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ASSESSMENT OF GESTATIONAL AGE FROM AMNIOTIC FLUID
493
Study suggesting increased cardiovascular disease in diabetics treated with insulin injections compared with
ONCOGENICITY OF IMMUNOSUPPRESSIVE DRUGS
ham
other forms of treatment." Other retrospective studies have not shown any deleterious effect of oral antidiabetic
drugs.12. 13 One cannot recommend the suppression of free exchange of information on this important issue, but it is to be hoped that the scene will not be filled with conflicting and selective results of uncontrolled studies. As the prospective studies differ in their results, it seems unlikely that retrospective analyses will contribute much to the debate. Department of Medicine, Guy’s Hospital Medical School, London S.E.1.
R. J. JARRETT H. KEEN.
ASSESSMENT OF GESTATIONAL AGE FROM AMNIOTIC FLUID
SIR,-In your editorial (Jan. 15, p. 132) you state that estimation of gestational age from amniotic fluid is accurate. You suggest that the biochemical and cytological features may reflect the physiological maturity rather than the age of the fetus and that predictions are apparently no less accurate in the presence of retarded fetal growth. This is not correct.
Of the several biochemical and cytological methods of amniotic-fluid examination for the estimation of fetal maturity evaluated in 1969 by Droegemuller and associates,14 creatinine content was then held to provide the most reliable index. A later study from Manchester 15 revealed that amniotic-fluid creatinine concentration is not a reliable index of maturity if the fetus is small for gestational age. While low creatinine values are indicative of prematurity when fetal growth is normal, such values may be associated with maturity when fetal growth is retarded. The weight a baby attains relative to the duration of gestation is variable and, in one series, one-third of lowbirth-weight infants were, in fact, not premature infants but term infants with intrauterine growth retardation.ls In cases of retarded intrauterine growth, the fetus is small
SiR,—Iam puzzled by Dr. McEwan and Dr. Petty’ss letter (Feb. 5, p. 326) and their assertion that Casey did not use cyclophosphamide in his experiments on the New Zealand black and white hybrid mice. Certainly he did not in the work reported in the paper they refer to1 but certainly he did in the work reported in the paper that I (Nov. 13, p. 1096) referred to.2 After reporting the absence of carcinogenic effects in young and old NZB x NZW hybrid mice treated long-term with cyclophosphamide (in contrast to his earlier experience with azathioprine), Casey drew attention to " the prospect of using these mice to study the carcinogenic effects of antimitotic drugs with particular reference to the effects of such drugs on immune mechanisms ". WB Pharmaceuticals Limited, Fulton House, Empire Way, J. M. SIMISTER, Wembley, Middlesex, HA9 0LX.
Medical Director.
* ** Dr. Simister sent a copy of his letter to Dr. Petty, who asks us to publish the following reply.-ED. L. SIR,-We must apologise to Dr. Simister for the unintentional slur on his integrity arising from inadequate attention on our part to his reference, and hope that the occurrence of the papers concerned in the same journal within the same year will allow the error to be understandable, even if unpardonable. However, we do not feel that the validity of our arguments is affected and would draw attention to the recent report3 of an augmented incidence of neoplasia in female NZB/ NZW mice treated with long-term cyclophosphamide. Burroughs Wellcome and Co. (U.K.) Ltd., Dartford, Kent. Department of Clinical Immunology, Wellcome Research Laboratories, Beckenham, Kent.
L. G. PETTY.
A. L. WEINBERG.
and malnourished ; it fails to grow with continuing pregnancy and may die before delivery. Premature induction of labour in suspected cases is hazardous if the duration of gestation is uncertain owing to unreliable menstrual data, because it could result in the delivery of a truly immature baby. How are these two classes of low-weight babies in utero to be distinguished ? What is required is ani ndex of fetal lung maturity so that the risk of respiratory distress syndrome, the principal cause for failure of immature infants to survive, can be assessed. Thus the potential usefulness of amniotic-fluid creatinine, which may be an index of fetal glomerular filtration-rate, has been superseded by the reports from Cardiff (Jan. 22, p. 159) and Leeds (Feb. 5, p. 321) on measurement of amniotic-fluid lecithin. Both reports suggest that lecithin concentration in the amniotic fluid is an index of fetal lung maturity and, consequently, of the potential risk of respiratory distress developing in the
SIR,-Although Dr. Wilson (Feb. 12, p. 381) points out that data from the Hospital Inpatient Enquiry has been used in the way I suggested (Jan. 29, p. 259), the use of this data in fact fell short of my suggestions in two fundamental respects. Firstly, information about patients’ occupations obtained in hospital cannot be reliably used to code social class. Patients’ occupations are often described in hospital notes in such vague terms as " Civil Servant ", or " engineer ", or " company director ", and such descriptions are too imprecise to be coded. Furthermore, accurate social-class coding requires information about employment status-whether employed or self-employed-and degree of responsibility held. None of this information is, at present, obtained in hospital routinely. Secondly, I suggested that all hospital patients should be included, not merely in-
baby.
patients.
University Department of Obstetrics and Gynæcology, Manchester M13 9PL.
W. M. O. MOORE.
Garcia, M. Proceedings of the 2nd Conference on Early Diabetes, 1972 (in the press). 12. Constam, G. R. Diabetologia, 1971, 7, 237. 13. Balodimos, M. C., Gleason, R. E., Bradley, R. F., Marble, A. in Tolbutamide after Ten Years. Int. Congr. Ser., Excerpta Med. Found. 1967, no. 149, p. 270. 14. Droegemueller, W., Jackson, C., Makowski, E. L., Battaglia, F. C. Am. J. Obstet. Gynec. 1969, 104, 424. 15. Moore, W. M. O., Murphy, P. J., Davis, J. A. ibid. 1971, 110, 908. 16. Gruenwald, P. Pediatrics, 1964, 34, 157. 11.
MORTALITY AND MORBIDITY IN RELATION TO SOCIAL CLASS
The reasons why a smaller proportion of the population recorded in social class v in 1961 compared with 1951 are complex. Part of the answer is probably due to error in the 1961 sample census, which over-represented class I by about 6%, and due to movement by people out of class v into higher social classes. However, this does not alter the conclusion that those people in social class v in 1961 are dying at nearly twice the rate of those people in were
Casey, T. P. Blood, 1968, 31, 396. Casey, T. P. ibid. 1968, 32, 436. 3. Walker, S. E., Bole, G. G. J. Lab. clin. Med. 1971, 78, 978. 1. 2.
Study suggesting increased cardiovascular disease in diabetics treated with insulin injections compared with
ONCOGENICITY OF IMMUNOSUPPRESSIVE DRUGS
ham
other forms of treatment." Other retrospective studies have not shown any deleterious effect of oral antidiabetic
drugs.12. 13 One cannot recommend the suppression of free exchange of information on this important issue, but it is to be hoped that the scene will not be filled with conflicting and selective results of uncontrolled studies. As the prospective studies differ in their results, it seems unlikely that retrospective analyses will contribute much to the debate. Department of Medicine, Guy’s Hospital Medical School, London S.E.1.
R. J. JARRETT H. KEEN.
ASSESSMENT OF GESTATIONAL AGE FROM AMNIOTIC FLUID
SIR,-In your editorial (Jan. 15, p. 132) you state that estimation of gestational age from amniotic fluid is accurate. You suggest that the biochemical and cytological features may reflect the physiological maturity rather than the age of the fetus and that predictions are apparently no less accurate in the presence of retarded fetal growth. This is not correct.
Of the several biochemical and cytological methods of amniotic-fluid examination for the estimation of fetal maturity evaluated in 1969 by Droegemuller and associates,14 creatinine content was then held to provide the most reliable index. A later study from Manchester 15 revealed that amniotic-fluid creatinine concentration is not a reliable index of maturity if the fetus is small for gestational age. While low creatinine values are indicative of prematurity when fetal growth is normal, such values may be associated with maturity when fetal growth is retarded. The weight a baby attains relative to the duration of gestation is variable and, in one series, one-third of lowbirth-weight infants were, in fact, not premature infants but term infants with intrauterine growth retardation.ls In cases of retarded intrauterine growth, the fetus is small
SiR,—Iam puzzled by Dr. McEwan and Dr. Petty’ss letter (Feb. 5, p. 326) and their assertion that Casey did not use cyclophosphamide in his experiments on the New Zealand black and white hybrid mice. Certainly he did not in the work reported in the paper they refer to1 but certainly he did in the work reported in the paper that I (Nov. 13, p. 1096) referred to.2 After reporting the absence of carcinogenic effects in young and old NZB x NZW hybrid mice treated long-term with cyclophosphamide (in contrast to his earlier experience with azathioprine), Casey drew attention to " the prospect of using these mice to study the carcinogenic effects of antimitotic drugs with particular reference to the effects of such drugs on immune mechanisms ". WB Pharmaceuticals Limited, Fulton House, Empire Way, J. M. SIMISTER, Wembley, Middlesex, HA9 0LX.
Medical Director.
* ** Dr. Simister sent a copy of his letter to Dr. Petty, who asks us to publish the following reply.-ED. L. SIR,-We must apologise to Dr. Simister for the unintentional slur on his integrity arising from inadequate attention on our part to his reference, and hope that the occurrence of the papers concerned in the same journal within the same year will allow the error to be understandable, even if unpardonable. However, we do not feel that the validity of our arguments is affected and would draw attention to the recent report3 of an augmented incidence of neoplasia in female NZB/ NZW mice treated with long-term cyclophosphamide. Burroughs Wellcome and Co. (U.K.) Ltd., Dartford, Kent. Department of Clinical Immunology, Wellcome Research Laboratories, Beckenham, Kent.
L. G. PETTY.
A. L. WEINBERG.
and malnourished ; it fails to grow with continuing pregnancy and may die before delivery. Premature induction of labour in suspected cases is hazardous if the duration of gestation is uncertain owing to unreliable menstrual data, because it could result in the delivery of a truly immature baby. How are these two classes of low-weight babies in utero to be distinguished ? What is required is ani ndex of fetal lung maturity so that the risk of respiratory distress syndrome, the principal cause for failure of immature infants to survive, can be assessed. Thus the potential usefulness of amniotic-fluid creatinine, which may be an index of fetal glomerular filtration-rate, has been superseded by the reports from Cardiff (Jan. 22, p. 159) and Leeds (Feb. 5, p. 321) on measurement of amniotic-fluid lecithin. Both reports suggest that lecithin concentration in the amniotic fluid is an index of fetal lung maturity and, consequently, of the potential risk of respiratory distress developing in the
SIR,-Although Dr. Wilson (Feb. 12, p. 381) points out that data from the Hospital Inpatient Enquiry has been used in the way I suggested (Jan. 29, p. 259), the use of this data in fact fell short of my suggestions in two fundamental respects. Firstly, information about patients’ occupations obtained in hospital cannot be reliably used to code social class. Patients’ occupations are often described in hospital notes in such vague terms as " Civil Servant ", or " engineer ", or " company director ", and such descriptions are too imprecise to be coded. Furthermore, accurate social-class coding requires information about employment status-whether employed or self-employed-and degree of responsibility held. None of this information is, at present, obtained in hospital routinely. Secondly, I suggested that all hospital patients should be included, not merely in-
baby.
patients.
University Department of Obstetrics and Gynæcology, Manchester M13 9PL.
W. M. O. MOORE.
Garcia, M. Proceedings of the 2nd Conference on Early Diabetes, 1972 (in the press). 12. Constam, G. R. Diabetologia, 1971, 7, 237. 13. Balodimos, M. C., Gleason, R. E., Bradley, R. F., Marble, A. in Tolbutamide after Ten Years. Int. Congr. Ser., Excerpta Med. Found. 1967, no. 149, p. 270. 14. Droegemueller, W., Jackson, C., Makowski, E. L., Battaglia, F. C. Am. J. Obstet. Gynec. 1969, 104, 424. 15. Moore, W. M. O., Murphy, P. J., Davis, J. A. ibid. 1971, 110, 908. 16. Gruenwald, P. Pediatrics, 1964, 34, 157. 11.
MORTALITY AND MORBIDITY IN RELATION TO SOCIAL CLASS
The reasons why a smaller proportion of the population recorded in social class v in 1961 compared with 1951 are complex. Part of the answer is probably due to error in the 1961 sample census, which over-represented class I by about 6%, and due to movement by people out of class v into higher social classes. However, this does not alter the conclusion that those people in social class v in 1961 are dying at nearly twice the rate of those people in were
Casey, T. P. Blood, 1968, 31, 396. Casey, T. P. ibid. 1968, 32, 436. 3. Walker, S. E., Bole, G. G. J. Lab. clin. Med. 1971, 78, 978. 1. 2.