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Review Article

Hypertensive Disorders in PregnancyLalita Nemani1

1Department of Cardiology, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad, Telangana, India

Address for correspondence Lalita Nemani, DM Cardiology, Associate Professor, Department of Cardiology, Nizam’s Institute of Medical Sciences, Punjagutta 500082, Hyderabad, Telangana, India (e-mail: [email protected]).

Hypertension in pregnancy is defined as systolic blood pressure (SBP) ≥ 140 mm Hg or diastolic blood pressure (DBP) ≥ 90 mm Hg or both on two different occasions at least 6 hours apart. Severe hypertension is SBP ≥ 160 mm Hg or DBP ≥ 110 mm Hg. Hyper-tension is the most common medical problem in pregnancy and one of the major causes of maternal and perinatal mortality and morbidity. Hypertensive disorders in pregnancy (HDP) are classified as (1) chronic hypertension, (2) chronic hypertension with superimposed preeclampsia, (3) preeclampsia-eclampsia, and (4) gestational hypertension. HDP contributes to increased risk of hypertension, stroke, and maternal cardiovascular disease (CVD) in later life. HDP can be considered as a failed cardiovas-cular stress test identifying women susceptible to CVD in later life. Further research is required to identify the mechanisms in HDP that contribute to CVD in later life so as to initiate appropriate prevention measures.

Abstract

Keywords ► eclampsia ►gestational hypertension ► hypertension ►postpartum ►preeclampsia

Indian J Cardiovasc Dis Women-WINCARS 2018;3:68–78

DOI https://doi.org/ 10.1055/s-0038-1677626

©2018 Women in Cardiology and Related Sciences

IntroductionHypertension in pregnancy is defined as systolic blood pressure(SBP)≥140mmHgordiastolicbloodpressure(DBP)≥90mmHgorbothontwodifferentoccasionsatleast6hoursapartbutnomorethan1weekapart.AnSBPof140to159andaDBPof90to109areconsideredasmildtomoderatehypertension. Severehypertension is SBP≥160mmHgorDBP≥110mmHg1 (►Fig. 1).

Incidence and prevalenceHypertensionisthemostcommonmedicalprobleminpreg-nancy. Hypertensive disorders in pregnancy (HDP) occurin 10% pregnancies.1 They are one of the major causes ofmaternal and perinatal mortality and morbidity. Chronichypertension accounts for 30% of HDP, and pregnancy-inducedhypertension (PIH) occurs in 70%.2 Chronichyper-tensioncomplicatesabout1to5%ofpregnancies,gestationalhypertensioncomplicatesaround5to6%,andpreeclampsiacomplicatesnearly3to6%pregnanciesaccordingtopopula-tion-baseddata.3,4

Classification Hypertensivedisordersduringpregnancyareclassifiedintofour categories5 (►Fig. 2).

Chronic HypertensionChronic hypertensionisdefinedashypertensionknownpriortoconception,isdetectedbefore20weeksofgestation,andusuallypersistsbeyond12weekspostpartum. Occasionallyblood pressure (BP) may be normal in the first trimesterwithhypertensiondetectedbefore20weeks.Insuchcases,gestationalhypertensionorearlypreeclampsiamustalsobeconsidered.

• Etiology:Chronichypertensionisaprimaryhypertensioninmajority(90–95%)ofthecases.However,secondaryandpotentiallytreatablecausesareseeninafew(5–10%)thatneedtobeevaluatedand,iftimelytreated,couldimproveoutcomeinpregnancy(►Fig. 3).

• Incidence:Chronichypertensionisseeninaround22%ofwomenofchildbearingagewithincreasingincidenceduetoincreasingageofthemotheratthetimeofconceiving.

69Hypertensive Disorder in Pregnancy Nemani

Indian Journal of Cardiovascular Disease in Women-WINCARS Vol. 3 No. 2-3/2018

• Maternal and fetal outcome:Preexistinghypertensionisariskfactorforpreeclampsia.Uncomplicatedchronichyper-tensioninpregnancyisassociatedwithincreasedmaternalmortalityandmorbiditythoughquitelesscomparedwiththosewhodevelopsuperimposedpreeclampsia(►Fig. 4).Adverse maternal outcome is more in uncomplicated

chronichypertensiveswhencomparedwithnormotensives.However,acceleratedhypertensionandorgandamageareless likelywithout superimposed preeclampsia. Perinatalmortalityishigherinuncomplicatedchronichypertension(relativerisk[RR]2.3)overnormotensiveandstillhigherinthosewithsuperimposedpreeclampsia.

Preconception counseling: All women diagnosedwith hypertension before or in early pregnancy should be

counseledregardingtherisksposedbyhypertensioninpreg-nancy.Theyshouldbeeducatedaboutthesignsandsymp-toms of preeclampsia. Whenever secondary hypertension(►Fig. 5)issuspected,thepatientshouldbethoroughlyeval-uatedtoruleofcorrectablecausesofhypertension.Investigations

• All patients should undergo routine biochemical testssuchas:

◦ Serumcreatinine,uricacid,electrolytes,liverfunctionaltest(LFT),thyroidassessment,andurineprotein.

◦ Ifproteinuriaisdetected,24-hoururineproteinorurineprotein-to-creatinine ratio spot urine should be doneandultrasonographyofthekidneysshouldbedone.

Fig. 1 Grading of hypertension in pregnancy. DBP, diastolic blood pressure; SBP, systolic blood pressure.

Fig. 2 Classification of hypertensive disorders in pregnancy.

70 Hypertensive Disorder in Pregnancy Nemani


◦ Glucose tolerance test should be done in all as thesepatientsareproneforgestationaldiabetes.

◦ Abaselineechocardiographyforleftventricularhyper-trophyandfunctionassessmentisideal.

◦ Case-basedevaluationtoruleout treatableconditionssuchaspheochromocytomaandrenalarterystenosis.

Treatment and ManagementThe goal of treating chronic hypertension in pregnancy isto avoid its acute complications and reduce the fetal riskposedbyhypertensionitselfandthemedicationsusedforit.Theaimistoensureahealthyandsafepregnancyifpossibletillterm.

American College of Obstetricians and Gynecologists(ACOG)taskforcerecommendations1forhypertensionman-agementinpregnancyare:

• HomeBPmonitoringtoensurebettercontrolinpatientswithpoorlycontrolledhypertension.

• Ambulatory BPmonitoring to rule out suspectedwhitecoathypertensiontoavoidovertreatinghypertension.

• Patientswithchronichypertensiononmedicationscanbe

◦ Off their medications and closely monitored as BPnormallydropsduringpregnancy

◦ Continuetheirmedicationsifwarrantedandsafe ◦ Shifttoalternategroupofmedicationsif theirantihy-pertensivemedicationisnotsafeinpregnancy.

◦ Closelymonitored for symptoms ofworsening hyper-tensionand/orpreeclampsia.

Most patients with mild to moderate hypertension canbe managed without medications. AntihypertensivedrugsaremandatoryifSBPexceeds160orifDBPexceeds110mmHg.However,lowerthresholds(►Fig. 6) for initi-atingantihypertensivedrugsarerecommendedinspecialcircumstances.

Fig. 3 Causes of chronic hypertension (HTN) in pregnancy.

Fig. 4 Maternal and fetal outcome in chronic hypertension in pregnancy.

Fig. 5 Clues to evaluate for secondary hypertension.



Nonpharmacologic Measures

• The role of aerobic exercise and Dietary Approaches toStopHypertension(DASH)diettoreduceBPinpregnantwomenisnotestablished.Itsharmfuleffects,ifany,havealsonotbeenstudied.Thoseaccustomedtoexercisewithno obstetric contraindications and well-maintained BPcancontinuewithmoderatelessofaerobicexercise.

• Weightlossandextremelylow-saltdiet(<100mEq/d)arenotrecommendedinpregnancy.

Pharmacologic MeasuresPatientsofchronichypertensiononmedicationshouldmain-taintheirSBPbetween120and160mmHgandDBPbetween80and105mmHg.

• Labetalol, nifedipine, andmethyldopa are the preferredagents for initial treatment of chronic hypertension inpregnancy.

• Angiotensin-convertingenzyme(ACE)inhibitor,angioten-sinreceptorblockers(ARBs),andspironolactoneagonistsshouldbeavoided.

• Meta-analysis and systemic reviews have suggested abeneficialroleforlow-doseaspirinwhenstartedearlyinpregnancy(asmallbutdefinitereductioninincidenceofpreeclampsiainhigh-riskpatients).

• Calcium supplementation positively reduces the inci-denceofhypertension,preventspreeclampsiainhigh-riskpatients,andisrecommended.

Optimaltimingfordeliveryinuncomplicatedchronichyper-tensioninpregnancyis38to39weeksofgestation.Normalvaginal delivery is recommended, and cesarean section islimitedtoobstetricindications.

Chronic Hypertension with Superimposed PreeclampsiaWhenorgandamageispresent,itisknownassuperimposedpreeclampsiawithseverefeatures(►Fig. 6).

Superimposed preeclampsia develops in 13 to 40% ofpatientswithchronichypertension.

InvestigationsThemagnitudeofproteinuriashouldbeassessedandcom-paredwith baseline levels. A complete blood picturewithhemoglobin,platelet count, andLFT isessential. Lacticaci-dosis, uric acid, and creatinine assessment are required insevere preeclampsia to assess prognosis. Fetal growth andwell-beingshouldbemonitoredperiodically.

Maternal and Fetal OutcomeAdverse maternal outcome in terms of abruptio placenta,postpartum hemorrhage, and accelerated hypertension ismoreinsuperimposedpreeclampsia,especiallywithseverefeature.Perinatalmortalityisalsomore(RR3.6)overuncom-plicatedchronichypertension.

Treatment and Management

• Treatment of patients with mild to moderate hyper-tensionhas shown todecrease theoccurrenceof severehypertensionby50%butdoesnotpreventdevelopmentofpreeclampsia (Cochrane database reviews).6–8 β-Blockersand calcium channel blockers (CCBs) appear superiorto α-methyldopa in preventing preeclampsia.8 Acutetreatment of severe hypertension can be achieved byintravenous(IV)labetalolororalnifedipineorhydralazine.Oral labetalol,nifedipine,andmethyldopaare the initialagentsformaintenanceofBPafteracutecontrol.

• Antepartummanagementincludescorticosteroidadmin-istrationforfetalmaturityif<34weeksofgestation.Thisisprovedtoreduceperinatalmortalityandmorbidity.

• Eclampsia is seen in 0 to 2.4% cases of superimposedpreeclampsia. Role of intrapartummagnesium sulphatefor seizure prevention in this subset of superimposedpreeclampsia has not been studied. Task force recom-mendation is to administer prophylactic intrapartummagnesiumsulphateforpreventionofseizureinsuperim-posedpreeclampsiawithseverefeatures.

Nearly 34 to 37 weeks of gestation is the ideal time fordelivery. However, delivery of the fetus is recommendedirrespective of the gestational age after stabilizationof themother when superimposed preeclampsia complicated byuncontrolled BP, eclampsia, pulmonary edema, abruptioplacenta, disseminated intravascular coagulation (DIC), orfetusinjeopardy.

Preeclampsia-EclampsiaPreeclampsiaisdefinedasnewonsetofhypertensiondetectedafter 20th week of gestation association with proteinuria.The revised definition according to the ACOG has definedpreeclampsiaindependentofthepresenceofproteinuria.Intheabsenceofproteinuria,preeclampsia isdefinedasnewonsetofhypertensionwithanyoneofthefollowing:throm-bocytopenia, renal insufficiency, impaired LFT, pulmonaryedema,andcerebralorvisualsymptoms(►Fig. 7).

PreeclampsiawithseverefeaturesisconsideredwhenBPis≥160/110mmHgandisassociatedwiththrombocytopenia,

Fig. 6 Criteria for chronic hypertension with superimposed preeclampsia.



renal insufficiency, impaired liver function, pulmonaryedema,andvisualorcerebralsymptoms.

Eclampsia refers to new onset of generalized seizure(grandmalepilepsy)inpatientswithpreeclampsia.

HELLPsyndromeisconsideredasasubtypeofpreeclamp-sia in which pregnant women present with constellationof finding thatareHemolysis,ElevatedLiverenzymes, and LowerPlateletcount.

EtiologyPreeclampsia is a syndrome characterized by widespreadendothelial dysfunction and vasospasm (►Fig. 8). Alteredmaternal immune response to fetal/placental tissue alsocontributes.

Risk Factors for PreeclampsiaPreeclampsia iscommoninfirstpregnancy,extremeageofpregnancy(<18yearsand>35years),obesewomen,fam-ilyhistoryofpreeclampsia (two- to fourfold), andmultiplepregnancies. Chronic hypertension, especially secondary,diabetes, obesity, systemic lupus erythematosus (SLE), andmigraineallincreasetheriskfordevelopmentofpreeclamp-sia.Preeclampsiarecursinsubsequentpregnancies,andthehistoryofpreeclampsiainpreviouspregnancyincreasestheriskforrecurrencebysevenfold.

However, preeclampsia is noted most times in healthynulliparous women with no comorbidity. Prediction ofpreeclampsia based on clinical risk factors could predictpreeclampsia in 37% patients with a false-positive rate of10%.9 Uterine artery Doppler studies and combination of

biomarkers could enhance the clinical accuracy of earlydetectionofpreeclampsia.

InvestigationsAllwomenshouldgetabaselinecompletebloodcount(CBC),serum creatinine, uric acid, LFTs, and proteinuria assess-ment.Plateletcounts,liverenzymes,andproteinuriashouldbe reassessedweekly inmild preeclampsia. In severe pre-eclampsiaCBC,serumcreatinine,andLFTsneedtoberepeat-eddaily(alternatedayifthemotherappearsstable).

Treatment and ManagementMild Preeclampsia

• Saltrestriction,strictbedrest,andrestrictionofphysicalactivityarenotrecommended.

• Mothershouldbeeducatedtoreportsymptomsofseverepreeclampsiasuchassevereheadache,visualdisturbanc-es,epigastricpain,andshortnessofbreath.

• Mother should be taught to monitor fetal movementsdaily.

• BP measurements should be done twice weekly otherthanatantenatalvisits.

• PreeclampsiawithBPpersistently<160/110mmHg,anti-hypertensivesneednotbeadministered.

• Optimaltimingofdeliveryis37weeks.Mildpreeclampsiaatorbeyond37weeks,delivery is recommendedratherthanexpectantmanagement.

• Magnesiumsulphateforpreventionofseizuresisnotrou-tinelyadvisedintheabsenceofmaternalsymptoms.

Severe Preeclampsia

• Severehypertensionshouldbecontrolledwithantihyper-tensivestopreventthecardiovascular(CV),cerebrovascu-larandrenalcomplications.

• Hydralazine, labetalol, and nifedipine remain the initialagentsofchoicetobeusedinseverehypertension.

• Allpatientsshouldreceiveprophylacticmagnesiumsul-phateforpreventionofseizures.

• Promptdeliveryisthesafestoptionforseverepreeclamp-siawithorganinvolvement.Inthefewcasesinwhichthemotherisstable,optimaltimingfordeliveryis34weeks.

• Corticosteroid for fetal lung maturity should be givenif<34weeksofgestation.

Eclampsia

• All patients should receive intrapartum magnesiumsulphate.Ideallyitshouldbecontinuedfor24hoursafterlastseizure.

• Loading dose of 4 to 6mg IV followed bymaintenancedoseof1to2mg/hforatleast24hours.

• Magnesiumsulphateshouldbecontinuedintraoperativelyfor those undergoing cesarean section. The half-life ofMgSO4is5hours;ifthemedicationisdiscontinuedbeforedeliveryorCS,theserumlevelsdecreaseandthepatientisatriskofpostpartumseizures.

• Allwomenshouldundergodeliveryfollowingstabilization.

Fig. 7 Diagnostic criteria for preeclampsia with their definitions. DBP, diastolic blood pressure; SBP, systolic blood pressure.

Fig. 8 Etiopathogenesis of preeclampsia.



HELLP Syndrome

• Promptdeliveryisadvised. • A course of corticosteroids are beneficial in term ofimprovingmaternalplateletcountswithoutanyeffectonmaternalandperinatalmortality.

Gestational HypertensionGestational hypertension is defined as sustained hyperten-siondetected after 20thweek of pregnancy in a previouslynormotensive woman without the evidence of proteinuria.Itusuallydisappearsby12weekspostpartum.Itisthemostcommoncauseofhypertensionduringpregnancy.Incidencevariesfrom6to17%innulliparouswomento2to4%inmul-tiparouswomen.Thoughatransientcondition,thesepatientsshouldbecarefullymonitoredaspreeclampsiacandevelopinone-thirdofthesepatients.Gestationalhypertensionisariskfactorfordevelopmentofchronichypertensionatlaterage.

Postpartum HypertensionBlood pressure usually dips and remains low for 48 hoursafterdeliveryandthenstartstorise.Hypertensiondetectedafter72hourspostpartumisknownaspostpartumhyper-tension (►Fig. 9).

Though transient in nature, it could be a harbinger ofchronichypertensioninlaterlife.

Evaluation of Hypertension in PregnancyAproperhistory, clinical examination, andbasic investiga-tionsarenecessaryinallcasesofhypertensioninpregnancy.All women with hypertension in pregnancy should beeducated to report symptoms of preeclampsia, which arerepresented in ►Fig. 10.

Guidelines for Blood Pressure Measurement in Pregnant Women

• Bloodpressureshouldberecordedateachantenatalvisit.Itshouldbemeasuredafteraperiodofrestinaquietenvi-ronmentinthesittingpositionwiththearmattheleveloftheheartusinganappropriatelysizedcuff(i.e.,length1.5timesthecircumferenceofthearm).

• Manualmeasurementwithastandardmercurysphygmo-manometeristherecommended.AutomateddevicesarenotrecommendedinPIH.

• Supine recording and left lateral position recording could bespuriouslylowduetoinferiorvenacava(IVC)compres-sionbythegraviduterus.

• ThearmwithhigherBPvaluesshouldbeusedforfurtherBPmonitoring.

• RepeatBPmeasurementafteragapofatleast15minuteswhenBPishigh.

• Korotkoff’sfirstandfifthsoundsaretakenassystolicanddiastolic pressure, respectively, in a few patients; fourthsoundisconsideredwhenthefifthsoundapproacheszero.

Cardiovascular Findings

• S4isabnormalinpregnancyandsuggestsleftventricularhypertrophy due to chronic hypertension or diastolicdysfunctionduetopreeclampsia-inducedvasospasm.

• S3 isnormallyheardinpregnancy;however,S3 gallop is abnormal.

• Carotid bruit is in favor of atherosclerosis and suggestschronichypertension.

• Diminishedpulses/unequalpulsessuggestcoarctationoftheaorta.

Fig. 9 Features of postpartum hypertension.

Fig. 10 Warning symptoms of preeclampsia.



Other Systems

• Systolic bruit in the abdomen or flank suggests renalarterystenosis.

• Retinal spasm/edema and macular detachment—severepreeclampsia.

• Liver swelling and capsular stretch—pain in the rightupperquadrant.

• Clonusinseeninseverepreeclampsia.Seizuresareasignofeclampsia.

InvestigationsAll patients should have these routine investigations oncediagnosedwithPIH:

• Completebloodpicture. • Bloodureanitrogen(BUN),creatinineandserumelectro-lytes,calcium,andmagnesium.

• Liverfunctiontests. • Urinedipsforproteins(urineprotein-to-creatinineratio). • Twenty-fourhoursurineforcreatinineclearanceandpro-teinexcretion.

◦ Proteinuria>300mgisconsideredabnormal. ◦ Creatinine clearance < 100 mL/min is abnormal andsuggestiveofrenaldysfunction.

• Hemoglobin (HbA1C), thyroid function tests, and serumuricacidarerecommended.

◦ Uricacidlevels>5mgareabnormalandsuggestiveoftubulardysfunction.

• Evaluation of lipid profile, hyperaldosteronism, andhypercortisolism should be deferred till postpartumperiod.

• Screening for preeclampsia: Although algorithms basedonriskfactors,uterineDoppler,andbiomarkershavebeensuggested, no guidelines recommend them other thanscreeningbyriskfactors.

◦ Testingforprothrombintime–internationalnormalizedratio/activated partial thromboplastin time (PT-INR/aPTT)isrecommendedinthepresenceofthrombocyto-peniaandabnormalLFT.

◦ Testing for DIC and hemolysis by checking levels oflactate dehydrogenase (LDH), D-dimer, fibrinogen,andhaptoglobulin is recommendedwhen coagulationdefectsaredetected.

• Electrocardiogram (ECG) and 2D echocardiography arerecommendedinallcasesofPIH.

• Chest X-ray, computed tomography (CT) of the brain,magneticresonanceimaging(MRI)ofthebrain,magneticresonance angiography (MRA), and magnetic resonancevenography canbedone safelywithout fetal risk as thesituationdemands.

• Close monitoring of the fetus is essential as placentalhypoperfusion resulting in fetal restricted growth andintrauterine death are common. Monthly ultrasoundfor fetalgrowthandweeklybiophysicalprofileor twiceweeklynonstresstestsaresuggested.

Treatment and Management • Acute severe hypertension: This is amedical emergencyand requires immediate attention and treatment. TheACOG10,11CommitteeonObstetricPractice issuedupdatedguidelines(2015and2017)regardingtheemergencytreat-mentofacute-onsetseverehypertensionduringpregnancy:

◦ Acute severe hypertension (SBP > 160 and DBP> 110mmHg) diagnosed using standard devices andtechniquethatispersistentfor15minutesisamedicalemergency.BPshouldbereducedtosafelevelswithin30minutestopreventmaternalstroke.Pharmacologicalgorithmismentionedin►Fig. 11.

◦ Oral nifedipine or oral labetalol 200mg can be givenwhile procuring an IV access with dose repeated in30minutesisrequired.

◦ Magnesiumsulfateisrecommendedforseizureprophy-laxisinseverepreeclampsiaandforcontrollingseizuresineclampsia.

◦ Sodiumnitroprusside is for extremeemergencies andfortheshortestpossibletime—cyanideandthiocyanatetoxicity in themother and fetus, aggravating cerebraledemainthemother.

◦ Individuals and institutions should adopt standardguidelines for managing patients with preeclamp-sia and be equipped to initiate prompt treatment forhypertensive emergency. Drugs and their dosages arementionedin►Table 1.

Thereisnodifferencebetweenintheefficacyofthethreefirstagent drugs12intermsofcontrolofhypertension,andpreferenceofoneoverotherislefttothetreatingphysiciandiscretion.10–12

• Mild to moderate hypertension: Nonpharmacologictreatment is recommended. According to the Cochranedatabase,13–15 treatment of mild-to-moderate hyperten-sionduringpregnancywithantihypertensivereducestheriskofprogressiontoseverehypertensionby50%butdoesnot prevent preeclampsia. Another large multinationalRCTalsosupports this fact.β-BlockersandCCBsappearsuperiortoα-methyldopainpreventingpreeclampsia:

◦ Bedrestandsaltrestrictionarenotrecommended. ◦ All patients need close monitoring for detection ofdiseaseprogression.

Fig. 11 Pharmacologic treatment for acute severe hypertension in pregnancy.



◦ ReviewofsmalltrialsshowednoimprovedoutcomewithstrictBPcontroltoatarget<130/80.However,inwomenwith preexisting end-organ damage due to chronichypertension, a lower threshold for initiating antihyper-tensivemedication (>139/89mmHg) is recommended.Inthesepatients,theaimisforalowertargetBP,thatis,<140/90mmHg.

◦ All patients at risk for preeclampsia should receive75mgofaspirindailyandcalciumsupplementation.

• Severe hypertension: SBP > 160 mm Hg increases theriskof intracerebralhemorrhageinthemother,whereasDBP > 110 mm Hg is associated with abruptio placen-ta and fetal growth restriction. Hence antihypertensivemedication should be started when SBP is > 160 and/orDBP>110mmHg.Multipletrailshavecomparedthe

differentantihypertensives inpregnancy,andnonehaveproved superior to other in terms of efficacy. However,β-blockers and CCBs appear superior to methyldopa inpreventionofpreeclampsia.16Thedifferentdrugsavailableforuseinseverehypertensionarementionedin►Table 2.

AccordingtoEuropeanSocietyofCardiology,recommenda-tionsforthemanagementofhypertensioninpregnancyare:

A.Underclass1C:

1. NonpharmacologicalmanagementforpregnantwomenwithSBPof140–150mmHgorDBPof90–99mmHg.

2. Inwomenwith gestational hypertension, or preexist-ing hypertension superimposed by gestational hyper-tension, or with hypertension and subclinical organdamage or symptoms at any time during pregnancy,

Table 1 Drug dosage and caution in acute severe hypertensionDrug Dose Onset of

action (min)Caution

Labetalol Initial dose: 20 mg IV, followed by 20–80 mg IV q30minOr1–2 mg/min, max 300 mg (then oral)

5 Contraindicated in asthma, heart failure

Nifedipine 5–10 mg capsule (swallowed/chewed) repeat every 30 min

5–10 Sudden hypotension in mother

Hydralazine Initial dose of 5 mg IV, followed by 5–10 mg IV every 30 minOr0.5–10 mg/h IV, (max of 20 mg IV (or 30 mg IM)

5 Sudden hypotension in mother

Sodium nitroprusside

0.25–5.0 µg/kg/min IV DOC in hypertensive crisis-Caution—causes fetal cyanide poisoning

Nitroglycerine IV infusion of 5 mg/min, and gradually increased every 3–5 min to a maximum dose of 100 mg/min

DOC in preeclampsia with pulmonary edema

Abbreviations: DOC, IV, intravenous.

Table 2 Drugs for severe hypertension in pregnancy

Drug mechanism Onset of action duration Dosage Comments

Labetalol Nonselective β-blocker with A receptor blocking action

200–2,400 mg/d in 2 or 3 divided doses

Well tolerated and rela-tively safeContraindicated in asthma and congestive heat failureSafe on fetus

Nifedipine Calcium channel blocker

30–120 mg/d either as short acting or SR

Well tolerated and safe Avoid sublingual form—high risk of maternal hypotensionSafe on fetus

Methyldopa Centrally acting α2-adrenergic ago-nist activity

0.5–3.0 g/d in 2–3 divided doses

Safe in pregnancy and fetusGradual control of blood pressure (BP). Not effec-tive for rapid reduction

Thiazide diuretics Second-line agents May cause intravascular depletion and fetal restricted growth, howev-er, not proven in trials

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are not approved for use during pregnancy; they are fetotoxic. Patients with chronic hypertension who are on these agents should be switched to other recommended first class agents.

Among the agents recommended, no specific agent is first choice because there are no data supporting one over another.



initiationofdrugtreatmentisrecommendedataBPof140/90mmHg.Inanyothercircumstances,initiationofdrugtreatmentisrecommendedifSBP≥150mmHgorDBP≥95mmHg.

3. SBP ≥ 170 mm Hg or DBP ≥ 110 mm Hg in a preg-nant woman is an emergency, and hospitalization isrecommended.

4. Induction of delivery is recommended in gestationalhypertensionwithproteinuriawithadverseconditionssuchasvisualdisturbances,coagulationabnormalities,orfetaldistress.

5. In preeclampsia associated with pulmonary edema,nitroglycerinadministeredasanintravenousinfusionisrecommended.

6. In severe hypertension, drug treatment with intra-venous labetalol or oral methyldopa or nifedipine isrecommended.

B.Underclass2A:Women with preexisting hypertension should be con-

sideredtocontinuetheircurrentmedicationexceptforACEinhibitors, ARBs, and direct renin inhibitors under closeBP-monitoring.

Management of postpartum hypertension: Antihy-pertensive drugs safe in breast-feeding are recommended(►Fig. 12).Drugsthatareboundtoplasmaproteinsarelesslikelytobetransmittedinbreastmilk.Water-solubledrugsarepreferredtolipidsoluble.

Hypertension in Pregnancy and Future Cardiovascular Risk

• Hypertensivedisordersinpregnancyareassociatedwithincreased risk (sevenfold) of hypertension, stroke, andmaternalcardiovasculardisease(CVD)inlaterlife.

• Therisk ishigher in thosewithhistoryof preeclampsia,recurrent preeclampsia, preterm delivery, and fetal

restriction.TheriskofCVDiscompoundedbythepresenceofobesityoroverweight.

• All women with any subtype of HDP face the brunt.Women with gestational hypertension are at greaterrisk.Nodifferencebetweenpatientswhohavereceivedmedication or not for hypertension during pregnancy.Severityofhypertensioncorrelatedwithhypertensioninlaterlife.

• Thesewomenexperiencechronichypertensionandcar-diovascular (CV) risk almost a decade earlier than theirnormotensivecounterparts.

PathophysiologyThereisnouniformconsensusonthemechanismsthatcon-tributetoincreasedCVriskinHDPpatients.Infact,HDPandCVD share common risk factors such as insulin resistance,inflammation, obesity, and hypertension.17,18 Parity is an independentlyriskfactorforfutureCVD;theyarerelatedinaJ-shapedfashion,withthetwohavingthelowestrisk.17,19ThetwohypothesesfortheincreasedCVriskincludeendothelialdysfunctionandfamilialpropensitytohypertensionandCVD.

• Thesepatientsdemonstrateanabnormalresponsetopla-centaknownas ischemicplacentawherein theplacentashows shallow invasion of trophoblasts. The abnormalplacenta releases antiangiogenic proteins resulting in endothelial dysfunction. Endothelial dysfunction wasinitially thought to reverse to prepregnancy state by12weekspostpartum.However,studieshavedemonstrat-edthatthisendothelialdysfunctionpersistsandcontrib-utestotheriskofCVDinlaterlife(►Fig. 13).Theriskisequaltothatcontributedbyobesityand/orsmoking.HDPwomenarefoundtohaveincreasedarterialstiffness.

◦ A familial disposition in these patients to chronichypertension has been suggested. It was noticed thathypertension and CV manifestation occurred even innormotensivessiblingsofHDPwomen.

Fig. 12 Drug classes for management of postpartum hypertension. ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; DOC.



ScreeningforCVD:TheACOGtaskforceonhypertensioninpregnancyemphasizesonearlyidentificationofyoungwom-enatriskforCVDinlaterlifethroughproperscreeningandprevention.

Currently, HDP women are routinely discharged fromobstetric department without a proper CV advice andfollow-up despite established data about the associatedincreased CVD risk. Unfortunately, there are no standardguidelinesonscreeningandtreatmentforCVriskfactorsinwomenwithahistoryofHDP.20,21Nospecifictimeframeforscreeninghasbeenstudied.

• The American Heart Association (AHA) (2014) recom-mends(►Fig. 14)thatwomenwithpreeclampsiashouldbeevaluated6monthsto1yearpostpartumtoassessand

potentially treatCV risk factors, includinghypertension,obesity,smoking,anddyslipidemia.

• The 2012 Dutch Society of Obstetrics and Gynecologyrecommendations for CV risk management after HDP(especiallypreeclampsia)are:

◦ Six weeks postpartum 49 years of age: All womenshould be educated about the increased CV risk thattheywouldfaceandencouragelifestylemodificationtooptimizemodifiableCVriskfactors.

◦ A complete CV risk profile assessment at the age of50years.

AllwomenwhohadHDPshouldbecloselymonitoredforCVriskfactorssuchashypertension,hyperglycemia,anddyslipidemia.

Lifestyleinterventionsarethecornerstoneofpreventionstrategies afterHDP (►Fig. 15). They have the potential todecreaseCVriskby4to13%.

ConclusionHypertensivedisordersofpregnancyareamajor issueofconcernforthemotherandherinfant.Pregnancywithitsenormous influenceon theCVphysiology is likea stresstestinawoman’slife.HypertensivedisordersinpregnancycanbeconsideredasafailedCVstresstestidentifyingthewomansusceptibletoCVDin later life.PregnancycanbeconsideredasachanneltoidentifywomenwhoareatriskforfutureCVD.Asclinicians,weshouldutilizethischannelto implement lifestylemodification inwomen to reducetheir future burden of CVD. Further research is requiredto identify the mechanisms in pregnancy and HDP thatcontributetoCVDinlaterlifesoastoinitiateappropriatepreventivemeasures.

Fig. 13 Pathophysiology of HDP and cardiovascular disease (CVD) in later life.

Fig. 14 Recommendations for CV risk screening.

Fig. 15 Recommendations for prevention of CV risk follow-ing hypertensive disorders in pregnancy (HDP). DASH, Dietary Approaches to Stop Hypertension.



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