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Pregnancy-related diseases, their long-term health consequences and opportunities for interventions.
Kara Nerenberg, MD, MSc, FRCPC
Assistant Professor,
University of Alberta
Objectives
1. To understand the associations b/t pregnancy related diseases (preeclampsia & GDM) and future chronic diseases (vascular & renal).
1. To outline opportunities for interventions to reduce a woman’s risk of future chronic diseases.
Life-course model of pregnancy-associated diseases
•CAD
•CVD
•PAD
•CKD
Chronic Diseases
•T2DM
•HTN
Postpartum
• Gluc
• Lipids
• BMI
• MA
•GDM
•PEC
Pregnancy
• Gluc
• Lipids
• BMI
•HTN
•CKD
Pre-pregnancy
Offspring • T2DM • Obesity • Atherosclerosis
Questions to answer:
1. What chronic diseases do I need to look for? (awareness & screening)
1. Do we both have the same risk? (individualized risk assesment)
1. What can I do to prevent these chronic diseases? (prevention)
Preeclampsia
•CAD
•CVD
•PAD
•CKD
Long-term Chronic Diseases
•T2DM
•HTN
Postpartum
• Gluc
• Lipids
• BMI
• MA
•GDM
•PEC
Pregnancy
• Gluc
• Lipids
• BMI
•HTN
•CKD
Pre-pregnancy
A hypertensive disorder of pregnancy.
BP ≥ 140/90 AND proteinuria ≥ 300 mg/24 hrs.
5-10% of all pregnancies
maternal and fetal morbidity & mortality.
A disease of maternal vascular endothelial dysfunction.
JOGC. 2008;30: S1-S48.
Preeclampsia Pathophysiology
Phase I Abnormal Placentation
Phase II Maternal Syndrome
Circulation. 2011;123: 2856-2869. Clin J Am Nephrol. 2007;2:543-549.
T2DM: • PEC – 3.97 / 1000 • No PEC 2.21 / 1000
• HR: 1.82* (1.26, 2.62)
HTN in pregnancy. 2009;28:435-447.
Am J Kidney Dis. 2010;55:1026-1039.
Microalbuminuria* at 7.1 yrs PP: PEC Severe PEC 4x 8x * MA also with CVD
CV Outcome Study Risk 95% CI
Cardiac Disease Case-control (n=4)
OR: 2.47 1.22, 5.01
Cohort (n=10) RR: 2.33 1.95, 2.78
Cerebrovascular Cohort (n=6) RR: 2.03 1.54, 2.67
Peripheral Arterial Cohort (n=3) RR: 1.87 0.94, 3.73
CV Mortality Cohort (n=5) RR: 2.29 1.73, 3.04
Am Heart J 2008;145:918-930.
Metaregression Severity of Preeclampsia
Relative Risk 95% CI
Cardiac Disease Mild 2.00 1.83, 2.19
Moderate 2.99 2.51, 3.58
Severe 5.36 3.96, 7.27
P<0.0001.
Preeclampsia and CVD Death
14403 women:
481 PEC
244 CVD deaths
RF for CVD (HR):
PEC – 2.14 (1.3-3.6)
<34 wk – 9.54(4.5-20.3)
Survival at 30 yrs (56y)
Early PEC – 85.9%
Late PEC – 98.3%
No PEC – 99.3%
Preeclampsia
Pregnancy
CNS: Cerebral edema
Eclampsia / PRES
CVS: HTN (severe)
CHF / MI
Renal: Proteinuria
AKI
Liver: Edema: AST/ALT
Hematoma / rupture
Heme: HELLP
Thromboembolism
Post-partum
Stroke / CNS deficits
? Seizure disorder
Chronic HTN
CAD/PAD cardiomyopathy
Microalbuminuria
CKD / Dialysis
? Cirrhosis
VTE
Metabolic: Obesity,
T2DM, Dyslipidemia
Endo: hypothyroidism
Gestational Diabetes (GDM)1
•CAD
•CVD
•PAD
•CKD
Long-term Chronic Diseases
•T2DM
•HTN
Postpartum
• Gluc
• Lipids
• BMI
•MA
•GDM
•PEC
Pregnancy
• Gluc
• Lipids
• BMI
•HTN
•CKD
Pre-pregnancy
“Glucose intolerance with onset or first recognition during pregnancy”.
1. CDA. CPG 2008. Cdn J Diabetes. 2008;32:Suppl 1.
GDM – Risk Factors
Age ≥ 35*
Ethnicity*
Aboriginal
Hispanic
South Asian
Asian
African
FHx DM
Previous GDM
Delivery of macrosomic infant
BMI ≥ 30*
PCOS*
Acanthosis Nigricans
Corticosteroids
* Similar RF to preeclampsia
Gestational Diabetes
Pregnancy
GDM
Preeclampsia
Post-partum
Type 2 Diabetes
Chronic HTN
CAD / CVD
Obesity
Dyslipidemia
Microalbuminuria
CV Risk Period CVD Risk Score
OR (95% CI) P-value
10-Year ≥ 5% 13.1 (3.4-85.5) <0.001
30-Year ≥ 10% 8.4 (3.5-23.2) <0.001
Lifetime ≥ 39% 3.3 (1.8-6.1) <0.001
(n=99 women with preeclampsia; n= 118 controls)
Interventions
•CAD
•CVD
•PAD
•CKD
Long-term Chronic Diseases
•T2DM
•HTN
Postpartum
• Gluc
• Lipids
• BMI
• MA
•GDM
•PEC
Pregnancy
• Gluc
• Lipids
• BMI
•HTN
•CKD
Pre-pregnancy
Offspring • T2DM • Obesity • Atherosclerosis
Part 2: Recommendations for
Hypertension Treatment
2012 Canadian Hypertension Education
Program Recommendations
From CHEP - http://www.hypertension.ca/chep-recommendations
Part 2: Recommendations for
Hypertension Treatment
2012 Canadian Hypertension Education
Program Recommendations
From CHEP - http://www.hypertension.ca/chep-recommendations
Preeclampsia Foundation Post-partum Recommendations
Eat a heart healthy diet.
Exercise 30 mins, 5 days a week.
Maintain a BMI 19-25.
Stop smoking.
1. www.preeclampsia.org. Accessed on-line, Feb 29, 2012.
Women appreciative of info received
Women preferred:
Individualized counseling
Ongoing monitoring of lifestyle
Balanced use of computer resources
Flexibility in scheduling / Child care
3 arms: 1. Placebo 2. Metformin 850 mg bid 3. “Lifestyle” goals
- 7% weight loss - 150 mins activity
1. NEJM. 2002;346:393-403. 2. Diabetes Care. 2007:30; S242-245.
P: Pregnant women with GDM at Dx
Otherwise healthy
I: “DEBI” lifestyle intervention (DPP)
Diet, exercise and breastfeeding intervention
Telephone & in person sessions (RD / Lact)
Antenatal to 1 year post-partum
C: Usual care / lifestyle information
O: 10 meet PP wt goal / 20 BF x 6/12
M: RCT
Diabetes Care. 2011;34: 1519-1525.
Results
Authors suggested:
Earlier implementation of DEBI program
To minimize Gestational wt gain (GWG)
Participants suggested:
Physical Activity: Website
Support needed from family / social network
Tips on exercising with a newborn
Diet: Low-fat recipes
Tips on transitioning from diabetic diet.
Lessons from Lifestyle Programs
Pregnant / Post-partum women are interested and will participate.
Dietary education needs to be more comprehensive.
Specific physical activity advice.
Website preferred mode of delivery.
Awaiting results of Cochrane review of Lifestyle interventions post GDM
Knowledge & Knowledge Translation %
Increased risk of chronic HTN with HDP ~ 50%
Specialist communicate this risk to patients ~ 60%
Specialist arrange for follow-up of BP ~ 60%
GP’s actually informed of C-HTN risk ~ 10%
Life-course model of pregnancy-associated diseases
•CAD
•CVD
•PAD
•CKD
Chronic Diseases
•T2DM
•HTN
Postpartum
• Gluc
• Lipids
• BMI
• MA
•GDM
•PEC
Pregnancy
• Gluc
• Lipids
• BMI
•HTN
•CKD
Pre-pregnancy
Offspring • T2DM • Obesity • Atherosclerosis
Summary:
PE and GDM
Context of a “life-course model”
Future maternal disease risk
Vascular risk in offspring
Recurrence in future pregnancies
Vascular RF monitoring & management
Frequency unclear – “annual”
Optimal targets unclear – “high risk”
Lifestyle intervention counseling – first line
Extensive Research Opportunities