Hypertensive Disorders of Pregnancy - Idaho Perinatal Project

2/19/2019

       Hypertensive Disorders
           of Pregnancy
                Kylie Cooper, MD
             Maternal Fetal Medicine
             St. Luke’s Health System

                 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
 Learning         pregnancies
                 Identify acute hypertension and employ appropriate
Objectives        and timely treatment
                 Summarize the long term health effects of
                  preeclampsia and the role for risk reducing
                  interventions

                                                                                   1

2/19/2019

                       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
   Case                 creatinine 0.9, Platelets 98,000, LFTs WNL.
                           Does she have preeclampsia?
                           Management?
                           Long term issues?
                           Management in future pregnancies?

                Hypertensive disorders of pregnancy complicate
                up to 10% of pregnancies worldwide
                   Major contributor to prematurity
                Preeclampsia
                   Complicates 5% of pregnancies
Epidemiology       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

                                                                                      2

2/19/2019

Preeclampsia Related
 Maternal Mortality

                                                  Photo cred Bahareh Biseh

                Preeclampsia
                   Leading cause of maternal and
                   perinatal morbidity and mortality in
                   the US
 Maternal          Worldwide estimated 50,000-60,000
 Mortality         maternal deaths/year
                   For each preeclampsia related death,
                   estimated 50-100 near misses

                                                                             3

2/19/2019

             How do women with preeclampsia die?
             MacKay et al:
                14 years US data (1979-1992)
                >4000 fatalities
                    19% from preeclampsia-eclampsia

Maternal            38% death due to stroke
                        90% hemorrhagic
Mortality       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

             CA-PAMR Cohort/CMQCC
             Contributing factors related to health care
              providers

Maternal         Delay in diagnosis
                 Ineffective treatment
Mortality        Misdiagnosis

                                                             CMQCC

                                                                              4

2/19/2019

                   “Aim is to improve the health of mothers,
                   babies and children by carrying out
  Centre for       confidential enquires and related work on a
Maternal and       nationwide basis…”

Child Enquiries    “Top Ten” recommendations for those
                   involved in providing maternity services
  (CMACE)
                   Systolic hypertension requires treatment

                                                        CMACE BJOG 2011

                   22 deaths Preeclampsia-Eclampsia
                      14 cerebral causes (64%)
                          9 intracranial hemorrhage (64%)
                          5 anoxia following cardiac arrest (36%)
  Centre for
Maternal and       20/22 cases associated with substandard care
Child Enquiries    Single largest cause of death=intracranial
  (CMACE)          hemorrhage
                   Conclusion: Systolic blood pressure is the
                   greatest risk for cerebral hemorrhage

                                                        CMACE BJOG 2011

                                                                                 5

2/19/2019

                Contributing Factors

 DELAY IN           INEFFECTIVE                       MISDIAGNOSIS
DIAGNOSIS           TREATMENT

                      History preeclampsia/HTN disorder
                      Nulliparous
                      Extremes of age
                      Race/ethnicity
                      Lower socioeconomic status
                      Obesity
Preeclampsia          Medical comorbidities
 Risk Factors             Diabetes
                          Hypertension
                          Autoimmune Disease
                          Renal disease
                      Multiple gestations
                      ART
                      OSA                          Lo et al 2013, ACOG 2019

                                                                                      6

2/19/2019

             Diagnosis

              Chronic hypertension
                  Predates pregnancy
                  < 20 weeks
              Gestational hypertension
                  HTN > 20 weeks
                  Absence of proteinuria/systemic symptoms
                  *severe GHTN
Categories    Preeclampsia-Eclampsia
                  Preeclampsia without severe features
                  Preeclampsia with severe features
                  HELLP
                  Eclampsia
              Chronic hypertension with superimposed
               preeclampsia

                                                       ACOG 2013, Tuffnell BJOG 2005

                                                                                       7

2/19/2019

                0.9-1.5% of pregnancies
                   67% increase over decade
                   AMA and obesity
                Hypertension pre-pregnancy or < 20 weeks*
                > 12 weeks postpartum
  Chronic       AHA and ACC: 4 categories
Hypertension       More people meeting criteria
                   Unclear what change in diagnostic
                    criteria will have on OB outcomes
                   How to approach treatment? In
                    pregnancy?
                                                               ACOG 2019

                 HTN > 20 weeks, resolves by 12 weeks
                postpartum
                 Absence of proteinuria/systemic symptoms
                   NOT BENIGN
                   High rate of progression to preeclampsia
 Gestational           ~50% preeclampsia, 10% severe

Hypertension           More likely if dx 
                increased maternal morbidity and mortality
                   Recommendation to diagnose and treat as
                    preeclampsia with severe features

                                                                             8

2/19/2019

               Preeclampsia

                          Causality of preeclampsia:
                             “Two Stage” model: Sequence of
                                placentally derived
                                abnormalities/substances in
                                combination with maternal factors

Salafia 2008

                 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
Preeclampsia            minutes to facilitate treatment
                 Proteinuria
                    ≥ 300mg/24 hours OR
                     Protein/creatinine ratio ≥ 0.3

                                                            ACOG 2013

                                                                           9

2/19/2019

                   OR in absence of proteinuria
                      Thrombocytopenia ( 1.1, or doubling
                       of creatinine in absence of renal
                       disease)
Preeclampsia          Liver Function (≥ Twice normal
                       concentration)
                      Pulmonary edema
                      Cerebral/Visual symptoms

                                                           ACOG 2013

                   Blood Pressure (≥160/110)
                   Thrombocytopenia ( 1.1, or doubling of
                   creatinine in absence of renal disease)
                   Liver Function (≥ Twice normal
Severe Features
                   concentration)
                   Pulmonary edema
                   Cerebral/Visual symptoms
                   Severe persistent RUQ/epigastric pain

                                                           ACOG 2013

                                                                         10

2/19/2019

                20-50% of women with cHTN may
                develop superimposed Preeclampsia
                   75% If end organ damage
   Chronic      Difficult diagnosis
Hypertension    Dx of exclusion
     with
Superimposed    Lab changes, symptoms worsening of
                blood pressure and/or proteinuria
 Preeclampsa
                Vague criteria

                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%)
   HELLP        15% lack hypertension and/or proteinuria

                Adverse Outcomes-abruption, IUFD, renal
                 failure, subcapsular hematoma, maternal
                 death

                                                            ACOG 2019

                                                                        11

2/19/2019

             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
Eclampsia
            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

                                                                                       12

2/19/2019

                Baseline 24 hour urine and labwork early in
                pregnancy
                ASA
                Weekly BP check third trimester
                   BP parameters
  Chronic          >120/80 but same approach as PEC w/ SF
                   Delivery at or beyond 34 weeks
                                                  ACOG 2019, Barton et al 2001

                                                                                 13

2/19/2019

                      Twice weekly BP check
                      Weekly HELLP labs
                      Daily assessment of maternal symptoms
                          and fetal movement
Preeclampsia          Serial fetal growth assessment
without Severe        Weekly antenatal testing
   Features           Delivery at 37 weeks
                      Not universal magnesium
                            1 in 200
                            NNT for asymptomatic 129

                      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
Preeclampsia       and:

 with Severe          PPROM, labor, severe lab abnl’s, oligo, REDF, IUGR

2/19/2019

              Continue magnesium infusion throughout
              surgery
              Endotracheal intubation can exacerbate
Management    severe hypertension
 Cesarean     Airway edema, especially with preeclampsia
  section        Failed airway ~1:300
              Fluid management

              Late onset preeclampsia-eclampsia occurs >
              48 hrs postpartum
              Estimated up to 26% eclamptic seizures
              occur late
Postpartum
              Discharge follow-up recommended within 72
              hrs and again at 7-10 days postpartum for
              blood pressure monitoring

                                                                  15

2/19/2019

                         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.
   The National              A combination of drugs may be necessary
Institute for Health     Target SBP 150 mmHg
    and Clinical         Admit to hospital for urgent treatment
     Excellence:         Anesthesia involvement, ICU, team approach with explicit
        NICE              communication of systolic pressures

                         Automated blood pressure monitoring systems
                          systematically under-estimate SBP

                         Avoid methergine use in third stage

                                                                               CMACE BJOG 2011

                   Acute Hypertension

                                                                                                 16

2/19/2019

                Hypertensive Emergency: Acute-onset,
   Acute        severe hypertension that is accurately
                measured using standard techniques and is
Hypertension    persistent for 15 minutes or more

                                                        ACOG 2017

                Treatment within 30-60 minutes of confirmed
                severe hypertension
                   reduce risk of stroke
                First Line agents:
 Treatment
                   IV labetalol
                   IV hydralazine
                   Immediate release oral nifedipine
                Magnesium

                                                        ACOG 2017

                                                                          17

2/19/2019

              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
Medications              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

                                                                                            18

2/19/2019

 Nifedipine Regimen

       10mg po
                 20 min BP check

       20mg po
                 20 min BP check

       20mg po
              20 min BP check

  Labetalol 40mg IV

Emergency Consultation

                                         19

2/19/2019

                  Nicardipine infusion
                  Esmolol infusion
                  Sodium nitroprusside reserved for extreme
                  emergencies
Resistant HTN        Fetal/maternal cyanide toxicity
                     Worsening maternal cerebral edema

                  Once goal BP achieved:
Post-treatment       BP q 10 minutes x 1 hour
                     BP q 15 minutes x 1 hour
 Monitoring
                     BP q 30 minutes x 1 hour
                     BP q hour x 4 hours

                                                                     20

2/19/2019

               Mechanism of action largely unknown
                   Cerebral vasodilation
                   Competitive calcium blocker, altered
                    neuromuscular transmission
               Greater than 50% relative reduction in the risk of
Magnesium       eclampsia

 Sulfate       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

               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
Diagnosis &    No universal magnesium for preeclampsia without
                severe features
Management     Early onset preeclampsia (

2/19/2019

                                  Risk Reduction

                 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
Risk Reduction
                     24% Preeclampsia
in Subsequent        14% Preterm birth
  Pregnancy          20% IUGR
                 Dose Dependent Response
                 Timing: Begin 12-13 weeks

                                              Sibai 1994, Caritis 1998, NEJM 2017

                                                                                     22

2/19/2019

      High Risk             Moderate Risk             Low Risk
History preeclampsia          Nulliparity             Previous
 Multifetal gestation     Obesity (BMI >30)       uncomplicated full
Chronic hypertension      Family history PEC        term delivery
      Diabetes            Sociodemographic
    Renal Disease           Age ≥ 35 years
Autoimmune Disease      Personal hx-SGA, poor
                               outcome

   (≥ 1 risk factor)     (Several risk factors)
Aspirin Recommended        Consider aspirin          No Aspirin

                                                                       USPTF

                 Cardiovascular Risk

                                                                                     23

2/19/2019

                 Preeclampsia linked to hypertension, stroke,
                 ischemic heart disease, and thromboembolism
                     HTN 3.7
Cardiovascular       Ischemic heart disease 2.16
                     Stroke 1.81
     Risk            VTE 1.79

                                                             ACOG 2013

                  Graded    relationship between       severity of
                   preeclampsia-eclampsia    and         risk    for
                   cardiovascular disease
                  Independent risk factor for cardiovascular
                   disease

Cardiovascular       Term preeclampsia has a 1.5-fold increased
                      risk of CVD related death
     Risk            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

                                                                                24

2/19/2019

                 Absolute risk for renal failure low
                 Four fold increased risk of subsequent end
Renal Disease    stage renal disease

                                                        Vikse et al NEJM 2008

                        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.
    Case                    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

                                                                                      25

2/19/2019

                                                                       References
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.

                                                                        References
  “Hypertension in Pregnancy.” Obstetrics & Gynecology, vol. 122, no. 5, 2013, pp. 1122–1131., doi:10.1097/01.aog.0000437382.03963.88.

  Mongraw-chaffin ML, Cirillo PM, Cohn BA. Preeclampsia and cardiovascular disease death: prospective evidence from the child health and development studies
  cohort. Hypertension. 2010;56(1):166-71.

  Lo JO, Mission JF, Caughey AB. Hypertensive disease of pregnancy and maternal mortality. Current Opinion in Obstetrics and Gynecology. 2013;25(2):124-132.
  doi:10.1097/gco.0b013e32835e0ef5.

  Centre for Maternal and Child Enquiries (CMACE). Saving Mothers’ Lives: reviewing maternal deaths to make motherhood safer: 2006–08. The Eighth Report on
  Confidential Enquiries into Maternal Deaths in the United Kingdom. BJOG 2011;118(Suppl. 1):1–203

  Salafia, C, Popek, E, Glob. libr. women's med., (ISSN: 1756-2228) 2008; DOI 10.3843/GLOWM.10150

  Duley L, Gülmezoglu AM, Henderson-Smart DJ, Chou D. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. Cochrane Database Syst
  Rev. 2010 Nov 10;(11):CD000025. Review. PubMed PMID: 21069663.

  Weeks AD, Ononge S. The magpie trial. Lancet. 2002 Oct 26;360(9342):1331; author reply 1331-2. PubMed PMID: 12414232.

  Shaukat, N, Walker G. Magnesium for Pre-Eclampia – TheNNT. TheNNT. http://www.thennt.com/nnt/magnesium-for-pre-eclampia/. Accessed November 10,
  2018.

  Sibai BM, Caritis SN, Thom E, Klebanoff M, McNellis D, Rocco L, et al; National Institute of Child Health and Human Development Network of Maternal-Fetal
  Medicine Units. Prevention of preeclampsia with low-dose aspirin in healthy, nulliparous pregnant women. N Engl J Med. 1993;329(17):1213-18.

  Caritis S, Sibai B, Hauth J, Lindheimer MD, Klebanoff M, Thom E, et al; National Institute of Child Health and Human Development Network of Maternal-Fetal
  Medicine Units. Low-dose aspirin to prevent preeclampsia in women at high risk. N Engl J Med. 1998;338(11):701-5.

  Espinoza et al. Gestational Hypertension and Preeclampsia. Practice Bulletin 202. ACOG. January 2019.

  Vidaeff et al. Chronic Hypertension in Pregnancy. Practive Bulletin 203. ACOG . January 2019.

  ACOG Practice Bulletin #33, Reaffirmed 2012; ACOG Committee Opinion #514, 2012; Tuffnell D, Jankowitcz D, Lindow S, et al. BJOG 2005;112:875-880.
  Zhang et al. Late postpartum eclampsia complicated with posterior reversible encephalopathy syndrome: a case report and a literature review. Quantitative
  Imaging in Medicine and Surgery. Vol 5, No 6, December 2015.

                                                                                                                                                                                  26

2/19/2019

Questions?

             Heathpolicyproject.com

                                      27