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Lecture Notes 5/27/2021 The Biologic Components of Breastmilk; Conflicts of Interest Infant and Maternal Risks of Not Breastfeeding Liliana Simon, MD, IBCLC, FAAP, FABM Pediatric Critical Care and Breastfeeding Medicine [email protected] 1 © IABLE 2 ◼ The AAFP has reviewed Comprehensive Clinical Breastfeeding Objectives Medicine Course for Physicians and Other Providers and deemed it acceptable for up to 27.25 In-Person, Live (could include online) AAFP Prescribed credit. Term of Approval is from 06/01/2021 to 06/05/2021. ◼ Recite 3 components of breastmilk Physicians should claim only the credit commensurate with the extent of their participation in the activity. that provide immunologic protection ◼ This course has been assigned 27.25 (L) Continuing Education from illness. Recognition Points (CERPs) by IBLCE. Long Term Provider #CLT117-04. ◼ Describe the modes of immunologic protection afforded by breastmilk “In all mammalian species the reproductive cycle comprises both pregnancy and breastfeeding: in the absence of latter, none of these species, man included, could have survived”. Over time we (Bo Vahlquist, 1909-1978) have gone from here to here. So what? 1 5/27/2021 World Health Organization, • Exclusive bfeeding until 6 mo Incidence • Add solids at 6 mo American Academy • Nurse at least until 2 yrs of Family Physicians Allergies • Exclusive bfeeding until about 6 mo American Academy • Add solids at around 6 mo of Pediatrics • Continue for at least 1 year or as Celiac Disease long as desired American College of • Exclusive bfeeding for 6 mo Obstetrics and • Continue for 1 year or longer Gynecology 8 © IABLE 8 Immune System in Fetus ◼ Immune system of fetus is actively downregulated during pregnancy ◼ Prevent “immune abortion” ◼ At birth – stress and hypoxia during labor and uterine contractions ◼ Activates innate response ◼ Innate Immunity: physical (skin, mucosa), chemical barriers and local, non specific cells ◼ J. Nutr. September 2008 vol. 138 no. 9 1782S-1790S Adaptive Immunity: antigen-specific 1y 4 m What’s In The Milk And How Does It Help? Innate Immune system also includes physical barriers (skin, mucosa) and chemical barriers 2 5/27/2021 Human Milk Comparing Breastmilk and Formula = Under the Microscope Comparing Apples and Water Oranges Protein Carbs DHA/ARA Formula Fat Vitamins Minerals Water PLUS: 1 Enzyme Amino Acids Carbs Hormones Soy lecithin Protein- 1 Antibodies Formula Breastmilk ++Oligosaccharides Nucleotides type Active white cells Anti-allergy factors HMO- one Fats- 4 or 5 Enzymes Carotenoids Minerals Anti-viral proteins Protaglandins Vitamins Antibacterial Cytokines agents Peptides Etc!!! 4000 cells/cubic mm What are the most important Does the Colostrum Matter? immunoglobulins in breastmilk? A. IgA B. IgG C. IgM D. IgA and IgG E. IgM and IgG F. IgA, IgM and IgG 16 Rev Assoc Med Bras 2016; 62(6):584-593 Stages of Human Milk • Colostrum- More trophic than nutritional: rich in secretory IgA, lactoferrin, leukocytes, and developmental factors such as epidermal growth factor, low levels of lactose. Higher Na, Cl, Mg, lower K and Ca. High in anti-oxidants e.g. Beta carotene • Transitional milk- from day 5 to 2 weeks, gradual decline in protein as it transitions to mature milk, lower in carotenoids, increase in water, lactose, fat • Mature milk- after 2-3 weeks, reaches a steady state of protein, fat, lactose, bioactive factors, enzymes, antioxidants, etc. • After 1 year, decrease in water and carbs, higher in protein and fat Milk from breast nursing ill child Milk from breast nursing well child • Preterm milk- higher in protein during the first month as compared to term milk © IABLE 18 3 5/27/2021 Direct Breastfeeding Retrograde Ductal Flow • Immune changes in milk happen when baby is sick even if mother is not sick Transfer of antigen, antibodies and leukocytes also TNF-alpha • Mother specifically tailors milk to her infants needs – how does this happen? 19 Clin Transl Immunology. 2013:2(4):e3; Pediatr Res 2012 Feb;71(2)220-225 Let's Look at Examples of How E coli IgA in milk and Maternal exposure Human Milk Alters the Infants’ Immune System and Metabolism ◼ From Sri Lanka, • E coli antibodies in Sri Lanka in breastmilk despite lack of ◼ From Sri Lanka, exposure immigrated to UK • Suggest immunologic ◼ From UK, in UK memory in maternal secretory system Archives of Disease in Childhood 1994:71(F192-197) Breastmilk Factor Interleukin-7 keeps the thymus larger in breastfed infants, until weaning, improving infant immunity Front. Pediatr 2017 (5) article 178 4 5/27/2021 Epigenetics Obesity in Adolescents ◼ Breastfeeding prevents obesity genes from turning on ◼ Personalized medicine Health imprinting for life! Genotype + Environment = Phenotype Diabetes Care 2010 Jan; 33(1): 190-196 Enteromammary Circulation Human Milk Oligosaccharides 800 mL/27 oz milk = 100,000 to 10,000,000 bact/day Pharmacol Research 2013,69(1):1-10 Human Milk Oligossacharides Development of the Human Microbiome CMAJ 185,5 (2013) GlycobiologyGlycobiology 2012 Sep; 2012;22:114722(9): 1147–1162-1162 5 5/27/2021 Lactoferrin ◼ Iron-binding glycoprotein ◼ Anti-bacterial, fungal, viral and parasite ◼ Modulates immune system and prevents Just one bottle; the push for inflammation ◼ Promotes brain development, bone and exclusive breastfeeding. cartilaginous growth Is it really that big of a deal? ◼ Prevents obesity (reduce insulin resistance) Evidence for Protection by BF against After just one formula bottle… Infant Death from Diarrhea in Brazil Results adjusted for several confounding variables Formula or Formula exposure changes the gut 14.2 microbiome, leading to microbial cow's milk imbalance (dysbiosis), impaired innate Breast + formula or 3.6 Each daily feed with fluids immunity and aberrant development of cow's milk (water, teas, juice) tolerance. increased the risk of Breastmilk 1 diarrhea death by 70% ** Changes occur within 24 hours and can take weeks to change back. ** 0 5 10 15 Lancet, 1987 Odds ratio for diarrhea mortality Courtesy Dana Silver Andersson, et al. J Immunol. 2009 Oct 1;183(7):4322-8 Courtesy Cesar Victora Data on mortality according to amount of Mortality breastfeeding in low/middle income Low / Middle Income Country countries. Which one is true? ◼ Never BF vs. Exclusive BF: 8 x mortality A. A strong protective effect was evident and ever more significant with exclusive breastfeeding. ◼ Never BF vs. ever, any BF ◼ B. Exclusively breastfed children have only 12% the risk <6 mo: 4 x mortality of death compared to non breastfed children. ◼ 6-23 mo: 2 x mortality C. Protection decreases by half when breastfeeding is not exclusive. D. Protection decreases with age, but when compared with any breastfeeding, no breastfeeding was associated with twice mortality in kids 6 to 23 months. E. All of the above Lancet 2016 6 5/27/2021 If 90% of woman were able to follow the WHO Lives Saved Through Breastfeeding recommendations and breastfed for 2 years, every year how many lives of children less than 5 years EVERY YEAR were expected to be saved? ◼ If 90% of woman A. ~ 225,000 breastfed for 2 years 823,000 child deaths B. ~ 425,000 (< 5 years of age) C. ~ 625,000 D. ~ 825,000 20,000 breast cancer E. ~ 1,2500,000 deaths Lancet Victora et al Vol 387 January 30, 2016 Maternal Risks of Less Breastfeeding % protection by exclusive breastfeeding ◼ Postpartum bleeding ◼ Child spacing (lactation amenorrhea) ◼ Post partum depression ◼ Breast cancer 22% Do Mothers Benefit? ◼ 6 % for every 12 months ◼ Ovarian cancer 30% ◼ Metabolic syndrome ◼ Type 2 diabetes 47% ◼ Cardiovascular disease AAP 2012, Lancet 2016 39 AJOG 2013, JAMA Int Med 2018 Breastfeeding Reduces Risk of Infants are at Risk Vascular Disease and Abd Fat Immature immune • Menopause transition increases abdominal obesity system at birth – Increased abd fat increases risk of insulin resistance High risk for • Increased insulin resistance => increased risk of HBP, CVA, MI infection Breastmilk • Breastfeeding found to: ✓ Protects from – Lower risk of visceral fat in a dose-related manner (Asian Nurs infection Res 2020 Aug;14(3)) ✓ Promotes brain and immune – Lower risk of CVA in a dose-response relationship (J Am Heart system maturity Assoc 2018;7) ✓ Reduces – Lower risk of postmenopausal HBP (Breastfeeding Med 2018 Nov inflammation 13(9)) ✓ Optimal – Lower risk of perimenopausal metabolic syndrome in a nutrition dose- related manner (Nutrients 2020, 12, 2691) 42 7 5/27/2021 Short Term Risks of Less Breastfeeding for Children % protection by exclusive breastfeeding ◼ Infection 50% ◼ Hospital admission 70% ◼ NEC 58% ◼ SIDS 73% ◼ Vaccine response https://www.positivemed.com/2012/10/27/the-breastfed-baby/ Lancet Victora January 30, 2016 Long Term Risks of Less Breastfeeding for Children Breastfed Children have % protection by exclusive breastfeeding less Risk of Obesity ◼ Malignancy (ALL) 35 - 50% ◼ Neuroblastoma 40% ◼ Child Abuse 62% Possible Reasons: ✓ Differences in metabolism ◼ Dental malocclusion ✓ Hormones in breastmilk ◼ Metabolic ✓ Bfed infants drink smaller volumes ◼ Obesity 26% ✓ Epigenetics ◼ DM 30% ◼ Type I 50% ◼ Cognition (IQ) 3-4 BMC Medicine (2021) 19:90; Lancet Victora January 30, 2016 Risk of Early Supplementation with Cows Milk Protein Formula Breastfeeding, Immune Tolerance and Autoimmune Diseases Risk of cows milk allergy higher when supplemented with cows milk based formula in the first 3 days, and then exclusively bfed • 1.75x risk of CMA- (Meta-analysis Brit J Midwifery 20(5) 2012) • 7x increased risk of CMA- study of 55 CMA children (Pediatr Allergy Immunol 2019 July) • Higher risk of CMA among bfed infants if given cow milk based formula in the first 3 days vs hydrolyzed formula- Japan, 312 infants – (JAMA Pediatrics Oct 2019) Am J Reprod Immunol. 2018;79:e12778 8 5/27/2021 Environmental cost ◼ Breastmilk is a “natural, renewable food” that is environmentally safe and produced and delivered to the consumer without pollution, unnecessary packaging, or waste. What’s the impact for the child? They… A. Complete 4.6 more grades of school ◼ Breast milk substitutes: B.
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