscribed.","article-title":"It might be more realistic to suppose that anencephaly is caused not by one environmental agent but several. Let us assume, for example, that tea caused 1 anencephalic in 5, and tinned meat caused another 1 in 5. It would require experimental and control samples each numbering 5326 to stand an 80 % chance of detecting, at the one-tailed 5 % level of significance, the expected diminution in rate from 5% to 4% after proscribing one of those items. However, it would only require samples of 1187 to detect the expected diminution in rate from 5 % to 3 % after proscribing both. So for practical purposes, it might be more politic to devise, if mothers were willing, a trial in which both items were proscribed"},{"key":"ref_8","article-title":"The Biology of Twinning in Man","author":"Bulmer, M.G.","year":"1970","unstructured":"Bulmer, M. G. (1970). The Biology of Twinning in Man. Clarendon Press, Oxford."},{"key":"ref_9","first-page":"174","article-title":"A study of 137 cases of anencephaly","volume":"11","author":"Coffey, V.P.; Jessop, W.J.E.","year":"1957","unstructured":"Coffey, V. P., and Jessop, W. J. E. (1957). A study of 137 cases of anencephaly. British Journal of Preventive and Social Medicine, 11, 174-180.","journal-title":"British Journal of Preventive and Social Medicine"},{"key":"ref_10","first-page":"205","article-title":"Major malformations of the central nervous system in Hungary","volume":"24","author":"Czeizel, A.; Revesz, C.","year":"1970","unstructured":"Czeizel, A., and Revesz, C. (1970). Major malformations of the central nervous system in Hungary. British Journal of Preventive and Social Medicine, 24, 205-222.","journal-title":"British Journal of Preventive and Social Medicine"},{"key":"ref_11","first-page":"22","article-title":"Seasonal variation in anencephalus in Canada","volume":"29","author":"Elwood, J.M.","year":"1975","unstructured":"Elwood, J. M. (1975). Seasonal variation in anencephalus in Canada. British Journal of Preventive and Social Medicine, 29, 22-26.","journal-title":"British Journal of Preventive and Social Medicine"},{"key":"ref_12","first-page":"29","article-title":"Twinning and anencephalus occurrence in relation to fetus-fetus interaction","volume":"30","author":"Elwood, J.M.","year":"1976","unstructured":"Elwood, J. M. (1976). Twinning and anencephalus occurrence in relation to fetus-fetus interaction. British Journal of Preventive and Social Medicine, 30, 29-31.","journal-title":"British Journal of Preventive and Social Medicine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1002\/tera.1420050206","article-title":"The incidence of congenital malformations in a Chinese population: the Taipei Collaborative Study","volume":"5","author":"Emanuel, I.; Huang, S.-W.; Gutman, L.T.; Yu, F.-C.; Lin, C.-C.","year":"1972","unstructured":"Emanuel, I., Huang, S.-W., Gutman, L. T., Yu, F.-C., and Lin, C.-C. (1972). The incidence of congenital malformations in a Chinese population: the Taipei Collaborative Study. Teratology, 5, 159-169.","journal-title":"Teratology"},{"key":"ref_14","first-page":"356","article-title":"Anencephalus and maternal tea drinking: evidence for a possible association","volume":"67","author":"Fedrick, J.","year":"1974","unstructured":"Fedrick, J. (1974). Anencephalus and maternal tea drinking: evidence for a possible association. Proceedings of the Royal Society of MHedicine, 67, 356-360.","journal-title":"Proceedings of the Royal Society of MHedicine"},{"key":"ref_15","article-title":"Genetics and the Epidemiology of Chronic Diseases","volume-title":"US Public Health Service Publication No","author":"Gittelsohn, A.M.; Milham, S.","year":"1965","unstructured":"Gittelsohn, A. M., and Milham, S. (1965). Genetics and the Epidemiology of Chronic Diseases. Ed. by J. V. Neel, M. J. Shaw, and W. J. Schull. US Public Health Service Publication No. 1163, Washington."},{"key":"ref_16","first-page":"174","article-title":"On Edwards' criterion of seasonality and a non-parametric alternative","volume":"25","author":"Hewitt, D.; Milner, J.; Csima, A.; Pakula, A.","year":"1971","unstructured":"Hewitt, D., Milner, J., Csima, A., and Pakula, A. (1971). On Edwards' criterion of seasonality and a non-parametric alternative. British Journal of Preventive and Social Medicine, 25, 174-176.","journal-title":"British Journal of Preventive and Social Medicine"},{"key":"ref_17","article-title":"The sex ratio in anencephaly and spina bifida-a hypothesis. Teratology","author":"James, W.H.","year":"1979","unstructured":"James, W. H. (1979). The sex ratio in anencephaly and spina bifida-a hypothesis. Teratology. (In the press.)"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1093\/oxfordjournals.aje.a112073","article-title":"Female excess in anencephaly and spina bifida: possible gestational influences","volume":"101","author":"Janerich, D.T.","year":"1975","unstructured":"Janerich, D. T. (1975). Female excess in anencephaly and spina bifida: possible gestational influences. American Journal of Epidemiology, 101, 70-76.","journal-title":"American Journal of Epidemiology"},{"key":"ref_19","first-page":"219","article-title":"Anencephalus and dietary intakes","volume":"26","author":"Knox, E.G.","year":"1972","unstructured":"Knox, E. G. (1972). Anencephalus and dietary intakes. British Journal of Preventive and Social Medicine, 26, 219-223.","journal-title":"British Journal of Preventive and Social Medicine"},{"key":"ref_20","first-page":"73","article-title":"Twins and neural tube defects","volume":"28","author":"Knox, E.G.","year":"1974","unstructured":"Knox, E. G. (1974). Twins and neural tube defects. British Journal of Preventive and Social Medicine, 28, 73-80.","journal-title":"British Journal of Preventive and Social Medicine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1002\/tera.1420050305","article-title":"The etiology of human malformations: insights from epidemiology","volume":"5","author":"Leck, 1","year":"1972","unstructured":"Leck, 1. (1972). The etiology of human malformations: insights from epidemiology. Teratology, 5, 303-314.","journal-title":"Teratology"},{"key":"ref_22","first-page":"25","author":"Lemire, R.J.; Beckwith, J.B.; Warkany, J.","year":"1978","unstructured":"Lemire, R. J., Beckwith, J. B., and Warkany, J. (1978). Anencephaly, pp. 25-31. Raven Press, New York.","journal-title":"Anencephaly"},{"key":"ref_23","first-page":"265","article-title":"A note on the sex ratio in anencephalus","volume":"6","author":"MacMahon, B.; McKeown, T.","year":"1952","unstructured":"MacMahon, B., and McKeown, T. (1952). A note on the sex ratio in anencephalus. British Journal ofSocial Medicine, 6, 265-266.","journal-title":"British Journal ofSocial Medicine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1542\/peds.47.3.577","article-title":"Anencephaly and spina bifida in Israel","volume":"47","author":"Naggan, L.","year":"1971","unstructured":"Naggan, L. (1971). Anencephaly and spina bifida in Israel. Pediatrics, 47, 577-586.","journal-title":"Pediatrics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1056\/NEJM196711232772104","article-title":"Ethnic differences in the prevalence of anencephaly and spina bifida in Boston, Massachusetts","volume":"277","author":"Naggan, L.; MacMahon, B.","year":"1967","unstructured":"Naggan, L., and MacMahon, B. (1967). Ethnic differences in the prevalence of anencephaly and spina bifida in Boston, Massachusetts. New England Journal of Medicine, 277, 1119-1123.","journal-title":"New England Journal of Medicine"},{"key":"ref_26","article-title":"Anencephalie in Nederland 1951-68","author":"Overbeke, J.","year":"1971","unstructured":"Overbeke, J. (1971). Anencephalie in Nederland 1951-68. Ph.D. Thesis. University of Leiden, Holland."},{"key":"ref_27","first-page":"183","article-title":"Congenital malformations of the central nervous system","volume":"3","author":"Record, R.G.; McKeown, T.","year":"1949","unstructured":"Record, R. G., and McKeown, T. (1949). Congenital malformations of the central nervous system. British Journal of Social Medicine, 3, 183-219.","journal-title":"British Journal of Social Medicine"},{"key":"ref_28","first-page":"81","article-title":"Anencephalus: a changing sex ratio","volume":"27","author":"Rogers, S.C.; Morris, M.","year":"1973","unstructured":"Rogers, S. C., and Morris, M. (1973). Anencephalus: a changing sex ratio. British Journal of Preventive and Social Medicine, 27, 81-84.","journal-title":"British Journal of Preventive and Social Medicine"},{"key":"ref_29","article-title":"Anencephalus, Spina Bifida and Congenital Hydrocephalus: England and Wales 1964-1972","volume":"32","author":"Rogers, S.C.; Weatherall, J.A.C.","year":"1976","unstructured":"Rogers, S. C., and Weatherall, J. A. C. (1976). Anencephalus, Spina Bifida and Congenital Hydrocephalus: England and Wales 1964-1972. OPCS Studies on Medical and Population Subjects No. 32. HMSO, London.","journal-title":"OPCS Studies on Medical and Population Subjects"},{"key":"ref_30","first-page":"222","article-title":"Statistical Methods","author":"Snedecor, G.W.; Cochran, W.G.","year":"1967","unstructured":"Snedecor, G. W., and Cochran, W. G. (1967). Statistical Methods, 6th ed., p. 222. Iowa State University Press, Iowa.","edition":"6th ed"},{"key":"ref_31","first-page":"316","article-title":"Anencephaly-a five year survey in Cork","volume":"62","author":"Spellman, M.P.","year":"1969","unstructured":"Spellman, M. P. (1969). Anencephaly-a five year survey in Cork. Journal of the Irish Medical Association, 62, 316-320.","journal-title":"Journal of the Irish Medical Association"},{"issue":"9","key":"ref_32","article-title":"Congenital malformations: a report of a study of series of consecutive births in 24 centres","volume":"34","author":"Stevenson, A.C.; Johnston, H.A.; Stewart, M.I.P.; Golding, D.R.","year":"1966","unstructured":"Stevenson, A. C., Johnston, H. A., Stewart, M. I. P., and Golding, D. R. (1966). Congenital malformations: a report of a study of series of consecutive births in 24 centres. Bulletin of the World Health Organization, 34, Suppl. 9.","journal-title":"Bulletin of the World Health Organization"},{"key":"ref_33","first-page":"67","article-title":"Incidence of congenital malformations in the regions of England and Wales","volume":"24","author":"Stocks, P.","year":"1970","unstructured":"Stocks, P. (1970). Incidence of congenital malformations in the regions of England and Wales. British Journal of Preventive and Social Medicine, 24, 67-77.","journal-title":"British Journal of Preventive and Social Medicine"},{"key":"ref_34","first-page":"713","article-title":"Anencephalus in North Carolina: a 25 year experience","volume":"38","author":"Turnbull, C.D.; Scurletis, T.D.; Danielson, A.H.","year":"1977","unstructured":"Turnbull, C. D., Scurletis, T. D., and Danielson, A. H. (1977). Anencephalus in North Carolina: a 25 year experience. 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