Pregnancy ROLO and PRoPS Prof Fionnuala McAuliffe University - - PowerPoint PPT Presentation

Maternal Nutrition and Fetal Health – intervention studies in Pregnancy ‘ROLO and PRoPS’

Prof Fionnuala McAuliffe University College Dublin National Maternity Hospital

Note: for non-commercial purposes only

Background

Childhood obesity

Obesity in Pregnancy

Maternal Obesity - maternal risk

Fetal problems

Walsh, McAuliffe 2012

The westernised diet rich in carbohydrates is thought to contribute to the rates of obesity

Background

• Glucose is the main energy substrate for

intrauterine growth

Clapp JF 2002, McGowan, McAuliffe BJN 2010

Background

• Glucose is the main energy substrate for

intrauterine growth

Clapp JF 2002, McGowan, McAuliffe BJN 2010

• Maternal glucose concentrations below those

diagnostic of diabetes associated with increased birthweight and adverse outcomes

HAPO 2008

Background

• Maternal diet, particularly its carbohydrate

type and content, influences maternal blood glucose concentrations

Clapp JF 2002, McGowan, McAuliffe BJN 2010

Not all carbohydrate foods are created equal

Low GI Medium GI High GI

Not all carbohydrate foods are created equal

Low GI Medium GI High GI

Not all carbohydrate foods are created equal

Low GI Medium GI High GI

Not all carbohydrate foods are created equal

Low GI Medium GI High GI

Glycemic Index

• The incremental area under the blood glucose

curve after ingestion of 50 grams of a test food

Jenkins 1981

Glycemic Index

• The incremental area under the blood glucose

curve after ingestion of 50 grams of a test food

Jenkins 1981

Incremental blood glucose concentration

Time (minutes)

Background

• Pregnancy is a condition in which the

glycaemic index may be of particular relevance

Fraser 1988

Hypothesis

• A low glycemic index diet in pregnancy could

prevent recurrence of fetal macrosomia

Walsh J, Mahony R, Foley M, McAuliffe F. BMC Pregnancy Childbirth 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 J, Mahony R, Foley M, McAuliffe F. Walsh, McGowan, Mahony, Foley, McAuliffe BMJ 2012

ROLO - Objectives

• Primary outcome: Birthweight
• Secondary outcome: Gestational weight gain

Walsh J, Mahony R, Foley M, McAuliffe F. BMC Pregnancy Childbirth 2010 Walsh, McGowan, Mahony, Foley, McAuliffe BMJ 2012

ROLO

• Recruited and randomized at first antenatal

consultation

Walsh, McGowan, Mahony, Foley, McAuliffe BMJ 2012

ROLO

Control Arm:

• Routine antenatal care
• No formal dietary advice
• No advice on weight gain in pregnancy

Walsh, McGowan, Mahony, Foley, McAuliffe BMJ 2012

ROLO

Intervention arm:

• Dietary education session: re-enforcement

during pregnancy

• Small groups of 2 – 6 people
• Lasted 2 hours
• Gestation 15.7+/-3.0 weeks

Walsh, McGowan, Mahony, Foley, McAuliffe BMJ 2012

Dietary Intervention

• Women were first given advice on healthy

eating guidelines for pregnancy

Dietary Intervention

• Focused on the glycemic index
• Exchange high GI carbohydrates for low GI

alternatives

• Written information and low GI recipes
• No advice on gestational weight gain

Walsh, McGowan, Mahony, Foley, McAuliffe BMJ 2012

Results – Glycaemic Load

Intervention Group Low GI diet Control Group Early pregnancy 132± 33 136± 38 Second trimester 124± 32 140± 32* Third trimester 127 ± 30 140 ± 37 *

Walsh, McGowan, Mahony, Foley, McAuliffe BMJ 2012

Results – Glycaemic Load

Intervention Group Low GI diet Control Group Early pregnancy 132± 33 136± 38 Second trimester 124± 32 140± 32* Third trimester 127 ± 30 140 ± 37 *

Walsh, McGowan, Mahony, Foley, McAuliffe BMJ 2012

Results – Glycaemic Load

Intervention Group Low GI diet Control Group Early pregnancy 132± 33 136± 38 Second trimester 124± 32 140± 32* Third trimester 127 ± 30 140 ± 37 *

Walsh, McGowan, Mahony, Foley, McAuliffe BMJ 2012

Results – Glycaemic Load

Intervention Group Low GI diet Control Group Early pregnancy 132± 33 136± 38 Second trimester 124± 32 140± 32* Third trimester 127 ± 30 140 ± 37*

Walsh, McGowan, Mahony, Foley, McAuliffe BMJ 2012

Results – Primary Outcome

Primary outcome - Birthweight

Intervention Group Low GI diet Control Group Birthweight (grams) 4034±510 4006±497 Birthweight centile 70.5±25.6 72.8±25.6 Length at birth (cm) 52.9±2.7 52.6±2.1 Head circumference at birth (cm) 35.8±1.3 35.7±1.5 Ponderal Index at birth (Kg/cm3) 2.76+/-3.8 2.75+/-0.33 Birthweight difference (grams)

• 214.2±541
• 250.8±512

Fetal macrosomia (>4000g) 50.7% 51.5%

Results – Secondary Outcome

Results – Gestational weight gain

Intervention Group Low GI diet Control Group Weight gain at 24 weeks (kg) 5.3±2.7 5.5±2.7 Weight gain at 28 weeks (kg) 7.1±2.8 7.7±3.0 * Weight gain at 34 weeks (kg) 10.1±3.7 10.9±3.9* Weight gain at 40 weeks (kg) 12.2±4.4 13.7±4.9 * Exceeded IOM gestational weight gain guidelines (%) 37.7% 47.9% *

Results – Gestational weight gain

Intervention Group Low GI diet Control Group Weight gain at 24 weeks (kg) 5.3±2.7 5.5±2.7 Weight gain at 28 weeks (kg) 7.1±2.8 7.7±3.0 * Weight gain at 34 weeks (kg) 10.1±3.7 10.9±3.9* Weight gain at 40 weeks (kg) 12.2±4.4 13.7±4.9 * Exceeded IOM gestational weight gain guidelines (%) 37.7% 47.9% *

Results – Gestational weight gain

Intervention Group Low GI diet Control Group Weight gain at 24 weeks (kg) 5.3±2.7 5.5±2.7 Weight gain at 28 weeks (kg) 7.1±2.8 7.7±3.0 * Weight gain at 34 weeks (kg) 10.1±3.7 10.9±3.9* Weight gain at 40 weeks (kg) 12.2±4.4 13.7±4.9 * Exceeded IOM gestational weight gain guidelines (%) 37.7% 47.9% *

Results – Maternal glucose

Intervention Group Low GI diet Control Group 28 week fasting glucose >5.1mmol/L 24 / 321 (7.5%) 41/352 (11.6%) GCT >7.8 54/350 (15.4%) 79/371 * (21.3%)* 28 week fasting glucose >5.1mmol/L or GCT>7.8mmol/L 67/320 (20.9%) 100/352 (28.4%) * GCT >8.3mmol/L 42/350 (12%) 52/371 (14%) Gestational diabetes Carpenter and Coustan criteria 7/350 (2%) 9/371 (2.4%) Gestational diabetes American Diabetes Association criteria 12/350 (3.4%) 18/371 (4.9%)

Intervention Group Low GI diet Control Group 28 week fasting glucose >5.1mmol/L 24 / 321 (7.5%) 41/352 (11.6%) GCT >7.8 54/350 (15.4%) 79/371 * (21.3%)* 28 week fasting glucose >5.1mmol/L or GCT>7.8mmol/L 67/320 (20.9%) 100/352 (28.4%) * GCT >8.3mmol/L 42/350 (12%) 52/371 (14%) Gestational diabetes Carpenter and Coustan criteria 7/350 (2%) 9/371 (2.4%) Gestational diabetes American Diabetes Association criteria 12/350 (3.4%) 18/371 (4.9%)

Intervention Group Low GI diet Control Group 28 week fasting glucose >5.1mmol/L 24 / 321 (7.5%) 41/352 (11.6%) GCT >7.8 54/350 (15.4%) 79/371 * (21.3%)* 28 week fasting glucose >5.1mmol/L or GCT>7.8mmol/L 67/320 (20.9%) 100/352 (28.4%) * GCT >8.3mmol/L 42/350 (12%) 52/371 (14%) Gestational diabetes Carpenter and Coustan criteria 7/350 (2%) 9/371 (2.4%) Gestational diabetes American Diabetes Association criteria 12/350 (3.4%) 18/371 (4.9%)

Results - Compliance

Compliance Scale % Followed the diet ‘all of the time’ 3.8 Followed the diet ‘most of the time’ 76.4 Followed the diet ‘some of the time’ 17.0 Followed the diet ‘none of the time’ 2.8

Walsh, McGowan, Mahony, Foley, McAuliffe BMJ 2012

Results - Compliance

Compliance Scale % Followed the diet ‘all of the time’ 3.8 Followed the diet ‘most of the time’ 76.4 Followed the diet ‘some of the time’ 17.0 Followed the diet ‘none of the time’ 2.8

Walsh, McGowan, Mahony, Foley, McAuliffe BMJ 2012

Maternal Nutrient Intakes

Trimester 1 Trimester 2 Trimester 3 Int Control Int Control Int Control Energy (MJ) Protein (%TE) CHO (% TE) Fibre (g)

P value – independent samples t test

McGowan, McAuliffe J Nut 2014

Maternal Nutrient Intakes

Trimester 1 Trimester 2 Trimester 3 Int Control Int Control Int Control Energy (MJ) 7.7 7.8 7.6 8.1** 7.6 8.1* Protein (%TE) 17.2 16.8 17.8 16.8*** 17.6 16.7** CHO (% TE) 50.3 50.3 49.0 50.0 49.1 50.1 Fibre (g) 19.9 18.9 20.2 19.2 20.3 18.8**

P value – independent samples t test

McGowan, McAuliffe J Nut 2014

Maternal Nutrient Intakes

Trimester 1 Trimester 2 Trimester 3 Int Control Int Control Int Control

Energy

7.7 7.8

7.6 8.1** 7.6 8.1*

Protein (%TE) 17.2 16.8 17.8 16.8*** 17.6 16.7** CHO (% TE) 50.3 50.3 49.0 50.0 49.1 50.1 Fibre (g) 19.9 18.9 20.2 19.2 20.3 18.8**

P value – independent samples t test

McGowan, McAuliffe J Nut 2014

Maternal Nutrient Intakes

Trimester 1 Trimester 2 Trimester 3 Int Control Int Control Int Control Energy (MJ) 7.7 7.8 7.6 8.1** 7.6 8.1*

Protein

17.2 16.8

17.8 16.8*** 17.6 16.7**

CHO (% TE) 50.3 50.3 49.0 50.0 49.1 50.1 Fibre (g) 19.9 18.9 20.2 19.2 20.3 18.8**

P value – independent samples t test

McGowan, McAuliffe J Nut 2014

Maternal Nutrient Intakes

Trimester 1 Trimester 2 Trimester 3 Int Control Int Control Int Control Energy (MJ) 7.7 7.8 7.6 8.1** 7.6 8.1* Protein (%TE)

17.2 16.8

17.8 16.8*** 17.6 16.7** CHO (% TE) 50.3 50.3 49.0 50.0 49.1 50.1

Fibre (g)

19.9 18.9

20.2 19.2 20.3 18.8**

P value – independent samples t test

McGowan, McAuliffe J Nut 2014

% Consumers of Food Groups

Trimester 1 Trimester 2 Trimester 3 I C I C I C White Breads Wgrain BF cereals Yogurts ↑energy beverage

*p<0.05, **p<0.01, ***p<0.001

McGowan, McAuliffe J Nut 2014

% Consumers of Food Groups

Trimester 1 Trimester 2 Trimester 3 I C I C I C White Breads 83 88 73 86*** 76 87*** Wgrain BF cereals 65 57 73 60* 70 58** Yogurts 58 52 66 50*** 62 51** ↑energy beverage 49 52 39 56*** 42 50

*p<0.05, **p<0.01, ***p<0.001

McGowan, McAuliffe J Nut 2014

% Consumers of Food Groups

Trimester 1 Trimester 2 Trimester 3 I C I C I C

White Breads

83 88

73 86*** 76 87***

Wgrain BF cereals 65 57 73 60* 70 58** Yogurts 58 52 66 50*** 62 51** ↑energy beverage 49 52 39 56*** 42 50

*p<0.05, **p<0.01, ***p<0.001

McGowan, McAuliffe J Nut 2014

% Consumers of Food Groups

Trimester 1 Trimester 2 Trimester 3 I C I C I C White Breads 83 88 73 86*** 76 87***

Wgrain BF cereals

65 57

73 60* 70 58**

Yogurts 58 52 66 50*** 62 51** ↑energy beverage 49 52 39 56*** 42 50

*p<0.05, **p<0.01, ***p<0.001

McGowan, McAuliffe J Nut 2014

% Consumers of Food Groups

Trimester 1 Trimester 2 Trimester 3 I C I C I C White Breads 83 88 73 86*** 76 87*** Wgrain BF cereals 65 57 73 60* 70 58**

Yogurts

58 52

66 50*** 62 51**

↑energy beverage 49 52 39 56*** 42 50

*p<0.05, **p<0.01, ***p<0.001

McGowan, McAuliffe J Nut 2014

% Consumers of Food Groups

Trimester 1 Trimester 2 Trimester 3 I C I C I C White Breads 83 88 73 86*** 76 87*** Wgrain BF cereals 65 57 73 60* 70 58** Yogurts 58 52 66 50*** 62 51**

↑energy beverage

49 52

39 56*** 42 50

*p<0.05, **p<0.01, ***p<0.001

McGowan, McAuliffe J Nut 2014

Other Dietary Changes

• Fruit consumption was significantly higher at T3 among the

intervention group (91% vs. 85%; p<0.05)

• Vegetable consumption was significantly higher at T3 among

the intervention group (98% vs. 94%; p<0.05)

• Oily fish consumption was significantly higher at T2 among

the intervention group (21% vs. 13%; p<0.05)

McGowan, McAuliffe J Nut 2014

Conclusion

• A low glycemic index diet in pregnancy has no

effect on infant birthweight in a group at risk

• f fetal macrosomia

Walsh, McGowan, Mahony, Foley, McAuliffe BMJ 2012

Conclusion

• A low glycemic index diet in pregnancy has no

effect on infant birthweight in a group at risk

• f fetal macrosomia
• Maternal benefits

– Less gestational weight gain – Improved glucose homeostasis – Improved nutrient and food intakes

Walsh, McGowan, Mahony, Foley, McAuliffe BMJ 2012

Discussion

• Our results show that a low glycemic index

diet alone is not sufficient to reduce the incidence of fetal macrosomia

Walsh, McGowan, Mahony, Foley, McAuliffe BMJ 2012

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 excessive 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

Heery et al, 2013 BMC Pregnancy and Childbirth

Women’s views

• Following cravings
• Reduced exercise
• Physical condition and discomforts limited

maternal control over weight and lifestyle practices

• Little concern re weight gain

Heery et al, 2013 BMC Pregnancy and Childbirth

Donnelly et al, 2014 Paed Obesity

Impact of low GI diet on neonatal anthropodometry

• 265 neonates had anthropodometry
• 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

Donnelly et al, 2014 Paed Obesity

Discussion

• Maternal Low GI diet impacted on

neonatal anthropodometry

• ROLO kids: 6 mo, 2 yr and 5 yr

Donnelly et al, 2014 Paed Obesity

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

Future Interventions & Studies

Food choices Exercise and daily activities Limiting gestational weight gain Nutritional supplements

Am J Clin Nut in press 2014

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)

• Human gut microbes help regulate gene expression

for lipid & CHO metabolism  influence on nutrient supply, energy balance and body weight

Lindsay et al, 2013 JMFNM

Probiotics in Pregnancy (ProP) Study

• Beneficial effects of probiotics in healthy

pregnancy:

• Improved glycaemic control and reduced GDM (13%

vs 36%) (Laitinen et al., 2009, Luoto et al., 2010)

• Lower maternal serum insulin levels (Asemi et al.,

2013)

• Effects of probiotics on maternal metabolic
• utcomes among obese pregnant women have

yet to be evaluated

Lindsay et al, 2013 JMFNM

Study Design

• Double-blind, randomised controlled trial of

probiotic vs placebo capsule for 4 weeks in

• bese, non-diabetic pregnant women, 24-28

wks

• 3 day food diary
• Fasting bloods pre and post intervention

Lindsay et al, 2014 AJCN [in press]

Study Design

• Primary outcome: change in fasting glucose

from pre- to post-intervention

• Secondary outcomes: incidence of GDM,

neonatal anthropometry

Lindsay et al, 2014 AJCN [in press]

Study Design

• Power analysis: 100 women to detect 0.4 mmol/l

difference in fasting glucose of with 80% power.

• Active capsules contained Lactobacillus salivarius

UCC118 (Alimentary and Pharmabiotic centre, Ireland)

Lindsay et al, 2014 AJCN [in press]

Demography

Lindsay et al, 2014 AJCN [in press]

Nutrient intakes

Lindsay et al, 2014 AJCN [in press]

Maternal metabolic profile before and after the intervention

Probiotic Group (N=63) Placebo Group (N=75) Coefficient for group (95% CI) P-value Pre Post Pre Post Fasting glucose (mmol/l) Insulin (mU/l) HOMA-IR C-peptide (ng/ml) Total cholesterol (mmol/l) HDL cholesterol (mmol/l) LDL cholesterol (mmol/l) Triglycerides (mmol/l)

Data presented as mean (SD). P-values reflect differences in the change in each parameter between the groups from pre- to post-intervention, calculated using General Linear Model adjusting for maternal BMI.

Maternal metabolic profile before and after the intervention

Probiotic Group (N=63) Placebo Group (N=75) Coefficient for group (95% CI) P-value Pre Post Pre Post Fasting glucose (mmol/l) 4.69 (0.43) 4.60 (0.40) 4.76 (0.47) 4.69 (0.46)

• 0.05 (-0.17, 0.07)

0.391 Insulin (mU/l) 13.85 (4.62) 15.63 (6.35) 16.67 (7.85) 16.88 (5.75) 2.06 (-0.46, 4.58) 0.108 HOMA-IR 2.94 (1.17) 3.26 (1.58) 3.54 (1.91) 3.53 (1.32) 0.47 (-0.15, 1.08) 0.135 C-peptide (ng/ml) 2.83 (0.89) 3.32 (1.14) 3.03 (0.76) 3.37 (0.76) 0.18 (-0.09, 0.45) 0.184 Total cholesterol (mmol/l) 6.25 (1.02) 6.33 (1.12) 6.43 (1.04) 6.60 (1.16)

• 0.06 (-0.28, 0.15)

0.571 HDL cholesterol (mmol/l) 2.04 (0.47) 1.90 (0.47) 2.01 (0.55) 1.87 (0.41) 0.00 (-0.11, 0.12) 0.967 LDL cholesterol (mmol/l) 3.38 (0.91) 3.55 (0.95) 3.54 (0.97) 3.78 (1.16) 0.02 (-0.24, 0.20) 0.839 Triglycerides (mmol/l) 1.73 (0.56) 1.94 (0.67) 2.00 (0.69) 2.11 (0.59) 0.10 (-0.06, 0.25) 0.218

Data presented as mean (SD). P-values reflect differences in the change in each parameter between the groups from pre- to post-intervention, calculated using General Linear Model adjusting for maternal BMI.

Pregnancy outcome

Lindsay et al, 2014 AJCN [in press]

Secondary outcomes

No differences between probiotic and placebo groups in (BMI adjusted):

– Incidence of GDM (16% vs 15%; p=0.59) – Birth weight centile (45.9±27.2 vs 45.0±30.3; p=0.90) – Mean energy or nutrient intakes – Total gestational weight gain (10.5±5.9 vs. 9.1±5.4 kg; p=0.65) – Other pregnancy outcomes: preeclampsia, preterm labour, caesarean delivery, NICU admission

Lindsay et al, 2014 AJCN [in press]

Capsule acceptability

Lindsay et al, 2014 Int J Ob Gynecol

Strengths:

• First RCT to investigate metabolic effects of probiotics in
• bese pregnancy
• Good compliance and acceptability, low drop-out rate

(1.4%) (Lindsay et al, 2014)

• No adverse effects

Limitations:

• Did not collect faecal samples – alteration of gut

microbiota unknown

• Short intervention period

Lindsay et al, 2014 AJCN [in press]

PRoP conclusions

In an obese pregnant cohort, probiotics were safe and well tolerated No impact of 4 week probiotic capsule intervention on:

• fasting glucose
• other markers of metabolic health
• pregnancy outcomes

Lindsay et al, 2014 AJCN [in press]

PRoP conclusions

Conclusion

• Lifestyle interventions have beneficial

impact on maternal, fetal health

• Long-term follow-up studies will evaluate

impact on child health

Obstetrics Paediatrics Michael Foley Eleanor Molloy Rhona Mahony Jean Donnelly (PhD) Endocrinology Midwifery Richard Firth Cecilia Mulcahy Brendan Kinsley Mary Moran (PhD) Claire Gavin Mary Coffey Research Fellows Dietician Noirin Russell (MD) Sinead Curran Mary Higgins (MD) Ciara McGowan (PhD) Jennifer Walsh (PhD) Mary Horan (PhD) Maria Kennelly (PhD) Karen Lindsay (PhD) Orna O’Brien (MSc) Basic Science Pathology Niamh Corrigan (PhD) Eoghan Mooney Daniel Dowling (MsC) Peter Kelehan Paul Downey Funding Health Research Board Ireland Ivo Drury Award EU FP7 National Maternity Hospital Medical Fund