Obesity and metabolic disorders in pregnancy Consequences for the next generation CASE Overvekt i svangerskap og fødsel 10 oktober 2013 Kvinne innlagt på barsel, sectioforløst på annet sykehus BMI 42,9 Forløst uke 36 + 3 Barn vekt 4580 ( ) Gestasjonell diabetes (insulinkrevende) Pre-eklampsi (BT 160/105, prot ++) Barn på barneklinikken, alvorlig hjertefeil Nasjonalt kompetansesenter for kvinnehelse og Kvinneklinikken, OUS Nanna Voldner jordmor, PhD Developmental Origin of Health and Disease Påvirkning i fosterlivet har betydning for senere helse 1
Fosterlivets betydning for senere helse Anders Forsdahl (Sør-Varanger) (1) dårlig ernæring og levekår ved starten av livet kunne påvirke helsen mange tiår senere David Barker (UK) (2) Lav fødselsvekt gir økt risiko for kardiovaskulære sykdommer, diabetes og overvekt Lars Bygren (Overkalix) (3) En vinter med tilgang til mye mat i en unggutts liv kunne medføre at hans fremtidige barnebarn døde langt tidligere enn sine samtidige Maternal size Metabolism Nutrition XX DOHaD Developmental Origin of Health and Disease Fetal nutrition and growth Birth size and body composition Current concept of the Developmental Origins of Health and Disease (DOHaD). The figure shows the influence of early life factors (including maternal factors and childhood growth) on the burden of type 2 diabetes and other non communicable diseases Yajnik, Rev.Endocr Mtab Diord (2008) Infant and childhood growth Risk factors Morbidity Mortality (1) Forsdahl A; Are poor living conditions in childhood and adolescence an important risk factor for arteriosclerotic heart disease? Br J Prev Soc Med. 1977 (2) Barker, DJ. The fetal and infant origins of disease. Eur J Clin Invest 1995 (3) Kaati G, Bygren LO, Pembrey M, Sjøstrøm M. Transgenerational response to nutrition, early life circumstances and longevity. Eur J Hum Genet. 2007 Body Mass Index (BMI) weight / height ² Underweight: BMI < 20 (18.5) Normal weight: BMI (18.5) 20 24,9 Overweight: BMI 25 29,9 Obese: BMI 30 - grade 1 BMI 30-35 - grade 2 BMI 35-40 -grade 3 BMI 40 Trender i overvekt og fedme og diabetes fra 1990-2030 Svarte søyler: overvekt & fedme (BMI >25 kg/m2) & (BMI >30 kg/m2). Grå søyler: fedme Røde søyler: type 2 and type 1 diabetes, (type 2 ca 90 % av alle med diabetes) Adapted from Haffner& Shaw,Catalano 2011. 2
The World Health Organization s life course model of non communicable disease Fowden A L et al. Physiology 2006;21:29-37 The model suggests that non communicable diseases have their origins in early life. The risk progressively accumulates throughout the life course and the disease becomes manifest in later life Owen J, Non communicable disease: A Welcome and Long Needed Addition to the WHO's 2012 World Heath Statistics. Curr Hypertens Rep. 2012 Fowden A L et al. Physiology 2006;21:29-37 Consequences for maternal metabolic syndrome Long term survival of mothers after their first delivery, according to whether they had preeclampsia and gestational age of baby at birth (term=37 weeks or more). Maternal consequences Short term Long term Short term Fetal consequences Long term Irgens H U et al. BMJ 2001;323:1213-1217 2001 by British Medical Journal Publishing Group 3
Programming of Adult Cardiovascular Disease following Exposure to Late Gestation Hyperglycemia Percentage fat at birth Nyere data begynner å vise at barn født av mødre med diabetes har høyere risiko for hjerte-karsykdom senere i livet, selv om det kun finnes noen få studier foreløpig. Melissa Agoudemos m.fl Neonatology 2011;100:198 205 The metabolic environment intrauterin influence primarily fetal fatmass and not fatfree muscelmass Catalano 2011 Body Composition of Newborn Fat Muscle Viscera Other 3500g 2700g White Caucasian, 3500 g Indian, 2700 g Yajnik et al, JCEM, 2002 Yajnik et al, Int J Ob, 2003 4
Total adipocyte number : a, The adipocyte number increases in childhood and adolescence,. b, c, Major weight loss by bariatric surgery results in a significant decrease in cell volume (b), however fails to reduce adipocyte cell number (c), 1 2 yr post surgery Catalano, P. M. J Clin Endocrinol Metab, 2003 Kirsty L. Spalding, Nature 2008 Professor James: BBC news The epidemic of obesity has now come so far that a common global politic is nessecary to handle this in the best possible way There are now twice as many obese as undernourished children in the world There is no point in blaming individuals for being overweight we need real political leadership to change the environment that is rapidly making the world fat: The fat content of food needs to be labelled clearly Advertisers must be prevented from targeting children and Governments must encourage people to get out of their cars Association of caesarean delivery with child adiposity from age 6 weeks to 15 years. There may be long term consequences [of caesareans] to children that we don t know about Researchers believe that babies by natural childbirth are exposed to bacteria in the birth canal which helps regulate metabolism in later life. The other possibilities are that these are children that would have been heavier anyway. Being heavy as a woman is a risk factor for C section, so that s the problem with trying to figure out whether this is real or if it s simply a matter of selection. Int J Obes (Lond Int J OBesity, 2013 Apr 8. doi: 10.1038/ijo.2013.49. [Epub ahead of print] 5
Delivery by caesarean section and risk of obesity in preschool age children: a prospective cohort study Infants delivered by caesarean section may be at increased risk of childhood obesity. Further studies are needed to confirm our findings and to explore mechanisms underlying this association Infants delivered by caesarean section had twofold higher odds of childhood obesity, even after adjusting for maternal body mass index, birth weight and other confounding variables. Expectant mothers choosing caesarean delivery in the absence of a medical indication should be aware that their children may have a higher risk of obesity Arch Dis Child.. 2012 May 23. Arch Dis Child.. 2012 May 23. EPIGENETIKK Epigenetikk er studier av hvordan miljøet påvirker aktiviteten og funksjonen til våre gener. Vi er vant til å tenke på den genetiske koden som det som avgjør vår biologiske skjebne. Men genkoden er ikke alene om å bestemme hvilke egenskaper vi har og gir videre til etterkommerne. Viktige mekanismer utenfor genomet sørger for å slå genene på og av. Slike såkalte epigenetiske modifikasjoner betyr bl.a. at egenskaper som planter eller dyr opparbeider seg f.eks. gjennom (Wikipedia) kosten, kan gå i arv til de neste generasjonene One can compare with an orchestra where changes in the music are made while the concert is being played. If you replace the first violin or add a harmonica to the right, the play will be different 6
Agouiti mus Agoutimus har et gen som gjør at de blir gule, syke og fete. Ved å mate musene med folinsyre fødte de fete, gule musene sunne, friske og slanke brune musebarn. Og disse musebarna fødte i sin tur flere slanke, brune museunger selv om de bare fikk normal kost. Fremtidige mødres helse må få mer oppmerksomhet enn kolesterolnivået og vekten til menn og kvinner i 50-60 årsalderen T.Henriksen, Aftenposten, 2010 Takk for oppmerksomheten 7