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).

2. 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)

2. Do we both have the same risk? (individualized risk assesment)

3. 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.

Preeclampsia Pathophysiology – Maternal Vascular Endothelium

Circulation. 2011;123: 2856-2869.

Endothelial dysfunction Atherosclerosis

1. http://www.robertsfox.com/EndoPAT.htm

Risk Factors for Preeclampsia

JOGC. 2008;30: S1-S48.

Resolution of HTN Post-PEC

Resolution of HTN Post-PEC

Resolution of Proteinuria Post-PEC

Resolution of Proteinuria Post-PEC

Am J Obstet Gynecol. 2009;200:58.e1-58.e8.

Preeclampsia and Chronic HTN

Am J Obstet Gyncol. 1986;155:1011-6.

Preeclampsia and Chronic HTN

BMJ. 2007; 974-977.

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

NEJM. 2008;359:800-809.

Lancet. 2005; 366;1797-803.

Lancet. 2005; 366;1797-803.

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.

1

Preeclampsia & CVD:

Mild: 2.0 (1.8, 2.2)

Mod: 3.0 (2.5, 3.6)

Severe: 5.4 (4.0, 7.3)

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

1. CDA. CPG 2008. Cdn J Diabetes. 2008;32:Suppl 1.

CMAJ. 2008;179:229-234.

Diabetes Care. 2008;31:1668-1669.

Normoglycemic

Mild: HR 1.19 (1.02-1.39)

GDM: HR 1.66 (1.30-2.13)

CMAJ. 2009; 181: 371-376.

Gestational Diabetes

Pregnancy GDM

Preeclampsia

Post-partum Type 2 Diabetes

Chronic HTN

CAD / CVD

Obesity

Dyslipidemia Microalbuminuria

Pregnancy and Future Disease

Circulation. 2011;123: 2856-2869.

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

No clear recommendations Adoption of “heart healthy” lifestyle

Part 2: Recommendations for Hypertension Treatment

2012 Canadian Hypertension Education Program Recommendations

From CHEP - http://www.hypertension.ca/chep-recommendations

Women with

Preeclampsia and GDM

Not Addresse

d

Women with

Preeclampsia and GDM

Not Addresse

d

Women with Preeclampsia

Not

Addressed

SOGCPost-partum Recommendations

1. JOGC. 2008;30: S1-S48.

SOGC Recommendations – Modified from CHEP 2008

1. JOGC. 2008;30: S1-S48.

Preeclampsia FoundationPost-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.

Post-partum Preeclampsia Interventions

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. Placebo2. Metformin 850 mg bid3. “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