BMJ 1998;317:241-245 ( 25 July )

Papers

Reduced fetal growth rate and increased risk of death from ischaemic heart disease: cohort study of 15 000 Swedish men and women born 1915-29

David A Leon, senior lecturer, a Hans O Lithell, professor, b Denny Vågerö, professor, c Ilona Koupilová, lecturer, a Rawya Mohsen, programmer, b Lars Berglund, statistician, b Ulla-Britt Lithell, assistant professor, b Paul M McKeigue, reader. a

a Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London WC1E 7HT, b Institute of Geriatrics, University of Uppsala, S-751 25 Uppsala, Sweden, c Department of Sociology, Stockholm University, S-106 91 Stockholm, Sweden

Correspondence to: Dr Leon dleon{at}lshtm.ac.uk

Objective: To establish whether fetal growth rate (as distinct from size at birth) is associated with mortality from ischaemic heart disease.
Design: Cohort study based on uniquely detailed obstetric records with 97% follow up over the entire life course and linkage to census data in adult life.
Subjects: All 14 611 babies delivered at the Uppsala Academic Hospital, Sweden, during 1915-29 followed up to end of 1995. 
Main outcome measures: Mortality from ischaemic heart disease and other causes.
Results: Cardiovascular disease showed an inverse association with birth weight for both men and women, although this was significant only for men. In men a 1000 g increase in birth weight was associated with a proportional reduction in the rate of ischaemic heart disease of 0.77 (95% confidence interval 0.67 to 0.90). Adjustment for socioeconomic circumstances at birth and in adult life led to slight attenuation of this effect. Relative to the lowest fourth of birth weight for gestational age, mortality from ischaemic heart disease in men in the second, third, and fourth fourths was 0.81 (0.66 to 0.98), 0.63 (0.50 to 0.78), and 0.67 (0.54 to 0.82), respectively. The inclusion of birth weight per se and birth weight for gestational age in the same model strengthened the association with birth weight for gestational age but removed the association with birth weight.
Conclusion: This study provides by far the most persuasive evidence of a real association between size at birth and mortality from ischaemic heart disease in men, which cannot be explained by methodological artefact or socioeconomic confounding. It strongly suggests that it is variation in fetal growth rate rather than size at birth that is aetiologically important.

Key messages

  • Adult mortality from ischaemic heart disease increases as size at birth declines

  • This association cannot be explained by artefact including selection bias or socioeconomic confounding

  • The effect of size at birth (birth weight, ponderal index) is explained by the more fundamental association of reduced fetal growth rate with increased mortality from ischaemic heart disease

  • The relevant determinants of fetal growth rate that drive this association have yet to be identified



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