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Low birthweight and ischaemic heart disease
resides in the fact that the intrauterine growth pattern of twins is very similar to that of singletons until late in gestation. The most critical period for organ and tissue development is early gestation. The follow-up of the Dutch winter famine study also showed that maternal in-utero exposure in early gestation was related to reduced birthweight and length in their infants.5 These mothers themselves had normal birthweights, since their own mothers’ nutrition was re-established during their third trimester of intrauterine life, when the 1939-45 war ended. By contrast, mothers who were exposed to the famine during their third trimester of intrauterine life were of reduced birthweight, but later, as adults, had babies who were not smaller than expected. It is possible that, as for future reproductive events, twins’ birthweight is not indicative of the important intrauterine developmental factors for cardiovascular disease. Van Assche and colleagues (March 19, p 731) suggest that a valid test of the fetal origins hypothesis would be a comparison of monozygotic twin pairs with a substantial difference in birthweight. I question whether this would be a valid test, in view of the evidence about reproductive outcomes of twin mothers that I have cited. The mortality of twins has been so much greater than that of singletons, especially in the period of Vagero and Leon’s series. We have suggested that such twins who reach adulthood represent healthy survivors who are not directly comparable to singletons born at the same time.2 That Vagero and Leon found twins to have a slightly lower risk for coronary disease mortality would seem to support that
probably
95% Cl in parentheses. *Mutually adjusted odds ratios birth. Non-manual class=reference category.
(OR) shown. All ORs adjusted for year of
Mortality odds ratios for all causes and lschaemic heart disease (IHD) among men born 1946-55 by social class In childhood and
Table:
adulthood
(not shown). Having non-employed parents therefore seems to contribute both to employment chances and mortality risk in adulthood. Thus, health and social achievement become linked in adult life. Those who change class between childhood and adulthood are likely to have been subject to different circumstances in childhood than those who remain in the same class, which may be important for their health risks as adults.’ Moreover, as Davey Smith and Phillips pointed out,2 the imprecision inherent in the use of socioeconomic class because global measures of childhood and adult circumstances may cause residual confounding in the analysis. An earlier analysis of morbidity in the Finnislr cohort3 concluded that socioeconomic state in childhood was associated with IHD in middle-aged men. The failure of Lynch and co-workers to reach the same conclusion may in part be attributed to the small number of deaths on which it was based (n=166) as well as to difficulties with identifying relevant indicators in the childhood environment. On the basis of our data we conclude that childhood circumstances do contribute to adult mortality, at least in the age groups studied here, although the interpretation of this independent effect is difficult. parents
Denny Vågerö, David Leon
hypothesis. Irvin Emanuel Departments of Epidemiology and Paediatrics, Maternal and Child Health Program, SC-36, University of Washington, Seattle, WA 98195, USA
1
2
Swedish Institute for Social Research, S-106 91 Stockholm, Sweden; and Department of Epidemiology and Population Sciences, London School of Hygiene and Tropical Medicine, London WC1, UK
3
1 Nyström Peck M. The importance of childhood socio-economic group for adult health. Soc Sci Med (in press) 2 Davey Smith G, Phillips A. Socio-economic conditions and ischaemic heart disease. BMJ 1991; 302: 113-14. 3 Kaplan G, Salonen J. Socioeconomic conditions in childhood and ischaemic heart disease during middle age. BMJ 1990; 301: 1121-23.
Low
birthweight and ischaemic heart disease
SIR-That Vagero and Leon (Jan 29, p 260) record no excess risk of ischaemic heart disease in their lowbirthweight twin population is not necessarily evidence against the hypothesis of fetal origins in coronary disease.1 Final birthweight in twins is probably not an appropriate indicator of their intrauterine development. 2,3 There is now substantial evidence that mother’s birthweight is significantly related to infant’s birthweight.3 However, monozygous female twins who differed in birthweight by at least 300 g had babies who did not differ in birthweight, which was similar to that of the general population.4 We showed that mothers who were twins produced babies whose mean birthweight was significantly greater than those of singleton mothers.2 However, the mean birthweight of the twin mothers was 2550 g (50% low birthweight [LBW]) versus 3251 g (7% LBW) for their singleton counterparts. The explanation for this paradox
4
5
Barker DJP, Gluckman P, Godfrey K, Harding J, Owens J, Robinson J. Fetal nutrition and cardiovascular disease in adult life. Lancet 1993; 341: 938-41. Emanuel I, Filakti H, Alberman E, Evans SJW. Intergenerational studies of human birthweight from the 1958 birth cohort. II. Do parents who were twins have babies as heavy as those born to singletons? Br J Obstet Gynaecol 1992; 99: 836-40. Emanuel I. Intergenerational factors in pregnancy outcome. Implications for teratology? Issues Rev Teratol 1993; 6: 47-84. Magnus P, Berg K, Bjerkedal T. No significant differences in birthweight for offspring of discordant monozygotic twins. Early Human Develop 1985; 12: 55-59. Lumey LH. Decreased birthweights in infants after in utero exposure to the Dutch famine of 1944-1945. Paediatr Perinat Epidemiol 1992; 6: 240-53.
Effect of thrombolysis in inferior infarction Fibrinolytic Therapy Trialists’ Collaborative Group (Feb 5, p 311) concludes that fibrinolytic therapy reduces mortality among patients presenting with ST elevation irrespective of the site of infarction. However, in the case of inferior infarction (n=16 203) they do not show a reduction in mortality during the first 35 days (7-5% after fibrinolytic therapy vs 8-4% in controls). They calculate a non-significant benefit of 8 lives per 1000 patients, which is obtained at the price of 4-0 excess strokes per 1000 patients. SiR-The
If we consider the individual studies on the basis of which the meta-analysis is done, then, again, in ISIS-2 there was in inferior infarction non-significant reduction in mortality due to streptokinase alone (7-2% after treatment with streptokinase vs 8-8% after conventional treatment), unless it was administered with aspirin. Aspirin alone reduced significantly mortality in inferior infarction in ISIS-2.’ Comparable results in inferior infarction were obtained in 1225
probably
95% Cl in parentheses. *Mutually adjusted odds ratios birth. Non-manual class=reference category.
(OR) shown. All ORs adjusted for year of
Mortality odds ratios for all causes and lschaemic heart disease (IHD) among men born 1946-55 by social class In childhood and
Table:
adulthood
(not shown). Having non-employed parents therefore seems to contribute both to employment chances and mortality risk in adulthood. Thus, health and social achievement become linked in adult life. Those who change class between childhood and adulthood are likely to have been subject to different circumstances in childhood than those who remain in the same class, which may be important for their health risks as adults.’ Moreover, as Davey Smith and Phillips pointed out,2 the imprecision inherent in the use of socioeconomic class because global measures of childhood and adult circumstances may cause residual confounding in the analysis. An earlier analysis of morbidity in the Finnislr cohort3 concluded that socioeconomic state in childhood was associated with IHD in middle-aged men. The failure of Lynch and co-workers to reach the same conclusion may in part be attributed to the small number of deaths on which it was based (n=166) as well as to difficulties with identifying relevant indicators in the childhood environment. On the basis of our data we conclude that childhood circumstances do contribute to adult mortality, at least in the age groups studied here, although the interpretation of this independent effect is difficult. parents
Denny Vågerö, David Leon
hypothesis. Irvin Emanuel Departments of Epidemiology and Paediatrics, Maternal and Child Health Program, SC-36, University of Washington, Seattle, WA 98195, USA
1
2
Swedish Institute for Social Research, S-106 91 Stockholm, Sweden; and Department of Epidemiology and Population Sciences, London School of Hygiene and Tropical Medicine, London WC1, UK
3
1 Nyström Peck M. The importance of childhood socio-economic group for adult health. Soc Sci Med (in press) 2 Davey Smith G, Phillips A. Socio-economic conditions and ischaemic heart disease. BMJ 1991; 302: 113-14. 3 Kaplan G, Salonen J. Socioeconomic conditions in childhood and ischaemic heart disease during middle age. BMJ 1990; 301: 1121-23.
Low
birthweight and ischaemic heart disease
SIR-That Vagero and Leon (Jan 29, p 260) record no excess risk of ischaemic heart disease in their lowbirthweight twin population is not necessarily evidence against the hypothesis of fetal origins in coronary disease.1 Final birthweight in twins is probably not an appropriate indicator of their intrauterine development. 2,3 There is now substantial evidence that mother’s birthweight is significantly related to infant’s birthweight.3 However, monozygous female twins who differed in birthweight by at least 300 g had babies who did not differ in birthweight, which was similar to that of the general population.4 We showed that mothers who were twins produced babies whose mean birthweight was significantly greater than those of singleton mothers.2 However, the mean birthweight of the twin mothers was 2550 g (50% low birthweight [LBW]) versus 3251 g (7% LBW) for their singleton counterparts. The explanation for this paradox
4
5
Barker DJP, Gluckman P, Godfrey K, Harding J, Owens J, Robinson J. Fetal nutrition and cardiovascular disease in adult life. Lancet 1993; 341: 938-41. Emanuel I, Filakti H, Alberman E, Evans SJW. Intergenerational studies of human birthweight from the 1958 birth cohort. II. Do parents who were twins have babies as heavy as those born to singletons? Br J Obstet Gynaecol 1992; 99: 836-40. Emanuel I. Intergenerational factors in pregnancy outcome. Implications for teratology? Issues Rev Teratol 1993; 6: 47-84. Magnus P, Berg K, Bjerkedal T. No significant differences in birthweight for offspring of discordant monozygotic twins. Early Human Develop 1985; 12: 55-59. Lumey LH. Decreased birthweights in infants after in utero exposure to the Dutch famine of 1944-1945. Paediatr Perinat Epidemiol 1992; 6: 240-53.
Effect of thrombolysis in inferior infarction Fibrinolytic Therapy Trialists’ Collaborative Group (Feb 5, p 311) concludes that fibrinolytic therapy reduces mortality among patients presenting with ST elevation irrespective of the site of infarction. However, in the case of inferior infarction (n=16 203) they do not show a reduction in mortality during the first 35 days (7-5% after fibrinolytic therapy vs 8-4% in controls). They calculate a non-significant benefit of 8 lives per 1000 patients, which is obtained at the price of 4-0 excess strokes per 1000 patients. SiR-The
If we consider the individual studies on the basis of which the meta-analysis is done, then, again, in ISIS-2 there was in inferior infarction non-significant reduction in mortality due to streptokinase alone (7-2% after treatment with streptokinase vs 8-8% after conventional treatment), unless it was administered with aspirin. Aspirin alone reduced significantly mortality in inferior infarction in ISIS-2.’ Comparable results in inferior infarction were obtained in 1225