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Antenatal interventions to improve
maternal and fetal health – what are
the benefits?
Prof Fionnuala McAuliffeUniversity College Dublin
National Maternity Hospital
Pregnancy
• Unique opportunity for intervention to improve health of two individuals
• Mother• Baby
Pregnancy Research
• HRB Centre for Health and Diet Research
• HRB Perinatal Ireland – Perinatal Clinical trials Network
HRB Centre for Health and Diet Research
Cluster 3Diet/obesity
& health inadults
Cluster 4Management
of morbid obesity
Cluster 2Diet, obesity
& healthin pregnancy& childhood
Food choiceand obesity
Food marketing
Food policy analysis
Cluster 5ConsumerCognitive Response to Food
Cluster 1PopulationHealthModelling
Diet/nutrition/obesity archive
Burden ofdisease study
Obesity Knowledge hub
Measured BMI BMI> 25 BMI > 30
Austria 2006 53% 21%
England 2010 58% 26%
France 2006 41% 17%
Germany 2007 50% 21%
Ireland 2010 52% 21%
Netherland 2010 38% 10%
Poland 2007 52% 24%
Spain 2007 54% 21%
Sweden 2002 38% 11%
International association of study of obesity IASO
Measured BMI BMI> 25 BMI > 30
Austria 2006 53% 21%
England 2010 58% 26%
France 2006 41% 17%
Germany 2007 50% 21%
Ireland 2010 52% 21%
Netherland 2010 38% 10%
Poland 2007 52% 24%
Spain 2007 54% 21%
Sweden 2002 38% 11%
International association of study of obesity IASO
Maternal Obesity - maternal risk
• Gestational diabetes – T2DM• Pre-eclampsia• Postpartum weight retention – T2DM• Caesarean Section• Haemorrhage• Venous thrombo-embolism
Fetal problems
Walsh, McAuliffe 2012
Background
• The large for gestational age infant is predisposed to a variety of adverse obstetric and neonatal outcomes (Baird 2005, Eriksson 2003)
• Offspring of obese pregnancy at increased risk of cardiovascular disease and DM in adult life (Taylor 2012)
The westernised diet rich in carbohydrates is thought to contribute to the rates of obesity
Intervention Studies
Background
Glucose is the main energy substrate for intrauterine growth
Clapp JF 2002, McGowan, McAuliffe BJN 2010
RCT Of LOw glycaemic index diet vs usual
diet to prevent macrosomia ROLO study
Walsh, McGowan, Mahony, Foley, McAuliffe BMJ 2012
ROLO
• Randomized control trial n=800
• Inclusion criteria:– Secundigravid– Previous birthweight >4000g
• Exclusion criteria:– Previous gestational diabetes
Walsh, McGowan, Mahony, Foley, McAuliffe BMJ 2012
ROLO - Objectives
• Primary outcome: Birthweight
• Secondary outcome: Gestational weight gain, glucose intolerance, gestational diabetes
Walsh, McGowan, Mahony, Foley, McAuliffe BMJ 2012
ROLO - intervention arm• Dietary education session: re-enforcement during
pregnancy
• Small groups of 2 – 6 people
• Gestation 15.7+/-3.0 weeks
• Exchange high GI carbohydrates for low GI
alternatives
Walsh, McGowan, Mahony, Foley, McAuliffe BMJ 2012
ROLO Conclusion (n=800)
• A low glycemic index diet in pregnancy has no effect on infant birthweight in a group at risk of fetal macrosomia
Walsh, McGowan, Mahony, Foley, McAuliffe BMJ 2012
ROLO Conclusion (n=800)
• A low glycemic index diet in pregnancy has no effect on infant birthweight in a group at risk of fetal macrosomia
• Maternal benefits– Less gestational weight gain (12.2Kg vs 13.7kg)– less glucose intolerance (21% vs 28%)– Improved nutrient and food intakes
Walsh, McGowan, Mahony, Foley, McAuliffe BMJ 2012
ROLO Discussion
• Our results show that a low glycemic index diet alone is not sufficient to reduce the incidence of fetal macrosomia
• It is, however, a simple, safe and effective measure to improve maternal glucose homeostasis and reduce maternal weight gain during pregnancy
Walsh, McGowan, Mahony, Foley, McAuliffe BMJ 2012
Impact of low GI diet on M-F metabolic markers
Walsh et al, 2014 Reproductive Sciences
Impact of low GI diet on M-F metabolic markers
• No impact on leptin and inflammatory markers (IL6, TNF alpha)
• Attenuation in the typical increase in insulin resistance seen in pregnancy with advancing gestation
Walsh et al, 2014 Reproductive Sciences
Donnelly et al, 2014 Paed Obesity
Impact of low GI diet on neonatal anthropometry
• 265 neonates had anthropometry• 126 intervention / 139 control• Head, abdominal, chest, thigh and mid upper
arm circumferences measured• 219 had skinfolds (subscapular, thigh, biceps,
triceps)
Donnelly et al, 2014 Paed Obesity
Donnelly et al, 2014 Paed Obesity
Donnelly et al, 2014 Paed Obesity
Discussion
• Maternal Low GI diet impacted on neonatal anthropometry
• ROLO kids: 6 mo, 2 yr and 5 yr• Long-term impact important in
pregnancy studies
Donnelly et al, 2014 Paed Obesity
Mother and baby follow up at 6mths, 2yrs and 5yrs
ROLO Kids Study
Impact of Low GI diet at 3 mo postpartum
Horan et al, 2014 Nutrients
Impact of Low GI diet at 3 mo postpartum
• Comparison of intervention group to control group at 3 months postpartum
• Lower glycaemic load (128 ± 48 vs 145 ± 92, p=0.014)
• Greater weight loss from pre-pregnancy (-1.3 vs 0.12 kg, p=0.022)
• Reading food labels• Sustained health improvement behaviours
Horan et al, 2014 Nutrients
ROLO summary• Low GI diet no impact on birthweight in an at
risk population with mean BMI 26.8• Less gestational weight gain• Less glucose intolerance – attenuated insulin
resistance
ROLO summary• Low GI diet no impact on birthweight in an at
risk population with mean BMI 26.8• Less gestational weight gain• Less glucose intolerance – attenuated insulin
resistance• Less neonatal adiposity• Postnatal adherence to healthy eating
behaviors
Thangaratinam et al BMJ 2012
Systematic review of pregnancy interventions
Diet and exercise interventions in pregnancy•With any intervention less gestational weight gain•Dietary intervention resulted in largest reduction in gestational weight gain•Physical activity interventions reduced birthweight•No impact on small for gestational age•Further large studies with longterm follow up required
Thangaratinam et al BJOG 2012
Intervention Studies
Compliance with dietary intervention
• Compliance with intervention a challenge
• 80% pregnant women have a smart phone
• Could we use smart phone to re-enforce lifestyle
interventions in pregnancy?
Systematic review of technology in pregnancy
• Potential benefits
• Paucity of data on effectiveness
• Further studies required on communication technology
PEARS RCT Pregnancy Exercise, nutrition with App support Research Study
Controlled trials registration ISRCTN 29316280
Hypothesis &Primary outcome
• The introduction of a “healthy lifestyle package with app support’ for overweight and obese women in pregnancy could reduce the incidence of Gestational Diabetes.
PEARS Randomised Controlled Trial
• Population: overweight and obese pregnant women (n=500)
• Intervention: lifestyle package (low GI diet, exercise prescription, smart phone app)
• Control group: usual care
• Outcome: Gestational diabetes
Controlled trials registration ISRCTN 29316280
Three key components:Nutrition:Healthy recipes for different meals of the day (low GI, eucaloric for pregnancy, correct macro and micronutrients)Exercise:Daily exercise prescription based on SMART goalsMotivation:Positive thought of the day, a joke, a nutrition thought or an exercise thought
Specific research app designed
Smart phone app
• Possible improvement in compliance to healthy lifestyle intervention
• Detailed feedback sought: qualitative and quantitative
• Correlate patient use of app with clinical parameters
Intervention Studies
Probiotics in Pregnancy (ProP) Study
Probiotics in Pregnancy (ProP) Study
• Probiotics defined as: ‘Live microorganisms which, when consumed in adequate amounts, may confer a health benefit on the host’ (FAO/WHO, 2001)
• Beneficial effects of probiotics in healthy pregnancy:- Improved glycaemic control and reduced GDM - Lower maternal serum insulin levels
Lindsay et al, 2013 JMFNM
Probiotics in Pregnancy (ProP) Study
• Probiotics defined as: ‘Live microorganisms which, when consumed in adequate amounts, may confer a health benefit on the host’ (FAO/WHO, 2001)
• Beneficial effects of probiotics in healthy pregnancy:- Improved glycaemic control and reduced GDM - Lower maternal serum insulin levels
• Effects of probiotics on maternal metabolic outcomes among obese pregnant women not evaluated
Lindsay et al, 2013 JMFNM
• Lactobacillus salivarius UCC118 probiotic:
- Human origin, non-pathogenic
- Transits and persists in human gut (Collins et al., 2003)
- Glucose lowering effect in healthy non-pregnant females
• Lactobacillus salivarius UCC118 probiotic
• 1 capsule/day, 24-28 weeks gestation
• No impact on maternal metabolic parameters in obese pregnancy
• Safe and acceptable (Lindsay et al., Int J Gynecol Obstet, 2014)
Impact of Probiotics in women with Gestational Diabetes on Metabolic
Health: A Randomized Controlled Trial
Lindsay et al, 2015 AJOG
Probiotics in Gestational Diabetes
• Population: new diagnosis of gestational diabetes (n=100)
• Intervention: Daily probiotic until delivery
• Control group: placebo and usual care
• Outcome: Fasting Glucose, HOMA, Triglycerides (Total and LDL cholesterol)
Controlled trials registration ISRCTN 97241163
SMFM, San Diego 2015Lindsay et al, 2015 AJOG
Primary Outcome – ITT analysis
Probiotic group (N=74) Placebo group (N=75) P-valuePre Post Pre Post
Fasting glucose (mmol/l) 4.90 (0.62) 4.65 (0.53) 5.01 (0.77) 4.65 (0.53) 0.373
Primary Outcome – Per-protocol analysis*
Lindsay et al, 2015 AJOG
Maternal metabolic profile before and after the intervention:
Per-protocol analysis
Probiotic group (N=48) Placebo group (N=52) P-valuePre Post Pre Post
HbA1c (mmol/mol)
Insulin (mU/l)
HOMA Index
C-peptide (ng/ml)
Total chol (mmol/l)
HDL chol (mmol/l)
LDL chol (mmol/l)
Triglycerides (mmol/l)
Maternal metabolic profile before and after the intervention:
Per-protocol analysis
Probiotic group (N=48) Placebo group (N=52) P-valuePre Post Pre Post
HbA1c (mmol/mol) 34.66 (3.55) 35.45 (4.09) 32.96 (4.06) 33.20 (3.67) 0.401
Insulin (mU/l) 13.88 (6.40) 13.04 (5.08) 14.61 (9.34) 13.58 (7.73) 0.927
HOMA Index 2.95 (1.42) 2.65 (1.06) 3.27 (2.40) 2.85 (1.78) 0.875
C-peptide (ng/ml) 2.95 (1.12) 3.00 (0.94) 2.98 (1.22) 3.05 (1.06) 0.843
Total chol (mmol/l) 6.26 (1.10) 6.53 (0.96) 6.24 (1.10) 6.74 (1.12) 0.031
HDL chol (mmol/l) 1.73 (0.36) 1.68 (0.38) 1.70 (0.33) 1.69 (0.35) 0.341
LDL chol (mmol/l) 3.47 (1.10) 3.55 (0.88) 3.45 (1.08) 3.76 (0.98) 0.011
Triglycerides (mmol/l) 2.46 (0.84) 2.85 (0.95) 2.40 (0.71) 2.83 (0.86) 0.687
Conclusion: RCT Probiotics in GDM pregnancy
• Among women with a new diagnosis of GDM, a probiotic capsule intervention did not impact:– fasting glucose / insulin resistance– maternal and neonatal outcome
• An attenuation of the pregnancy-induced rise in total and LDL-cholesterol was observed among probiotic group versus placebo– Potential role for probiotics to improve metabolic health for this
at risk group
Lindsay et al, 2015 AJOG
Conclusion – lifestyle interventions• Lifestyle interventions have beneficial
impact on maternal, fetal health
Conclusion – lifestyle interventions• Lifestyle interventions have beneficial
impact on maternal, fetal health
• These benefits may extend beyond the period of pregnancy
• Long-term follow-up studies will evaluate impact on mother and child health
TEST – Trial of aspirin to prevent pre-eclampsia
• Pre-eclampsia important cause of maternal morbidity and mortality
• Accounts for 20% of preterm deliveries
TEST – Trial of aspirin to prevent pre-eclampsia
• Administration of Aspirin in ‘high-risk’ pregnancies leads to a 17% reduction in the risk of pre-eclampsia
• There is a paucity of research into use of Aspirin in ‘low-risk’ women
TEST – Trial of aspirin to prevent pre-eclampsia
Dodd JM, et al. Antithrombotic therapy for improving maternal or infant health
outcomes in women considered at risk of placental dysfunction. Cochrane
Database 2013
Low dose Aspirin is felt to be a ….. o Safeo Effective o Affordable
Prophylactic treatment for pre-eclampsia in pregnancy
TEST Study Hypothesis
• It is beneficial in terms of efficacy and patient acceptability
• to routinely prescribe low dose aspirin to nulliparous low risk women
• compared with ‘test indicated aspirin’ on the basis of a positive early pregnancy screening test for pre-eclampsia
• Randomised controlled Trial of Aspirin vs no aspirin vs test indicated aspirin in low risk first time mothers
• First drug trial in pregnancy in Ireland
• UCD clinical Sponsor• HRB Perinatal Ireland• HRB Ireland Perinatal Clinical Trials Network
TEST – Trial of aspirin to prevent pre-eclampsia
TEST (PILOT)TEST (PILOT)
500 Low Risk Nulliparous Women
AspirinAspirinNo AspirinNo Aspirin Screen/
Treat
Screen/
Treat
Three Armed Randomized Controlled
Study
Three Armed Randomized Controlled
Study
TEST Pilot Aims
To Determine
1.Proportion of eligible women who agree to participate2.Patient acceptability3.Protocol compliance4.Proportion of women with a completed screening issued the result within one week5.Proportion of women in whom it is possible to obtain a trans-abdominal uterine artery doppler at 14 weeks
Pregnancy
• Unique opportunity for intervention to improve health of two individuals
• Mother• Baby
Policies aimed at improving health especially maternal nutrition, may have beneficial effects not only for mother but also for her child and their adult health
Maternal Health
Research Impact• Irish and UK national pregnancy guidelines
• Food safety authority of Ireland – working group
• International Federation of Gynaecology and Obstetrics – Maternal nutrition committee
• UK Maternal Medicine Clinical Studies Group
Obstetrics PaediatricsMichael Foley Eleanor MolloyRhona Mahony Jean Donnelly (PhD)
Endocrinology MidwiferyRichard Firth Cecilia MulcahyBrendan Kinsley Mary Moran (PhD)Mensud Hatunic Mary Coffey
Research Fellows NutritionNoirin Russell (MD) Sinead CurranMary Higgins (MD) Ciara McGowan (PhD)Jennifer Walsh (PhD) Mary Horan (PhD)Maria Kennelly (PhD) Karen Lindsay (PhD)
Orna O’Brien (MSc)Basic Science
Eileen O’Brien (PhD)Niamh Corrigan (PhD) Kate Ainscough (PhD)
Aisling Geraghty (PhD)