Overvekt og svangerskapsutfall: Hva er evidensen for at det nytter å intervenere Tore Henriksen Oppsummering av betydningen av intervensjon for overvekt/fedme for svangerskapsutfall Tiltak som kan redusere overvekt/fedme før svangerskapet og uønsket vektøkning under svangerskapet bør iverksettes fordi det med rimelig sannsynlighet reduserer risikoen for svangerskapskomplikasjoner. Det er basert på en samlet vurdering av evidens fra intervensjonsstudier, obervasjonsstudier, indirekte evidens fra den ikke gavide befolkning, fysiologisk kunnskap og klinisk erfaring. Overweight/obesity Risks of pregnancy and delivery complications Det går en grunnleggende forskjell mellom A. Observasjonsstudier 1. Risks of being overweight/obese at start of pregnancy (pre-pregnancy overweight/obesity) 2. Risks of high weight gain during pregnancy og B. Intervensjonsstudier (clinical trials)
Observasjonsstudier Observasjonsstudier Normalvektige Normalvektige Svangerskapsdiabetes, forekomst (prevalens). Observasjonsstudier beskriver statistiske sammenhenger Svangerskapsdiabetes, forekomst. mellom variable (f eks mellom fedme og diabetes), men sier ikke nødvendig noe om årsakssammeheng. Overvektige Overvektige Årsak? Overvekten (BMI)? Fordelingen av kroppsfett? Liten fysisk aktivitet? Ulik genetisk aktivitet (epigenetikk?) Gener? Intervensjonsstudier (randomisert studier, clinical trials) Overvektige? Kontrollgruppe Intervensjonsgruppe Evidensbasert medisin bygger på hierarki av informasjon med ulik evidensstyrke. 1.Systematiske oversikter av randomiserte studier 2.Systematiske oversikter over observasjonsstudier 3.Fysiologiske studier 4.Klinisk erfaring Intervensjon: Fysisk aktivitet
Obervasjonsstudier av sammenhenger mellom overvekt/fedme og svangerkskapsutfall OvervektFedme ved start av svangerskapet Økt risiko for 1. Preeklampsi 2. Svangerskapsdiabetes 3. Fosterdød 4. Keisersnitt (total og akutt) 5. Instrumentelle forløsninger 6. Post partumblødninger 7. Maternelle infeksjoner 8. Lengde av sykehusoppholdet 9. Makrosomi 10.Opphold på neonatal Overweight/obesity and pregnancy outcomes Observational : For stor vektøkning i svangerskapet Økt risiko for 1. Makrosomi (IOM kriterier*) 2. Keisersnitt (redusert hos overvektige, < 8 kg) 3. Vektretensjon etter svangerskapet (IOM-kriterier) Stillbirth Flenady V et al The Lancet 2011. Metaanalysis* BMI (kg/m 2 ) OR CI PAR* < 25 1.0 8 18% 25 30 1.2 1.09 1.28 >30 1.6 1.35 1.95 * IOM: Intistute of Medicine, anbefalinger I henhold til BMI-grupper) * High income countries **PAR: population attributable risk
Overweight/obesity and pregnancy outcomes Observational : Overall Cesarean delivery: Obese versus ideal weight* Heslehurst N et al Obes Rev 2008 Cesarean delivery * BMI >30kg/m 2 versus BMI 20 25 Emergency Cesarean delivery: Obese versus ideal weight* Heslehurst N et al Obes Rev 2008 Elective Cesarean delivery: Obese versus ideal weight* Heslehurst N et al Obes Rev 2008 * BMI >30kg/m 2 versus BMI 20 25 * BMI >30kg/m 2 versus BMI 20 25
Overweight/obesity and pregnancy outcomes Observational : Instrumental vaginal delivery: Obese versus ideal weight* Heslehurst N et al Obes Rev 2008 Cesarean section: Dose response Barau G et al BJOG 2006: * BMI >30kg/m 2 versus BMI 20 25 Mean length hospital stay Obese versus ideal weight* Heslehurst N et al Obes Rev 2008 Neonatal Intensive Care Unit. Obese versus ideal weight* Heslehurst N et al Obes Rev 2008 * BMI >30kg/m 2 versus BMI 20 25 * BMI >30kg/m 2 versus BMI 20 25
Maternal haemorrhage: Obese versus ideal weight* Heslehurst N et al Obes Rev 2008 Maternal infection Obese versus ideal weight* Heslehurst N et al Obes Rev 2008 * BMI >30kg/m 2 versus BMI 20 25 * BMI >30kg/m 2 versus BMI 20 25 Overweight/obesity and pregnancy outcomes Observational Preeclampsia After You et al 2006 Groups with various BMI Overweight/obesity and pregnancy outcomes Observational : Gestational diabetes (GDM) * >29 * * * * 20 26 20 26 25 30 20 25 26 35 26 29 >30 25 30 >35 >29 >30 BMI (kg/m 2 ) < 25 1.0 Risk for GDM. RR(95% CI)* 25 30 1.21 (0.66 2.21) >30 2.10 (1.17 3.79) * BMI Ref group Odds ratio *Athukorala C et al 2010
Observations : Gestational weight gain (GWG) and pregnancy outcomes Observations Gestational weight gain(gwg) and Macrosomia /Large for Gestational Age (LGA) Siega Riz et al AJOG 2009: A systematic review 35 included: Strong evidence to support independent associations between excessive weight gain (IOM 1990 terms) and risk of macrosomia (>4000g) or LGA. Observations : Gestational weight gain(gwg) and pregnancy outcomes Prevalence of Large Birth Weight by BMI groups and Gestational Weight Gain Dietz PM et al AJOG 2009 The associations between GWG and pregnancy outcomes according to pregestational BMI groups.
Prevalence of Large for Gestational Age by BMI groups and IOM Recommendations for Weight Gain Dietz PM et al AJOG 2009 Observational : Effect of gestational weight gain (GWG) accordng to BMI categories Cesarean delivery (overall rate) Cedergren M 2006 Cesarean section: OR (95% CI) BMI (kg/m 2 ) GWG < 8 kg 8 16 kg >16 kg <20 1.07 (0.89 1.19) 1.0 1.29 (1.17 1.43) 20 25 0.98 (0.92 1.05) 1.0 1.24 (1.19 1.29) 25 30 0.88 (0.82 0.95) 1.0 1.23 (1.17 1.30) 30 35 0.81 (0.73 0.90) 1.0 1.22 (1.10 1.35) >35 0.75 (0.66 0.87) 1.0 1.27 (1.05 1.52) Observations : Gestational weight gain(gwg) and: Post partum weight retention Siega Riz et al AJOG 2009: A systematic review 35 included. Moderate evidence to support the associations between excessive weight gain (IOM 1990 terms) post partum maternal weight retention Overweight/obesity Observational : Conclusion: There is extensive evidence that both overweight/obesity and excessive weight gain are associated with adverse pregnancy outcomes
Men det at observasjonsstudier viser at overvekt/fedme er en risikofaktor for en rekke uheldige svangerskapsutfall betyr ikke nødvendigvis at det hjelper å intervenere Overweight/obesity Help for (outcomes)?: First question: Help for what? Maternal outcomes: Gestational weight gain? Preeclampsia? Gestational diabetes? Cesarean section? Vaginal operative deliveries? Perineal injuries? Long term health of the mother? Several of these? Etc Newborn outcomes Birth weight? Neonatal body composition? Birth asphyxia? Need for Neonatal Unit Care? Long term health of the child? Etc. Overweight/obesity In other words: Which endpoints (outcomes) of intervention are we (or should we be!) talking about? Overweight/obesity Second question: What kind of intervention do we mean?
Overweight/obesity Overweight/obesity Kinds of intervention: Nutritional? Physical activity? Combined Nutritional and Physical? Life style/behavioral? Bariatric surgery? Psychosocial intervention? Food prices? Structural changes in the society? Etc. Nutritional? Physical activity? Combined Nutritional and Physical? Life style/behaviorial? Bariatric surgery? Psychosocial intervention? Food prices? Structural changes in the society? Etc. Timing of intervention Timing of intervention: Pregestational? During pregnancy Early? Late? Post partum? Overweight/obesity Nutritional? Physical activity? Combined Nutritional and Physical? Life style/behaviorial? Bariatric surgery? Psychosocial intervention? Food prices? Structural changes in the society? Etc. Timing of intervention Timing of intervention: Pregestational? During pregnancy Early? Late? Post partum? Intensity of Intervention?! Interventional of overweight/obesity Gestational Weight Gain (GWG) is the outcome best studied Mother: Gestational weight gain Preeclampsia? Gestational diabetes? Cesarean section? Vaginal operative deliveries? Perineal injuries? Long term health of the mother? Several of these? Etc Baby: Birth weight? Neonatal body composition? Birth asphyxia? Need for Neonatal Unit Care? Long term health of the child? Etc.
Interventional Total gestational weight gain following dietary intervention (some also include physical activity) Interventional Total gestational weight gain following dietary intervention (some also include physical activity) The 2012 metaanalysis 2: Thangaratinam S et al BMJ May 2012* The 2012 metaanalysis 2: Thangaratinam S et al BMJ May 2012 * Study population: Any BMI 18.5 kg/m 2 Interventional Total gestational weight gain Effect of Behavioral intervention Interventional Total gestational weight gain following dietary intervention (some also include physical activity) 2011 Meta analysis 1: Campbell F et al 2011* Meta-analysis 2012 1: Oteng-Ntim BMC Medicine 2012* * Study population: Any BMI group * Study Population: overweight/obese
Interventional Total gestational weight gain following dietary intervention (some also include physical activity) The 2011 metaanalysis 2: Ida Tanentsapf et al BMC Pregn Childbirth 2011;11:81* Interventional Gestational Weight Gain Effect of Physical activity (as the only intervention) Streuling I et al BJOG 2010. A meta analysis Study populations: any BMI group *Study population: any BMI group Interventional Pregnancy complications gain following dietary intervention (some also include physical activity) The 2012 metaanalysis: Thangaratinam S et al BMJ May 2012 Interventional for overweight/obesity Large for Gestational Age Preeclampsia: Gestational Diabetes: Preterm Delivery: Mother: Gestational weight gain? Preeclampsia? Gestational diabetes? Cesarean section? Vaginal operative deliveries? Perineal injuries? Long term health of the mother? Several of these? Etc Baby: Birth weight Neonatal body composition? Birth asphyxia? Need for Neonatal Unit Care? Long term health of the child? Etc.
Interventional SGA and LGA following dietary intervention (some also include physical activity) Interventional Mean birth weight following dietary intervention (some also include physical activity) The 2012 metaanalysis: Thangaratinam S et al BMJ May 2012 The 2012 metaanalysis: Thangaratinam S et al BMJ May 2012 Interventional LGA (Dietary intervention) The 2010 meta analysis: Dodd JM et al. BJOG 2010;117:1316 Interventional Neonatal outcomes gain following dietary intervention (some also include physical activity) The 2012 metaanalysis: Thangaratinam S et al BMJ May 2012 Shoulder dystocia
Physical activity and Gestational Diabetes Mellitus (GDM) Tobias DK et al. Physical activity before and during pregnancy and risk of gestational diabetes mellitus: A meta analysis Diabetes Care 2011;34:223 29 Risk of GDM OR (95% CI) Physical activity before pregnancy 0.45 (0.28 0.75) Physical activity early pregnancy 0.76 (0.70 0.83) Summary interventional : Dietary (with or without physical activity) intervention for overweight/obesity in pregnancy: PREGNANCY and NEONATAL OUTCOMES Overall evidence rating is Moderate for weight gain and risk of SGA, Low/very low (preterm delivery, preeclampsia, GDM, Causes: Statistical heterogeneity, study limitations, publication bias ( Thangaratinam, BMJ 2012) (But absence of evidence dose to mean evidence of absence(!)) Summary interventional : Dietary (with or without physical activity) intervention for overweight/obesity in pregnancy: PREGNANCY OUTCOMES 1. Gestational weight gain: reduced, largest with diet only (by order of magnitude 2 4 kg) 2.Preeclampsia: Reduction by around 30 % (only for those with GDM or responders?)(thangaratinam) 2.Gestational diabetes: With only diet : 60 % reduction (Thangaratinam ). With only physical activity: 25 50 % (Tobias DK) 6. Preterm delivery: With only diet: 30 % reduction 7.Other: Cesarean: no effect. Induction of labour: no effect. Summary interventional : Dietary (with or without physical activity) intervention for overweight/obesity in pregnancy: NEONATAL OUTCOMES (Thangaratinam) 1. Shoulder dystocia: 60% reduction 2. Mean birth weight: Trend of 50 g reduction, borderline significance 3. Fetal death: Trend RR 0.15 (CI 0.02 1.25) 4. Birth trauma: Trend RR 0.36 (CI 0.11 1.23) 5. Risk of SGA: no effect. Risk of LGA: no effect 6. NICU admission: no; Respiratory distress: no; Hypoglycemia: no
Summary of interventional of overweight/obesity in pregnancy: Subgroup and sensitivity analyses (Thangaratinam, 2012) Women who did reduce gestational weight gain (responders): 40 % reduction I preeclampsia (p for interaction = 0.009). Women who did reduce gestational weight gain: 170 g lower birth weight (p for interaction= 0.002) Summary. Interventional of overweight/obesity in pregnancy: Intervention before pregnancy: Current data not sufficient for analysis But: in a general population: Physical activity before pregnancy seems to reduce the risk of GDM The hierarchy in preventing obesity related pregnancy and delivery complications 1. Reducing the prevalence of obesity and increase the level of physical activity in the whole population of young women (major task!) 2. Pre conceptional counseling, the longer before pregnancy the better, but more that 50% of pregnancies are unplanned. (Bariatric surgery? whom?) 3. Intervention during pregnancy. Require considerable resources, efficacy remains unclarified (practically difficult to achieve sufficient intensity of the intervention etc). Oppsummering av betydningen av intervensjon for overvekt/fedme for svangerskapsutfall Tiltak som kan redusere overvekt/fedme før svangerskapet og uønsket vektøkning under svangerskapet bør iverksettes fordi det med rimelig sannsynlighet reduserer risikoen for svangerskapskomplikasjoner. Det er basert på en samlet vurdering av evidens fra intervensjonsstudier, obervasjonsstudier, indirekte evidens fra den ikke gavide befolkning, fysiologisk kunnskap og klinisk erfaring.
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