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.
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.
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.
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.
This is a preview of subscription content
Subscribe to Journal
Get full journal access for 1 year
only $9.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
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.
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.
Gluckman PD, Hanson MA, Pina LC. The developmental origins of adult disease. Matern Child Nutr. 2005;1:130–41.
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.
Rooney K, Ozanne SE. Maternal over-nutrition and offspring obesity predisposition: targets for preventative e interventions. Int J Obes. 2011;35:883–90.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Doneray H, Orbak Z, Yildiz L. The relationship between breast milk leptin and neonatal weight gain. Acta Paediatr. 2009;98:643–7.
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.
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.
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.
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.
Druet C, Ong KK. Early childhood predictors of adult body composition. Best Pr Res Clin Endocrinol Metab. 2008;22:489–502.
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.
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.
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.
Fichorova RN. et al. Maternal microbe-specific modulation of inflammatory response in extremely low-gestational-age newborns. MBio. 2011;2:e00280–00210.
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.
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.
Olsen IE, Groveman SA, Lawson ML, Clark RH, Zemel BS. New intrauterine growth curves based on United States data. Pediatrics. 2010;125:e214–24.
WHO Multicentre Growth Reference Study Group. WHO Child Growth Standards based on length/height, weight and age. Acta Paediatr. 2006;450:76–85.
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.
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.
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.
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.
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.
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.
Simopoulos AP. An increase in the Omega-6/Omega-3 fatty acid ratio increases the risk for obesity. Nutrients. 2016;8:128.
Innis SM. Human milk and formula fatty acids. J Pediatr. 1992;120:S56–S61.
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.
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.
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.
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.
James MJ, Gibson RA, Cleland LG. Dietary polyunsaturated fatty acids and inflammatory mediator production. Am J Clin Nutr. 2000;71:343S–348S.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Meister B. Control of food intake via leptin receptors in the hypothalamus. Vitam Horm. 2000;59:265–304.
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.
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.
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.
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.
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.
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.
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.
Rigo J. Body composition during the first year of life. Nestle Nutr Workshop Ser Pediatr Program. 2006;58:65–67.
We would like to thank Dr. Thu Huong Pham and Peter O. Isesele for their expertise in breast milk analyte analysis.
National Institutes of Health (NIH) 5R01HD043921, NIH RR01070, NIH P30 DK040561, NIH/National Center for Advancing Translational Sciences UL1 TR000062.
Conflict of interest
The authors declare that they have no conflict of interest.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
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
European Journal of Clinical Nutrition (2021)
European Journal of Clinical Nutrition (2021)