Skip to main content

Advertisement

Log in

Breastfeeding and ApoB in late adolescence: a Hong Kong birth cohort study

  • RESEARCH
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Breastfeeding is widely promoted. Experimental evidence concerning long-term benefits is limited. Observational studies are open to bias from confounding by socio-economic position. We assessed the association of breastfeeding with late adolescent lipid sub-fractions, particularly apolipoprotein B (ApoB) and non-high-density lipoprotein cholesterol (non-HDL-c), overall and by sex. We took advantage of a setting where breastfeeding has little association with higher socio-economic position and where several results from randomized controlled trials of breastfeeding promotion have been replicated. We used the population-representative “Children of 1997” birth cohort comprising 88% of births in Hong Kong in April and May 1997. Associations of breastfeeding in the first 3 months of life (never, mixed, exclusive) with lipid sub-fractions were obtained using linear regression adjusted for potential confounders including parental socio-economic position, maternal place of birth, type of delivery, gestational age, and birth weight. Differences by sex were assessed. Multiple imputation and inverse probability weighting were used to recover the original sample. Of the 3462 participants included, mean age was 17.6 years and 48.8% were girls. Mean ApoB was 0.74 g/L (standard deviation 0.15). Exclusive versus never breastfeeding was associated with lower ApoB (−0.027 g/L, 95% confidence interval (CI)−0.046 to−0.007, p = 0.007) and lower non-HDL-c (−0.143 mmol/L, 95% CI−0.237 to−0.048) with similar estimates by sex.

Conclusion: Breastfeeding may provide some population-level lifelong protection against cardiovascular disease. This study supports policies promoting breastfeeding as a modifiable exposure that contributes to a healthy start in life as an investment for lifelong cardiovascular disease prevention.

What is Known:

• Apolipoprotein B (ApoB) is a recognized risk factor for cardiovascular disease, but whether breastfeeding affects ApoB in later life overall and by sex is unknown.

What is New:

• Exclusive breastfeeding in the first 3 months of life was associated with lower ApoB in late adolescence, with similar estimates for both sexes.

• The inverse association of breastfeeding with ApoB suggests that breastfeeding could reduce cardiovascular disease and overall mortality over the lifespan.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Data availability

The data used here is available on request.

Abbreviations

ApoB:

Apolipoprotein B

HDL-c:

High-density lipoprotein cholesterol

LDL-c:

Low-density lipoprotein cholesterol

MCHC:

Maternal and Child Health Centre

Q-Q:

Quantile-quantile

SHS:

Second-hand smoking

US:

United States

References

  1. Singhal A (2016) The role of infant nutrition in the global epidemic of non-communicable disease. Proc Nutr Soc 75:162–168

    Article  PubMed  Google Scholar 

  2. Delplanque B, Gibson R, Koletzko B, Lapillonne A, Strandvik B (2015) Lipid quality in infant nutrition: current knowledge and future opportunities. J Pediatr Gastroenterol Nutr 61:8–17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Wong WW, Hachey DL, Insull W, Opekun AR, Klein PD (1993) Effect of dietary cholesterol on cholesterol synthesis in breast-fed and formula-fed infants. J Lipid Res 34:1403–1411

    Article  CAS  PubMed  Google Scholar 

  4. Demmers TA, Jones PJ, Wang Y, Krug S, Creutzinger V, Heubi JE (2005) Effects of early cholesterol intake on cholesterol biosynthesis and plasma lipids among infants until 18 months of age. Pediatrics 115:1594–1601

    Article  PubMed  Google Scholar 

  5. George AD, Burugupalli S, Paul S, Mansell T, Burgner D, Meikle PJ (2022) The role of human milk lipids and lipid metabolites in protecting the infant against non-communicable disease. Int J Mol Sci;23(14):7490

  6. Juhola J, Magnussen CG, Viikari JS, Kähönen M, Hutri-Kähönen N, Jula A, Lehtimäki T, Åkerblom HK, Pietikäinen M, Laitinen T, Jokinen E, Taittonen L, Raitakari OT, Juonala M (2011) Tracking of serum lipid levels, blood pressure, and body mass index from childhood to adulthood: the Cardiovascular Risk in Young Finns Study. J Pediatr 159:584–590

    Article  CAS  PubMed  Google Scholar 

  7. Singhal A, Cole TJ, Fewtrell M, Lucas A (2004) Breastmilk feeding and lipoprotein profile in adolescents born preterm: follow-up of a prospective randomised study. Lancet 363:1571–1578

    Article  CAS  PubMed  Google Scholar 

  8. Bergstrom E, Hernell O, Persson LA, Vessby B (1995) Serum lipid values in adolescents are related to family history, infant feeding, and physical growth. Atherosclerosis 117:1–13

    Article  CAS  PubMed  Google Scholar 

  9. Brion MJ (2010) Commentary: assessing the impact of breastfeeding on child health: where conventional methods alone fall short for reliably establishing causal inference. Int J Epidemiol 39:306–307

    Article  PubMed  Google Scholar 

  10. Kwok MK, Schooling CM, Lam TH, Leung GM (2010) Does breastfeeding protect against childhood overweight? Hong Kong’s ‘Children of 1997’ birth cohort. Int J Epidemiol 39:297–305

    Article  PubMed  Google Scholar 

  11. Kwok MK, Leung GM, Schooling CM (2013) Breastfeeding and adolescent blood pressure: evidence from Hong Kong’s “Children of 1997” birth cohort. Am J Epidemiol 178:928–936

    Article  PubMed  Google Scholar 

  12. Leung JY, Kwok MK, Leung GM, Schooling CM (2016) Breastfeeding and childhood hospitalizations for asthma and other wheezing disorders. Ann Epidemiol 26(21–27):e21-23

    Article  Google Scholar 

  13. Kwok MK, Leung GM, Schooling CM (2013) Breast feeding and early adolescent behaviour, self-esteem and depression: Hong Kong’s ‘Children of 1997’ birth cohort. Arch Dis Child 98:887–894

    Article  PubMed  Google Scholar 

  14. Kramer MS, Guo T, Platt RW, Shapiro S, Collet JP, Chalmers B, Hodnett E, Sevkovskaya Z, Dzikovich I, Vanilovich I (2002) Breastfeeding and infant growth: biology or bias? Pediatrics 110:343–347

    Article  PubMed  Google Scholar 

  15. Flohr C, Henderson AJ, Kramer MS, Patel R, Thompson J, Rifas-Shiman SL, Yang S, Vilchuck K, Bogdanovich N, Hameza M, Martin RM, Oken E (2018) Effect of an intervention to promote breastfeeding on asthma, lung function, and atopic eczema at age 16 years: follow-up of the PROBIT randomized trial. JAMA Pediatr 172:e174064

    Article  PubMed  Google Scholar 

  16. Kramer MS, Matush L, Vanilovich I, Platt R, Bogdanovich N, Sevkovskaya Z, Dzikovich I, Shishko G, Mazer B (2007) Effect of prolonged and exclusive breast feeding on risk of allergy and asthma: cluster randomised trial. BMJ 335:815

    Article  PubMed  PubMed Central  Google Scholar 

  17. Kramer MS, Fombonne E, Igumnov S, Vanilovich I, Matush L, Mironova E, Bogdanovich N, Tremblay RE, Chalmers B, Zhang X, Platt RW (2008) Effects of prolonged and exclusive breastfeeding on child behavior and maternal adjustment: evidence from a large, randomized trial. Pediatrics 121:e435-440

    Article  PubMed  Google Scholar 

  18. Kramer MS, Matush L, Vanilovich I, Platt RW, Bogdanovich N, Sevkovskaya Z, Dzikovich I, Shishko G, Collet JP, Martin RM, Smith GD, Gillman MW, Chalmers B, Hodnett E, Shapiro S (2009) A randomized breast-feeding promotion intervention did not reduce child obesity in Belarus. J Nutr 139:417s–421s

    Article  CAS  PubMed  Google Scholar 

  19. Kramer MS, Matush L, Vanilovich I, Platt RW, Bogdanovich N, Sevkovskaya Z, Dzikovich I, Shishko G, Collet JP, Martin RM, Davey Smith G, Gillman MW, Chalmers B, Hodnett E, Shapiro S (2007) Effects of prolonged and exclusive breastfeeding on child height, weight, adiposity, and blood pressure at age 6.5 y: evidence from a large randomized trial. Am J Clin Nutr 86:1717–1721

    Article  CAS  PubMed  Google Scholar 

  20. White-Al Habeeb NMA, Higgins V, Wolska A, Delaney SR, Remaley AT, Beriault DR (2023) The present and future of lipid testing in cardiovascular risk assessment. Clin Chem 69:456-469

  21. Ezzati M, Obermeyer Z, Tzoulaki I, Mayosi BM, Elliott P, Leon DA (2015) Contributions of risk factors and medical care to cardiovascular mortality trends. Nat Rev Cardiol 12:508–530

    Article  PubMed  PubMed Central  Google Scholar 

  22. Jungner I, Marcovina SM, Walldius G, Holme I, Kolar W, Steiner E (1998) Apolipoprotein B and A-I values in 147576 Swedish males and females, standardized according to the World Health Organization-International Federation of Clinical Chemistry First International Reference Materials. Clin Chem 44:1641–1649

    Article  CAS  PubMed  Google Scholar 

  23. Schooling CM, Hui LL, Ho LM, Lam TH, Leung GM (2012) Cohort profile: ‘Children of 1997’: a Hong Kong Chinese birth cohort. Int J Epidemiol 41:611–620

    Article  PubMed  Google Scholar 

  24. Mora S, Otvos JD, Rifai N, Rosenson RS, Buring JE, Ridker PM (2009) Lipoprotein particle profiles by nuclear magnetic resonance compared with standard lipids and apolipoproteins in predicting incident cardiovascular disease in women. Circulation 119:931–939

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Holmes MV, Millwood IY, Kartsonaki C, Hill MR, Bennett DA, Boxall R, Guo Y, Xu X, Bian Z, Hu R, Walters RG, Chen J, Ala-Korpela M, Parish S, Clarke RJ, Peto R, Collins R, Li L, Chen Z (2018) Lipids, lipoproteins, and metabolites and risk of myocardial infarction and stroke. J Am Coll Cardiol 71:620–632

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bareinboim E, Pearl J (2016) Causal inference and the data-fusion problem. Proc Natl Acad Sci U S A 113:7345–7352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Paternoster R, Brame R, Mazerolle P, Piquero A (1998) Using the correct statistical test for the equality of regression coefficients. Criminology 36:7

    Article  Google Scholar 

  28. Seaman SR, White IR, Copas AJ, Li L (2012) Combining multiple imputation and inverse-probability weighting. Biometrics 68:8

    Article  Google Scholar 

  29. Sterne JA, White IR, Carlin JB, Spratt M, Royston P, Kenward MG, Wood AM, Carpenter JR (2009) Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls. BMJ 338:b2393

    Article  PubMed  PubMed Central  Google Scholar 

  30. Harrell FE (2001) Regression modeling strategies: with applications to linear models, logistic regression, and survival analysis. Springer, New York, London

    Book  Google Scholar 

  31. Moons KG, Donders RA, Stijnen T, Harrell FE Jr (2006) Using the outcome for imputation of missing predictor values was preferred. J Clin Epidemiol 59:1092–1101

    Article  PubMed  Google Scholar 

  32. Schafer JL (1999) Multiple imputation: a primer. Stat Methods Med Res 8:3–15

    Article  CAS  PubMed  Google Scholar 

  33. Hui LL, Kwok MK, Nelson EAS, Lee SL, Leung GM, Schooling CM (2018) The association of breastfeeding with insulin resistance at 17 years: prospective observations from Hong Kong’s “Children of 1997” birth cohort. Matern Child Nutr 14:e12490

  34. Matthay EC, Hagan E, Gottlieb LM, Tan ML, Vlahov D, Adler N, Glymour MM (2021) Powering population health research: considerations for plausible and actionable effect sizes. SSM Popul Health 14:100789

    Article  PubMed  PubMed Central  Google Scholar 

  35. Rose G (1981) Strategy of prevention: lessons from cardiovascular disease. Br Med J (Clin Res Ed) 282:1847–1851

    Article  CAS  PubMed  Google Scholar 

  36. Fall CH, Barker DJ, Osmond C, Winter PD, Clark PM, Hales CN (1992) Relation of infant feeding to adult serum cholesterol concentration and death from ischaemic heart disease. BMJ 304:801–805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Dathan-Stumpf A, Vogel M, Hiemisch A, Thiery J, Burkhardt R, Kratzsch J, Kiess W (2016) Pediatric reference data of serum lipids and prevalence of dyslipidemia: results from a population-based cohort in Germany. Clin Biochem 49:740–749

    Article  CAS  PubMed  Google Scholar 

  38. Liu J, Dai Y, Yuan E, Li Y, Wang Q, Wang L, Su Y (2019) Age-specific and sex-specific reference intervals for non-fasting lipids and apolipoproteins in 7260 healthy Chinese children and adolescents measured with an Olympus AU5400 analyser: a cross-sectional study. BMJ Open 9:e030201

    Article  PubMed  PubMed Central  Google Scholar 

  39. Contois JH, McNamara JR, Lammi-Keefe CJ, Wilson PW, Massov T, Schaefer EJ (1996) Reference intervals for plasma apolipoprotein B determined with a standardized commercial immunoturbidimetric assay: results from the Framingham Offspring Study. Clin Chem 42:515–523

    Article  CAS  PubMed  Google Scholar 

  40. Yang Z, Kwok MK, Schooling CM (2022) Do deaths from competing risks influence COPD patterns in China and high socio-demographic index countries?: a cross-sectional analysis of summary statistics from the Global Burden of Disease Study 2017. BMJ Open 12:e050080

    Article  PubMed  Google Scholar 

  41. Hui LL, Kwok MK, Nelson EAS, Lee SL, Leung GM, Schooling CM (2019) Breastfeeding in infancy and lipid profile in adolescence. Pediatrics 143:e20183075

  42. Richardson TG, Sanderson E, Palmer TM, Ala-Korpela M, Ference BA, Davey Smith G, Holmes MV (2020) Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: a multivariable Mendelian randomisation analysis. PLoS Med 17:e1003062

    Article  PubMed  PubMed Central  Google Scholar 

  43. Ference BA, Kastelein JJP, Ray KK, Ginsberg HN, Chapman MJ, Packard CJ, Laufs U, Oliver-Williams C, Wood AM, Butterworth AS, Di Angelantonio E, Danesh J, Nicholls SJ, Bhatt DL, Sabatine MS, Catapano AL (2019) Association of triglyceride-lowering LPL variants and LDL-C-lowering LDLR variants with risk of coronary heart disease. JAMA 321:364–373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Wells JC, Chomtho S, Fewtrell MS (2007) Programming of body composition by early growth and nutrition. Proc Nutr Soc 66:423–434

    Article  PubMed  Google Scholar 

  45. Stearns SC (2005) Issues in evolutionary medicine. Am J Hum Biol 17:131–140

    Article  PubMed  Google Scholar 

  46. Thompson AL, Lampl M (2013) Prenatal and postnatal energetic conditions and sex steroids levels across the first year of life. Am J Hum Biol 25:643–654

    Article  PubMed  PubMed Central  Google Scholar 

  47. Laustsen JM, Jensen MS, Thulstrup AM, Gabel P, Toft G, Bonde JP, Olsen J, Ramlau-Hansen CH (2011) Does breastfeeding influence future sperm quality and reproductive hormones? Int J Androl 34:165–172

    Article  CAS  PubMed  Google Scholar 

  48. Martin RM, Middleton N, Gunnell D, Owen CG, Smith GD (2005) Breast-feeding and cancer: the Boyd Orr cohort and a systematic review with meta-analysis. J Natl Cancer Inst 97:1446–1457

    Article  PubMed  Google Scholar 

  49. Robinson GA, Peng J, Peckham H, Radziszewska A, Butler G, Pineda-Torra I, Jury EC, Ciurtin C (2021) Sex hormones drive changes in lipoprotein metabolism. iScience 24:103257

  50. Schooling CM, Lam TH, Thomas GN, Cowling BJ, Heys M, Janus ED, Leung GM (2007) Growth environment and sex differences in lipids, body shape and diabetes risk. PLoS One 2:e1070

    Article  PubMed  PubMed Central  Google Scholar 

  51. Xu L, Freeman G, Cowling BJ, Schooling CM (2013) Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials. BMC Med 11:108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Schooling CM, Luo S, Au Yeung SL, Thompson DJ, Karthikeyan S, Bolton TR, Mason AM, Ingelsson E, Burgess S (2018) Genetic predictors of testosterone and their associations with cardiovascular disease and risk factors: a Mendelian randomization investigation. Int J Cardiol 267:171–176

    Article  PubMed  PubMed Central  Google Scholar 

  53. Luo S, Au Yeung SL, Zhao JV, Burgess S, Schooling CM (2019) Association of genetically predicted testosterone with thromboembolism, heart failure, and myocardial infarction: mendelian randomisation study in UK Biobank. BMJ 364:l476

    Article  PubMed  PubMed Central  Google Scholar 

  54. Schooling CM, Zhao JV (2021) Investigating the association of testosterone with survival in men and women using a Mendelian randomization study in the UK Biobank. Sci Rep 11:14039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Ritchie RF, Palomaki GE, Neveux LM, Ledue TB, Marcovina S, Navolotskaia O (2006) Reference distributions for apolipoproteins AI and B and B/AI ratios: comparison of a large cohort to the world’s literature. J Clin Lab Anal 20:218–226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Richardson TG, Wang Q, Sanderson E, Mahajan A, McCarthy MI, Frayling TM, Ala-Korpela M, Sniderman A, Smith GD, Holmes MV (2021) Effects of apolipoprotein B on lifespan and risks of major diseases including type 2 diabetes: a Mendelian randomisation analysis using outcomes in first-degree relatives. Lancet Healthy Longev 2:e317–e326

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was supported by the Health and Medical Research Fund, Food and Health Bureau, Hong Kong SAR Government (#17181271). This work is a sub-study of the “Children of 1997” birth cohort which was initially supported by the Health Care and Promotion Fund, Health and Welfare Bureau, Government of the Hong Kong SAR (HCPF Grant # 216106) and re-established in 2005 funded by the Health and Health Services Research Fund (HHSRF Grant # 03040771, 05060671, 07080751, 07080841) and the Research Fund for the Control of Infectious Diseases in Hong Kong (RFCID Grant # 04050172, 06060592), Government of the Hong Kong SAR. The birth cohort has also received funding from the University Research Committee Strategic Research Theme (SRT) of Public Health Granted Research, The University of Hong Kong. The most recent follow-up was partly funded by the WYNG Foundation; analysis of the follow-up was partly funded by a pre-emptive retention/Start up fund, LKS Faculty of Medicine, The University of Hong Kong (S.L.A.Y). We are very grateful to the “Children of 1997” birth cohort participants for their invaluable contribution and to the legions of people who have made this study possible by building this birth cohort over almost 30 years, including the late Dr. Connie O for coordinating the project and all the fieldwork for the initial study in 1997–1998.

Funding

This study was supported by the Health and Medical Research Fund, Food and Health Bureau, Hong Kong SAR Government (#17181271).

Author information

Authors and Affiliations

Authors

Contributions

CMS designed the study and wrote the analysis plan, performed the data analyses, and interpreted the results, with feedback from SLAY, MK, and GML. CMS wrote the first draft of the manuscript with feedback from SLAY, MK, and GML. All authors gave final approval of the version to be published. CMS is the guarantor of work.

Corresponding author

Correspondence to Man Ki Kwok.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Communicated by Gregorio Milani.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 212 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Schooling, C., Au Yeung, S.L., Kwok, M.K. et al. Breastfeeding and ApoB in late adolescence: a Hong Kong birth cohort study. Eur J Pediatr 182, 3733–3741 (2023). https://doi.org/10.1007/s00431-023-05033-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-023-05033-w

Keywords

Navigation