Hypertension in Pregnancy
Louise Kenny Director
The Irish Centre for Fetal and Neonatal Translation Research
• 287 000 maternal deaths occurred in 20101
• Hypertensive disorders of pregnancy account for nearly 18% of all maternal deaths world-wide, with an estimated 62 000–77 000 deaths per year2
• Eclampsia complicates 0.28% of pregnancies in low resource settings3 cf 2.7 cases per 10,000 maternities in the UK4 (Incidence in 1992 4.9 per 10,000 95% CI 4.5-5.4)5
1. World Health Organization, UNICEF, UNFPA and the World Bank. Trends in Maternal Mortality: 1990 to 2010. Geneva: World Health Organization, 2012
2. Khan KS, Wojdyla D, Say L, Gulmezoglu AM, Van Look PF. WHO analysis of causes of maternal death: a systematic review. Lancet 2006;367:1066–74.
3. WHO Multicountry Survey on Maternal and Newborn Health Research Network. Pre-eclampsia, eclampsia and adverse maternal and perinatal outcomes: a secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health. BJOG 2014; 121(Suppl. 1): 14–24.
4. Knight, M. (2007), Eclampsia in the United Kingdom 2005. BJOG: An International Journal of Obstetrics & Gynaecology, 114: 1072–1078
5. Douglas and Redman 1994 BMJ 309:1395-1400
Incidence
0
20
40
60
80
100
120
52-54
55-57
58-60
61-63
64-66
67-69
70-72
73-75
76-78
79-81
82-84
85-87
88-90
91-93
94-96
97-99
00-02
Eclampsia Preeclampsia
Maternal Mortality
• Remains 2nd most common cause of Direct Death – rate unchanged over last 2 reports
• 22 deaths (including 3 from AFLP) • 9 due to intracranial haemorrhage directly related to
uncontrolled blood pressure • 5 after eclamptic fit • 3 from cardiac arrest post fit and 2 unknown cause
Standards of care: CMACE 2011
• 20 of the 22 cases demonstrated substandard care
• In 14 cases this was classed as ‘major’
• “There were, undoubtedly, avoidable deaths”
Standards of care: CMACE 2011
• National Institute for Health and Clinical Excellence (NICE, UK), “Hypertension in Pregnancy”
• Revised January 2011
Clinical practice guidelines
• HSE & Institute of Obstetricians and Gynaecologist’s Guideline on “The Diagnosis and Management of Pre-eclampsia and Eclampsia”
• Published September 2011
Clinical practice guidelines CLINICAL PRACTICE GUIDELINE THE DIAGNOSIS AND MANAGEMENT OF PRE-ECLAMPSIA AND ECLAMPSIA
1
THE DIAGNOSIS AND MANAGEMENT OF PRE-ECLAMPSIA AND ECLAMPSIA CLINICAL PRACTICE GUIDELINE
Institute of Obstetricians and Gynaecologists, Royal College of Physicians of Ireland
and
Clinical Strategy and Programmes Directorate, Health Service Executive
Version 1.0
Guideline No. 3
Date of publication – September 2011
Revision date – September 2013
What happens to Blood Pressure in Pregnancy
• Generalised vasodilatation causes a fall in peripheral vascular
resistance • There is also an increase in heart-rate and plasma volume
expansion (leading to increase in stroke volume) • However, the fall in peripheral vascular resistance exceeds the
increase in stroke volume and blood pressure falls • This reaches a nadir by the end of the first trimester and blood
pressure slowly returns to pre-pregnancy values by term
Definition of Hypertension in Pregnancy
• The booking blood pressure (or pre-pregnancy blood pressure) are important...
• BUT hypertension is still defined as two measurement of 140/90 taken on two separate occasions and at least 4 hours apart
• Significant proteinuria is defined as >1+ or >300mg in 24 hour collection of urine
How to Measure Blood Pressure
• Position – Sitting or Supine (left lateral with 30 degree tilt)
• Sphygmomanometer – At the level of the heart (the patient’s, not yours)
• Manual or automatic? – Most automated systems under-estimate BP in pregnancy. Use a manual system
initially and to validate your automated recordings • Which Karotkoff sound?
– Sound 5 is the most reproducible in pregnancy
• There are three types of hypertension in pregnancy – Hypertension that exists before pregnancy (chronic hypertension) – Hypertension that develops during pregnancy without proteinuria
(gestational hypertension) – Hypertension that develops during pregnancy with proteinuria (pre-
eclampsia
• It is VITAL that you make a diagnosis and correctly classify which type of hypertension the patient has.
Classification of Hypertension in Pregnancy
• Hypertension that exists before pregnancy – Is chronic hypertension – Remember ‘essential hypertension’ is a diagnosis of exclusion – Chronic hypertension may co-exist with renal impairment – Chronic hypertension (with or without renal involvement) = a high risk
pregnancy
Chronic Hypertension in Pregnancy
• Benign hypertension occurring after 20 weeks gestation but most commonly in the 3rd trimester
• Not accompanied by proteinuria • ‘Complicates’ 10% of pregnancies • Does not need treating and is associated with good outcomes for
mother and baby • BUT….at least 30% of women with gestational hypertension will
develop pre-eclampsia.
Gestational Hypertension
• Multi-system disease unique to pregnancy
• Defined as hypertension and proteinuria arising after the 20th week of gestation in a previously normotensive woman
What is pre-eclampsia?
Who is at risk of pre-eclampsia?
• First pregnancies: RR 2.91 (95% CI 1.28-6.61) • Family history: RR 2.90 (95% CI, 1.70-4.93) • Mothers over 40: primips RR 1.68, (95% CI 1.23-2.29) and multips
RR 1.96 (98% CI 1.34-2.87) women • Obese women: RR 2.12 (95% CI, 1.56-2.88) • Multiples: RR of 2.93 (95% CI 2.04-4.21) • Previous pre-eclampsia: RR7.19 (95%CI 5.85-8.83) • Women with pre-existing medical conditions
Who is at risk of pre-eclampsia?
MAP >84
BMI >30 FH PET PET N
No PET N
% MAP/BMI/FH with PET
% PET
N N N 102 3506 3% 37%
Y N N 65 852 8% 23%
Y Y N 33 376 9% 12%
N Y N 30 373 8% 11%
N N Y 16 323 5% 6%
Y N Y 17 98 17% 6%
Y Y Y 12 47 26% 4%
N Y Y 3 48 6% 1%
BP, BMI and FH to predict pre-eclampsia
MAP >84
BMI >30 FH PET PET N
No PET N
% MAP/BMI/FH with PET
% PET
N N N 102 3506 3% 37%
Y N N 65 852 8% 23%
Y Y N 33 376 9% 12%
N Y N 30 373 8% 11%
N N Y 16 323 5% 6%
Y N Y 17 98 17% 6%
Y Y Y 12 47 26% 4%
N Y Y 3 48 6% 1%
BP, BMI and FH to predict pre-eclampsia
• Known essential hypertension on treatment – If contempla:ng pregnancy-‐ refer to CUMH for pre-‐conceptual advice – Op:mise modifiable risk factors, alter drugs – In par:cular d/c ACE and ARBs – Labetalol 1st line, nifedipine (long ac:ng) 2nd line, methyldopa 3rd line – Aspirin: meta-‐analysis showed that low-‐dose aspirin prophylaxis at or before 16 weeks’
gesta:on resulted in a 89% reduc:on of preeclampsia delivered before 37 weeks’ gesta:on, but had no effect on the risk of term preeclampsia.
– If already pregnant refer to Perinatal Medicine Clinic
How to manage the hypertensive pregnant patient
• Newly hypertensive in pregnancy – Check for proteinuria – If posi:ve, refer urgently – If nega:ve, refer to clinic – In hypertensive crisis: give 200mg oral labetalol immediately – Do NOT give sub lingual nifedipine
How to manage the hypertensive pregnant patient
• Pregnancy is a stress test
• Women who develop pre-eclampsia or have a growth restricted fetus:
– Have 4-‐7 :mes increased risk of long term hypertension – Have 2-‐3 :mes increased risk of coronary artery disease – Have 4-‐7 :mes increased risk of chronic renal failure
• Opportunity for intervention: well woman clinic
The hypertensive pregnant patient: long term follow up
Consequences of poor placentation STAGE 1
8–18 weeks
STAGE 2 > 20 weeks
Pre-eclampsia with FGR
Poor Placentation
Placental Oxidative
Stress
FGR Pre-eclampsia without FGR
Complications
Consequence of management: • Prematurity
Maternal consequences of placental dysfunction • HELLP Syndrome • Eclampsia
Fetal consequence of placental dysfunction • Severe FGR • Stillbirth
Maternal endothelial / inflammatory dysfunction
Predisposition to maternal disease
Typically preterm Typically term ?
What’s new in pre-eclampsia?
l PlGF as a diagnostic test l Various screening tests l Viagra for fetal growth restriction
Placental Growth Factor
l Angiogenic, pro-inflammatory factor produced by trophoblast cells l Four isoforms (PlGF-1, -2, -3, -4) l Receptor: Cell surface Flt-1 and soluble Flt-1 (VEGFR-1) l PlGF circulates free or in complexes (with sFlt-1) l Modern assays measure only free PlGF l Abnormally low PlGF likely to be a good marker of oxidatively
damaged placenta
*** ***
*†† †
Control * p<0.05 ** p<0.01 *** p<0.001 Case † p<0.05 †† p<0.01
Rises then falls in normal pregnancy
Significantly decreased when preeclampsia
diagnosed
**
**
*
*
*
Lower in women destined to develop preeclampsia
0100200300400500600700800900
10001100
8-12 13-16 17-20 21-24 25-28 29-32 33-36 37-41
Gestational Age (wks)
PlGF
(pg/m
l)Control Case Endpoint
Adapted from Levine et al 2004, Levine et al. NEJM 2004;350:672-83
Placental Growth Factor (PlGF)
... Potential as a diagnostic & prognostic marker?
• Features • Quantitative assay • Specific to “free” PlGF-1 • Dynamic range 12-3,000 pg/mL • Plasma EDTA sample • Whole blood capable soon • Rapid results in only 15 minutes • Built-in QC, QA functions
Alere Triage® PLGF Test
1. UNIVERSITY COLLEGE CORK2. ACCELOPMENT AG3. ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM 4. KAROLINSKA INSTITUTET 5. UNIVERSITY OF KEELE 6. MEDSCINET AB 7. METABOLOMIC DIAGNOSTICS LIMITED 8. PRONOTA NV 9. REGION HOVEDSTADEN
10. RIJKSUNIVERSITEIT GRONINGEN 11. KLINIKUM DER UNIVERSITAET ZU KOELN 12. THE UNIVERSITY OF LIVERPOOL
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Irish innovation in perinatal healthcare research leading the world: scientific excellence with societal and economic impact
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A pregnant woman dies every minute
CONNECTED HEALTH
Prof. Louise Kenny Professor of Obstetrics, UCC Prof. Geraldine Boylan Professor of Neonatal Physiology, UCC Dr. Gene Dempsey Neonatologist and Senior Lecturer, CUMH Dr. Deirdre Murray Paediatrician and HRB Clinician Scien:st, UCC Dr. Liam Marnane Senior Lecturer, Electrical and Electronic Engineering, UCC Dr. Gordon Lightbody Senior Lecturer, Electrical and Electronic Engineering, UCC Dr. David Henshall Professor, Physiology & Medical Physics, RCSI Prof. Fred Adams Professor, Health Informa:on Systems Research Centre, UCC Dr Mariead Kiely Senior Lecturer, Food Science
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