955 load give a very reliable index of lactose intolerance, I do not think the experience of Mitchell et al. with the clinitest should necessarily lead to their denigration of such a test. In my experience it is more likely to give a false positive result than a false negative. Certainly the effect of lactose maldigestion on nutrition may be more subtle than is commonly accepted, particularly in the mfant over 1 year of age. However, before suggesting widespread modification of cow’s milk, one needs more evidence that the use of a lactose hydrolysed milk will make a significant contribution to nutrition in the longer term, as well as more knowledge of the cost of this modification and of the possibility that the process may make some other subtle change in the product which might be beneficial. Evidence of long-term palatability is necessary since this is often the problem with
specialised milk products. Institue of Child
Health, Birmingham B16 8ET
CHARLOTTE M. ANDERSON
FOLATES AND THE FETUS
SIR,-We are puzzled by the responses of Dr Hall (March 19, p. 648) and Professor Emery (March 26, p. 703) to your editorial (Feb. 26, p. 462) which referred to our contribution’
the
that folate deficiency may be a factor the of neural-tube defects. They causation contributing measured serum-folate in mid-pregnancy or post partum, and their results do not support the hypothesis. We measured redblood-cell folate in the first trimester, and our results are compatible with the hypothesis. However, there is no inconsistency between their observations and ours, only a difference of interpretation. Dr Hall claims that her study "represents the real situation (i.e., that folic acid deficiency is not the cause of C.N.S. malformations)" and Professor Emery agrees with her "that there is no convincing evidence to implicate a deficiency of folic acid in the aetiology of fetal c.N.s. malformations". We do not suggest that folic-acid deficiency causes c.N.s. malformations, but neither do we accept that Dr Hall’s and Professor Emery’s studies disprove the hypothesis stated above. Dr Hall refers to serum-folate as "a more sensitive index of fbhc-acid deficiency than red-cell folate". It certainly responds more quickly to changes in dietary intake2 3 such as the in’creased food consumption (e.g., of milk) which is common amongst mothers who know they are pregnant. On the other hand, red-cell folate measured towards the end of the first trimester could reflect whole-body folate reserves earlier in pregnancy’4 which is more relevant to the present investigation. Professor Emery’s case-history is interesting. Folic-acid supplementation started at the 6th week of pregnancy could not influence closure of the neural tube in that pregnancy, but the massive dosage (10 mg daily) given throughout the remainder of the pregnancy should have provided substantial maternal reserves which would have lasted several months at least. If the following pregnancy started within a year the earlier supplementation might even have contributed to the normality of the to
hypothesis to
next
baby.
We hope that our current trial of vitamin supplementation started before conception will be helpful, and we do not prejudge the outcome. Department of
Pædiatrics and
Child
Health, University of Leeds, Leeds LS1 3ET
1
R. W. SMITHELLS SHEILA SHEPPARD C. J. SCHORAH
Smithells, R. W., Sheppard, S., Schorah, C. J. Archs Dis. Childh. 1976, 51, 944.
2 Leeming,
R. J., Portman-Graham, H., Blair, J. A.
J.
clin. Path.
1972, 25,
491. 3 Chanarin, I. The Megaloblastic Anæmias; chap. 2. Oxford, 1969. 4 Herbert, V., Colman, N., Spivack, M., Ocasio, E., Ghanta, V., Kimmel, K., Brenner, L., Freundlich, J., Scott, J. Am. J. Obstet. Gynec. 1975, 123, 175
WHOOPING-COUGH VACCINATION
SIR,-All would agree with Professor Stewart (April 9, p. 804), that a risk from vaccination, however low, is unacceptable if the vaccination programme is "both ineffective and unnecessary for the
of the recipients and the comthe evidence of Dr Stephenson than I do, he is wrong to suggest
protection he
munity". Although (Feb. 12, p. 357) less highly that my letter of Feb. 12 depended on (or even referred to) this. In a paper published on Feb. 26’ I listed five sources of Scottish data: besides observations corresponding to those recorded by Dr Stephenson and Dr Wilson (Feb. 19, p. 419) I drew attention to the absence of brain damage from whooping-cough vaccination recorded in the discharge diagnoses of Scottish hospital patients in the two years 1968 and 1969.2 None of the data were derived from fallible notifications. They do not disprove the existence of whooping-cough vaccine damage, but together they demonstrate that it is elusively rare rates
in Scotland. Is the vaccine effective? Professor Stewart himself suggests 70%,3 an estimate not far from that of others.4 In this connection, it should be noted that in socioeconomically advanced West Germany the vaccine is specifically recommended for infants with chronic diseases of the heart (e.g., congenital valvular defects) and lungs (e.g., bronchiectasis and mucoviscidosis) and for those overcrowded in institutions and poor living conditions for whom the risk of whooping-cough is recognised to be too great for them to be deprived of the benefit of an effective vaccine. Is the vaccine, in general, necessary? The morbidity, complications, and mortality of whooping-cough are well-recorded. Events will show whether the trends of incidence in the next few years will follow Professor Stewart’s linear exponential decay-rates5: substantial opinion doubts this. Perhaps Dr Cater’s suggestion (April 9, p. 804) could be modified: financial resources released by reduction in pertussis immunisation may be required to expand the psediatric intensive-care facilities required for babies with whooping-cough.6 Is prevention not better than treatment? University of Glasgow, Department of Infectious Diseases, Ruchill Hospital, Glasgow G20 9NB
N. R. GRIST
AMNIOTIC FLUID ALPHA-FETOPROTEIN AND TURNER’S SYNDROME
StR,—The suggestion by Dr Sutherland and his colleagues (March 19, p. 649) that a raised amniotic-fluid alpha-fetoprotein (A.F.P.) level when the fetus has a 45, X chromosome constitution is due to the puncture of a cystic hygroma certainly does not apply to our three cases.7 Our amniotic-fluid samples were aspirated under direct vision from intact sacs which had been spontaneously aborted. We were thus able to ensure that the needle was well away from the fetus. I still feel that the suggestion7 I that raised amniotic-fluid A.F.P. levels in these cases are due to leakage through the cervical hygromas is valid. The pouches are covered by skin, but in specimens I have seen, although the posterior cervical area of the hygroma is covered by a continuation of the scalp skin complete with hair, the lateral aspects are covered by only a thin membrane. A.F.P. could well permeate through these areas. The fact that Sutherland et al. found a high level of 1. Grist, N. R. Br. med. J. 1977, i, 573. 2. Commun. Dis. Scotland spec. Rep. 77/6, 1977. 3. Bassili, W. R., Stewart, G.T. Lancet, 1976, i, 474. 4. Noah, N. D. Br. med. J. 1976, i, 128. 5. Stewart, G. T., Lancet, 1977, i, 234. 6. Barrie, H. ibid. p. 648. 7. Seller, M. J., Creasy, M. R., Alberman, E. D. Br. med. J. 1974, ii, 524. 8. Seller, M. J. in Alpha-fetoprotein (edited by R. Massayeff); p.383. INSERM, Nice, 1974.
specialised milk products. Institue of Child
Health, Birmingham B16 8ET
CHARLOTTE M. ANDERSON
FOLATES AND THE FETUS
SIR,-We are puzzled by the responses of Dr Hall (March 19, p. 648) and Professor Emery (March 26, p. 703) to your editorial (Feb. 26, p. 462) which referred to our contribution’
the
that folate deficiency may be a factor the of neural-tube defects. They causation contributing measured serum-folate in mid-pregnancy or post partum, and their results do not support the hypothesis. We measured redblood-cell folate in the first trimester, and our results are compatible with the hypothesis. However, there is no inconsistency between their observations and ours, only a difference of interpretation. Dr Hall claims that her study "represents the real situation (i.e., that folic acid deficiency is not the cause of C.N.S. malformations)" and Professor Emery agrees with her "that there is no convincing evidence to implicate a deficiency of folic acid in the aetiology of fetal c.N.s. malformations". We do not suggest that folic-acid deficiency causes c.N.s. malformations, but neither do we accept that Dr Hall’s and Professor Emery’s studies disprove the hypothesis stated above. Dr Hall refers to serum-folate as "a more sensitive index of fbhc-acid deficiency than red-cell folate". It certainly responds more quickly to changes in dietary intake2 3 such as the in’creased food consumption (e.g., of milk) which is common amongst mothers who know they are pregnant. On the other hand, red-cell folate measured towards the end of the first trimester could reflect whole-body folate reserves earlier in pregnancy’4 which is more relevant to the present investigation. Professor Emery’s case-history is interesting. Folic-acid supplementation started at the 6th week of pregnancy could not influence closure of the neural tube in that pregnancy, but the massive dosage (10 mg daily) given throughout the remainder of the pregnancy should have provided substantial maternal reserves which would have lasted several months at least. If the following pregnancy started within a year the earlier supplementation might even have contributed to the normality of the to
hypothesis to
next
baby.
We hope that our current trial of vitamin supplementation started before conception will be helpful, and we do not prejudge the outcome. Department of
Pædiatrics and
Child
Health, University of Leeds, Leeds LS1 3ET
1
R. W. SMITHELLS SHEILA SHEPPARD C. J. SCHORAH
Smithells, R. W., Sheppard, S., Schorah, C. J. Archs Dis. Childh. 1976, 51, 944.
2 Leeming,
R. J., Portman-Graham, H., Blair, J. A.
J.
clin. Path.
1972, 25,
491. 3 Chanarin, I. The Megaloblastic Anæmias; chap. 2. Oxford, 1969. 4 Herbert, V., Colman, N., Spivack, M., Ocasio, E., Ghanta, V., Kimmel, K., Brenner, L., Freundlich, J., Scott, J. Am. J. Obstet. Gynec. 1975, 123, 175
WHOOPING-COUGH VACCINATION
SIR,-All would agree with Professor Stewart (April 9, p. 804), that a risk from vaccination, however low, is unacceptable if the vaccination programme is "both ineffective and unnecessary for the
of the recipients and the comthe evidence of Dr Stephenson than I do, he is wrong to suggest
protection he
munity". Although (Feb. 12, p. 357) less highly that my letter of Feb. 12 depended on (or even referred to) this. In a paper published on Feb. 26’ I listed five sources of Scottish data: besides observations corresponding to those recorded by Dr Stephenson and Dr Wilson (Feb. 19, p. 419) I drew attention to the absence of brain damage from whooping-cough vaccination recorded in the discharge diagnoses of Scottish hospital patients in the two years 1968 and 1969.2 None of the data were derived from fallible notifications. They do not disprove the existence of whooping-cough vaccine damage, but together they demonstrate that it is elusively rare rates
in Scotland. Is the vaccine effective? Professor Stewart himself suggests 70%,3 an estimate not far from that of others.4 In this connection, it should be noted that in socioeconomically advanced West Germany the vaccine is specifically recommended for infants with chronic diseases of the heart (e.g., congenital valvular defects) and lungs (e.g., bronchiectasis and mucoviscidosis) and for those overcrowded in institutions and poor living conditions for whom the risk of whooping-cough is recognised to be too great for them to be deprived of the benefit of an effective vaccine. Is the vaccine, in general, necessary? The morbidity, complications, and mortality of whooping-cough are well-recorded. Events will show whether the trends of incidence in the next few years will follow Professor Stewart’s linear exponential decay-rates5: substantial opinion doubts this. Perhaps Dr Cater’s suggestion (April 9, p. 804) could be modified: financial resources released by reduction in pertussis immunisation may be required to expand the psediatric intensive-care facilities required for babies with whooping-cough.6 Is prevention not better than treatment? University of Glasgow, Department of Infectious Diseases, Ruchill Hospital, Glasgow G20 9NB
N. R. GRIST
AMNIOTIC FLUID ALPHA-FETOPROTEIN AND TURNER’S SYNDROME
StR,—The suggestion by Dr Sutherland and his colleagues (March 19, p. 649) that a raised amniotic-fluid alpha-fetoprotein (A.F.P.) level when the fetus has a 45, X chromosome constitution is due to the puncture of a cystic hygroma certainly does not apply to our three cases.7 Our amniotic-fluid samples were aspirated under direct vision from intact sacs which had been spontaneously aborted. We were thus able to ensure that the needle was well away from the fetus. I still feel that the suggestion7 I that raised amniotic-fluid A.F.P. levels in these cases are due to leakage through the cervical hygromas is valid. The pouches are covered by skin, but in specimens I have seen, although the posterior cervical area of the hygroma is covered by a continuation of the scalp skin complete with hair, the lateral aspects are covered by only a thin membrane. A.F.P. could well permeate through these areas. The fact that Sutherland et al. found a high level of 1. Grist, N. R. Br. med. J. 1977, i, 573. 2. Commun. Dis. Scotland spec. Rep. 77/6, 1977. 3. Bassili, W. R., Stewart, G.T. Lancet, 1976, i, 474. 4. Noah, N. D. Br. med. J. 1976, i, 128. 5. Stewart, G. T., Lancet, 1977, i, 234. 6. Barrie, H. ibid. p. 648. 7. Seller, M. J., Creasy, M. R., Alberman, E. D. Br. med. J. 1974, ii, 524. 8. Seller, M. J. in Alpha-fetoprotein (edited by R. Massayeff); p.383. INSERM, Nice, 1974.
