Christina VinterMD, PhD

Department of Gynaecology and ObstetricsOdense University Hospital

University of Southern Denmark

Lifestyle intervention during pregnancy

Today´s presentation

• Types of lifestyle intervention• RCT• Systematic reviews and metaanalysis• IPD metaanalysis• Weight loss prior to conception• Future perspectives

Fertility

Childhood AdulthoodPostpartum

Fertility Embryo Fetus Pregnancy

InfertilityMiscarriageCongenital anomalies

StillbirthFetal growthMonitoring

GDMPreeclampsiaThromboembolism

InfectionsThromboembolismLow breastfeeding rateWeight retention

Childhood obesity

ObesityMetabolic syndrome

Delivery

Induction of labourInstrumental deliveryCesarean deliveryAnaesthetic compl.Intrapartum monitoring

Sebire et al 2001, Chu et al 2007, Metwally et al 2008, Heslehurst et al 2008, Stothard et al 2009, Ovesen et al 2011, Nøhr et al 2012

Gestational Weight Gain(Institute of Medicine 2009)

Prepregnancy BMI category

Total weight gain

Underweight

(< 18.5 kg/m2)

12.5-18 kg

Normal-weight

(18.5-24.9 kg/m2)

11.5-16 kg

Overweight

(25.0-29.9 kg/m2)

7-11.5 kg

Obese

(≥ 30.0 kg/m2)

5-9 kg

IOM: Weight gain during pregnancy: reexamining the guidelines, 2009

Intervention in pregnancy

+ Pregnancy is a ”window” of opportunities+ Women concerned with the health of their baby+ Frequent contact with health care professionals

-9 months of pregnancy / a life with obesity-Two lifes to consider - Potential harm for the infants

Intervention in pregnancy

Diet Physical activity

Behavioral

Evaluation of intervention

• Gestational Weight Gain (GWG)

• >/< IOM weight gain recommendations

• Maternal outcomes• Neonatal outcomes• Metabolic parameters• Psychological parameters• Long term outcomes

“Globesity”

World Health Organization:

• Worldwide obesity has more than doubled since 1980• In 2008 over 200 million men and 300 million women were obese• 43 million children under the age of five were overweight in 2010• Obesity is preventable

• RCT, BMI>30, n= 50• 10 times individual 1h dietary counseling with

dieticians• Reduction in GWG: 6.6 vs 13.3 kg, p=0.002• No effect on clinical outcomes

Denmark

Wolff S et al, Int J Obes, 2008

• RCT, BMI>29, n= 205• 1) Normal care 2) Brochure 3) Intervention • Intervention: 4 group sessions with a midwife, focus

on energy intake and expenditure, healthy food pyramid

• Significant reduction in GWG: normal care 13.5kg vs brochure 9.5kg vs intervention 10.6kg

• Level of anxiety significantly decreased in intervention group and increased in normal care group

• No effect on obstetric and neonatal outcomes

Belgium

Bogaerts et al, Int J Obesity, 2012

• RCT, BMI>25, n=132• Continuity of care provider

Weight monitoringShort dietary interventionPsychology assistance when needed

• Reduction in GWG: 7.0 vs 13.8 kg, p<0.0001 Reduction in GDM: 6% vs 29%, p<0.04

Australia

Quinlivan JA et al, Aust NZJ Obstet Gynecol, 2011

• RCT, BMI 20-40, n=401• Low intensity behavioral intervention

One face-to-face visitMailed materialIndividual graphs of weight gain

• Significant reduction in exceeding IOM recommendations: 40.2% vs 52.1%, p=0.003

In normal weight women only! No effect in overweight and obese women

USA

Phelan S et al, Am J Clin Nutr, 2011

The LiP (Lifestyle in Pregnancy) Study: A randomized controlled trial of lifestyle intervention in 360 obese pregnant women

Vinter C, Jensen DM, Ovesen P, Beck-Nielsen H, Jorgensen JS. Diabetes Care, 2011

Ringkjøbing

Ribe

Vejle

Århus

Fyn

BMI > 30

Danish National Board of Health 2012N= 402.955

The LiP (Lifestyle in Pregnancy) Study: A randomized controlled trial of lifestyle intervention in 360 obese pregnant women.

AimTo study the clinical effects of diet

and physical activity during pregnancy

among Danish obese women

InclusionBMI 30-45, age 18-40 years

ExclusionDiabetes, major medical disorders, non

Danish-speaking,

multiple pregnancy, prior serious obstetric

complications including preterm birth

Vinter C, Jensen DM, Ovesen P, Beck-Nielsen H, and Jorgensen JS. Diabetes Care, 2011

Diet

• Individual face-to-face diet counseling sessions 4 times during pregnancy

• Gestational weight gain 5 kilos

Physical activity

• 30-60 min of daily physical activity

• Free membership in fitness center

• Aerobic classes 1 h weekly• Coaching in small groups• Pedometer• Activity calender

Flowchart participation

GA 35 Intervention n=144

Controln=148

P

GWG (kg) 7.0 (4.7-10.6) 8.6 (5.7-11.5) 0.014

GWG < 5 kilos 41 (28.5%) 30 (20.3%) 0.102

GWG < 9 kilos 93 (64.6%) 79 (53.4%) 0.052

Gestational Weight Gain (GWG)

Obstetric and neonatal outcomes

Vinter C et al, Diabetes Care, 2011

What to do?

Strengths and limitations

• Largest RCT among obese pregnant women• Power calculations were based on the expectation of a larger difference in GWG• Detailed follow-up program also among control group ”passive intervention”• Recruiting the most healthy and motivated mothers• LiPO – follow-up on offspring at 3 years of age

PubMed ResultsItems 1 -10 of 10 (Display the 10 citations in PubMed)

• 1. Antenatal interventions for reducing weight in obese women for improving pregnancy outcome. Furber CM, McGowan L, Bower P, Kontopantelis E, Quenby S, Lavender T. Cochrane Database Syst Rev. 2013 Jan 31;1:CD009334. doi: 10.1002/14651858.CD009334.pub2. Review

• 2. Interventions to reduce or prevent obesity in pregnant women: a systematic review. Thangaratinam S, Rogozińska E, Jolly K, Glinkowski S, Duda W, Borowiack E, Roseboom T, Tomlinson J, Walczak J, Kunz R, Mol BW, Coomarasamy A, Khan KS. Health Technol Assess. 2012 Jul;16(31):iii-iv, 1-191. doi: 10.3310/hta16310. Review.

• 3. A systematic review investigating healthy lifestyle interventions incorporating goal setting strategies for preventing excess gestational weight gain. Brown MJ, Sinclair M, Liddle D, Hill AJ, Madden E, Stockdale J. PLoS One. 2012;7(7):e39503. doi: 10.1371/journal.pone.0039503. Epub 2012 Jul 5. Review.

• 4. Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence. Thangaratinam S, Rogozinska E, Jolly K, Glinkowski S, Roseboom T, Tomlinson JW, Kunz R, Mol BW, Coomarasamy A, Khan KS. BMJ. 2012 May 16;344:e2088.

• 5. Lifestyle interventions for overweight and obese pregnant women to improve pregnancy outcome: systematic review and meta-analysis. Oteng-Ntim E, Varma R, Croker H, Poston L, Doyle P. BMC Med. 2012 May 10;10:47. Review.

• 6. Antenatal exercise to improve outcomes in overweight or obese women: A systematic review. Sui Z, Grivell RM, Dodd JM. Acta Obstet Gynecol Scand. 2012 May;91(5):538-45. Epub 2012 Feb 28.

• 7. Antenatal dietary interventions in obese pregnant women to restrict gestational weight gain to Institute of Medicine recommendations: a meta-analysis. Quinlivan JA, Julania S, Lam L. Obstet Gynecol. 2011 Dec;118(6):1395-401. doi: 10.1097/AOG.0b013e3182396bc6. Review.

• 8. Systematic review of clinical trials on dietary interventions to prevent excessive weight gain during pregnancy among normal weight, overweight and obese women. Tanentsapf I, Heitmann BL, Adegboye AR. BMC Pregnancy Childbirth. 2011 Oct 26;11:81. doi: 10.1186/1471-2393-11-81. Review

• 9. Behavioural interventions for weight management in pregnancy: a systematic review of quantitative and qualitative data. Campbell F, Johnson M, Messina J, Guillaume L, Goyder E. BMC Public Health. 2011 Jun 22;11:491. doi: 10.1186/1471-2458-11-491. Review.

• 10. Changing diet and physical activity to reduce gestational weight gain: a meta-analysis. Gardner B, Wardle J, Poston L, Croker H. Obes Rev. 2011 Jul;12(7):e602-20. doi: 10.1111/j.1467-789X.2011.00884.x. Epub 2011 Apr 27. Review.

Systematic reviews on intervention

Effects of interventions in pregnancy on maternal weight and obstetric outcomes: metaanalysis of randomised evidence

• BMJ 2012• Study selection: 44 RCT (7278 women)

evaluating any dietary or lifestyle intervention to influence maternal weight and pregnancy outcomes

• Diet – physical activity – mixed approach

Thangaratinam S et al. BMJ 2012

Mean difference in gestational weight gain (kg) with dietary and lifestyle interventions in pregnancy .

Thangaratinam S et al. BMJ 2012;344:bmj.e2088

©2012 by British Medical Journal Publishing Group

Relative risk of effect on size for gestational age with dietary and lifestyle interventions in pregnancy .

Thangaratinam S et al. BMJ 2012;344:bmj.e2088

©2012 by British Medical Journal Publishing Group

Relative risk of effects of weight management interventions in pregnancy on maternal outcomes.

Thangaratinam S et al. BMJ 2012;344:bmj.e2088

Fig 7 Relative risk of effects of weight management interventions in pregnancy on fetal and neonatal outcomes.

Thangaratinam S et al. BMJ 2012;344:bmj.e2088

©2012 by British Medical Journal Publishing Group

Effects of interventions in pregnancy on maternal weight and obstetric outcomes: metaanalysis of randomised evidence

Conclusion:•Dietary and lifestyle intervention in pregnancy are effective in reducing GWG without adverse effect on the risk of SGA•Dietary intervention was associated with the greatest reduction in GWG•Intervention significantly reduced the risk of preeclampsia•Quality of evidence: Moderate for GWG Low for clinical outcomes

Thangaratinam S et al. BMJ 2012

Systematic review of clinical trials on dietary interventions to prevent excessive weight during pregnancy among normal

weight, overweight and obese women

• BMC Pregnancy and childbirth, 2011 • Study selection: 13 RCT (1434 women),

normal weight, overweight and obese women• Evaluating any dietary intervention to

influence maternal weight gain and secondarily child and maternal outcomes

Tanentsapf I et al, BMC Pregnancy and childbirth, 2011

Tanentsapf I et al, BMC Pregnancy and childbirth, 2011

Systematic review of clinical trials on dietary interventions to prevent excessive weight during pregnancy among normal

weight, overweight and obese women

Conclusion:•Dietary intervention in pregnancy are effective in decreasing GWG, but not preventing excessive GWG (IOM).•No significant difference in weight retention 6 weeks postpartum, but at 6 months postpartum•Dietary intervention had no significant effect on birthweight or maternal outcomes•Low methodological quality of included studies

Tanentsapf I et al, BMC Pregnancy and childbirth, 2011

Lifestyle interventions for overweight and obese pregnant women to improve pregnancy outcome: systematic review

and meta-analysis

• BMC Medicine, 2012• Study selection: 13 RCT , 6 non-RCT,

overweight and obese women (excluding NW only)

• Evaluating any antenatal dietary, activity, behavior or lifestyle intervention to improve maternal and perinatal outcomes

Oteng-Ntim E et al, BMC Medicine, 2012

Forest plot of randomised trials investigating the effect of lifestyle advice versus standard care on gestational weight gain

(kg).

Oteng-Ntim E et al, BMC Medicine, 2012

Forest plot of randomised trials investigating the effect of lifestyle advice versus standard care on risk of gestational

diabetes.

Oteng-Ntim E et al, BMC Medicine, 2012

Lifestyle interventions for overweight and obese pregnant women to improve pregnancy outcome: systematic review

and meta-analysis

Conclusion:•Antenatal intervention in overweight and obese pregnant women is associated with restricted GWG •A trend towards a reduction in GDM•Studies of low to medium quality - findings should be interpreted with caution•Further metaanalysis not needed•Large-scale well-designed prospective trials

Oteng-Ntim E et al, BMC Medicine, 2012

Overall conclusion

• Lifestyle intervention restricts gestational weight gain• Conflicting results on the effect on maternal and neonatal outcomes• No major adverse effect (stillbirth, SGA)• Level of evidence is low• Long-term maternal and offspring follow-up is needed

Interpregnancy weight change and risk of adversepregnancy outcomes: a population-based study

Adjusted odds ratios for adverse pregnancy outcomes for those who gained 3 or more BMI units (~10 kg) during an average of 2 years

– Pre-eclampsia 1.78 (95% CI 1.52–2.08)– Gestational hypertension 1.76 (1.39–2.23)– Gestational diabetes 2.09 (1.68–2.61)– Caesarean delivery 1.32 (1.22–1.44)– Stillbirth 1.63 (1.20–2.21) – LGA infants 1.87 (1.72–2.04)

Eduardo Villamor, Sven Cnattingius, Lancet 2006

Weight loss before conception: A systematic literature review

”Is there scientific evidence for positive health effects of weight loss prior to conception for overweight and obese women?”

Glazer et al, Epidemiology, 2004 (n=4000) Villamor and Cnattingius, Lancet, 2006 (n=150.000)

•4.5 kg weight loss between pregnancies reduced the risk of gestational diabetes•Women with BMI > 25 in first pregnancy had decreased risk of LGA infants with weight loss > 1 BMI unit•Lack of studies investigating the effect of dietary induced intervention before pregnancy!

Forsum E. et al, Food and Nutrition Research, 2013

Research gap

Lack of

Evidence

Public Health Priority

Ongoing studies

TOP study, DenmarkFit for Delivery, NorwayETIP, NorwayLIMIT, AustraliaSPRING, AustraliaHealthy Moms, USAMOM trial, Canada………………….

"Effects of weight management interventions on

maternal and fetal outcomes in pregnancy: Individual

patient data (IPD) meta-analysis of randomised trials

and model based economic evaluation (iWIP)"

Women's Health Research UnitCentre for Primary Care and Public Health

Blizard InstituteBarts and The London School of Medicine and Dentistry

Project’s overview

• Maternal obesity and excess weight gain in pregnancy are associated with maternal and fetal complications in

pregnancy and in the long term.

• HTA report published in 2012 (Thangaratinam et al. 2012) on diet and lifestyle interventions showed that weight

management interventions in pregnancy are effective in reducing maternal weight gain compared to standard

care, with diet based interventions most effective.

• The findings were based published studies. However, the effects of weight management interventions in women with

varied pre pregnancy weight, ethnicity, age and socioeconomic status was difficult to ascertain. Furthermore, the

relationship between the amount of weight change in pregnancy and risk of maternal and fetal complications was not

known.

• To address the above gaps in evidence, project team have established a Collaborative Network of researchers who

have conducted studies on weight management interventions in pregnancy. As to the date The Network has access to

around 5000 individual patient data from 16 datasets.

• By pooling the individual data together, we will be able to estimate with increased confidence, the differential effects if

any of the weight management interventions in various groups, allowing us to target the population that needs the

most support for a beneficial outcome. It will also generate recommendations on optimal weight gain in pregnancy to

minimise maternal and fetal complications and the cost effectiveness of these interventions.

Project’s objectives and design

MAIN OBJECTIVES:  

The primary objective will be to determine the differential effects of weight

management interventions in pregnancy by:

i) BMI ii) age iii) ethnicity iv) parity and v) physical and mental medical

conditions like diabetes and depression on:

a) maternal weight gain and

b) composite pregnancy outcome of maternal and fetal complications.

DESIGN: Individual patient data (IPD) meta analysis of randomised trials

Contact details

Project Lead: Professor Shakila Thangaratinam s.thangaratinam@qmul.ac.uk

Project’s Co-ordinator: Ms Ewelina Rogozinska e.a.rogozinska@qmul.ac.uk

Project’s details

http://blizard.qmul.ac.uk/research-dissemination/756-iwip.html

Future perspectives

• Should interventions be considered prepregnant to be able to alter short term obstetric and neonatal outcomes?• Nature, duration and intensity of such intervention? • Further research is necessary to identify such interventions and what benefits these confer on health and wellbeing in later life clinical implication and implementation

Thank you for the attention!

christina.vinter@rsyd.dk