213 at the end of the first month after conception. The infant was born with a thoracolumbar meningomyelocele. The second mother had had influenza for 7 days during the third and fourth weeks after conception with fever that peaked at 40°C. The pregnancy resultedin a child with a nasal encephalocele. A third instance of maternal hyperthermia resulted from sauna usage of 45 min duration on four occasions during the fifth week after conception. On one of these occasions the temperature of the sauna rose to 43 °C. The infant was born with a posterior encephalocele and a meningocele. The control group for this study came from two different sources. Since only 20 matched controls could be obtained (friends or neighbours pregnant at the same time as the mothers of the babies with neural-tube defects), another 28 controls were obtained from a group of women who were in the City of Memphis Hospital after giving birth to normal babies. 1 mother of the 48 controls had had hyperthermia due to pelvic inflammatory disease, but this had been during the sixth week after conception, well after the expected date of closure of the neural tube. Our findings support those of Smith and his colleagues (7 instances of hyperthermia in 63 mothers of infants with anencephalyl and 3 of hyperthermia in 43 mothers of infants with meningomyelocele.2 We suggest that hyperthermia lowers the threshold for the expression of these polygenically inherited neural tube defects. A thorough prospective evaluation of maternal hyperthermia and neural-tube defects is needed.
pharyngitis
,
Department of Pediatrics,
University of
Tennessee Center for the Health Services, Memphis, Tennessee 38163, U.S.A.
LINDA RUTH HALPERIN ROBERT S. WILROY, JR
MATERNAL AGE AND DOWN SYNDROME
SIR,-Substantial data
the maternal-age-specific incidence of Down syndrome and other chromosome aberrations derived from the results of prenatal diagnosis were presented at the 3rd European Prenatal Diagnosis Conference held in Munich in April, 1978. Over thirty centres in Europe (and one in Israel) contributed results from 16 273 pregnancies tested in women 35 years of age and over. On average, the rates for Down syndrome in these pregnancies are 33% above the rates determined from live births. This effect is seen at all maternal ages above 35 years and not just in the 40-44 year old mothers as suggested in your editorial of July 1. In fact, the major effect is seen in the 35-39 year age-group where the rate of 0.84% is 37% above the expected rate; at 40-44 and 45-49 years the rates are 2.31% and 4.87%, respectively, and the increases over the expected rate are 33% and 26%. (In these calculations the maternal age is the age at delivery and not the age at amniocentesis.) These figures show that earlier reports2-4 on the discrepancy between prenatal and postnatal rates were not just chance observations in small samples. Up to two-thirds of the discrepancy may be attributable to fetal loss between 16 weeks’ gestation and term, and some may be due to the selection of older mothers for amniocentesis for reasons other than maternal age.4 An important possibility mentioned in your editorial which has not been sufficiently emphasised in the past, is that the age-specific incidence may have been increasing,56 the effect being most marked in the 35-39 year age-group.? The New York studyl appears to be the most up-to-date live-birth study and this relates to births in 1963-74, whereas most of on
the amniocentesis data have been obtained in 1976-77 and almost all since 1974. Prenatal rates for chromosome aberrations may thus reflect current postnatal rates more closely than is generally supposed. There was much discussion in your correspondence columns of June 17 about which risk to quote to the older mother con-
templating prenatal diagnosis. Epidemiologists seem to prefer to use the risk of the birth of an affected living child, on the grounds of burden to the family and community. However, the parental distress associated with late abortion and stillbirth must not be discounted. Genetic counsellors appreciate that parents want to take account of all the facts. Ideally, these should include up-to-date prenatal and postnatal rates for both Down syndrome and all other chromosome aberrations. With the increasing use of prenatal diagnosis it will soon be difficult to obtain accurate postnatal rates and it may be that the best estimate of this will be the prenatal rate suitably corrected for fetal loss between 16 weeks and term. Maternal-age-specific rates for chromosome aberrations other than Down syndrome are not available from live birth studies, but the Munich data show that they add about 1% to the prenatal rate calculated for Down syndrome in women 35 years of age and over. It seems likely that many obstetricians are deterred from offering amniocentesis to their patients in the 35-39 years age group because they use obsolete and incomplete information and believe the risk of a fetal chromosome abnormality may not be sufficiently different from the risk of fetal loss after amniocentesis to justify the procedure. It would be preferable if all older mothers in need of pre-amniocentesis counselling were given the current age-specific prenatal rates for chromosome
aberrations and
1976, ii, 516. 5. Mikkelsen, M., Fischer, G., Stene, J., Stene, E., Petersen, E. Ann. hum. Genet. 1976, 40, 177. 6. Holloway, S., Emery, A. E. H.J. biosoc. Sci. 1977, 9, 453. 7. Evans, J. A., Hunter, A. G. W., Hamerton, J. L. J. med. Genet. 1978, 15, 43.
advised that up
to
20% of abnormal
research into the maternal-age-specific incidence of chromosome aberrations in late abortions and stillbirths. Department of Medical Genetics, Royal Hospital for Sick Children, Glasgow G3 8SJ
M. A. FERGUSON-SMITH
TREATMENT OF PAGET’S DISEASE
SIR,-Recent letters have raised some important points conthe treatment of Paget’s disease. Professor Milhaud’ advocates a very-low-dose regimen of (porcine) calcitonin which has given favourable therapeutic results. We agree that small doses of calcitonin may relieve pain in some cases of Paget’s disease and that the ideal dosage scheme remains to be established. However, it is clear that higher doses of calcitonin are required to heal the bones in the osteolytic phase of the disease, and low doses cannot be recommended in this situation since they are insufficient to check the advance of the resorptive process. 2-4 Dr Hamdy5 states that the main aim of treating Paget’s disease is to prevent complications and believes that pagetic pain usually responds to ordinary analgesics. Our experience is different. Simple analgesics may relieve mild pagetic pain but are ineffective in the more severe cases. We have seen many patients with frankly pagetic pain (i.e., not associated with concomitant osteoarthritis) who have gained pain relief with calcitonin after conventional analgesics had proved completely ineffective.
cerning
Endocrine Unit,
Royal Postgraduate Medical School, London W12 0HS
1. Hook, E., Chambers, G. C. Birth Defects orig. Art. Ser. 1977, 13 (3A), 123. 2. Ferguson-Smith, M. A. Lancet, 1976, ii, 252. 3. Ferguson-Smith, M. A., Ferguson-Smith, M. E. in Prenatal Diagnosis (edited by A. Boué); p. 81. INSERM, Paris, 1976. 4. Polani, P. E., Alberman, E., Berry, A. C., Blunt, S., Singer, J. D. Lancet,
were
conceptions might be lost between 16 weeks and term. Improvement in this advice can only come from more detailed
IMOGEN M. A. EVANS I. MACINTYRE
Milhaud, G. Lancet, 1978, i, 1153. Doyle, F. H., Pennock, J., Greenberg, P. B., Joplin, G. F., MacIntyre, I. in Endocrinology 1973 (edited by S. Taylor); p. 425. London, 1974. 3. Evans, I. M. A., Doyle, F. H., Banks, L., Pennock, J., Joplin, G. F., MacIn-
1. 2.
tyre, I. in Molecular Endocrinology (edited by I. Maclntyre and M. Szelke); p. 235. Amsterdam, 1977. 4. Nagant de Deuxchaisnes, C., Rombauts-Lindemans, C., Huaux, J. P., Malghem, J., Laldague, B. ibid. p. 213. 5. Hamdy, R. Lancet, 1978, i, 1267.
pharyngitis
,
Department of Pediatrics,
University of
Tennessee Center for the Health Services, Memphis, Tennessee 38163, U.S.A.
LINDA RUTH HALPERIN ROBERT S. WILROY, JR
MATERNAL AGE AND DOWN SYNDROME
SIR,-Substantial data
the maternal-age-specific incidence of Down syndrome and other chromosome aberrations derived from the results of prenatal diagnosis were presented at the 3rd European Prenatal Diagnosis Conference held in Munich in April, 1978. Over thirty centres in Europe (and one in Israel) contributed results from 16 273 pregnancies tested in women 35 years of age and over. On average, the rates for Down syndrome in these pregnancies are 33% above the rates determined from live births. This effect is seen at all maternal ages above 35 years and not just in the 40-44 year old mothers as suggested in your editorial of July 1. In fact, the major effect is seen in the 35-39 year age-group where the rate of 0.84% is 37% above the expected rate; at 40-44 and 45-49 years the rates are 2.31% and 4.87%, respectively, and the increases over the expected rate are 33% and 26%. (In these calculations the maternal age is the age at delivery and not the age at amniocentesis.) These figures show that earlier reports2-4 on the discrepancy between prenatal and postnatal rates were not just chance observations in small samples. Up to two-thirds of the discrepancy may be attributable to fetal loss between 16 weeks’ gestation and term, and some may be due to the selection of older mothers for amniocentesis for reasons other than maternal age.4 An important possibility mentioned in your editorial which has not been sufficiently emphasised in the past, is that the age-specific incidence may have been increasing,56 the effect being most marked in the 35-39 year age-group.? The New York studyl appears to be the most up-to-date live-birth study and this relates to births in 1963-74, whereas most of on
the amniocentesis data have been obtained in 1976-77 and almost all since 1974. Prenatal rates for chromosome aberrations may thus reflect current postnatal rates more closely than is generally supposed. There was much discussion in your correspondence columns of June 17 about which risk to quote to the older mother con-
templating prenatal diagnosis. Epidemiologists seem to prefer to use the risk of the birth of an affected living child, on the grounds of burden to the family and community. However, the parental distress associated with late abortion and stillbirth must not be discounted. Genetic counsellors appreciate that parents want to take account of all the facts. Ideally, these should include up-to-date prenatal and postnatal rates for both Down syndrome and all other chromosome aberrations. With the increasing use of prenatal diagnosis it will soon be difficult to obtain accurate postnatal rates and it may be that the best estimate of this will be the prenatal rate suitably corrected for fetal loss between 16 weeks and term. Maternal-age-specific rates for chromosome aberrations other than Down syndrome are not available from live birth studies, but the Munich data show that they add about 1% to the prenatal rate calculated for Down syndrome in women 35 years of age and over. It seems likely that many obstetricians are deterred from offering amniocentesis to their patients in the 35-39 years age group because they use obsolete and incomplete information and believe the risk of a fetal chromosome abnormality may not be sufficiently different from the risk of fetal loss after amniocentesis to justify the procedure. It would be preferable if all older mothers in need of pre-amniocentesis counselling were given the current age-specific prenatal rates for chromosome
aberrations and
1976, ii, 516. 5. Mikkelsen, M., Fischer, G., Stene, J., Stene, E., Petersen, E. Ann. hum. Genet. 1976, 40, 177. 6. Holloway, S., Emery, A. E. H.J. biosoc. Sci. 1977, 9, 453. 7. Evans, J. A., Hunter, A. G. W., Hamerton, J. L. J. med. Genet. 1978, 15, 43.
advised that up
to
20% of abnormal
research into the maternal-age-specific incidence of chromosome aberrations in late abortions and stillbirths. Department of Medical Genetics, Royal Hospital for Sick Children, Glasgow G3 8SJ
M. A. FERGUSON-SMITH
TREATMENT OF PAGET’S DISEASE
SIR,-Recent letters have raised some important points conthe treatment of Paget’s disease. Professor Milhaud’ advocates a very-low-dose regimen of (porcine) calcitonin which has given favourable therapeutic results. We agree that small doses of calcitonin may relieve pain in some cases of Paget’s disease and that the ideal dosage scheme remains to be established. However, it is clear that higher doses of calcitonin are required to heal the bones in the osteolytic phase of the disease, and low doses cannot be recommended in this situation since they are insufficient to check the advance of the resorptive process. 2-4 Dr Hamdy5 states that the main aim of treating Paget’s disease is to prevent complications and believes that pagetic pain usually responds to ordinary analgesics. Our experience is different. Simple analgesics may relieve mild pagetic pain but are ineffective in the more severe cases. We have seen many patients with frankly pagetic pain (i.e., not associated with concomitant osteoarthritis) who have gained pain relief with calcitonin after conventional analgesics had proved completely ineffective.
cerning
Endocrine Unit,
Royal Postgraduate Medical School, London W12 0HS
1. Hook, E., Chambers, G. C. Birth Defects orig. Art. Ser. 1977, 13 (3A), 123. 2. Ferguson-Smith, M. A. Lancet, 1976, ii, 252. 3. Ferguson-Smith, M. A., Ferguson-Smith, M. E. in Prenatal Diagnosis (edited by A. Boué); p. 81. INSERM, Paris, 1976. 4. Polani, P. E., Alberman, E., Berry, A. C., Blunt, S., Singer, J. D. Lancet,
were
conceptions might be lost between 16 weeks and term. Improvement in this advice can only come from more detailed
IMOGEN M. A. EVANS I. MACINTYRE
Milhaud, G. Lancet, 1978, i, 1153. Doyle, F. H., Pennock, J., Greenberg, P. B., Joplin, G. F., MacIntyre, I. in Endocrinology 1973 (edited by S. Taylor); p. 425. London, 1974. 3. Evans, I. M. A., Doyle, F. H., Banks, L., Pennock, J., Joplin, G. F., MacIn-
1. 2.
tyre, I. in Molecular Endocrinology (edited by I. Maclntyre and M. Szelke); p. 235. Amsterdam, 1977. 4. Nagant de Deuxchaisnes, C., Rombauts-Lindemans, C., Huaux, J. P., Malghem, J., Laldague, B. ibid. p. 213. 5. Hamdy, R. Lancet, 1978, i, 1267.
