Breastmilk as Epigenetic Medium
NPO Conference, Portland Oct 2018
Sylvia Metzger
Breastmilk as Epigenetic Medium NPO Conference, Portland Oct 2018 - - PowerPoint PPT Presentation
Breastmilk as Epigenetic Medium NPO Conference, Portland Oct 2018 Sylvia Metzger Objectives 1. Introduce the concept of epigenetics 2. Discuss epigenetic effects of breastmilk and lactation programming on infant health outcomes 3. Compare
NPO Conference, Portland Oct 2018
Sylvia Metzger
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1. Introduce the concept of epigenetics
infant health outcomes
microbiome and infant health outcomes
mother-baby breastfeeding dyads in clinical practice
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Globally, only 38% of infants are exclusively breastfed US: only 13-14% are exclusively breastfed for 6 months Nutritional epigenetics – the diet changes the gene expression
Verduci et al. ( 2014). Epigenetic effects of human breast milk. Nutrients, 6 : 1711-1724
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Modification of gene expression without changes in DNA (the genetic code itself)
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1. DNA methylation 2. Histone modification 3. miRNA
https://en.wikipedia.org/wiki/File:Epigenetic_mechanisms.jpg
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e.g. Breastfeeding – baby LEPTIN “ I am full” The longer she BF, the less chance that the gene will be methylated (silenced), which sends signals of satiety
Obermann-Borst, S.A. et al (2013). Duration of breastfeeding and gender are associated with methylation of the LEPTIN gene in very young children. Pediatric Research, 74(3):344-349.
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e.g. DM Type 1: Altered histone methylation induced by hyperglycemia
Picascia et al. (2015). Epigenetic control of autoimmune diseases: from bench to bedside. Clinical Immunology, 157(1):1-15.
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Do not code, but regulate gene expression
identical
Melnik, B.C., & Schmitz, G. (2017). MicroRNAs: Milk’s epigenetic regulators. Best Practice & Research Clinical Endocrinology & Metabolism, 31:427-442.
miRNA
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immune factors
Le Doare, K.L., Holder, B., Bassett, A, & Pannaraj, P.S. (2018). Mothers’s Milk : A purposeful contribution to the development of the infant microbiota and immunity. Frontiers in Immunology,9(361):1-10. Pannaraj, P.S., Rollie, A. & Bailey, A. (2017). Association between breast milk bacterial communities and establishment and development of the infant gut microbiome. JAMA Pediatrics, 17(7):647-654.
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Condition % Lower risk Breastfeeding comment Otitis media Recurrent OM 23% 50% 77% Any BF compared to formula >3 or 6 mon of EBF (exclusive) > 6 mon EBF compared to 4-6 BF Upper respiratory tract infection (serious colds, ear and throat infections) 63% >6 mon (EBF) Lower respiratory tract infection – risk of hospitalization in 1st yr of life 72% 77% >4 mon EBF > 6 mon EBF compared to BF 4-6 mon Asthma 40% 26% >3 mon (if atopic family history) >3 mon (if no atopic family history) RSV bronchiolitis – severity (duration of hospitalization / O2 requirements) 74% > 4 mon EBF NEC (1 case could be prevented if 10 babies EBF) 77% NICU, preterm – exclusive human milk Atopic dermatitis 27% 42% > 3 mon (EBF negative family history) > 3mon (EBF positive family history)
American Academy of Pediatrics (2012). Breastfeeding and the Use of Human Milk, 129(3)”827-841 http://pediatrics.aappublications.org/content/129/3/e827/T2.expansion.html
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Condition % Lower risk Breastfeeding comment Gastroenteritis (effect lasts for 2 m after BF is stopped) 64% Any BF SIDS 36% Any BF > 1 mon Inflammatory bowel disease (intestinal colonization is different in BF babies) 31 % Any BF Obesity 24% Any BF Celiac disease (if BF when exposed to gluten) 52% > 2mo Type 1 DM 30% >3 mon EBF Type 2 DM 40% Any BF Leukemia (ALL) Leukemia (AML) 20% 15% > 6 mon > 6 mon
American Academy of Pediatrics (2012). Breastfeeding and the Use of Human Milk, 129(3)”827-841 http://pediatrics.aappublications.org/content/129/3/e827/T2.expansion.html
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American Academy of Pediatrics (2012). Breastfeeding and the Use of Human Milk. Pediatrics 129(3): e827-e841 Lund-Blix et al. (2017). Infant feeding and risk of type 1 diabetes in two large Scandinavian Birth Cohorts. Diabetes Care, 40(7): 921-927
colitis)
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Decreased risk of
Schwarz, E.B., & Nothnagle, M. (2015). The Maternal Health Benefits of Breastfeeding. Am Fam Physician, 91 (9):604-4 American Academy of Pediatrics (2012). Breastfeeding and the Use of Human Milk, 129(3):827-841 http://pediatrics.aappublications.org/content/129/3/e827/T
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significant early life programming medium
Cunha, A.J., Leite, A.J., & Almeida, I.S. (2015). The pediatrician’s role in the first thousand days of the child: the pursuit of healthy nutrition and development. J Pediatri (Rio J), 91(6 Suppl 1): S44-51
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Alsaweed, M., Hartmann, P.E., Geddes, D.T., & Kakulas, F. (2015). MicroRNAs in Breastmilk and the Lactating Breast: potential immunoprotectors and developmental regulators for the infant and the mother. International Journal of Environmental Research and Public Health, 12(11):13981-14020. Melnik, B.C., & Schmitz. G. (2017). MicroRNAs: Milk’s epigenetic regulators. Best Practice and Research. Clinical Endocrinology and Metabolism, 31(4):427-442.
miRNA
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Canadian longitudinal birth cohort (N=3296)
Results
coughing/wheezing episodes by 1 yr compared to babies directly BF
Klopp et al. (201 7). Modes of Infant Feeding and the Risk of Childhood Asthma: A Prospective Birth Cohort Study. The Journal of Pediatrics, 190:192-199.
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Ellsworth, L., Harman, E., Padmanabhan, V., & Gregg, B. (2018). Lactational programming of glucose homeostasis: a window of opportunity. Reproduction, 156(2):R23-R42
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Mischke & Plösch (2013). More than just a gut instinct- the potential interplay between a baby’s nutrition, its gut microbiome, and the epigenome.
American Journal of Physiology. Regulatory, Integrative, and Comparative Physiology, 304(12):R1065-9.
hepatocytes, and adipocytes- predisposes to obesity
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Australian peri/post epigenetic twin study
obesity
= Leptin is awake and working) – Obermann-Borst,2013
Temples et al (2016). Breastfeeding and Growth of Children in the Peri/Postnatal Epigenetic Twins Study (PETS): Theoretical Epigenetic Mechanisms. Journal of Human Lactation, 32(3):481-488 Obermann-Borst, S.A. et al (2013). Duration of breastfeeding and gender are associated with methylation of the LEPTIN gene in very young children. Pediatric Research, 74(3):344-349.
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Bartol, et al. (2017). Physiology and endocrinology symposium: Postnatal reproductive development and the lactocrine hypothesis. Journal of Animal Science, 95(5):2200-2210.
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Ruowei, L, et al. (2008). Why mothers stop breastfeeding: mother’s self-reported reasons for stopping during the first yet. Pediatrics, 122;S69 Newby, R.M. & Davies, P.S. (2016). Why do women stop breast-feeding? Results from a contemporary prospective study in a cohort of Australian women. European Journal of Clinical Nutrition, . 70(12):1428-1432
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For babies:
For mothers
Moore ER, Anderson GC, Bergman N, Dowswell T. Early skin-to-skin contact for mothers and their healthy newborn infants. Cochrane Database of Systematic Reviews 2012, Issue 5. Art. No.: CD003519. DOI: 10.1002/14651858.CD003519.pub3
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Flaherman et al. (2015). Early weight loss nomograms for exclusively breastfed newborns. Pediatrics, 135(1) Tawia, S. & McGuire, L. (2014). Early weight loss and weight gain in healthy, full-term, exclusively-breastfed infants. Breastfeeding Review, 22(1):32-42
Newborn weight loss nomogram https://www.newbornweight.org
normal in the first few days of life
150-200 g per week once milk is in but this can vary
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Volume of Supplement Average intake of colostrum per feeding Birth to 24 hr 2-10 mL 24-48 hr 5-15 mL 48-72 hr 15-30 mL 72-96 hr 30-60 mL
Academy of Breastfeeding Medicine Protocol #4, 2017
Choice of Supplement Expressed BM Donor Milk in the hospital Protein hydrolysate formulas
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Maternal Indications
poor milk production
(e.g.chemotx) or separation without expressed BM
ABM Clinical Protocol #3. Supplementary Feedings in the Healthy Term Breastfed Neonate. Breastfeeding Medicine, 12 (3)
Infant Indications
unresponsive to frequent BFs
percentile for age
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pathogens?
FAO/WHO. Enterobacter sakazakii and Salmonella in powdered infant formula; meeting report. Microbiological Risk Assessment Series 2006:10 Losio, M.N., et al. (2018). Preparation of Powdered infant formula: could product’s safety be improved? J Pediatr Gastroengerol Nutr, 67(4):543-546
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1. Nipple pain
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Puapompong, P et al. (2017). Nipple Pain Incidence, the Predisposing Factors, the Recovery Period After Care Management, and the Exclusive Breastfeeding
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For persistent pain with BF – see ABM Clinical Protocol #26
https://abm.memberclicks.net/assets/DOCUMENTS/PROTOCOLS/26-persistent-pain-protocol-english.pdf
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Swedish case-control study
making a diagnosis of C.albicans
Kaski, K. & Kvist, L. J. (2018). Deep breast pain during lactation: a case-control study in Sweden investigating the role of Candida albicans . International Breastfeeding Journal, 13:21.
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Berens, P., Brodribb, W., & The ABM. (2016). ABM Clinical Protocol #20: Engorgement, Revised 2016. Breastfeeding Medicine, 11 (4): 159- 163 Wong, B.B., et al (2017). Application of cabbage leaves compared to gel packs for mothers with breast engorgement: Randomized controlled trial. International Journal of Nursing Studies, 76:92-99 Cotterman KJ. Reverse pressure softening: A simple tool to prepare areola for easier latching during engorgement. J Hum Lact 2004;20:227–237 Khosravan S. et al. The effect of Hollyhock (Althaea officinalis L) leaf compresses combined with warm and cold compress on breast engorgement in lactating women: A randomized clinical trial. J Evid Based Complementary Altern Med 2015;pii: 2156587215617106.
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Risk factors
feeding, illness in mom or baby Management:
after feeds
Amir, L. H. & The Academy of Breastfeeding Medicine Protocol Committee. (2014). ABM Clinical Protocol #4. Mastitis. Breastfeeding Medicine, 9(5):239-243
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Analgesics
Antibiotics
Amir, L. H. & The Academy of Breastfeeding Medicine Protocol Committee. (2014). ABM Clinical Protocol #4. Mastitis. Breastfeeding Medicine, 9(5):239-243
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Witt, A.M., Bolman, M., Kredit, Sh., & Vanic, A. (2016). Therapeutic breast massage in lactation for the management of engorgmenet, plugged ducts, and
VIDEO http://bfmedneo.com/our-services/breast-massage/ Or https://vimeo.com/65196007
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Ndikom, C.M., Fawole, B., & Illesanmi, R.E. (2014). Extra fluids for breastfeeding mothers for increasing milk production. Cochrane Databased of Systematic Reviews, 6:CD008758. Riddle, S.W., Nommsen-Rivers, L.A. (2017). Low milk supply and the pediatrician. Current Opionion in Pediatrics, 29:249--256
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Riddle, S.W., Nommsen-Rivers, L.A. (2017). Low milk supply and the pediatrician. Current Opionion in Pediatrics, 29:249—256
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Riddle, S.W., Nommsen-Rivers, L.A. (2017). Low milk supply and the pediatrician. Current Opionion in Pediatrics, 29:249—256
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breasts more fully after breastfeeding if baby is not draining well
Lemay, D.G., et al. (2013). RNA sequencing of the human milk fat layer transcriptome reveals distinct gene expression profiles at three stages of lactation. PLoS One, 8:e67531 Nommsen-Rivers, L., Riddle, S., et al. (2016). Milk production in mothers with and without signs of insulin resistance. Breastfeeding Medicine, 11 ( Supplement 1, S3-S4) Pinheiro, T.V., Goldani, M.Z, & IVAPSA group. (2018). Maternal pre-pregnancy overweight/obesity and gestational diabetes interaction on delayed breastfeeding initiation. PLoS One, 13(6):e0194879
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http://purplecrying.info
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choose drugs with shorter half-life
Hale, T. (2018). Drug entry into human milk . Retrieved from https://www.infantrisk.com/content/drug-entry-human-milk
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morphin Epsomn salts, magnesium salts, aminoglycosides, vancomycin – poorly absorbed – very little gets to the baby
radioisotope is eliminated. Wait 4-5 half lives!
maternal exposure
indicate neonatal absorption
Hale, T. (2018). Drug entry into human milk . Retrieved from https://www.infantrisk.com/content/drug-entry-human-milk
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Controversies in research!
Berens, P., & Labbok, M. &, The ABM. (2015). ABM Clinical Protocol #13: Contraception during breastfee3ding, revised 2015. Breastfeeding Medicine, 10(1): 1-10.
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Helpline (806)352-2519 (M-F 8-5pm, CT)
https://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm
(factsheets or inquiries via email)
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Colorado, please call 720-777-3605.