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Early life body size, pubertal timing, and risks of benign breast disease in a large cohort of Danish female adolescents and women

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Abstract

A high childhood body mass index (BMI) may be protective against benign breast disease (BBD), but little is known about the effects of other early life body size measures. Thus, we examined associations between birthweight, childhood BMI, height, and pubertal timing and BBD risks. We included 171,272 girls, born from 1930 to 1996, from the Copenhagen School Health Records Register, which contains information on birthweight, childhood anthropometry (7–13 years), age at onset of the growth spurt (OGS), and peak height velocity (PHV). During follow-up, 9361 BBD cases (15–50 years) were registered in the Danish National Patient Register. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regressions. At all childhood ages, BMI was inversely but non-linearly associated with BBD. The association was slightly stronger in magnitude for BMI z-scores above 0 (HRage 7 = 0.86; 95%CI: 0.83–0.90 per z-score) than below 0 (HRage 7 = 0.95; 95%CI 0.91–0.99 per z-score). Associations between childhood height and BBD differed by age; at 7 years the association was an inverted U-shape, whereas at 13 years height was not associated with BBD. Ages at OGS and PHV were positively associated with BBD. Low and high birthweights were associated with lower BBD risks.

   Conclusion: A high childhood BMI, a short or tall stature at young childhood ages, an early pubertal onset, and low or high birthweights are associated with reduced risks of BBD. These complex associations suggest that the role of these factors in breast tissue development during early life warrants further investigation in relation to BBD etiology.

What is Known:

• Benign breast disease (BBD) is common and may be an intermediary marker of breast cancer risks.

• Early life body size may relate to the development of BBD, but currently little is known.

What is New:

• Girls with a high body mass index at school ages or with an early pubertal timing have decreased risks of BBD.

• Short and tall heights at young childhood ages and low and high birthweights are associated with lower BBD risks.

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Availability of data and material

The data used in this study are based on a combination of data with personal identification numbers from the Copenhagen School Health Records Register, hosted by the Center for Clinical Research and Prevention, and data from national health registers. According to Danish law, this information cannot be publicly available. Access to the subset of data included in this study can be gained through submitting a project application to Jennifer L. Baker, and pending approval by the data steering committee.

Code availability

Can be gained upon request to the corresponding author Julie Aarestrup.

Abbreviations

BBD:

Benign breast disease

BMI:

Body mass index

CI:

Confidence interval

CSHRR:

Copenhagen School Health Records Register

HR:

Hazard ratio

ICD:

International Classification of Disease

kg:

Kilogram

OR:

Odds ratio

OGS:

Onset of the growth spurt

PHV:

Peak height velocity

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Acknowledgements

The CSHRR was initiated and planned by Dr. Thorkild I.A. Sørensen and built by the Institute of Preventive Medicine, The Capital Region of Denmark.

Funding

The study was supported by the World Cancer Research Fund (grant number 2018/1760, 2018) to JLB. The funding source had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication.

Author information

Authors and Affiliations

  1. Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark

    Julie Aarestrup, Britt W. Jensen, Dorthe C. Pedersen, Jennifer L. Baker & Lise G. Bjerregaard

  2. Danish Cancer Society Research Center, Copenhagen, Denmark

    Niels Kroman & Lene Mellemkjær

  3. Department of Breast Surgery, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark

    Niels Kroman

Authors
  1. Julie Aarestrup
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  2. Britt W. Jensen
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  5. Lene Mellemkjær
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  6. Jennifer L. Baker
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  7. Lise G. Bjerregaard
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Contributions

JAA, JLB, and LGB conceived the study, and all authors were involved in the design of the study. JAA and LGB did the statistical analysis. All authors were involved in the data interpretation. JAA, JLB, and LGB drafted the manuscript. All authors critically revised the manuscript for important intellectual content and approved the final version of this manuscript. LGB had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Corresponding author

Correspondence to Julie Aarestrup.

Ethics declarations

Ethics approval

The study was approved by the Danish Data Protection Agency. According to Danish law, informed consent is not required for purely register-based research of pre-existing personal data nor is ethical approval.

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Not applicable.

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Not applicable.

Conflict of interest

The authors declare no competing interests.

Additional information

Communicated by Gregorio Paolo Milani

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Aarestrup, J., Jensen, B.W., Pedersen, D.C. et al. Early life body size, pubertal timing, and risks of benign breast disease in a large cohort of Danish female adolescents and women. Eur J Pediatr 181, 3023–3030 (2022). https://doi.org/10.1007/s00431-021-04363-x

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  • DOI: https://doi.org/10.1007/s00431-021-04363-x

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