Skip to main content Accessibility help

Birth characteristics and all-cause mortality: a sibling analysis using the Uppsala birth cohort multigenerational study

  • S. Juárez (a1) (a2), A. Goodman (a1) (a3), B. De Stavola (a3) and I. Koupil (a1) (a4)

This paper investigates the association between perinatal health and all-cause mortality for specific age intervals, assessing the contribution of maternal socioeconomic characteristics and the presence of maternal-level confounding. Our study is based on a cohort of 12,564 singletons born between 1915 and 1929 at the Uppsala University Hospital. We fitted Cox regression models to estimate age-varying hazard ratios of all-cause mortality for absolute and relative birth weight and for gestational age. We found that associations with mortality vary by age and according to the measure under scrutiny, with effects being concentrated in infancy, childhood or early adult life. For example, the effect of low birth weight was greatest in the first year of life and then continued up to 44 years of age (HR between 2.82 and 1.51). These associations were confirmed in within-family analyses, which provided no evidence of residual confounding by maternal characteristics. Our findings support the interpretation that policies oriented towards improving population health should invest in birth outcomes and hence in maternal health.

Corresponding author
*Address for correspondence: S. Juárez, Centre for Health Equity Studies, Stockholm University/Karolinska Institute, Sveavägen 160, Sveaplan, Stockholm, Sweden. (Email
Hide All
1. Breslau, N, Johnson, EO, Lucia, VC. Academic achievement of low birthweight children at age 11: the role of cognitive abilities at school entry. J Abnorm Child Psych. 2001; 29, 273279.
2. Tong, S, Baghurst, P, McMichael, A. Birthweight and cognitive development during childhood. J Paediatr Child Health. 2006; 42, 98103.
3. Godfrey, KM, Barker, DJ. Fetal programming and adult health. Public Health Nutr. 2001; 4, 611624.
4. Barker, DJ. Fetal origins of coronary heart disease. BMJ. 1995; 311, 171174.
5. Barker, DJ, Hales, CN, Fall, CH, et al. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia. 1993; 36, 6267.
6. Gillman, MW. A life course approach to obesity. In A Life Course Approach to Chronic Disease Epidemiology (eds. Diana K, Ben-Shlomo Y), 2004; pp. 189217. Oxford University Press: Oxford.
7. Leon, DA, Lithell, HO, Vagero, D, et al. 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, 241245.
8. Risnes, KR, Vatten, LJ, Baker, JL, et al. Birthweight and mortality in adulthood: a systematic review and meta-analysis. Int J Epidemiol. 2011; 40, 647661.
9. Baker, JL, Olsen, LW, Sorensen, TIA. Weight at birth and all-cause mortality in adulthood. Epidemiology. 2008; 19, 197203.
10. Wilcox, AJ, Russell, IT. Birthweight and perinatal mortality: II. On weight-specific mortality. Int J Epidemiol. 1983; 12, 319325.
11. Power, C, Li, L. Cohort study of birthweight, mortality, and disability. BMJ. 2000; 320, 840841.
12. Friedlander, Y, Paltiel, O, Deutsch, L, et al. Birthweight and relationship with infant, child and adult mortality in the Jerusalem perinatal study. Paediatr Perinat Epidemiol. 2003; 17, 398406.
13. Kajantie, E, Osmond, C, Barker, DJP, et al. Size at birth as a predictor of mortality in adulthood: a follow-up of 350,000 person-years. Int J Epidemiol. 2005; 34, 655663.
14. Malin, GL, Morris, RK, Riley, R, Teune, MJ, Khan, KS. When is birthweight at term abnormally low? A systematic review and meta-analysis of the association and predictive ability of current birthweight standards for neonatal outcomes. BJOG. 2014; 121, 515526.
15. Sovio, U, Jones, R, Dos Santos Silva, I, Koupil, I. Birth size and survival in breast cancer patients from the Uppsala Birth Cohort Study. Cancer Causes Control. 2013; 24, 16431651.
16. Andersen, AM, Osler, M. Birth dimensions, parental mortality, and mortality in early adult age: a cohort study of Danish men born in 1953. Int J Epidemiol. 2004; 33, 9299.
17. Eriksson, M, Wallander, MA, Krakau, I, Wedel, H, Svardsudd, K. The impact of birth weight on coronary heart disease morbidity and mortality in a birth cohort followed up for 85 years: a population-based study of men born in 1913. J Intern Med. 2004; 256, 472481.
18. Smith, GD, Hart, C, Blane, D, Gillis, C, Hawthorne, V. Lifetime socioeconomic position and mortality: prospective observational study. BMJ. 1997; 314, 547552.
19. Gluckman, P, Hanson, M. Developmental Origins of Health and Disease. 2006. Cambridge University Press: Cambridge.
20. Class, QA, Rickert, ME, Lichtenstein, P, D’Onofrio, BM. Birth weight, physical morbidity, and mortality: a population-based sibling-comparison study. Am J Epidemiol. 2014; 179, 550558.
21. Joseph, KS, Kramer, MS. Review of the evidence on fetal and early childhood antecedents of adult chronic disease. Epidemiol Rev. 1996; 18, 158174.
22. Barker, D. Fetal and Infant Origins of Adult Disease. 1992. Wiley-Blackwell: London.
23. Kuh, D, Ben-Shlomo, Y, Lynch, J, Hallqvist, J, Power, C. Life course epidemiology. J Epidemiol Community Health. 2003; 57, 778783.
24. Maggi, S, Irwin, LJ, Siddiqi, A, Hertzman, C. The social determinants of early child development: an overview. J Paediatr Child Health. 2010; 46, 627635.
25. Juarez, SP, Merlo, J. Revisiting the effect of maternal smoking during pregnancy on offspring birthweight: a quasi-experimental sibling analysis in Sweden. PLoS One. 2013; 8, e61734.
26. Koupil, I. The Uppsala studies on developmental origins of health and disease. J Intern Med. 2007; 261, 426436.
27. Koupil, I, Goodman, A. Health Equity: a life course approach. Public Service Review: European Union. 2011; 11, 3.
28. Cunningham, FG, Leveno, KJ, Bloom, SL, et al. Williams Obstetrics, 22nd edn, 2005. McGraw-Hill: New York.
29. Kramer, MS, Platt, RW, Wen, SW, et al. A new and improved population-based Canadian reference for birth weight for gestational age. Pediatrics. 2001; 108, E35.
30. Meddelanden i samordningsfrågor [Report on co-ordination issues], 1989. Statistics Sweden: Stockholm.
31. Goodman, A, Gisselman, MD, Koupil, I. Birth characteristics and early-life social charactristics predict unequal educational outcomes across the life course and across generations. Longit Life Course Stud. 2010; 1, 317338.
32. Mathers, CD, Bernard, C, Iburg, MK, et al. Global Burden of Disease in 2002: Data Sources, Methods and Results. 2003. World Health Organization: Geneva.
33. Clayton, D, Hill, M. Statistical Models in Epidemiology. 1993. Oxford Science Publications: Oxford.
34. Mann, V, De Stavola, BL, Leon, DA. Separating within and between effects in family studies: an application to the study of blood pressure in children. Stat Med. 2004; 23, 27452756.
35. Goodman, A, Heshmati, A, Malki, N, Koupil, I. Associations between birth characteristics and eating disorders across the life course: findings from 2 million males and females born in Sweden, 1975–1998. Am J Epidemiol. 2014; 179, 852863.
36. Frisell, T, Oberg, S, Kuja-Halkola, R, Sjolander, A. Sibling comparison designs bias from non-shared confounders and measurement error. Epidemiology. 2012; 23, 713720.
37. Swamy, GK, Ostbye, T, Skjaerven, R. Association of preterm birth with long-term survival, reproduction, and next-generation preterm birth. J Am Med Assoc. 2008; 299, 14291436.
38. Koupil, I, Leon, DA, Lithell, HO. Length of gestation is associated with mortality from cerebrovascular disease. J Epidemiol Community Health. 2005; 59, 473474.
39. Rajaleid, K, Manor, O, Koupil, I. Does the strength of the association between foetal growth rate and ischaemic heart disease mortality differ by social circumstances in early or later life? J Epidemiol Community Health. 2008; 62, e6.
40. Chauhan, SP, Grobman, WA, Gherman, RA, et al. Suspicion and treatment of the macrosomic fetus: a review. Am J Obstet Gynecol. 2005; 193, 332346.
41. Barker, DJP. In utero programming of chronic disease. Clin Sci. 1998; 95, 115128.
42. Silva dos Santos, I, De Stavola, B, McCormack, V. Factors and subsequent risk of breast cancer. Birth size and breast cancer risk: re-analysis of individual participant data from 32 studies. PLoS Med. 2008; 5, 13721386.
43. Ross, JA. High birthweight and cancer: evidence and implications. Cancer Epidem Biomar. 2006; 15, 12.
44. Wilcox, AJ. On the importance - and the unimportance - of birthweight. Int J Epidemiol. 2001; 30, 12331241.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Journal of Developmental Origins of Health and Disease
  • ISSN: 2040-1744
  • EISSN: 2040-1752
  • URL: /core/journals/journal-of-developmental-origins-of-health-and-disease
Please enter your name
Please enter a valid email address
Who would you like to send this to? *


Type Description Title
Supplementary materials

Juárez supplementary material

 Word (85 KB)
85 KB


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed