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Life expectancies in children with cerebral palsy
THE LANCET
children aged 5 years survived at least to the age of 10 years. This is a better outlook than that given previously.2 David Strauss Calfornia Life Ex pectancy Project, Department of Statistics, University of California, Riverside, California 92521-0138, USA
1 2
3
4
5
Anderson TW. Life expectancy in cerebral palsy. Lancet 1996; 348: 1516. Eyman RK, Grossman HJ, Chaney RH, Call TL. Survival of profoundly disabled people with severe mental retardation. Am J Dis Child 1993; 147: 329–36. Hutton JL, Cooke T, Pharoah POD. Life expectancy in children with cerebral palsy. BMJ 1994; 309: 431–35. Eyman RK, Grossman HJ, Call TL. Life expectancy in children with cerebral palsy. BMJ 1995; 310: 665. Ashwal S, Eyman RK, Call TL. Life expectancy of children in a persistent vegetative state. Pediatr Neurol 1994; 10: 27–33. 1
SIR—Anderson suggests that the study of Eyman et al2 is not an appropriate basis for estimating life expectancy due to the high percentage of young people who appear to be in a vegetative state. That 1993 study was a refinement of a 1990 one3 which showed that the study population had several conditions leading to brain impairment, including cerebral lipidosis, hepatocellular degeneration, and progressive subcortical encephalopathy. If a study group includes children with brain diseases known to cause early death the mean survival of the whole group will be lessened. Furthermore, arithmetic means are very sensitive to outliers, and the early demise of this group will tend to have a disproportionate effect on overall actuarial survival rates. Richard W Newton Department of Paediatric Neurology, Royal Manchester Children’s Hospital, Manchester M27 4HA, UK
1 2
3
Anderson TW. Life expectancy in cerebral palsy. Lancet 1996; 348: 1516. Eyman RK, Grossman HJ, Chaney RH, Call TL. Survival of profoundly disabled people with severe mental retardation. Am J Dis Child 1993; 147: 329–36. Eyman RK, Grossman HJ, Chaney RH, Call TL. The life expectancy of profoundly handicapped people with mental retardation. N Engl J Med 1990; 323: 584–89.
Analysis of IVF data SIR—We are surprised that Templeton and colleagues (Nov 23, p 1402),1 in their analysis of one of the world’s largest in-vitro fertilisation (IVF) databases, did not point out some important limitations of their study, especially with regard to the accuracy of data collection and the exclusion of some variables. The information was collected from IVF clinic forms which
284
do not specify criteria for a positive diagnosis. For example, many patients classified as having a tubal factor may not have had a laparoscopy confirming this diagnosis. Other confounding factors influencing fertility and possibly IVF success (eg, caffeine and smoking) have not been assessed as variables. The unexplained infertility incidence of over 30% is very high considering that patients were treated in tertiary fertility referral centres, and reflects the diagnostic inaccuracy in the series. Another important omission—the incidence of multiple pregnancy—is the raison d’être for the HFEA’s guideline limiting the number of embryos for transfer to a maximum of three. Women with poor reproductive potential (eg, those aged 肁40) produce fewer eggs in response to drug induction, have a low success and high miscarriage rate, and have a low multiple pregnancy risk. We have reported on the beneficial effects of transferring more than three embryos in this age group without adversely influencing the multiple pregnancy rate. The guideline is merely a recommendation to clinicians, not law. However, an IVF clinic’s licence could be under threat if the guideline was not strictly adhered to, even if it might be in the patient’s best interest for more embryos to be transferred. Templeton and colleagues report live birth rates per embryo transfer for women between 40 and 44 years, and 45 and above, of 8·1% and 3·5%, respectively, compared with 18·5% and 22% when donated eggs were used from women of 35 years of age, or under. It would be of interest to know the respective multiple pregnancy rates for women of these age groups with their own, or donated, eggs. Many women would prefer to increase their chance of having a singleton child from their own eggs by transferring more embryos, without risking a multiple pregnancy, rather than using donor eggs as a first option (possibly with an increased multiple pregnancy risk) because of constraints imposed on clinicians. Wagner’s accompanying commentary2 is curiously provocative, with its spurious argument against intracytoplasmic sperm injection (ICSI), for which data were excluded by Templeton and colleagues. However, the commentary does raise the important principle concerning evidence required to justify the implementation of a new technique. Some developments are so much better than standard treatment that controlled randomised trials become unethical: conventional IVF would have been delayed for years if randomised controlled studies comparing IVF and ineffective surgery for tubal damage had
been forced upon us. The most severe cases of oligospermia are not appropriate for standard IVF treatment because failure of fertilisation is high. With ICSI, however, fertilisation and pregnancy rates are at least equivalent to standard IVF when sperm quality is normal. Can there be any justification here in doing a randomised controlled trial when the outcome anticipated in the control group is already known to be poor? A technique can be effective but have an adverse safety profile. Several ongoing studies are addressing this point, but there is no doubt that ICSI is an important advance in assisted conception, in that it offers the possibility for genuinely successful fertility treatment to hitherto untreatable populations. *Ian Craft, Robert Forman London Gynaecology and Fertility Centre, London W1N 1AF, UK
1
2
Templeton A, Morris JK, Parslow W. Factors that affect outcome of in-vitro fertilisation treatment. Lancet 1996; 348: 1402–06. Wagner M. IVF: out-of-date evidence, or not. Lancet 1996; 348: 1394.
Insulin resistance syndrome and childhood social conditions SIR—The finding by Wannamethee and colleagues (Nov 9, p 1259)1 of an association between childhood socioeconomic circumstances and coronary heart disease morbidity should be considered along with reports linking unfavourable socioeconomic circumstances in childhood with obesity in adult life.2,3 Wannamethee and colleagues found lower highdensity-lipoprotein cholesterol concentrations and higher systolic blood pressure in men whose fathers were manual workers. We have found that, among more than 5100 men living in western Scotland, those with fathers who were manual workers have a higher body mass index in adulthood than those with non-manual fathers.3 Fasting triglyceride concentrations were higher in men with manual fathers in an ageadjusted analysis (table). Multiple regression analysis (adjusting for age and social class, in both childhood and adulthood) indicated that triglyceride concentrations were higher in men with manual work background. High body mass index and triglyceride concentrations are components of the insulin resistance syndrome. These components cluster in childhood4 and this clustering tracks into adulthood, suggesting that a
Vol 349 • January 25, 1997
children aged 5 years survived at least to the age of 10 years. This is a better outlook than that given previously.2 David Strauss Calfornia Life Ex pectancy Project, Department of Statistics, University of California, Riverside, California 92521-0138, USA
1 2
3
4
5
Anderson TW. Life expectancy in cerebral palsy. Lancet 1996; 348: 1516. Eyman RK, Grossman HJ, Chaney RH, Call TL. Survival of profoundly disabled people with severe mental retardation. Am J Dis Child 1993; 147: 329–36. Hutton JL, Cooke T, Pharoah POD. Life expectancy in children with cerebral palsy. BMJ 1994; 309: 431–35. Eyman RK, Grossman HJ, Call TL. Life expectancy in children with cerebral palsy. BMJ 1995; 310: 665. Ashwal S, Eyman RK, Call TL. Life expectancy of children in a persistent vegetative state. Pediatr Neurol 1994; 10: 27–33. 1
SIR—Anderson suggests that the study of Eyman et al2 is not an appropriate basis for estimating life expectancy due to the high percentage of young people who appear to be in a vegetative state. That 1993 study was a refinement of a 1990 one3 which showed that the study population had several conditions leading to brain impairment, including cerebral lipidosis, hepatocellular degeneration, and progressive subcortical encephalopathy. If a study group includes children with brain diseases known to cause early death the mean survival of the whole group will be lessened. Furthermore, arithmetic means are very sensitive to outliers, and the early demise of this group will tend to have a disproportionate effect on overall actuarial survival rates. Richard W Newton Department of Paediatric Neurology, Royal Manchester Children’s Hospital, Manchester M27 4HA, UK
1 2
3
Anderson TW. Life expectancy in cerebral palsy. Lancet 1996; 348: 1516. Eyman RK, Grossman HJ, Chaney RH, Call TL. Survival of profoundly disabled people with severe mental retardation. Am J Dis Child 1993; 147: 329–36. Eyman RK, Grossman HJ, Chaney RH, Call TL. The life expectancy of profoundly handicapped people with mental retardation. N Engl J Med 1990; 323: 584–89.
Analysis of IVF data SIR—We are surprised that Templeton and colleagues (Nov 23, p 1402),1 in their analysis of one of the world’s largest in-vitro fertilisation (IVF) databases, did not point out some important limitations of their study, especially with regard to the accuracy of data collection and the exclusion of some variables. The information was collected from IVF clinic forms which
284
do not specify criteria for a positive diagnosis. For example, many patients classified as having a tubal factor may not have had a laparoscopy confirming this diagnosis. Other confounding factors influencing fertility and possibly IVF success (eg, caffeine and smoking) have not been assessed as variables. The unexplained infertility incidence of over 30% is very high considering that patients were treated in tertiary fertility referral centres, and reflects the diagnostic inaccuracy in the series. Another important omission—the incidence of multiple pregnancy—is the raison d’être for the HFEA’s guideline limiting the number of embryos for transfer to a maximum of three. Women with poor reproductive potential (eg, those aged 肁40) produce fewer eggs in response to drug induction, have a low success and high miscarriage rate, and have a low multiple pregnancy risk. We have reported on the beneficial effects of transferring more than three embryos in this age group without adversely influencing the multiple pregnancy rate. The guideline is merely a recommendation to clinicians, not law. However, an IVF clinic’s licence could be under threat if the guideline was not strictly adhered to, even if it might be in the patient’s best interest for more embryos to be transferred. Templeton and colleagues report live birth rates per embryo transfer for women between 40 and 44 years, and 45 and above, of 8·1% and 3·5%, respectively, compared with 18·5% and 22% when donated eggs were used from women of 35 years of age, or under. It would be of interest to know the respective multiple pregnancy rates for women of these age groups with their own, or donated, eggs. Many women would prefer to increase their chance of having a singleton child from their own eggs by transferring more embryos, without risking a multiple pregnancy, rather than using donor eggs as a first option (possibly with an increased multiple pregnancy risk) because of constraints imposed on clinicians. Wagner’s accompanying commentary2 is curiously provocative, with its spurious argument against intracytoplasmic sperm injection (ICSI), for which data were excluded by Templeton and colleagues. However, the commentary does raise the important principle concerning evidence required to justify the implementation of a new technique. Some developments are so much better than standard treatment that controlled randomised trials become unethical: conventional IVF would have been delayed for years if randomised controlled studies comparing IVF and ineffective surgery for tubal damage had
been forced upon us. The most severe cases of oligospermia are not appropriate for standard IVF treatment because failure of fertilisation is high. With ICSI, however, fertilisation and pregnancy rates are at least equivalent to standard IVF when sperm quality is normal. Can there be any justification here in doing a randomised controlled trial when the outcome anticipated in the control group is already known to be poor? A technique can be effective but have an adverse safety profile. Several ongoing studies are addressing this point, but there is no doubt that ICSI is an important advance in assisted conception, in that it offers the possibility for genuinely successful fertility treatment to hitherto untreatable populations. *Ian Craft, Robert Forman London Gynaecology and Fertility Centre, London W1N 1AF, UK
1
2
Templeton A, Morris JK, Parslow W. Factors that affect outcome of in-vitro fertilisation treatment. Lancet 1996; 348: 1402–06. Wagner M. IVF: out-of-date evidence, or not. Lancet 1996; 348: 1394.
Insulin resistance syndrome and childhood social conditions SIR—The finding by Wannamethee and colleagues (Nov 9, p 1259)1 of an association between childhood socioeconomic circumstances and coronary heart disease morbidity should be considered along with reports linking unfavourable socioeconomic circumstances in childhood with obesity in adult life.2,3 Wannamethee and colleagues found lower highdensity-lipoprotein cholesterol concentrations and higher systolic blood pressure in men whose fathers were manual workers. We have found that, among more than 5100 men living in western Scotland, those with fathers who were manual workers have a higher body mass index in adulthood than those with non-manual fathers.3 Fasting triglyceride concentrations were higher in men with manual fathers in an ageadjusted analysis (table). Multiple regression analysis (adjusting for age and social class, in both childhood and adulthood) indicated that triglyceride concentrations were higher in men with manual work background. High body mass index and triglyceride concentrations are components of the insulin resistance syndrome. These components cluster in childhood4 and this clustering tracks into adulthood, suggesting that a
Vol 349 • January 25, 1997