Charlotte Clausen, M.D.

Assistant Professor

Division of Maternal Fetal Medicine

OHSU

Hypertension in Pregnancy

OverviewIncidence

Classification

Diagnosis

Complications

Management

Hypertension in PregnancyAffects 5-8% of pregnancies

15% of maternal mortality (2nd leading cause after embolism)

Major cause of fetal morbidityPreterm birthLink to cardiovascular and metabolic disease

Hypertension in Pregnancy Classification

Chronic Hypertension

Gestational Hypertension

Preeclampsia/Eclampsia

Preeclampsia superimposed on chronic hypertension

Chronic Hypertension3-5% of pregnancies

Diagnosed before pregnancy, before 20 weeks or persists after 12 weeks PP

Mild: SBP>140 or DBP>90 mmHg

Severe: SBP >160 or DBP >110 mmHg

Proper Measurement of BP

Korotkoff Phase V (mention IV if no V), slow drop in mmHg

Cuff size

Upright and rested > 10 min

Left lateral, arm at level of heart

No tobacco/caffeine for 30 min

Repeat, > 2 minutes apart

Chronic Hypertension in PregnancyWatch for normal decrease in BP after first trimester

Nadir at 16-18 weeks

BP returns in third trimester

Cr also decreases secondary to increased GFR

Chronic hypertension work-upPrimary hypertension

Secondary hypertensionBaseline labs

UA, culture, CMPTSHPhysical examRenal ultrasound

Complications of chronic hypertension

Fetal RisksPremature birth- 12-34%Intrauterine growth restriction(IUGR)- 8-16%Fetal demise- 3.5XPlacental abruption- 0.7-1.5%Cesarean delivery

Maternal RisksSuperimposed preeclampsia- 10-25%

Malignant hypertensionCNS hemorrhageCardiac decompensationRenal deterioration

Chronic Hypertension in PregnancyPrepregnancy-EKG, Echo, renal function (creat < 1.4), baseline labs, opthamology

Weight loss, 6 gm sodium diet w/ low fats, exercise, stop smoking, limit alcohol, maintain potassium and calcium

Baseline preeclampsia labs, 24 hour urine for total protein and creatinine clearance

Baby ASA?

Chronic Hypertension in Pregnancy -Treatment

No improvement in perinatal complications with treatment

Recommend starting treatment for SBP >150-160 or DBP >100-110 mmHg

Treat if mother has CV, connective tissue d/o, dyslipidemia, hx of stroke, diabetes or renal involvement

Control of Hypertension in pregnancy(CHIPS)

Primary research question: For pregnant women with non-severe, non-proteinuric maternal hypertension at 14 - 33 weeks, will 'less tight' control (target diastolic blood pressure [dBP] of 100 mmHg) versus 'tight' control (target dBP of 85 mmHg) increase (or decrease) the likelihood of pregnancy loss or Neonatal Intensive Care Unit (NICU) admission for greater than 48 hours?

Secondary research question: Will 'less tight' versus 'tight' control increase (or decrease) the likelihood of serious maternal complications?

Other research questions: Will 'less tight' versus 'tight' control: 1. Increase (or decrease) the likelihood of serious perinatal complications? 2. Increase (or decrease) the likelihood of severe hypertension and pre-eclampsia? 3. Increase (or decrease) the likelihood of maternal satisfaction with care? 4. Result in significant changes in dBP or health care costs?

Chronic Hypertension in Pregnancy -Treatment

Methyldopa

Labetalol (avoid in asthmatics)

Nifedipine

Atenolol (? 2.5 x risk of IUGR)

Diuretic (avoid if superimposed preeclampsia)

ACE/ARB - Avoid in all trimesters, decrease uterine blood flow, neonatal renal failure

Chronic Hypertension in Pregnancy

Hutcheon BJOG 2010

Morbidity associated with superimposed preeclampsia

Antepartum testing - no consensusYes if IUGR or preeclampsia

Guideline - 18-20 week US, then every 4-6 weeks.

Delivery

Chronic Hypertension in PregnancyRegional anesthesia OK

General anesthesia - Increase BP with intubation/extubation

Ketamine/methergine may increase BP

Gestational HypertensionElevated BP >140/90 after 20 weeks in the absence of proteinuria

Normal BP by 12 weeks PP

Replaces “Transient hypertension” and “PIH”

Some eventually develop preeclampsia

Some eventually diagnosed with CHTN

Antepartum testing

Preeclampsia/EclampsiaIncidence/risk factors

Definitions

Clinical manifestations

Pathogenesis

Management

Prediction

Prevention

Incidence3-7% of nulliparous patients

5-7% if mild pre-eclampsia in first pregnancy

<1% if no pre-eclampsia in first pregnancy

10% of cases are <34 weeks

Risk FactorsNulliparity

Hx of preeclampsia

Age >40 years or <18 years

Family history

Chronic hypertension

Chronic renal disease

Antiphospholipid antibody syndrome or inherited thrombophilia

Pregnancy interval

Vascular or connective tissue disease

Diabetes mellitus

Multifetal gestation

Obesity

Male partner whose previous partner had preeclampsia

Hydrops fetalis

Unexplained fetal growth restriction

PreeclampsiaBP > 140/90 after 20 weeks (except with mole)

Proteinuria (> 300 mg/24 hrs or 1+)

Increased certainty with increased severityFetal monitoringLabsSerial blood pressure

Edema or BP change no longer criteria

Severe Preeclampsia> 5 grams proteinuria/24 hours

Platelets < 100K

AST/ALT > 72

Cr > 1.2

Oliguria (<500ml/24 hours)

BP>160/110 mmHg

Neurologic sx(headache, hyperreflexia)

IUGR

Pulmonary edema

RUQ/Epigastric pain

Preclampsia Superimposed on Chronic Hypertension

New onset proteinuria in patient with chronic hypertension after 20 weeks

Suspected when sudden increase in BP or proteinuria

Clinical manifestationsBlood pressure

Renal

Hematologic

Hepatic

CNS

Cardiac

Edema

PathogenesisTrophoblast invasion

Cytotrophoblast invades decidua but not myometrium

Placental ischemia

Immunologic factorsExposureAutoantibodies

GeneticsTrisomy 13/ sFlt-1Chromosome 12 / HELLP

PathogenesisSystemic endothelial cell dysfunction

VEGF/PIGF – proangiogenicDecreased in preeclampsia

sFlt-1 – anti VEGF antiangiogenicElevated in preeclampsia

soluble endoglin (sEng) – antiangiogenic

Changes present prior to presentation

N Engl J Med 2004 Feb 12;350(7):672-83.Nat Med. 2006 Jul;12(6):642-649.

Proteinuria/renalGlomerular barrier altered

Altered tubular handling

20% of eclamptic patients have NO proteinuria

10% of patients with HELLP/severe Pre-e have no proteinuria

GFR decreases by 30%

Hematologic ChangesThrombocytopenia

Microangiopathic Hemolysis

Clotting disorders not typical unless other factors presentAbruptionLiver disease

Schistocytes

LiverFibrin or fat deposits, ischemic changes

Elevated LFT’s

Pain

Subcapsular bleeding or hepatic rupture

CNSHeadache, vision changes

Seizures

MRI/CT scanIschemic/hemorrhagic changes in posterior hemispheres

CardiovascularVasoconstriction= increased afterload

Hyperdynamic

Intravascular depletion with third spaced fluid

Low colloid oncotic pressure

Common to have decreased cardiac output

EdemaNot included in the diagnosis

Decreased intravascular volume

Significant edema common

No diuretics unless pulmonary edema

ComplicationsMaternal

Severe HTN, pulmonary edemaHepatic ruptureEclampsia, cerebral edema, hemorrhageAcute renal failure

FetalIUGR, abruption, Fetal distress/stillbirthChronic lung dz, ROP, CP, MR, adult disease

Treatment = DeliveryMild preeclampsia

Consider delivery at > 37 weeksExpectant management if premature

Inpatient vs Outpatient

Average = 22 days

2-3 days inpatient observation

Labs 1-2 x weekly

Close follow-up

Am J Obstet Gynecol 1994 Mar;170(3):765-9.

HYPITATRCT GHTN or mild pre-eclampsia

Singleton pregnancy36 0/7 to 41 6/7 weeks756 patients

Expectant management vs IOLDecreased adverse maternal outcomes with IOLDecrease c/s rate with IOL after 37 weeksTrend towards improved outcomes with IOL after 37 weeks

fullPIERS

von Dadelszen The Lancet 2011

2023 patients

Validated tool for risk stratificationIdentify risk of fatal or life-threatening complications in women with pre-eclampsia within 48 hrs of admission

Death, CNS, cardiorespiratory, hepatic, renal or hematologic morbidity.

Early GA, chest pain, dyspnea, low O2 sat, low plt count, elevated Cr, elevated AST

Expectant management of Severe Preeclampsia

Odendaal et al. n=58Prolonged pregnancy by 7 days1/3 required delivery <48hrs (not rand)

Sibai et al. n =95Prolonged pregnancy by 13 daysNo adverse maternal effectsImproved neonatal outcomes

Expectant management of Severe Preeclampsia

ContraindicationsMaternal/fetal instabilityMaternal request for deliverySymptomsWorsening lab valuesBPs persistently high despite meds> 34 weeksEnd organ damage

Proteinuria

If severe by proteinuria only don’t deliver

Rate of change and amount not correlated with outcome

Am J Obstet Gynecol 1996 Nov;175(5):1313-6.

Int J Gynaecol Obstet 2002 Apr;77(1):1-6.

Severe Preeclampsia / Delivery

Cesarean section vs induction of labor

3 retrospective studies

< 34 weeks – 50% c-section rate

28 weeks or less = 30% delivered vaginally

32 weeks or more = 63 % delivered vaginally

Bishop score

Am J Obstet Gynecol 2002 May;186(5):921-3.Am J Obstet Gynecol 1998 Nov;179(5):1210-3.

Obstet Gynecol 1999 Apr;93(4):485-8.

Incidence of EclampsiaSeizures with no other cause in a patient with preeclampsia0.5% of mild pre-eclamptics2.0% of severe pre-eclamptics

1/3 Antepartum1/3 Intrapartum1/3 Postpartum

25% of these are > 48 hours after delivery

EclampsiaTonic-clonic seizures

Last about 1 minute (no more than 3-4)

Fetal deceleration is the norm followed by tachycardia

STABILIZE MOTHER

If no improvement in 10-15 mins consider abruption/delivery

Eclampsia OutcomesAbruption 7-10 %

DIC 7-11%

Pulmonary edema 3-5 %

Acute renal failure 5-9%

Aspiration pneumonia 2-3%

Cardiopulmonary arrest 2-5 %

Liver hematoma 1 %

HELLP syndrome 10-15 %

Perinatal death 5.6-11.8 %

Preterm birth 50%

TreatmentMaintenance of maternal vital functions to prevent hypoxia

Control of convulsions and blood pressure

Prevention of recurrent seizures

Evaluation for prompt delivery.

Magnesium SulfateDrug of choice for prevention of eclampsiaRCT of 2138 patient at Parkland

Magnesium Sulfate 0/1049 with seizuresPhenytoin 10/1089

N Engl J Med 1995 Jul 27;333(4):201-5.

MgSO4 in Severe Preeclampsia4 RCT’s

MgSO4 = 0.6% had seizuresPlacebo/Other = 1.9-3.2% had seizures

BJOG 2000 Jul;107(7):903-8.

MgSO4 in Mild PreeclampsiaMagpie Trial

10,110 preeclamptics randomized to MgSO4 vsPlacebo75% mild pre-eclampsia0.8% seizures with MgSO41.9% seizures with placeboTrend towards less maternal mortality with MgSO4

ACOG – “lack of consensus”

MgSO4 in Mild Preeclampsia

2 Placebo controlled RCT’s Total N = 181 receiving placebo and no seizures

Sibai review400 mild preeclamptics need MgSO4 to prevent 1 seizureEven preventing seizures not proven to improve outcome“does not justify its routine use for that purpose”

Am J Obstet Gynecol 2004 Jun;190(6):1520-6.

Magnesium Toxicity8 to 10 mEq/L -- loss of DTR

10-15 mEq/L -- respiratory paralysis

20-25 mEq/L cardiac arrest

Calcium gluconate (1 g intravenously over 5 to 10 minutes) should be administered to counteract life threatening symptoms of magnesium toxicity

Seizure TreatmentMgSO4

4-6 g load then 2-3g/hr5 g IM q 4 hours

If on MgSO4 give an additional 2 gMay repeat x 1

Amobarbital 250mg IV

Lorazepam 0.02-0.03 mg/kg IV

Consider paralysis with intubation

BP TreatmentReview of 28 patients with CVA with Pre-eclampsia

93% were arterial54% mortalityOnly 3 patients had diastolic > 110 (mean 98)Systolic BP 159-198 (mean 175)Authors recommend tx sys BP >160

Obstet Gynecol 2005 Feb;105(2):246-54.

BP Treatment cont.Labetolol 20mg IV push

Repeat in 10 mins and double dose if neededMax = 300mg

Hydralizine 5mg IV pushRepeat in 20 mins with 5-10mg push prnMax = 30mg

Nifedipine 30mg XLAvoid the fast acting/sublingual

BP Treatment cont.BP goals

Systolic 130-150Diastolic 80-100

PostpartumBP changes usually resolve within a few weeks(average 16 days)

IncreaseIntravascular fluidMobilization of extracellular fluidNSAID use

PredictionRisk factors

Angiogenic factors

Uterine artery doppler

Serum tests

Routine clinical screening

Angiogenic FactorsMultiple small studies suggest changes present in the early third trimester

Especially predictive of early/severe pre-eclampsia

Insufficient data to recommend routine use

Blood? Urine? Ratios?

Further studies ongoing

? treatment

Obstet Gynecol. 2007 Jan;109(1):168-180.

Uterine artery dopplerDiastolic notching

Flow wave form studies

With risk factors can identify 90% pre-eclamptics

BUT 20% positive rate

Expensive and cumbersome

Am J Obstet Gynecol 2005 Aug;193(2):429-36.

Uterine artery doppler

Normal Abnormal

Serum screeningUric Acid

Thrombophilias

Antiphospholipid antibody syndrome

Second trimester serum analytes

PreventionAspirin theory

Effect on plateletsdecreased thromboxane synthesismaintain prostacyclin synthesis Increased thromboxane:prostcylin ratio

ASA early RCT’s (1985-1990)High Risk Patients

5 small RCT’s (n = 33-102)

Very high risk patients for Pre-eclampsia

All demonstrated significant reduction in preeclampsiaTreated 0-3% developed preeclampsiaPlacebo 12-35% developed preeclampsia

N Engl J Med 1989; 321:357.N Engl J Med 1989; 321:351.

Lancet 1986; 1:1.Lancet 1985; 1:840.

Lancet 1990; 335:1552.

ASA large RCT’sHigh Risk Patients

3 large RCTs1993 Italian Study Group n=11051994 CLASP trial n=93641998 NICHD n=2539

Moderate-High risk patientsNo difference in preeclampsia

Treated 6.7-18%Placebo 7.6-20%

Lancet 1993; 341:396.Lancet 1994; 343:619.

N Engl J Med 1998; 338:701.

ASA meta-analysisHigh Risk Patients

Askie LM The Lancet 5/2007

Decreased riskPreeclampsiaPerinatal deathPreterm birth <34 weeks

No decreased riskAbruption

Questionable improvementBirthweight

ASA meta-analysis

Bujold E Obstet Gynecol Aug 2010

Low dose ASA started <16 weeksModerate or high-risk

RR 0.47(CI 0.34-0.65) preeclampsiaRR 0.44(CI 0.30-0.65) IUGR

ASA RCT’sUnselected Nullips

NICHD study N=3000Preeclampsia 4.6% vs 6.3%No statistically significant difference in outcomeSubanalysis of pt’s with higher BP showed benefitHigher rates of abuption (spurious?)

French TrialN=3294No difference in outcomes

N Engl J Med 1993; 329:1213. BJOG 2003; 110:475.

Calcium SupplementsLower rates of preeclampsia in women with low baseline calcium intake

No benefit in low risk populations

Cochrane Database Syst Rev 2006

N Engl J Med 1997; 337:69.

Vitamin C + E Supp.Pilot study n=283

Reduced Preeclampsia from 17% 8%VIP trial n=3609

No difference in preeclampsiaTreated lower birth weight, stillbirth, earlier onset, more gestational htn.

Australian Study n=1877No difference

Lancet 1999 Sep 4;354(9181):810-6. Lancet. 2006 Apr 8;367(9517):1145-54.

N Engl J Med. 2006 Apr 27;354(17):1796-806.

Other failed interventionsFish oil

Antihypertensives

Magnesium

Dietary changes

Salt restriction

QUESTIONS?