hypertensive disorders of pregnancy - idaho perinatal...hypertensive disorders of pregnancy kylie...
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2/19/2019
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Hypertensive Disordersof Pregnancy
Kylie Cooper, MD
Maternal Fetal Medicine
St. Luke’s Health System
Learning Objectives
Explain the impact of hypertensive disorders on
maternal morbidity and mortality
Classify hypertensive disorders of pregnancy using up
to date diagnostic criteria
Articulate appropriate delivery timing for hypertensive
pregnancies
Identify acute hypertension and employ appropriate
and timely treatment
Summarize the long term health effects of
preeclampsia and the role for risk reducing
interventions
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Case
19 year old G1P0 at 37+1 wga who is noted to
have newly elevated blood pressure 145/93 at
her routine prenatal visit
work-up?
Persistent 140's/90's over 7 hours with Urine
P:C 0.25. Asymptomatic. Labs notable for
creatinine 0.9, Platelets 98,000, LFTs WNL.
Does she have preeclampsia?
Management?
Long term issues?
Management in future pregnancies?
Epidemiology
Hypertensive disorders of pregnancy complicate
up to 10% of pregnancies worldwide
Major contributor to prematurity
Preeclampsia
Complicates 5% of pregnancies
Incidence of preeclampsia has increased by
25% over the last two decades
40% of women with new onset hypertension
or proteinuria will develop classic
preeclampsia
ACOG 2013, Barton et al 2008, CMQCC
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Preeclampsia Related Maternal Mortality
Photo cred Bahareh Biseh
Maternal Mortality
Preeclampsia
Leading cause of maternal and
perinatal morbidity and mortality in
the US
Worldwide estimated 50,000-60,000
maternal deaths/year
For each preeclampsia related death,
estimated 50-100 near misses
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Maternal Mortality
How do women with preeclampsia die?
MacKay et al:
14 years US data (1979-1992)
>4000 fatalities
19% from preeclampsia-eclampsia
38% death due to stroke
90% hemorrhagic
African American women 3x more likely to die
than Caucasian
California data-CA-PAMR Cohort, 2002-2004
64% due to stroke
87% hemorrhagic
MacKay et al 2001, CMQCC
Maternal Mortality
CA-PAMR Cohort/CMQCC
Contributing factors related to health care
providers
Delay in diagnosis
Ineffective treatment
Misdiagnosis
CMQCC
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Centre for Maternal and Child Enquiries
(CMACE)
“Aim is to improve the health of mothers,
babies and children by carrying out
confidential enquires and related work on a
nationwide basis…”
“Top Ten” recommendations for those
involved in providing maternity services
Systolic hypertension requires treatment
CMACE BJOG 2011
Centre for Maternal and Child Enquiries
(CMACE)
22 deaths Preeclampsia-Eclampsia
14 cerebral causes (64%)
9 intracranial hemorrhage (64%)
5 anoxia following cardiac arrest (36%)
20/22 cases associated with substandard care
Single largest cause of death=intracranial
hemorrhage
Conclusion: Systolic blood pressure is the
greatest risk for cerebral hemorrhage
CMACE BJOG 2011
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Contributing Factors
DELAY IN
DIAGNOSIS
INEFFECTIVE
TREATMENT
MISDIAGNOSIS
Preeclampsia Risk Factors
History preeclampsia/HTN disorder
Nulliparous
Extremes of age
Race/ethnicity
Lower socioeconomic status
Obesity
Medical comorbidities
Diabetes
Hypertension
Autoimmune Disease
Renal disease
Multiple gestations
ART
OSA Lo et al 2013, ACOG 2019
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Diagnosis
Categories
Chronic hypertension
Predates pregnancy
< 20 weeks
Gestational hypertension
HTN > 20 weeks
Absence of proteinuria/systemic symptoms
*severe GHTN
Preeclampsia-Eclampsia
Preeclampsia without severe features
Preeclampsia with severe features
HELLP
Eclampsia
Chronic hypertension with superimposed
preeclampsia
ACOG 2013, Tuffnell BJOG 2005
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Chronic Hypertension
0.9-1.5% of pregnancies
67% increase over decade
AMA and obesity
Hypertension pre-pregnancy or < 20 weeks*
> 12 weeks postpartum
AHA and ACC: 4 categories
More people meeting criteria
Unclear what change in diagnostic
criteria will have on OB outcomes
How to approach treatment? In
pregnancy?
ACOG 2019
Gestational Hypertension
HTN > 20 weeks, resolves by 12 weeks
postpartum
Absence of proteinuria/systemic symptoms
NOT BENIGN
High rate of progression to preeclampsia
~50% preeclampsia, 10% severe
More likely if dx <32 weeks
Severe gestational hypertension: 160/110 ->
increased maternal morbidity and mortality
Recommendation to diagnose and treat as
preeclampsia with severe features
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Preeclampsia
Causality of preeclampsia:
“Two Stage” model: Sequence of
placentally derived
abnormalities/substances in
combination with maternal factors
Salafia 2008
Preeclampsia
Blood Pressure
> 20 weeks gestational age
≥ 140 systolic or 90 diastolic on two
occasions at least 4 hrs apart
If ≥ 160 /110 can confirm within
minutes to facilitate treatment
Proteinuria
≥ 300mg/24 hours OR
Protein/creatinine ratio ≥ 0.3
ACOG 2013
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Preeclampsia
OR in absence of proteinuria
Thrombocytopenia (<100,000)
Renal Insufficiency (> 1.1, or doubling
of creatinine in absence of renal
disease)
Liver Function (≥ Twice normal
concentration)
Pulmonary edema
Cerebral/Visual symptoms
ACOG 2013
Severe Features
Blood Pressure (≥160/110)
Thrombocytopenia (<100,000)
Renal Insufficiency (> 1.1, or doubling of
creatinine in absence of renal disease)
Liver Function (≥ Twice normal
concentration)
Pulmonary edema
Cerebral/Visual symptoms
Severe persistent RUQ/epigastric pain
ACOG 2013
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Chronic Hypertension
with Superimposed Preeclampsa
20-50% of women with cHTN may
develop superimposed Preeclampsia
75% If end organ damage
Difficult diagnosis
Dx of exclusion
Lab changes, symptoms worsening of
blood pressure and/or proteinuria
Vague criteria
HELLP
Hemolysis, Elevated Liver enzymes, Low
Platelets
20% of women with preeclampsia with
severe features
Insidious, atypical onset
Usual symptoms: RUQ pain, generalized
malaise (90%), N/V (50%)
15% lack hypertension and/or proteinuria
Adverse Outcomes-abruption, IUFD, renal
failure, subcapsular hematoma, maternal
death
ACOG 2019
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Eclampsia
tonic–clonic seizures
1.9% in preeclampsia
3.2% in preeclampsia with severe features
UK study-38% of eclampsia occurred without prior documented
HTN/proteinuria
Notion of Linear progression NOT accurate
Posterior reversible encephalopathy
syndrome (PRES):
Constellation neurologic signs
and symptoms
Dx: presence of vasogenic
edema and hyperintensities in
the posterior brain on MRI
ACOG 2019, Zhang et al
Management
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Chronic Hypertension
Baseline 24 hour urine and labwork early in
pregnancy
ASA
Weekly BP check third trimester
BP parameters
>120/80 but <160/110
Serial fetal growth assessment
Weekly antenatal testing
Delivery at 37 weeks if requiring
antihypertensive medications
Delivery at 38-39 if not requiring
antihypertensive medications
ACOG 2019
Gestational Hypertension
Not benign
High rate of progression to preeclampsia
46% preeclampsia, 9.6% severe
Weekly to Twice weekly BP check
Weekly labs and Urine protein
Daily assessment of maternal symptoms and
fetal movement
Serial growth US
Weekly antenatal testing
NO bed rest
Delivery at 37 weeks (no severe BP)
If severe GHTN->same approach as PEC w/ SF
Delivery at or beyond 34 weeks ACOG 2019, Barton et al 2001
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Preeclampsia without Severe
Features
Twice weekly BP check
Weekly HELLP labs
Daily assessment of maternal symptoms
and fetal movement
Serial fetal growth assessment
Weekly antenatal testing
Delivery at 37 weeks
Not universal magnesium
1 in 200
NNT for asymptomatic 129
Preeclampsia with Severe
Features
Unstable: maternal stabilization followed by delivery
Stable: expectant management until 34 weeks
Steroids for fetal lung maturity
Anti-hypertensives if sustained BP >160/110
Magnesium (4/200) NNT in symptomatic is 36
Defer delivery for 48 hour steroid course if ≤ 33+5 weeks
and:
PPROM, labor, severe lab abnl’s, oligo, REDF, IUGR
<5th%
No role for expectant management if :
Previable gestation
Uncontrollable HTN
Eclampsia
Pulmonary edema
abruption, DIC, NRFA, IUFD
Mode of delivery- Usual OB indications
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ManagementCesarean section
Continue magnesium infusion throughout
surgery
Endotracheal intubation can exacerbate
severe hypertension
Airway edema, especially with preeclampsia
Failed airway ~1:300
Fluid management
Postpartum
Late onset preeclampsia-eclampsia occurs >
48 hrs postpartum
Estimated up to 26% eclamptic seizures
occur late
Discharge follow-up recommended within 72
hrs and again at 7-10 days postpartum for
blood pressure monitoring
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The National Institute for Health
and Clinical Excellence:
NICE
Guidelines:
Moderate pre-eclampsia (SBP 150-160 mmHg) treat
with oral labetalol
Severe pre-eclampsia- treatment with either oral or IV
labetalol, oral nifedipine, or IV hydralazine.
A combination of drugs may be necessary
Target SBP 150 mmHg
Admit to hospital for urgent treatment
Anesthesia involvement, ICU, team approach with explicit
communication of systolic pressures
Automated blood pressure monitoring systems
systematically under-estimate SBP
Avoid methergine use in third stage
CMACE BJOG 2011
Acute Hypertension
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Acute Hypertension
Hypertensive Emergency: Acute-onset,
severe hypertension that is accurately
measured using standard techniques and is
persistent for 15 minutes or more
ACOG 2017
Treatment
Treatment within 30-60 minutes of confirmed
severe hypertension
reduce risk of stroke
First Line agents:
IV labetalol
IV hydralazine
Immediate release oral nifedipine
Magnesium
ACOG 2017
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Medications
Medications
Labetalol
Nonselective beta blocker
Decrease cardiac output and PVR
20mg (over 2 min)->40->80
Max dose 300mg
caution: neonatal bradycardia, avoided in women with
asthma, heart disease, or congestive heart failure
Hydralazine
hydrazinophthalazine
Arteriolar vasodilator, decrease PVR
5-10mg IV or IM q 15 min, max dose 20mg IV or 30mg IM
caution: maternal hypotension
Nifedipine
calcium channel blocker
Inhibits vasoconstriction, decrease PVR
10-20mg oral q 30 min, max dose 50mg (10->20->20)
Caution: maternal tachycardia, overshoot hypotension , HA
ACOG 2017, Hart et al 2012
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Nifedipine Regimen
10mg po
20mg po
20mg po
Labetalol 40mg IV
Emergency Consultation
20 min BP check
20 min BP check
20 min BP check
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Resistant HTN
Nicardipine infusion
Esmolol infusion
Sodium nitroprusside reserved for extreme
emergencies
Fetal/maternal cyanide toxicity
Worsening maternal cerebral edema
Post-treatmentMonitoring
Once goal BP achieved:
BP q 10 minutes x 1 hour
BP q 15 minutes x 1 hour
BP q 30 minutes x 1 hour
BP q hour x 4 hours
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Magnesium Sulfate
Mechanism of action largely unknown
Cerebral vasodilation
Competitive calcium blocker, altered
neuromuscular transmission
Greater than 50% relative reduction in the risk of
eclampsia
NNT for Severe Preeclampsia: 63 (36)
NNT for Preeclampsia without severe features: 91
(129)
Therapeutic range 4-8 mg/dL *
Shaukat 2003, Weeks et al Lancet 2002, Duley et al Cochrane 2010
Diagnosis & Management
Elimination of “mild preeclampsia” terminology
Removed proteinuria as a requirement for preeclampsia diagnosis in context of severe features
Eliminated >5g protein in 24 hours from severe diagnostic criteria
Stress importance of early treatment of severe HTN (160/110)
Magnesium for all preeclampsia with severe features
No universal magnesium for preeclampsia without severe features
Early onset preeclampsia (<34 weeks) should be managed in appropriately equipped facility
Delivery at 37 weeks for Gestational HTN and Preeclampsia without severe features
Manage severe GHTN like Preeclampsia with severe features-34 weeks
Patient education and close follow-up in postpartum period
ACOG 2013, 2019
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Risk Reduction
Risk Reductionin Subsequent
Pregnancy
US Preventative Services Task Force
In women at risk for preeclampsia, low dose
aspirin (60-150mg/d) reduced risk for
preeclampsia and related preterm birth and IUGR
demonstrating substantial benefit
24% Preeclampsia
14% Preterm birth
20% IUGR
Dose Dependent Response
Timing: Begin 12-13 weeks
Sibai 1994, Caritis 1998, NEJM 2017
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High Risk Moderate Risk Low Risk
History preeclampsia
Multifetal gestation
Chronic hypertension
Diabetes
Renal Disease
Autoimmune Disease
Nulliparity
Obesity (BMI >30)
Family history PEC
Sociodemographic
Age ≥ 35 years
Personal hx-SGA, poor
outcome
Previous
uncomplicated full
term delivery
(≥ 1 risk factor)
Aspirin Recommended
(Several risk factors)
Consider aspirin No Aspirin
USPTF
Cardiovascular Risk
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Cardiovascular Risk
Preeclampsia linked to hypertension, stroke,
ischemic heart disease, and thromboembolism
HTN 3.7
Ischemic heart disease 2.16
Stroke 1.81
VTE 1.79
ACOG 2013
Cardiovascular Risk
Graded relationship between severity of
preeclampsia-eclampsia and risk for
cardiovascular disease
Independent risk factor for cardiovascular
disease
Term preeclampsia has a 1.5-fold increased
risk of CVD related death
Preterm preeclampsia has an 8 fold increased
risk of CVD related death
Recurrent preeclampsia has a 7 fold increased
risk for CVD as compared to a single episode
Shared risk factors
Mongraw-chaffin et al
2010
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Renal Disease
Absolute risk for renal failure low
Four fold increased risk of subsequent end
stage renal disease
Vikse et al NEJM 2008
Case
19 year old G1P0 at 37+1 wga who is noted
to have newly elevated blood
pressure 145/93 at her routine prenatal visit
work-up? Serial BP’s, in hospital eval, U
P:C, HELLP labs
Persistent 140's/90's over 7 hours with Urine
P:C 0.25. Asymptomatic. Labs notable for
creatinine 0.9, Plts 98,000, LFTs WNL.
Does she have preeclampsia? Yes
thrombocytopenia without proteinuria
(w/ Severe features)
Management? Deliver (>34 weeks),
magnesium
Long term issues? CVD
Management in future pregnancies?
ASA at 13 weeks, baseline 24 hour urine
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ACOG. Emergent Therapy for Acute-Onset, Severe Hypertension During Pregnancy and the Postpartum Period. Number 692, April 2017
Barton JR, Sibai BM. Prediction and prevention of recurrent preeclampsia. Obstet Gynecol. 2008;112(2 PART 1): 359-372.
Califronia Maternal quality Care collaborative. Preeclampsia toolkit. Available: https://www.cmqcc.org/resources-tool-kits/toolkits/preeclampsia-toolkit
Tuffnell D, Jankowicz D, Lindow S, et al. Outcomes of severe pre-eclampsia/eclampsia in Yorkshire 1999/2003. BJOG: An International Journal of Obstetrics and
Gynaecology. 2005;112(7):875-880. doi:10.1111/j.1471-0528.2005.00565.x.
Koopmans CM, Bijlenga D, Groen H, et al. Induction of Labor Versus Expectant Monitoring for Gestational Hypertension or Mild Preeclampsia After 36 Weeks’
Gestation (HYPITAT): A Multicentre, Open-Label Randomized Controlled Trial. Obstetrical & Gynecological Survey. 2009;64(12):776-778.
doi:10.1097/01.ogx.0000363251.55157.f9.
Vikse BE, Irgens LM, Leivestad T, Skjærven R, Iversen BM. Preeclampsia and the Risk of End-Stage Renal Disease. New England Journal of Medicine. 2008;359(8):800-
809. doi:10.1056/nejmoa0706790.
Hart TD, Harris MB. Preeclampsia Revisited. US Pharmacist. 2012;37(9):48-53.
Rolnik, Daniel L., et al. “Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia.” New England Journal of Medicine, vol. 377, no. 7, 2017, pp. 613–
622., doi:10.1056/nejmoa1704559.
“Do Women With Pre-Eclampsia, and Their Babies, Benefit From Magnesium Sulfate? The Magpie Trial: A Randomised Placebo-Controlled Trial.” Obstetrical &
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“Final Recommendation Statement.” Home - US Preventive Services Task Force,
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preeclampsia-preventive-medication.
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