Overvekt og svangerskapsutfall: Hva er evidensen for at det nytter å intervenere

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1 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. Deterbasertpåen samlet vurdering av evidens fra intervensjonsstudier, obervasjonsstudier, indirekte evidens fra den ikke gavide befolkning, fysiologisk kunnskap og klinisk erfaring. Risks of pregnancy and delivery complications 1. Risks of being overweight/obese at start of pregnancy (pre-pregnancy overweight/obesity) 2. Risks of high weight gain during pregnancy Det går en grunnleggende forskjell mellom A. Observasjonsstudier 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?

2 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 and 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 Metaanalysis* BMI (kg/m 2 ) OR CI PAR* < % > * IOM: Intistute of Medicine, anbefalinger I henhold til BMI-grupper) * High income countries **PAR: population attributable risk

3 and Observational : Overall Cesarean delivery: Obese versus ideal weight* Cesarean delivery Emergency Cesarean delivery: Obese versus ideal weight* Elective Cesarean delivery: Obese versus ideal weight* and Observational : Instrumental vaginal delivery: Obese versus ideal weight* Cesarean section: Dose response Barau G et al BJOG 2006:

4 Mean length hospital stay Obese versus ideal weight* Neonatal Intensive Care Unit. Obese versus ideal weight* Maternal haemorrhage: Obese versus ideal weight* Maternal infection Obese versus ideal weight* and Observational Preeclampsia After You et al 2006 Groups with various BMI and Observational : Gestational diabetes (GDM) * >29 * * * * > >35 >29 >30 BMI (kg/m 2 ) < Risk for GDM. RR(95% CI)* ( ) > ( ) * BMI Ref group Odds ratio *Athukorala C et al 2010

5 Observations : Gestational weight gain (GWG) and 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 Prevalence of Large Birth Weight by BMI groups and Gestational Weight Gain Dietz PM et al AJOG 2009 The associations between GWG and 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 < ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) > ( ) ( )

6 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 Observational : Conclusion: There is extensive evidence that both overweight/obesity and excessive weight gain are associated with adverse Men det at observasjonsstudier viser at overvekt/fedme er en risikofaktor for en rekke uheldige svangerskapsutfall betyr ikke nødvendigvis at det hjelper å intervenere 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. In other words: Which endpoints (outcomes) of intervention are we (or should we be!) talking about? Second question: What kind of intervention do we mean?

7 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/behavioral? 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 of Intervention?!?! 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. Total gestational weight gain (some also include physical activity) The 2012 metaanalysis 2: Thangaratinam S et al BMJ May 2012* * Study population: Any BMI 18.5 kg/m 2 Total gestational weight gain (some also include physical activity) Total gestational weight gain Effect of Behavioral intervention The 2012 metaanalysis 2: Thangaratinam S et al BMJ May Meta analysis 1: Campbell F et al 2011* * Study population: Any BMI group

8 Total gestational weight gain (some also include physical activity) Meta-analysis : Oteng-Ntim BMC Medicine 2012* Total gestational weight gain (some also include physical activity) The 2011 metaanalysis 2: Ida Tanentsapf et al BMC Pregn Childbirth 2011;11:81* * Study Population: overweight/obese *Study population: any BMI group Gestational Weight Gain Effect of Physical activity (as the only intervention) Streuling I et al BJOG A meta analysis Study populations: any BMI group Pregnancy complications gain (some also include physical activity) The 2012 metaanalysis: Thangaratinam S et al BMJ May 2012 Preeclampsia: Gestational Diabetes: Preterm Delivery: for overweight/obesity Large for Gestational Age SGA and LGA (some also include physical activity) The 2012 metaanalysis: Thangaratinam S et al BMJ May 2012 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.

9 Mean birth weight (some also include physical activity) The 2012 metaanalysis: Thangaratinam S et al BMJ May 2012 LGA (Dietary intervention) The 2010 meta analysis: Dodd JM et al. BJOG 2010;117:1316 Neonatal outcomes gain (some also include physical activity) Physical activity and Gestational Diabetes Mellitus (GDM) The 2012 metaanalysis: Thangaratinam S et al BMJ May 2012 Tobias DK et al. Physical activity before and during pregnancy and risk of gestational diabetes mellitus: A meta analysis Diabetes Care 2011;34: Risk of GDM OR (95% CI) Shoulder dystocia Physical activity before pregnancy 0.45 ( ) Physical activity early pregnancy 0.76 ( ) 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: % (Tobias DK) 6. Preterm delivery: With only diet: 30 % reduction 7.Other: Cesarean: no effect. Induction of labour: no effect.

10 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 ) 4. Birth trauma: Trend RR 0.36 (CI ) 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. 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 Fedme over generasjoner Det nye tema Tiltak som kan redusere overvekt/fedme før svangerskapet og uønsket vektøkning under svangerskapet bør iverksettes fordi det med rimelig sannsynlighet reduserer risikoen for svangerskapskomplikasjoner. Deterbasertpåen samlet vurdering av evidens fra intervensjons studier, observasjonsstudier, indirekte evidens fra den ikke gravide befolkning, fysiologisk kunnskap og klinisk erfaring.