European Journal of Epidemiology

, Volume 30, Issue 6, pp 485–492 | Cite as

Size at birth and risk of breast cancer: update from a prospective population-based study

  • Marie Søfteland Sandvei
  • Pagona Lagiou
  • Pål Richard Romundstad
  • Dimitrios Trichopoulos
  • Lars Johan Vatten


Birth size variables (birth weight, birth length and head circumference) have been reported to be positively associated with adult breast cancer risk, whereas a possible association of placental weight has not been adequately studied. It has also been suggested that maternal height may modify the association of birth size with adult breast cancer risk, but this has not been studied in detail. We updated a long-term follow-up of 22,931 Norwegian women (average of 51 years of follow up during which 870 women were diagnosed with breast cancer) and assessed placental weight in relation to breast cancer risk, in addition to providing updated analyses on breast cancer risk in relation to birth weight, birth length and head circumference. Placental weight was not associated with risk for breast cancer in adulthood, but there was a positive association of breast cancer risk with birth length (HR 1.13, 95 % CI 1.05–1.21, per 2 cm increment), though not with birth weight (HR 1.02, 95 % CI 0.95–1.10 per 0.5 kg increment). For birth length, the graded increase in risk was particularly strong among women whose mothers were relatively tall (p for trend, 0.001), compared to the trend among women whose mothers were relatively short (p for trend, 0.221). The results showed a robust and positive association of birth length with breast cancer risk, and may be especially strong in women whose mothers were relatively tall. We found no association of placental weight with risk for breast cancer.


Breast cancer Birth size Birth length Prospective Population-based 



The St. Olav Birth Cohort study was established by a Grant from the National Institutes of Health (RO1 CA 78761), and subsequently supported by the Norwegian Cancer Society and the Norwegian Research Council. MSS is a postdoctoral fellow financed by the Norwegian Cancer Society.

Conflict of interest

The authors have no conflict of interest to declare.


  1. 1.
    Trichopoulos D. Hypothesis: does breast cancer originate in utero? Lancet. 1990;335:939–40.PubMedCrossRefGoogle Scholar
  2. 2.
    Vatten LJ, Nilsen TI, Tretli S, Trichopoulos D, Romundstad PR. Size at birth and risk of breast cancer: prospective population-based study. Int J Cancer. 2005;114:461–4.PubMedCrossRefGoogle Scholar
  3. 3.
    Russo J, Rivera R, Russo IH. Influence of age and parity on the development of the human breast. Breast Cancer Res Treat. 1992;23:211–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Trichopoulos D, Adami HO, Ekbom A, Hsieh CC, Lagiou P. Early life events and conditions and breast cancer risk: from epidemiology to etiology. Int J Cancer. 2008;122:481–5.PubMedCrossRefGoogle Scholar
  5. 5.
    Hoover RN, Hyer M, Pfeiffer RM, Adam E, Bond B, Cheville AL, et al. Adverse health outcomes in women exposed in utero to diethylstilbestrol. N Engl J Med. 2011;365:1304–14.PubMedCrossRefGoogle Scholar
  6. 6.
    Adami HO, Lagiou P, Trichopoulos D. Breast cancer following diethylstilbestrol exposure in utero: insights from a tragedy. Eur J Epidemiol. 2012;27:1–3.PubMedCrossRefGoogle Scholar
  7. 7.
    Lagiou P, Samoli E, Okulicz W, Xu B, Lagiou A, Lipworth L, et al. Maternal and cord blood hormone levels in the United States and China and the intrauterine origin of breast cancer. Ann Oncol. 2011;22:1102–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Michels KB, Xue F. Role of birthweight in the etiology of breast cancer. Int J Cancer. 2006;119:2007–25.PubMedCrossRefGoogle Scholar
  9. 9.
    dos Santos Silva I, De Stavola B, McCormack V. Birth size and breast cancer risk: re-analysis of individual participant data from 32 studies. PLoS Med. 2008;5:e193.PubMedCentralCrossRefGoogle Scholar
  10. 10.
    Park SK, Kang D, McGlynn KA, Garcia-Closas M, Kim Y, Yoo KY, et al. Intrauterine environments and breast cancer risk: meta-analysis and systematic review. Breast Cancer Res. 2008;10:R8.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Savarese TM, Strohsnitter WC, Low HP, Liu Q, Baik I, Okulicz W, et al. Correlation of umbilical cord blood hormones and growth factors with stem cell potential: implications for the prenatal origin of breast cancer hypothesis. Breast Cancer Res. 2007;9:R29.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Strohsnitter WC, Savarese TM, Low HP, Chelmow DP, Lagiou P, Lambe M, et al. Correlation of umbilical cord blood haematopoietic stem and progenitor cell levels with birth weight: implications for a prenatal influence on cancer risk. Br J Cancer. 2008;98:660–3.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Qiu L, Low HP, Chang CI, Strohsnitter WC, Anderson M, Edmiston K, et al. Novel measurements of mammary stem cells in human umbilical cord blood as prospective predictors of breast cancer susceptibility in later life. Ann Oncol. 2012;23:245–50.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Lagiou P, Hsieh CC, Samoli E, Lagiou A, Xu B, Yu GP, et al. Associations of placental weight with maternal and cord blood hormones. Ann Epidemiol. 2013;23:669–73.PubMedCrossRefGoogle Scholar
  15. 15.
    Vatten LJ, Maehle BO, Lund Nilsen TI, Tretli S, Hsieh CC, Trichopoulos D, et al. Birth weight as a predictor of breast cancer: a case-control study in Norway. Br J Cancer. 2002;86:89–91.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Ekbom A, Trichopoulos D, Adami HO, Hsieh CC, Lan SJ. Evidence of prenatal influences on breast cancer risk. Lancet. 1992;340:1015–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Ekbom A, Hsieh CC, Lipworth L, Adami HQ, Trichopoulos D. Intrauterine environment and breast cancer risk in women: a population-based study. J Natl Cancer Inst. 1997;89:71–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Lagiou P, Samoli E, Lagiou A, Hsieh CC, Adami HO, Trichopoulos D. Maternal height, pregnancy estriol and birth weight in reference to breast cancer risk in Boston and Shanghai. Int J Cancer. 2005;117:494–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Lagiou P, Trichopoulos D, Hsieh CC. Is maternal height a risk factor for breast cancer? Eur J Cancer Prev. 2013;22:389–90.PubMedCrossRefGoogle Scholar
  20. 20.
    Heinonen S, Taipale P, Saarikoski S. Weights of placentae from small-for-gestational age infants revisited. Placenta. 2001;22:399–404.PubMedCrossRefGoogle Scholar
  21. 21.
    Thame M, Osmond C, Bennett F, Wilks R, Forrester T. Fetal growth is directly related to maternal anthropometry and placental volume. Eur J Clin Nutr. 2004;58:894–900.PubMedCrossRefGoogle Scholar
  22. 22.
    Ekbom A, Thurfjell E, Hsieh CC, Trichopoulos D, Adami HO. Perinatal characteristics and adult mammographic patterns. Int J Cancer. 1995;61:177–80.PubMedCrossRefGoogle Scholar
  23. 23.
    McCormack VA, dos Santos Silva I. Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomark Prev. 2006;15:1159–69.CrossRefGoogle Scholar
  24. 24.
    Xue F, Michels KB. Intrauterine factors and risk of breast cancer: a systematic review and meta-analysis of current evidence. Lancet Oncol. 2007;8:1088–100.PubMedCrossRefGoogle Scholar
  25. 25.
    Potischman N, Troisi R. In-utero and early life exposures in relation to risk of breast cancer. Cancer Causes Control. 1999;10:561–73.PubMedCrossRefGoogle Scholar
  26. 26.
    Boyd PA, Scott A. Quantitative structural studies on human placentas associated with pre-eclampsia, essential hypertension and intrauterine growth retardation. Br J Obstet Gynaecol. 1985;92:714–21.PubMedCrossRefGoogle Scholar
  27. 27.
    Akhlaq M, Nagi AH, Yousaf AW. Placental morphology in pre-eclampsia and eclampsia and the likely role of NK cells. Indian J Pathol Microbiol. 2012;55:17–21.PubMedCrossRefGoogle Scholar
  28. 28.
    Teasdale F. Histomorphometry of the human placenta in maternal preeclampsia. Am J Obstet Gynecol. 1985;152:25–31.PubMedCrossRefGoogle Scholar
  29. 29.
    Risnes KR, Romundstad PR, Nilsen TI, Eskild A, Vatten LJ. Placental weight relative to birth weight and long-term cardiovascular mortality: findings from a cohort of 31,307 men and women. Am J Epidemiol. 2009;170:622–31.PubMedCrossRefGoogle Scholar
  30. 30.
    Burkhardt T, Schaffer L, Schneider C, Zimmermann R, Kurmanavicius J. Reference values for the weight of freshly delivered term placentas and for placental weight-birth weight ratios. Eur J Obstet Gynecol Reprod Biol. 2006;128:248–52.PubMedCrossRefGoogle Scholar
  31. 31.
    Farrar D, Airey R, Law GR, Tuffnell D, Cattle B, Duley L. Measuring placental transfusion for term births: weighing babies with cord intact. BJOG Int J Obstet Gynaecol. 2011;118:70–5.CrossRefGoogle Scholar
  32. 32.
    Lundberg C, Oian P, Klingenberg C. Umbilical cord clamping at birth–practice in Norwegian maternity wards. Tidsskr Nor Laegeforen. 2013;133:2369–73.PubMedCrossRefGoogle Scholar
  33. 33.
    Johnson TS, Engstrom JL, Gelhar DK. Intra- and interexaminer reliability of anthropometric measurements of term infants. J Pediatr Gastroenterol Nutr. 1997;24:497–505.PubMedCrossRefGoogle Scholar
  34. 34.
    Lagiou P, Hsieh CC, Trichopoulos D, Xu B, Wuu J, Mucci L, et al. Birthweight differences between USA and China and their relevance to breast cancer aetiology. Int J Epidemiol. 2003;32:193–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Lagiou P, Hsieh CC, Lipworth L, Samoli E, Okulicz W, Troisi R, et al. Insulin-like growth factor levels in cord blood, birth weight and breast cancer risk. Br J Cancer. 2009;100:1794–8.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Lagiou P, Samoli E, Hsieh CC, Lagiou A, Xu B, Yu GP, et al. Maternal and cord blood hormones in relation to birth size. Eur J Epidemiol. 2014;29:343–51.PubMedCrossRefGoogle Scholar
  37. 37.
    Horn J, Alsaker MD, Opdahl S, Engstrom MJ, Tretli S, Haugen OA, et al. Anthropometric factors and risk of molecular breast cancer subtypes among postmenopausal Norwegian women. Int J Cancer. 2014;135:2678–86.PubMedCrossRefGoogle Scholar
  38. 38.
    Horn J, Opdahl S, Engstrom MJ, Romundstad PR, Tretli S, Haugen OA, et al. Reproductive history and the risk of molecular breast cancer subtypes in a prospective study of Norwegian women. Cancer Causes Control. 2014;25:881–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Tamimi RM, Colditz GA, Hazra A, Baer HJ, Hankinson SE, Rosner B, et al. Traditional breast cancer risk factors in relation to molecular subtypes of breast cancer. Breast Cancer Res Treat. 2012;131:159–67.PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Yang XR, Chang-Claude J, Goode EL, Couch FJ, Nevanlinna H, Milne RL, et al. Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies. J Natl Cancer Inst. 2011;103:250–63.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Marie Søfteland Sandvei
    • 1
    • 2
  • Pagona Lagiou
    • 3
    • 4
  • Pål Richard Romundstad
    • 1
  • Dimitrios Trichopoulos
    • 3
    • 4
  • Lars Johan Vatten
    • 1
    • 4
  1. 1.Department of Public Health and General PracticeNorwegian University of Science and TechnologyTrondheimNorway
  2. 2.Nordland Hospital BodøBodøNorway
  3. 3.Department of Hygiene and Medical Statistics, School of MedicineUniversity of AthensAthensGreece
  4. 4.Department of EpidemiologyHarvard School of Public HealthBostonUSA

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