antenatal interventions to improve maternal and fetal health – what are the benefits? prof...

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)