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Nutrition during the early life cycle

The impact of maternal obesity and breast milk inflammation on developmental programming of infant growth

Abstract

Background

Little is known about how maternal obesity impacts breast milk (BM) composition and how BM composition may impact growth. We sought to determine the role of maternal body mass index (BMI) on BM inflammatory and oxidative stress markers and to delineate the role of these BM markers on infant growth.

Methods

This was a secondary analysis of 40 mother-infant dyads. We first assessed the association between maternal BMI and BM marker (omega-6:omega-3 polyunsaturated fatty acid ratio (n-6:n-3 PUFA), leptin, interleukin (IL)-8, IL-6, IL-1β and malondialdehyde (MDA)) concentration at one (V1) and four (V4) months postpartum. We then examined the association between BM markers on infant growth trajectory from birth to seven months.

Results

Higher maternal BMI was associated with higher BM n-6:n-3 PUFA (V1 β = 0.12, 95% CI 0.01, 0.2; V4 β = 0.13, 95% CI 0.01, 0.3) and leptin (V1 β = 107, 95% CI 29, 184; V4 β = 254, 95% CI 105, 403) concentrations. Infants exposed to high BM n-6:n-3 PUFA had higher BMI z-scores over time (p = 0.01). Higher BM leptin was associated with lower infant percent fat mass at V4 (β = −9, 95% CI −17, −0.6). Infants exposed to high BM IL-8, IL-6, or IL-1β had higher weight z-scores over time (IL-8 p < 0.001; IL-6 p < 0.001; IL-1β p = 0.02). There was no association between BM MDA and maternal BMI or infant growth.

Conclusions

Higher maternal BMI is associated with higher BM n-6:n-3 PUFA and leptin concentrations. In addition, higher BM n-6:n-3 PUFA and inflammatory cytokines were associated with accelerated weight gain in infancy.

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Fig. 1: Association between breast milk n-6:n-3 PUFA and infant growth trajectory.

References

  1. 1.

    Branum AM, Kirmeyer SE, Gregory EC. Prepregnancy body mass index by maternal characteristics and state: data from the birth certificate, 2014. Natl Vital Stat Rep. 2016;65:1–11.

    PubMed  Google Scholar 

  2. 2.

    Catalano PM, Farrell K, Thomas A, Huston-Presley L, Mencin P, de Mouzon SH, et al. Perinatal risk factors for childhood obesity and metabolic dysregulation. Am J Clin Nutr. 2009;90:1303–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Gluckman PD, Hanson MA, Pina LC. The developmental origins of adult disease. Matern Child Nutr. 2005;1:130–41.

    PubMed  PubMed Central  Google Scholar 

  4. 4.

    Waterland RA, Travisano M, Tahiliani KG, Rached MT, Mirza S. Methyl donor supplementation prevents transgenerational amplification of obesity. Int J Obes. 2008;32:1373–9.

    CAS  Google Scholar 

  5. 5.

    Rooney K, Ozanne SE. Maternal over-nutrition and offspring obesity predisposition: targets for preventative e interventions. Int J Obes. 2011;35:883–90.

    CAS  Google Scholar 

  6. 6.

    Gorski JN, Dunn-Meynell AA, Hartman TG, Levin BE. Postnatal environment overrides genetic and prenatal factors influencing offspring obesity and insulin resistance. Am J Physiol Regul Integr Comp Physiol. 2006;291:R768–78.

    CAS  PubMed  Google Scholar 

  7. 7.

    Sen S, Carpenter AH, Hochstadt J, Huddleston JY, Kustanovich V, Reynolds AA, et al. Nutrition, weight gain and eating behavior in pregnancy: a review of experimental evidence for long-term effects on the risk of obesity in offspring. Physiol Behav. 2012;107:138–45.

    CAS  PubMed  Google Scholar 

  8. 8.

    Whitaker KM, Marino RC, Haapala JL, Foster L, Smith KD, Teague AM, et al. Associations of maternal weight status before, during, and after pregnancy with inflammatory markers in breast milk. Obesity. 2017;25:2092–9.

    CAS  PubMed  Google Scholar 

  9. 9.

    Collado MC, Laitinen K, Salminen S, Isolauri E. Maternal weight and excessive weight gain during pregnancy modify the immunomodulatory potential of breast milk. Pediatr Res. 2012;72:77–85.

    CAS  PubMed  Google Scholar 

  10. 10.

    Fields DA, George B, Williams M, Whitaker K, Allison DB, Teague A, et al. Associations between human breast milk hormones and adipocytokines and infant growth and body composition in the first 6 months of life. Pediatr Obes. 2017;12:78–85.

    PubMed  PubMed Central  Google Scholar 

  11. 11.

    Panagos PG, Vishwanathan R, Penfield-Cyr A, Matthan NR, Shivappa N, Wirth MD, et al. Breastmilk from obese mothers has pro-inflammatory properties and decreased neuroprotective factors. J Perinatol. 2016;36:284–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Nuss H, Altazan A, Zabaleta J, Sothern M, Redman L. Maternal pre-pregnancy weight status modifies the influence of PUFAs and inflammatory biomarkers in breastmilk on infant growth. PLoS ONE. 2019;14:e0217085.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Fields DA, Demerath EW. Relationship of insulin, glucose, leptin, IL-6 and TNF-α in human breast milk with infant growth and body composition. Pediatr Obes. 2012;7:304–12.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Miralles O, Sanchez J, Palou A, Pico C. A physiological role of breast milk leptin in body weight control in developing infants. Obesity. 2006;14:1371–7.

    CAS  PubMed  Google Scholar 

  15. 15.

    Schuster S, Hechler C, Gebauer C, Kiess W, Kratzsch J. Leptin in maternal serum and breast milk: association with infants’ body weight gain in a longitudinal study over 6 months of lactation. Pediatr Res. 2011;70:633–7.

    CAS  PubMed  Google Scholar 

  16. 16.

    Doneray H, Orbak Z, Yildiz L. The relationship between breast milk leptin and neonatal weight gain. Acta Paediatr. 2009;98:643–7.

    CAS  PubMed  Google Scholar 

  17. 17.

    Brunner S, Schmid D, Zang K, Much D, Knoeferl B, Kratzsch J, et al. Breast milk leptin and adiponectin in relation to infant body composition up to 2 years. Pediatr Obes. 2015;10:67–73.

    CAS  PubMed  Google Scholar 

  18. 18.

    Uysal FK, Onal EE, Aral YZ, Adam B, Dilmen U, Ardicolu Y. Breast milk leptin: its relationship to maternal and infant adiposity. Clin Nutr. 2002;21:157–60.

    CAS  PubMed  Google Scholar 

  19. 19.

    Weyermann M, Brenner H, Rothenbacher D. Adipokines in human milk and risk of overweight in early childhood: a prospective cohort study. Epidemiology. 2007;18:722–9.

    PubMed  Google Scholar 

  20. 20.

    Ucar B, Kirel B, Bor O, Kiliç FS, Doğruel N, Aydoğdu SD, et al. Breast milk leptin concentrations in initial and terminal milk samples: relationships to maternal and infant plasma leptin concentrations, adiposity, serum glucose, insulin, lipid and lipoprotein levels. J Pediatr Endocrinol Metab. 2000;13:149–56.

    CAS  PubMed  Google Scholar 

  21. 21.

    Druet C, Ong KK. Early childhood predictors of adult body composition. Best Pr Res Clin Endocrinol Metab. 2008;22:489–502.

    Google Scholar 

  22. 22.

    Hollis BW, Wagner CL, Howard CR, Ebeling M, Shary JR, Smith PG, et al. Maternal versus infant vitamin D supplementation during lactation: a randomized controlled trial. Pediatrics. 2015;136:625–34.

    PubMed  PubMed Central  Google Scholar 

  23. 23.

    Vidal NP, Pham HT, Manful C, Pumphrey R, Nadeem M, Cheema M, et al. The use of natural media amendments to produce kale enhanced with functional lipids in controlled environment production system. Sci Rep. 2018;8:14771.

    PubMed  PubMed Central  Google Scholar 

  24. 24.

    Fichorova RN, Richardson-Harman N, Alfano M, Belec L, Carbonneil C, Chen S, et al. Biological and technical variables affecting immunoassay recovery of cytokines from human serum and simulated vaginal fluid: a multicenter study. Anal Chem. 2008;80:4741–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Fichorova RN. et al. Maternal microbe-specific modulation of inflammatory response in extremely low-gestational-age newborns. MBio. 2011;2:e00280–00210.

    PubMed  PubMed Central  Google Scholar 

  26. 26.

    Yuksel S, Yigit AA, Cinar M, Atmaca N, Onaran Y. Oxidant and antioxidant status of human breast milk during lactation period. Dairy Sci Technol. 2015;95:295–302.

    CAS  Google Scholar 

  27. 27.

    Vaidya H, Cheema SK. Breastmilk with a high omega-6 to omega-3 fatty acid ratio induced cellular events similar to insulin resistance and obesity in 3T3-LI adipocytes. Pediatr Obes. 2018;13:285–91.

    CAS  PubMed  Google Scholar 

  28. 28.

    Olsen IE, Groveman SA, Lawson ML, Clark RH, Zemel BS. New intrauterine growth curves based on United States data. Pediatrics. 2010;125:e214–24.

    PubMed  Google Scholar 

  29. 29.

    WHO Multicentre Growth Reference Study Group. WHO Child Growth Standards based on length/height, weight and age. Acta Paediatr. 2006;450:76–85.

    Google Scholar 

  30. 30.

    Sen S, Penfield-Cyr A, Hollis BW, Wagner CL. Maternal obesity, 25-hydroxy vitamin D concentration, and bone density in breastfeeding dyads. J Pediatr. 2017;187:147–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Young BE, Patinkin Z, Palmer C, de la Houssaye B, Barbour LA, Hernandez T, et al. Human milk insulin is related to maternal plasma insulin and BMI: but other components of human milk do not differ by BMI. Eur J Clin Nutr. 2017;71:1094–100.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB. Elevated C-reactive protein levels in overweight and obese adults. JAMA. 1999;282:2131–35.

    CAS  PubMed  Google Scholar 

  33. 33.

    Hawkes JS, Bryan DL, Gibson RA. Cytokine production by human milk cells and peripheral blood mononuclear cells from the same mothers. J Clin Immunol. 2002;22:338–44.

    CAS  PubMed  Google Scholar 

  34. 34.

    Hassiotou F, Hepworth AR, Metzger P, Tat Lai C, Trengove N, Hartmann PE, et al. Maternal and infant infections stimulate a rapid leukocyte response in breastmilk. Clin Transl Immunol 2013;2:e3.

    CAS  Google Scholar 

  35. 35.

    McCrory MA, Fuss PJ, McCallum JE, Yao M, Vinken AG, Hays NP, et al. Dietary variety within food groups: association with energy intake and body fatness in men and women. Am J Clin Nutr. 1999;69:440–70.

    CAS  PubMed  Google Scholar 

  36. 36.

    Simopoulos AP. An increase in the Omega-6/Omega-3 fatty acid ratio increases the risk for obesity. Nutrients. 2016;8:128.

    PubMed  PubMed Central  Google Scholar 

  37. 37.

    Innis SM. Human milk and formula fatty acids. J Pediatr. 1992;120:S56–S61.

    CAS  PubMed  Google Scholar 

  38. 38.

    Jensen CL, Maude M, Anderson RE, Heird WC. Effect of docosahexaenoic acid supplementation of lactating women on the fatty acid composition of breast milk lipids and maternal and infant plasma phospholipids. Am J Clin Nutr. 2000;71:292S–299S.

    CAS  PubMed  Google Scholar 

  39. 39.

    Tian HM, Wu YX, Lin YQ, Chen XY, Yu M, Lu T, et al. Dietary patterns affect maternal macronutrient intake levels and the fatty acid profile of breast milk in lactating Chinese mothers. Nutrition. 2018;58:83–8.

    PubMed  Google Scholar 

  40. 40.

    Amri EZ, Ailhaud G, Grimaldi PA. Fatty acids as signal transducing molecules: Involvement in the differentiation of preadipose to adipose cells. J Lipid Res. 1994;35:930–7.

    CAS  PubMed  Google Scholar 

  41. 41.

    Jump DB, Clarke SD, Thelen A, Liimatta M. Coordinate regulation of glycolytic and lipogenic gene expression by polyunsaturated fatty acids. J Lipid Res. 1994;35:1076–84.

    CAS  PubMed  Google Scholar 

  42. 42.

    James MJ, Gibson RA, Cleland LG. Dietary polyunsaturated fatty acids and inflammatory mediator production. Am J Clin Nutr. 2000;71:343S–348S.

    CAS  PubMed  Google Scholar 

  43. 43.

    Gaillard D, Negrel R, Lagarde M, Ailhaud G. Requirement and role of arachidonic acid in the differentiation of preadipose cells. Biochem J. 1989;257:389–97.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Mirnikjoo B, Brown SE, Kim HF, Marangell LB, Sweatt JD, Weeber EJ. Protein kinase inhibition by omega-3 fatty acids. J Biol Chem. 2001;276:10888–96.

    CAS  PubMed  Google Scholar 

  45. 45.

    Lonnqvist F, Arner P, Nordfors L, Schalling M. Overexpression of the obese (ob) gene in adipose tissue of human obese subjects. Nat Med. 1995;1:950–3.

    CAS  PubMed  Google Scholar 

  46. 46.

    Smith-Kirwin SM, O’Connor DM, De Johnston J, Lancey ED, Hassink SG, Funanage VL. Leptin expression in human mammary epithelial cells and breast milk. J Clin Endocrinol Metab. 1998;83:1810–3.

    CAS  PubMed  Google Scholar 

  47. 47.

    Wiens D, Park CS, Sotckdale FE. Milk protein expression and ductal morphogenesis in the mammary gland in vitro: hormone-dependent and -independent phases of adipocyte-mammary epithelial cell interaction. J Cell Biol. 1985;100:1415–22.

    Google Scholar 

  48. 48.

    Hosick HL, Beck JC. Growth of mouse mammary epithelium in response to serum-free media conditioned by mammary adipose tissue. Cell Biol Int Rep. 1988;12:85–97.

    PubMed  Google Scholar 

  49. 49.

    Eriksson J, Valle T, Lindstrom J, Haffner S, Louheranta A, Uusitupa M, et al. Leptin concentrations and their relation to body fat distribution and weight loss: a prospective study in individuals with impaired glucose tolerance. DPS-study group. Horm Metab Res. 1999;31:616–9.

    CAS  PubMed  Google Scholar 

  50. 50.

    Reseland JE, Anderssen SA, Solvoll K, Anderssen SA, Jacobs DR Jr, Urdal P, et al. Effect of long-term changes in diet and exercise on plasma leptin concentrations. Am J Clin Nutr. 2001;73:240–5.

    CAS  PubMed  Google Scholar 

  51. 51.

    Masuzaki H, Ogawa Y, Isse N, Satoh N, Okazaki T, Shigemoto M, et al. Human obese gene expression. Adipocyte‐specific expression and regional differences in the adipose tissue. Diabetes. 1995;44:855–8.

    CAS  PubMed  Google Scholar 

  52. 52.

    Meister B. Control of food intake via leptin receptors in the hypothalamus. Vitam Horm. 2000;59:265–304.

    CAS  PubMed  Google Scholar 

  53. 53.

    Kolaczynski JW, Ohannesian JP, Considine RV, Marco CC, Caro JF. Response of leptin to short‐term and prolonged overfeeding in humans. J Clin Endocrinol Metab. 1996;81:4162–5.

    CAS  PubMed  Google Scholar 

  54. 54.

    Cheng L, Yu Y, Zhang Q, Szabo A, Wang H, Huang XF. Arachidonic acid impairs hypothalamic leptin signaling and hepatic energy homeostasis in mice. Mol Cell Endocrinol 2015;412:12–18.

    CAS  PubMed  Google Scholar 

  55. 55.

    Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest. 2004;114:1752–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Gustafson B, Gogg S, Hedjazifar S, Jenndahl L, Hammarstedt A, Smith U. Inflammation and impaired adipogenesis in hypertrophic obesity in man. Am J Physiol Endocrinol Metab. 2009;297:E999–E1003.

    CAS  PubMed  Google Scholar 

  57. 57.

    McArdle MA, Finucane OM, Connaughton RM, McMorrow AM, Roche HM. Mechanisms of obesity-induced inflammation and insulin resistance: insights into the emerging role of nutritional strategies. Front Endocrinol. 2013;4:52.

    Google Scholar 

  58. 58.

    Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112:1796.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. 59.

    Huh JY, Park YJ, Ham M, Kim JB. Crosstalk between adipocytes and immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. Mol Cells. 2014;37:365–71.

    PubMed  PubMed Central  Google Scholar 

  60. 60.

    Rigo J. Body composition during the first year of life. Nestle Nutr Workshop Ser Pediatr Program. 2006;58:65–67.

    PubMed  Google Scholar 

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Acknowledgements

We would like to thank Dr. Thu Huong Pham and Peter O. Isesele for their expertise in breast milk analyte analysis.

Funding

National Institutes of Health (NIH) 5R01HD043921, NIH RR01070, NIH P30 DK040561, NIH/National Center for Advancing Translational Sciences UL1 TR000062.

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All authors were involved in the conceptualization of the study and design. SE and SS carried out analysis of data. SC, RT, and RF carried out experiments. CRM, POG, and CLW provided feedback on the analysis and results. All authors were involved in writing the paper and had final approval of the submitted and published versions.

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Correspondence to Samantha Enstad.

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Enstad, S., Cheema, S., Thomas, R. et al. The impact of maternal obesity and breast milk inflammation on developmental programming of infant growth. Eur J Clin Nutr 75, 180–188 (2021). https://doi.org/10.1038/s41430-020-00720-5

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