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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 &

Gynecological Survey, vol. 57, no. 11, 2002, pp. 719–721., doi:10.1097/00006254-200211000-00004.

“Final Recommendation Statement.” Home - US Preventive Services Task Force,

www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/low-dose-aspirin-use-for-the-prevention-of-morbidity-and-mortality-from-

preeclampsia-preventive-medication.

Al-Safi, Zain, et al. “Delayed Postpartum Preeclampsia and Eclampsia.” Obstetrics & Gynecology, vol. 118, no. 5, 2011, pp. 1102–1107.,

doi:10.1097/aog.0b013e318231934c.

Mackay, Andrea P., et al. “Pregnancy-Related Mortality From Preeclampsia and Eclampsia.” Obstetrics & Gynecology, vol. 97, no. 4, 2001, pp. 533–538.,

doi:10.1097/00006250-200104000-00011.

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Questions?

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