668
of publication space, we death calculations have a
must ruefully conclude that attributable long way to go.
The authors have in the past received support from the tobacco We thank Peter Lee for helpful suggestions. School of Computing Science, Faculty of Applied Sciences, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada 1
industry.
T. D. STERLING W. L. ROSENBAUM J. J. WEINKAM
US National Centre for Health Statistics. The national mortality followback survey, 1986. Public use tapes and/or documentation from Followback Survey Branch,
NCHS, Hyattsville, Maryland, USA. 2 US National Center for Health Statistics. The national health interview survey, 1987:
epidemiological supplement data set. Public use tapes and/or documentation from Followback Survey Branch, NCHS, Hyattsville, Maryland, USA. 3. Poe GS, McLaughlin JK, Powell-Griner E, et al. The time interval between death and next-of-kin contact and its effects on response rates and data quality. Am J cancer
Epidemiol 1991; 134: 1454-62. 4. Garfinkel L. Selection, follow-up and analysis in the American Cancer Society prospective studies. Presented at Workshop in Selection, Follow-up and Analysis in Prospective Studies (New York, October, 1983). Natl Cancer Inst Monogr 1985; 67: 49-52. 5. Hammond EC Tables on the American Cancer Society samples. Executive Council of the American Cancer Society, 1962.
Prepared
The meeting report
can
be obtained free from Maternal and Child Health
Programme, WHO Regional Office for Europe, Copenhagen, Denmark.
sampling SIR,-A few clusters of children bom with limb anomalies after chorionic villus sampling (CVS) have been reported.1-4 In contrast, many other large series showed no statistical increase in limb anomalies.5-11 The objective of our WHO/EURO meeting was to re-examine existing data on CVS and to produce an expert statement about the use of CVS in prenatal diagnosis. The global 10 year experience of CVS extends to over 150 000 cases. The technique is helpful for women at increased genetic risk, and when done by an expert at between 9 and 12 weeks’ gestation has an acceptably low rate of complications and fetal loss. An increased incidence of limb reduction defects has been reported in some centres, and the very early sampling (at or before 8 weeks) may be associated with some fetal limb malformations. However, the overall incidence of limb reduction defects after CVS is 6 per 10 000, not significantly different from the incidence of 5 42 per 10 000 in the general population (table). The absolute number of cases is therefore small. There is no evidence for any increased risk of congenital malformation when CVS is done after the eighth completed week, and the procedure should be performed at 9-12 weeks from last menstrual period. Centres vary in the risk of fetal loss associated with CVS, so similar variation may apply for risk of fetal malformation. CVS, and other fetal sampling techniques, should therefore be done only at centres with a high level of expertise that can use any sampling approach as appropriate, follow-up to delivery, and meet certain standards. These criteria are proposed for self-evaluation of centres’ expertise: (1) sampling success of about 90% at first insertion and up to 98 % after two insertions, and laboratory success in more than 95% of all sampled; (2) demonstrated ability to use both transcervical and transabdominal routes; (3) total fetal loss to 28 weeks of chromosomally normal pregnancies of less than 6% (with low-risk patient populations [young, economically advantaged, non-smoking, sampled close to 12 weeks] should do better than this); and (4) data collection and surveillance that includes follow-up to delivery and infants’ outcome for over 95 % of all cases. FREQUENCY OF LIMB REDUCTION DEFECT (LRD) AFTER CVS COMPARED WITH BACKGROUND INCIDENCE BASED ON BRITISH COLUMBIA REGISTRY
*Data from Jackson’s CVS registry; an ascertainment bias cannot be excluded-
8
Scherfigsvej, DK-2100,
A. M. KULIEV B. MODELL L. JACKSON, For the WHO/EURO Meeting in association
for the
Limb abnormalities and chorionic villus
tlncludes also Oxford and Chicago clusters 14
These criteria ordinarily would be achieved by groups with experience of 200-250 procedures. However, expertise cannot be maintained with occasional sampling; the more cases done per year, the better an operator’s results are likely to be. A system for collecting information on malformations in babies bom after fetal sampling (and in fetuses aborted because of severe congenital malformation after such procedures) has been established, to ensure consistent description of the conditions and to allow evaluation of a possible relation to fetal sampling. Because of the small numbers involved, all infants bom with congenital malformations after CVS since its introduction should be reported to the CVS registry, so that an improved assessment of risks can be calculated from existing data.
Reproductive Genetics Institute, 836 W Wellington, Chicago, IL 60657, USA
with the 6th International Conference on Early Prenatal Diagnosis of Genetic
Diseases, Milan, May 18-20, 1992.
HV, Body PA, Chamberlain P, MacKenzie IZ, Lindenbaum RH, Huson SM Severe limb abnormalities after chorionic villus sampling at 56-66 days’ gestation Lancet 1991; 337: 127-35. Hsieh FJ, Chen D, Tseng LH, et al. Limb-reduction defects and chorionic villus sampling. Lancet 1991; 337: 1091-92 Mastroiacovo P, Cavalcanti DP. Limb abnormalities and chorionic villus sampling. Lancet 1991, 337: 1423. Burton BK, Schulz CJ, Burd LI. Limb anomalies associated with chorionic villus sampling. Obstet Gynecol 1992; 79: 726-30 Monni G, Ibba RM, Lai R, Olla G, Cao A. Limb-reduction defects and chorionic villus sampling. Lancet 1991; 337: 1091. Mahoney MJ. Limb abnormalities and chorion villus sampling Lancet 1991; 337: 1422-23. Jackson LG, Wapner RJ, Brambati B. Limb abnormalities and chorionic villus sampling. Lancet 1991; 337: 1423. MRC Working Party on the Evaluation of Chorionic Villus Sampling. Medical Research Council European Trial of chorionic villus sampling Lancet 1991; 337: 1491-99. Lippman A, Tomkins DJ, Shime J, Hamerton JL and Canadian Collaborative CVS-Amniocentesis Clinical Trial Group. Canadian Multicentre randomized clinical trial of chorion villus sampling and amniocentesis. final report Prenat Diagn 1992; 12: 385-476. Schloo R, Miny P, Holzgreve W, Horst J, Lenz W. Distal limb deficiency following chononic villus sampling? Am J Med Genet 1992; 42: 404-13. Dolk H, Bertrand F, Lechat MF. Chorionic villus sampling and limb abnormalities Lancet 1992; 339: 876-77. Froster-Iskenius UG, Baird PA. Limb reduction defects in over one million consecutive live births. Teratology 1989; 39: 127-35.
1. Firth
2. 3. 4. 5.
6. 7
8.
9.
10. 11. 12.
Aluminium and dementia SIR,-Professor Whalley and colleagues (May 16, p 1235) mention preliminary results suggesting that people with Alzheimer’s disease constitute a mobile population. Prompted by this report we investigated this matter for 541 participants of the Ontario Longitudinal Study on Aging (LSA) and found an association between moving home more than once and showing some indication of medical impairment (table). We based our assessment of mental impairment on a modified mental status questionnaire that included nine questions that tested short-term memory. Responses were used to classify respondents showing some indications of impaired mental functioning (scored one or more errors) and those with no such impairment (answered all questions correctly). Our method showed results that were reasonably consistent with those of other studies. Whalley and colleagues also comment on the need for information about the quality of the public water supply to assess exposure within fairly small geographical regions. We have reasonably comprehensive information for at least 7 years about the quality of the water supplies where the LSA participants resided. The results (table) show an association between aluminium water concentration and mental impairment, an inverse association with fluoride, as reported previously, 1.2 and (unpublished) an association with ground water, a low level of education, and a high or low pH, in addition to the association with mobility or some factor associated with it.
669
ADJUSTED ODDS RATIOS FOR SYMPTOMS OF IMPAIRED MENTAL FUNCTIONING ON BASIS OF LOGISTIC REGRESSION MODEL*
three-dimensional time-of-flight technique showed irregular vessels in the circle of Willis. Posterior cerebral arteries could not be assessed. The findings were felt to be secondary to vasculitis or severe spasm. A four-vessel arteriogram confirmed the MR findings and demonstrated segmental narrowing of the distal internal carotid artery and proximal anterior and middle cerebral arteries bilaterally with slow flow distally (figure). The distal basilar artery was also involved and very slow flow was seen in the posterior cerebral arteries on vertebral injection. She was begun on acyclovir 800 mg intravenously every 8 h for presumed varicella-zostermediated vasculitis. She was also given cyclophosphamide 150 mg by mouth daily and prednisone was continued. The deficits persisted without much change over the next three weeks. A follow-up CT scan at that time demonstrated further progression of the previously identified infarction with new infarctions in the left occipital and the right frontal regions. She gradually improved during the next two weeks and was discharged home with a
persistent right hemiparesis. I
*Vanous other multivariate
tp
of publication space, we death calculations have a
must ruefully conclude that attributable long way to go.
The authors have in the past received support from the tobacco We thank Peter Lee for helpful suggestions. School of Computing Science, Faculty of Applied Sciences, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada 1
industry.
T. D. STERLING W. L. ROSENBAUM J. J. WEINKAM
US National Centre for Health Statistics. The national mortality followback survey, 1986. Public use tapes and/or documentation from Followback Survey Branch,
NCHS, Hyattsville, Maryland, USA. 2 US National Center for Health Statistics. The national health interview survey, 1987:
epidemiological supplement data set. Public use tapes and/or documentation from Followback Survey Branch, NCHS, Hyattsville, Maryland, USA. 3. Poe GS, McLaughlin JK, Powell-Griner E, et al. The time interval between death and next-of-kin contact and its effects on response rates and data quality. Am J cancer
Epidemiol 1991; 134: 1454-62. 4. Garfinkel L. Selection, follow-up and analysis in the American Cancer Society prospective studies. Presented at Workshop in Selection, Follow-up and Analysis in Prospective Studies (New York, October, 1983). Natl Cancer Inst Monogr 1985; 67: 49-52. 5. Hammond EC Tables on the American Cancer Society samples. Executive Council of the American Cancer Society, 1962.
Prepared
The meeting report
can
be obtained free from Maternal and Child Health
Programme, WHO Regional Office for Europe, Copenhagen, Denmark.
sampling SIR,-A few clusters of children bom with limb anomalies after chorionic villus sampling (CVS) have been reported.1-4 In contrast, many other large series showed no statistical increase in limb anomalies.5-11 The objective of our WHO/EURO meeting was to re-examine existing data on CVS and to produce an expert statement about the use of CVS in prenatal diagnosis. The global 10 year experience of CVS extends to over 150 000 cases. The technique is helpful for women at increased genetic risk, and when done by an expert at between 9 and 12 weeks’ gestation has an acceptably low rate of complications and fetal loss. An increased incidence of limb reduction defects has been reported in some centres, and the very early sampling (at or before 8 weeks) may be associated with some fetal limb malformations. However, the overall incidence of limb reduction defects after CVS is 6 per 10 000, not significantly different from the incidence of 5 42 per 10 000 in the general population (table). The absolute number of cases is therefore small. There is no evidence for any increased risk of congenital malformation when CVS is done after the eighth completed week, and the procedure should be performed at 9-12 weeks from last menstrual period. Centres vary in the risk of fetal loss associated with CVS, so similar variation may apply for risk of fetal malformation. CVS, and other fetal sampling techniques, should therefore be done only at centres with a high level of expertise that can use any sampling approach as appropriate, follow-up to delivery, and meet certain standards. These criteria are proposed for self-evaluation of centres’ expertise: (1) sampling success of about 90% at first insertion and up to 98 % after two insertions, and laboratory success in more than 95% of all sampled; (2) demonstrated ability to use both transcervical and transabdominal routes; (3) total fetal loss to 28 weeks of chromosomally normal pregnancies of less than 6% (with low-risk patient populations [young, economically advantaged, non-smoking, sampled close to 12 weeks] should do better than this); and (4) data collection and surveillance that includes follow-up to delivery and infants’ outcome for over 95 % of all cases. FREQUENCY OF LIMB REDUCTION DEFECT (LRD) AFTER CVS COMPARED WITH BACKGROUND INCIDENCE BASED ON BRITISH COLUMBIA REGISTRY
*Data from Jackson’s CVS registry; an ascertainment bias cannot be excluded-
8
Scherfigsvej, DK-2100,
A. M. KULIEV B. MODELL L. JACKSON, For the WHO/EURO Meeting in association
for the
Limb abnormalities and chorionic villus
tlncludes also Oxford and Chicago clusters 14
These criteria ordinarily would be achieved by groups with experience of 200-250 procedures. However, expertise cannot be maintained with occasional sampling; the more cases done per year, the better an operator’s results are likely to be. A system for collecting information on malformations in babies bom after fetal sampling (and in fetuses aborted because of severe congenital malformation after such procedures) has been established, to ensure consistent description of the conditions and to allow evaluation of a possible relation to fetal sampling. Because of the small numbers involved, all infants bom with congenital malformations after CVS since its introduction should be reported to the CVS registry, so that an improved assessment of risks can be calculated from existing data.
Reproductive Genetics Institute, 836 W Wellington, Chicago, IL 60657, USA
with the 6th International Conference on Early Prenatal Diagnosis of Genetic
Diseases, Milan, May 18-20, 1992.
HV, Body PA, Chamberlain P, MacKenzie IZ, Lindenbaum RH, Huson SM Severe limb abnormalities after chorionic villus sampling at 56-66 days’ gestation Lancet 1991; 337: 127-35. Hsieh FJ, Chen D, Tseng LH, et al. Limb-reduction defects and chorionic villus sampling. Lancet 1991; 337: 1091-92 Mastroiacovo P, Cavalcanti DP. Limb abnormalities and chorionic villus sampling. Lancet 1991, 337: 1423. Burton BK, Schulz CJ, Burd LI. Limb anomalies associated with chorionic villus sampling. Obstet Gynecol 1992; 79: 726-30 Monni G, Ibba RM, Lai R, Olla G, Cao A. Limb-reduction defects and chorionic villus sampling. Lancet 1991; 337: 1091. Mahoney MJ. Limb abnormalities and chorion villus sampling Lancet 1991; 337: 1422-23. Jackson LG, Wapner RJ, Brambati B. Limb abnormalities and chorionic villus sampling. Lancet 1991; 337: 1423. MRC Working Party on the Evaluation of Chorionic Villus Sampling. Medical Research Council European Trial of chorionic villus sampling Lancet 1991; 337: 1491-99. Lippman A, Tomkins DJ, Shime J, Hamerton JL and Canadian Collaborative CVS-Amniocentesis Clinical Trial Group. Canadian Multicentre randomized clinical trial of chorion villus sampling and amniocentesis. final report Prenat Diagn 1992; 12: 385-476. Schloo R, Miny P, Holzgreve W, Horst J, Lenz W. Distal limb deficiency following chononic villus sampling? Am J Med Genet 1992; 42: 404-13. Dolk H, Bertrand F, Lechat MF. Chorionic villus sampling and limb abnormalities Lancet 1992; 339: 876-77. Froster-Iskenius UG, Baird PA. Limb reduction defects in over one million consecutive live births. Teratology 1989; 39: 127-35.
1. Firth
2. 3. 4. 5.
6. 7
8.
9.
10. 11. 12.
Aluminium and dementia SIR,-Professor Whalley and colleagues (May 16, p 1235) mention preliminary results suggesting that people with Alzheimer’s disease constitute a mobile population. Prompted by this report we investigated this matter for 541 participants of the Ontario Longitudinal Study on Aging (LSA) and found an association between moving home more than once and showing some indication of medical impairment (table). We based our assessment of mental impairment on a modified mental status questionnaire that included nine questions that tested short-term memory. Responses were used to classify respondents showing some indications of impaired mental functioning (scored one or more errors) and those with no such impairment (answered all questions correctly). Our method showed results that were reasonably consistent with those of other studies. Whalley and colleagues also comment on the need for information about the quality of the public water supply to assess exposure within fairly small geographical regions. We have reasonably comprehensive information for at least 7 years about the quality of the water supplies where the LSA participants resided. The results (table) show an association between aluminium water concentration and mental impairment, an inverse association with fluoride, as reported previously, 1.2 and (unpublished) an association with ground water, a low level of education, and a high or low pH, in addition to the association with mobility or some factor associated with it.
669
ADJUSTED ODDS RATIOS FOR SYMPTOMS OF IMPAIRED MENTAL FUNCTIONING ON BASIS OF LOGISTIC REGRESSION MODEL*
three-dimensional time-of-flight technique showed irregular vessels in the circle of Willis. Posterior cerebral arteries could not be assessed. The findings were felt to be secondary to vasculitis or severe spasm. A four-vessel arteriogram confirmed the MR findings and demonstrated segmental narrowing of the distal internal carotid artery and proximal anterior and middle cerebral arteries bilaterally with slow flow distally (figure). The distal basilar artery was also involved and very slow flow was seen in the posterior cerebral arteries on vertebral injection. She was begun on acyclovir 800 mg intravenously every 8 h for presumed varicella-zostermediated vasculitis. She was also given cyclophosphamide 150 mg by mouth daily and prednisone was continued. The deficits persisted without much change over the next three weeks. A follow-up CT scan at that time demonstrated further progression of the previously identified infarction with new infarctions in the left occipital and the right frontal regions. She gradually improved during the next two weeks and was discharged home with a
persistent right hemiparesis. I
*Vanous other multivariate
tp
