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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

BMJ 1998; 317 doi: (Published 25 July 1998) Cite this as: BMJ 1998;317:241
  1. David A Leon (dleon{at}, senior lecturera,
  2. Hans O Lithell, professorb,
  3. Denny Vågerö, professorc,
  4. Ilona Koupilová, lecturera,
  5. Rawya Mohsen, programmerb,
  6. Lars Berglund, statisticianb,
  7. Ulla-Britt Lithell, assistant professorb,
  8. Paul M McKeigue, readera
  1. aDepartment of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London WC1E 7HT
  2. bInstitute of Geriatrics, University of Uppsala, S-751 25 Uppsala, Sweden
  3. cDepartment of Sociology, Stockholm University, S-106 91 Stockholm, Sweden
  1. Correspondence to: Dr Leon


    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.

    Conclusions: 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.


    • Contributors The planning of analyses and interpretation of the data was the product of discussions involving all authors, all of whom also commented on drafts of the paper. DAL and PMMcK had the original idea for the study and oversaw its conduct together with HOL and DV. The collection of the obstetric data and the tracing through the parish archives was supervised by RM and UBL. Advice on the use of socioeconomic data at birth was provided by UBL. Advice on obtaining and using the census data was provided by DV. RM and LB undertook the construction of the study database and its cleaning and documentation. IK assisted with the development of systematic checks on the quality of the obstetric and cause of death data and its documentation. Background and interim analyses of results were carried out by IK, LB, and RM. Final analyses and drafting of the original and revised manuscripts were undertaken by DAL, who will act as guarantor.

    • Funding This work was supported through grants from the UK Medical Research Council (grant No 9322050), the Swedish Council for Social Research (grant No 94/0157), and the Swedish Medical Research Council (grant No 5446). During part of her work on this study IK was in receipt of a Royal Society postdoctoral research fellowship.

    • Conflict of interest None

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