Amningens effekter på barnet og moderen Ammekonsulent uddannelsen September 2022

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1 Amningens effekter på barnet og moderen Ammekonsulent uddannelsen September 2022 Kim Fleischer Michaelsen Department of Nutrition, Exercise and Sports University of Copenhagen

2 Amingens effekter Fokus på raske børn født til tiden i høj-indkomst lande Hvad er de vigtigste effekter?

3 Metodemæssige problemer ved studier af amningens effekter Studierne er ikke randomiserede Ammende mødre er forskellige fra de der ikke ammer Social klasse, uddannelse, livsstil, fedme Børn der vokser hurtigt kræver måske anden mad hurtigere amning-vækst interaktion Reverse causality Definition af amning Aldrig ammet vs ammet Længden af eksklusiv amning eller delvis amning Alternativet til amning var ikke optimal årtier tilbage

4 Belarus BFHI intervention trial 32 hospitals randomized to 9-12 months of BFHI training or to continue routine practices 17,795 mothers recruited and followed up during infancy, at 11.5 y and 16 years Major outcomes were duration of breastfeding and episodes of gastrointestinal and respiratory infections 4

5 BFHI Belarus - Results Breastfeeding rates increased by 12-14% Exclusive breastfeeding rates at 3 months 6 times higher Prevalence of diarrea decreased by 40% No change in respiratory infections Deaths from SIDS lower in BFHI group (1) than in control group (5) but not significant Positive effect on IQ, but only on verbal ability at 16 y No effect on risk of obesity. No effect on asthma, lung function, and atopic eczema at Age 16 Years Many publications by Michael Kramer et al. 5

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8 Human Milk as a Biological System Parul Christian et al. AJCN 2021

9 Lars Bode et al, Science 2020

10 Lancet Breastfeeding series - January

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13 Adjusted Relative Odds of Mortality Relative Risk of Death from ARI and Diarrhea Among Non-Breastfed Children in Two Studies, Compared to Breastfed Infants (set at ARO of 1) WHO Collaborative Team on the Role of Breastfeeding in the Prevention of Infant Mortality, Lancet 2000;55:451-5 Rutstein,S. International Journal of Gyn/Obstet. 2005; 89:S7-S <2 mo 2-3 mo 4-5 mo 6-8 mo 9-11 mo mo 13

14 Hot research areas Effect on infant microbiome Human Milk Oligosaccarides - HMO Mothers enteromammary axis breast milk contains many live bacteria Breast milk affect epigenetic programming Breast milk stem cells?

15 Percentage receiving any breastmilk at 12 months

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19 Studies examining BF and later obesity in the offspring

20 Lancet breastfeeding series Victora et al 2016 Effects of breastfeeding on later overweight and obesity Based on meta-analysis by Horta et al Overall effect - OR 0 74 ( ) In High Income Countries, residual confounding by Socio Economic Position is a possibility; However, the effect size was similar in studies from Low- and Middle Income Countries (a third of all studies). 23 high-quality studies showed a smaller pooled reduction of 13% (95% CI 6 19) Conclusion: Suggestive evidence of protection, including high-quality studies and those from low-income or middle-income settings

21 Dewey K et al. AJCN articles, including 6 cohorts with sibling-pair analyses and 1 randomized controlled trial of a breastfeeding promotion intervention. Moderate evidence suggested that ever, compared with never, consuming human milk is associated with a lower risk of overweight and obesity at ages 2 y and older, particularly if the duration of human milk consumption is >6 mo. Further research, using strong study designs, is needed to disentangle the complex relation between infant feeding practices and the risk of subsequent overweight or obesity, as well as the biological and behavioral mechanisms if the relation is causal. 21

22 Association of infant diet with subsequent obesity at 2 5 years among children exposed to gestational diabetes: the SWIFT study Vandyuosefi et al. Diabetologia 2021 Inadequate duration of BF and EBF (<6mo) were each directly associated with child obesity in GDM exposed children at 2-5 y Sugar-sweetened beverages (SSB) and fruit juice intake in the first year year was each independently associated with a higher odds of child obesity Inadequate EBF combined with intake of fruit-juice and SSB was associated with a 6 and 12-fold higher odds of obesity, repectively 22

23 Hvordan beskytter amning mod fedme? Lavere protein indtag? Appetit regulerende hormoner i modermælk? Bedre appetit regulering pga ændringer i smag og fedtindhold Det ammede barn har en mere aktiv rolle Moren har tillid til at barnet får nok mælk 23

24 Dailymail.co.uk 24

25 Stor social ulighed! Socialt belastede familier har Kortere amning Dårligere kostmønstre Mere overvægt og fedme 25

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27 Residual confounding Reverse causality 27

28 AJCN 2007

29 HVORFOR HAR OVERVÆGTIGE SVÆRT VED AT AMME?

30 Faktorer der påvirker etablering af amning hos svært overvægtige mødre Problemer med brystets størrelse Interferens med start af lactogenesis II Faktorer der påvirker amningens længde Hormonelle faktorer Psykosociale faktorer Begrænset brystkirtelvæv?. International Breastfeeding Journal 2015 Gennemgår interventions studier, der har forsøgt at øge amningslængden. Fremhæver dansk studie af Malcau et al

31 Telephone based support prolongs breastfeeding duration in obese women: A randomized trial E Malchau Carlsen, A Kyhnaeb, K Renault, D Cortes, KF Michaelsen, O Pryds Am J Clin Nutr obese mothers randomised to structured interview and at least nine supportive telephone calls or standard care Improved support increased: Excl BF from median of 40 d to 120 d, p=0.003 Any BF from 108 to 184 d, p=

32 Program components Staff and provider training; Contemporary Clinical Trials 2018 Enhanced gestational weight gain and infant overweight tracking; Universal screening of adverse health behaviors and sociocontextual factors; Universal patient navigation to support individual behavior change and social needs, while strengthening integration of clinical and public health services; Individualized health coaching for mother-infant pairs at high risk of obesity; Educational materials to support behavior change. 32

33 Den tidlige ernærings betydning for udvikling af overvægt og fedme senere i livet - Oplæg på Videncenter for Forebyggelses møde februar 2019 Forslag til strukturelle tiltag: Opnormering af sundhedsplejen Fokus på socialt belastede familier og familier med overvægt. Bedre ressourcer til at hjælpe med Amme etablering overgang fra fødeafdeling til sundhedsplejen Rigtig overgangskost Etablering af gode mad- og måltidsvaner for hele familien Vækstmonitorering gennem hele småbarnsalderen Rådgivning om fysisk aktivitet Ressourcer Bedre tid til flere besøg i en længere periode hos familier, der har behov for hjælp Udvikling af metoder, der kan støtte og motivere de familier, der har brug for hjælp til at få bedre vaner i familien

34 2021 Udvalgte risikofaktorer fra hovedkonklusionen Overvægt hos mor og far, både før, under og efter graviditeten Stor vægtøgning under graviditeten Rygning under graviditeten Graviditetsdiabetes Genetiske og epigenetiske faktorer Kort varighed af eller manglende amning Højt proteinindhold i barnets mad i de første to leveår Søvnlængde og kvalitet Stress under graviditeten 34

35 WHO Growth Standards 0-5 years Based on breastfed infants 1 year 2 years 3 years 4 years 5 years

36 Mean Z-scores of healthy breastfed infants relative to the NCHS/WHO reference Source: An Evaluation of Infant Growth, WHO, 1994 Source: An Evaluation of Infant Growth, WHO, 1994

37 Eligibility criteria of individuals l l l l l l No health, environmental or economic constraints on growth Mother willing to follow feeding recommendations Full BF 4-6 mo and continued breastfeeding for at least 9-12 mo Term birth Single birth Lack of significant perinatal morbidity No smoking mothers (before and after delivery)

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39 Mean Length (cm) WHO Multicentre Growth Reference Study Group. Mean Mean Length length from from Birth birth Through to 24 months 2 Years for the for six Each MGRS Study sitessite Brazil Ghana India Norway Oman USA Age (days)

40 Comparison of WHO with Danish reference Else Andersen - boys Weight (kg) WHO Danish Comparison of WHO with Danish reference weight-for-age percentiles for boys 97th 90th 75th 50th 25th 10th 3rd Age (m onths)

41 BMI (kg/m²) Comparison of WHO with Danish reference Else Andersen - boys Comparison of WHO with Danish BMI-for-age percentiles for boys Birth to 60 months WHO Danish 97th 90th 75th 50th 25th 10th 3rd Age (m onths)

42 Danish 2014 vs WHO standard

43 Reference versus standard breastfeeding BW higher for girls 50 g BW for boys 3.3 kg in D 2014 and WHO Danish average 3.6 kg More referels with D 2014 than WHO?

44 Conclusions WHO 0-5 y growth standards More attention on early prevention of obesity Less infants referred with failure to thrive Less pressure to give breastfed infants formula Likely to be a growth pattern associated with less disease later in life Valuable tool for research and international comparisons

45 Kim F Michaelsen - kfm@kvl.dk - Obergurgl January

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47 Breastfeeding and the immune system

48 Immune systems in Human Milk Leucocytes B lymphocytes Macrophages Neutrofiles T lymphocytes Secretory immunoglobulin A (SIgA) Oligosacharides Bifidus factor Lysozyme Lactoferrin Interferon-gamma Nucleotides Cytokines

49 Secretory IgA antibodies

50 Stimulation of the child s own immune system The immune respons after some vaccines is better in breast-fed infants Hahn-Zoric et al. Acta Paed Scand 1990;79:1137 SIgA content in urine is higher in breast-fed infants Goldblum et al. Saunders 1996, 159 Kidney transplants from a maternal donor is surviving better if the recipient has been breast-fed Campbell et al. Transplantation 1984, 37,340 50

51 Thymic size at 4 mo and mode of feeding Hasselbalch et al Acta Paediatr 1996

52 BMC Pediatr Rytter et al. Correlates of thymus size and changes during treatment of children with SAM: a cohort study. Malnutrition and inflammation are associated with thymus atrophy

53 JAMA Pediatr Jun;169(6) The search identified 25 relevant studies, 18 of which met all inclusion criteria. No publication bias or heterogeneity among these 18 studies were detected Compared with no or shorter breastfeeding, any breastfeeding for 6 months or longer was associated with a 19% lower risk for childhood leukemia (odds ratio, 0.81; 95% CI, ) 14% to 19% of all childhood leukemia cases may be prevented by breastfeeding for 6 months or more. 53

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55 DOES BREASTFEEDING INCREASE INTELLIGENCE LATER IN LIFE?

56 Acta Paed 2015 Consistent effects of about 3 IQ points in observational studies Breastfeeding is related to improved performance in intelligence tests. A positive effect of breastfeeding on cognition was also observed in a randomised trial. This suggests that the association is causal. The review referred to in the Lancet 2016 paper

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59 2019 Conclusions Breastfeeding duration of 1 mo or shorter compared with longer periods was associated with approx. 3 points lower IQ There was no evidence of a dose response relation We were able to adjust for some of the most critical confounders, including maternal intelligence

60 JAMA individuals born Information on breastfeeding collected at 12 mo 973 men and women examined at 27.2y Wechsler Adult Intelligens Scale (WAIS) 2280 men examined at draft board at 18.7y Børge Prien Prøve

61 Results adjusted for these co-variates Parental social status Parental education Single mother status Mother s height Mother s age Parity Gestational age Birth weight Birth length Sex Pregnancy weight gain Smoking during 3rd trimester

62 973 males and females (27.7 y) IQ by WAIS <1 mo 2-3 mo 4-6 mo 7-9 mo >9 mo

63 2280 males (18.7 y) 41 IQ by BPP <1 mo 2-3 mo 4-6 mo 7-9 mo >9 mo

64 Conclusions cognitive development The majority of studies have shown a positive association between BF and IQ Some large well performed studies could not find an association The effect is not large in the individual, but likely to have a considerable impact at the population level Dose-response effect with duration of BF Stronger effects in preterm infants The effect seems stable over age once it is established 64

65 What is the cause of the better IQ?

66 Factors in human milk? DHA incorporation in cell membranes in CNS A plausible biological mechanism

67 Residual confounding Unregistered factors that correlate with both duration of breastfeeding and offspring intellectual development Maternal IQ? Caring ability?

68 Factors associated with the feeding situation? Physical and psychological contact during breastfeeding? - also a cause effect

69 Behavioral pattern of the mother Support and stimulation of child Breast feeding Oxytocin Prolactin Bonding LCPUFA Behavioral pattern of the mother Cognitive development Focus more on infant Affectionate touch Less depression

70 Temporal peri-partal impairment in memory and attention and its possible relation to oxytocin concentration Silber at al. Life Sci 1990;47: pregnant women and controls Cognitive tests of memory and attention Cases improved their performance significantly 6-12 months after delivery compared to late pregnancy and lactatioon (at 3 months)

71 Selective effects of oxytocin on human memory Heinrichs et al 2004, Physiology and behaviour healthy men Intranasal oxytocin or placebo 50 min before tests Oxytocin significantly impaired recall performance From discussion Other studies show impaired cognitive performance in the presence of improved social memory or social behaviour Isolate the mother from distracting stimuli during lactation Focus maternal attention on the interaction between mother and infant

72 Oxytoxin Guastella AJ et al. Biol Psychiatry. 2008;64: Administration of oxytocin to male humans enhances the encoding of positive social information to make it more memorable. Results suggest that oxytocin could enhance social approach, intimacy, and bonding in male humans Kosfeld M et al, Nature : Oxytocin increases trust in humans. These results concur with animal research suggesting an essential role for oxytocin as a biological basis of prosocial approach behaviour.

73 Oxytosin er et socialt hormon Amme hjerne giver mere fokus på barnet og er positivt

74 Hvordan kommunikerer vi de positive effekter af amning?

75 Negative effects of Breastfeeding

76 Breast feeding and HIV Etimate based on Southern Africa at the start of the HIV epidemic 1/3 of pregnant mothers HIV positive 33 out of 100 1/3 of those transmit HIV to the infant 11 out of 100 1/3 of these infants are infected through breast milk 3 out of 100 Now ART treatment is available for mother and infant

77 SST Anbefalinger om infektioner Amning og modermælk fra mor med COVID-19 Der er ikke påvist SARS-CoV-2 i brystmælk fra mødre med bekræftet COVID- 19 på fødselstidspunktet, og det er derfor anbefalingen, at moderen ammer sit barn, hvis hun ønsker det og har mulighed herfor. Det anbefales, at moderen under amning følger Sundhedsstyrelsens generelle hygiejneråd i forhold til at mindske risikoen for smitte med COVID-194. Derudover anbefales følgende smittebegrænsende tiltag: Mundbind til mor med bekræftet COVID-19 ved tæt kontakt til barnet (herunder amning), samt afvaskning af brystet, og god håndhygiejne før amning (sæbe og vand) med henblik på at reducere risikoen for smitte af barnet. Hiv og aids Hiv-positive mødre frarådes at amme. Hiv smitter via blod og kropsvæsker. Der er stor risiko for smitte (15-40 %) af barnet i graviditeten, ved fødsel og amning. Hovedparten af smitten foregår sent i graviditeten. Ved antiviral kombinationsbehandling i graviditeten reduceres smitterisikoen til under 1 %. Da hiv smitter gennem brystmælk, frarådes amning, og der gives modermælkserstatning 77

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79 Pollutants Metylmercury, dioxines, organocloride compounds levels are higher in breastmilk than in infant formula In mothers with high levels the intrauterine exposure is more likely to have negative effects than exposure through breastmilk There is consensus than any potential negative effects through breastmilk is outweighed by the positive effects of breastfeeding

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83 Hypernatiemic dehydration during the 2. week

84 Maternal effects

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87 Breast cancer and BF Collaborative group on Hormonal Factors in Breast Cancer Lancet 2002 Reanalysis of individual data from 47 studies in 30 countries with 50,302 women RR risk of breast cancer decreases by 4.3% for every 12 mo of breastfeeding (p<0.0001) 7% for each birth Can explain most of the difference between breast cancer in developed and developing countries

88 Maternal body composition Fat stores build up during pregnancy Used as energy stores during lactation Transfer of fat from mother to infant through milk with high milk content Especially fat stores at lower abdomen and thighs are released during lactation

89 Optimal Duration of Exclusive Breastfeeding 4-6 mo 6 mo WHO: Population based recommendation 6 (4)

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93 Information

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96 Breastmilk macronutrient content and infancy growth Prentice, Ong, Schoemaker, von Tol, Vervoort, Hughes, Acerinii and Dunger. Acta Paed milk samples at age 4-8 weeks Infant growth measured until 12 months of age Higher total caloric content associated with lower BMI at 12 mo % fat inversely associated with gain in weight and BMI 3-12 mo % protein positively associated with BMI at 12 mo Limitation: Hind milk samples milk intake not measured Same pattern - protein and fat - as in compl. feeding

97 The normally increasing fat content in breast-milk obviously cannot occur with cow s milk formula, which is of uniform composition. This may have an appetite-controlling (or fluidseeking) effect, the baby ceasing to take later hind-milk, possibly in response to changes in flavour or viscosity but restarting feeding when moved to the second breast 97

98 Breast milk composition and growth Multiple nutrients, hormones and other bioactive components present in breastmilk may influence growth May influence infant growth through effects on Digestive functions Gut development Regulation of appetite and energy homeostasis Need for bypassing the infants gastrointestinal system more or less intact possible through Protease inhibitors in breastmilk High gut ph in infancy Immature pancreatic enzymatic activity Fields et al. Pediatric Obesity 2016

99 Behavioral factors Bartok and Ventura. Int J Ped Obesity 2009 Breastfeeding mothers are more likely to trust the infants ability to self-regulate and be attentive to the infants expressions and cues indicating fullness and satiation Patterns of caregiver control over feeding established during infancy, may extent later into childhood infants s emerging ability to self-regulate intake can be overridden by caregiver behavior 99

100 Infants fed from the breast have improved appetite control later in life compared to infants fed breastmilk from a bottle 3-6 year children (n=104): 68% less likely to have high satiety responsiveness if fed breastmilk from bottle compared to from the breast ( DiSantis et al. Int J Behave Nutrition Phys Activ 2011) Bottle fed infants (incl. Breastmilk) less likely to empty bottle or cup in late infancy compared to breast fed (Rouwei et al, Pediatrics 2010) 100

101 Is human milk given to boys different from human milk given to girls? 101

102 Body Composition 102

103 Exclusively Breastfed at 6 mo Weight 12 kg

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105 6 mo: 15,1 kg 9 mo: 18,4 kg Department of Nutrition, Exercise and Sports 17 mo: 15,1kg Dias 105 GOWP

106 Exclusively breastfed boy 5 mo: 12,100 g BW: 3828 g 7 mo: 13,000 g 20 mo: 14,000 g

107 Modermælks erstatning er ikke farligt Hvordan kommunikerer vi de positive effekter af amning?

108 29/08/ Bevilling på 7,2 mill DKK til at undersøge modermælkens indhold hos 250 danske kvinder som vi følger fra sent i graviditeten til 8.5 mdrs alderen

109 Kim F. Michaelsen, Dr.Med., PI Akademiske medarbejdere Christian Mølgaard, Dr.Med., PhD, Head of the department Sophie Hilario Christensen, PhD student Anni Larnkjær, PhD, academic staff Tekniske medarbejdere Ammerådgivere Inge Rasmussen, Lab technician Birgitte Hermansen, Dietitian Birgitte Hyldebrandt Anne Kynæb Dorrit Vizel

110 Baggrund og formål Et internationalt samarbejde Vi vil undersøge Sammensætningen af modermælk specielt mhp vitaminer og mineraler Relatere data til barnets vækst og trivsel Formål Gambia Bangladesh At sikre en bedre forebyggelse af underernæring hos spæd- og småbørn i lavindkomstlande At få en bedre forståelse af effekten af amning 110 på børns vækst, udvikling og sundhed

111 PI: Prof Kim F. Michaelsen PI: Dr Lindsay Allen PI: Dr Sophie Moore PI: Dr Munir Islam PI: Prof Gilberto Kac

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113 For opdateringer:

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