Hypertensive disorders in pregnancy

105
Marwan Alhalabi MD PhD Professor in Reproductive Medicine Faculty of Medicine Damascus University And Medical Director Orient Hospital Assisted Reproduction Center Damascus Syria

Transcript of Hypertensive disorders in pregnancy

Marwan Alhalabi MD PhDProfessor in Reproductive Medicine Faculty of Medicine Damascus University

And

Medical Director Orient Hospital Assisted Reproduction Center Damascus – Syria

Hypertensivedisordersarethemostcommonandyetseriousconditionsseeninobstetrics

• Incidenceis5-10%.

• Themostfrequentcauseofiatrogenicprematurity.

• Pretermdelivery

• Intrauterinegrowthrestriction (IUGR)

• Perinataldeath

• Maternalcerebrovascularaccidents(CVA).

• Placentalabruption.

• Decreases during the first trimester,

• Reaching its lowest point at 20 weeks,

• Returns to pre-pregnancy levels during

the third trimester.

Classification

Pre-eclampsia

Eclampsia

Preeclampsia superimposed

on chronic hypertension

Chronic hypertension

with pregnancy

Gestational hypertension

BloodPressure≥140/90mmHgontwoormoreoccasions- inapreviouslynormotensivepatient- after20weeksgestation- withoutproteinuria- returningtonormal12weeksafterdeliveryAlmosthalfofthesedeveloppreeclampsiasyndrome

GESTATIONAL HYPERTENSION

GESTATION ≥ 20 WEEKS

SUSTAINED HYPERTENSION ( ≥ 140/90)

No proteinuria

DEFINITION

SYMPTOMS

EXAMINATION

GESTATIONAL HYPERTENSION

Sustained B.P No proteinuria

NONE

Unremarkable

GESTATIONALHYPERTENSION

CRITERIA FOR MILD GESTATIONAL HYPERTENSION

Blood Pressure > 140 to < 160 mm Hg, systolic> 90 to < 110 mm Hg, diastolic

Proteinuria < 300 mg per 24-hr collection

Platelet count > 100,000/mm3

Liver enzymes Normal

Maternal symptoms Absent

IUGR / Oligohydramnios Absent

• It is defined as hypertension of at least 140/90mm Hg

recorded on two separate occasions at least 4 hours

apart and in the presence of at least 300mg protein in a

24 hour collection of urine, arising after the 20th week of

gestation in a previously normotensive woman and

resolving completely by the 6th postpartumweek.

Preeclamsia GestationalHypertension Proteinuria

RISK FACTORS for PREECLAMPSIA

DEMOGRAPHIC

OBSTETRICS

MEDICAL

NULLIPARA(Age extremes <20yrs ,>35yrs )

1. Multiple gestation2. Molar pregnancy3. Non-immune

hydrops

1. Diabetes mellitus2. Chronic HTN3. Renal disease4. SLE

Genetic

GeneticPredisposition

FamilyHistory

Race&EthnicityMoreCommon inblack&Asians

Pregnancybyovumdonation

Age&Parity

Teenagepregnancy<18yrs

Age>35yrs

Longintervalbetween

pregnancy>10years

Nulliparity

PartnerFactors

Changeofpartner

Limitedspermexposure

Pregnancybydonor

insemination

Partner fatheredaneclampticpregnancy

PregnancyFactors

Multiplepregnancy

Hydatiformmole

Hydrops fetalis

Fetalchromosomalanomaly

(trisomy13)

UnderlyingMedicalDiseae

Chronichypertension

Diabetesmellitus

RenalDisease

Cardiovasculardisease

Hyperthyroidism

MetabolicSyndrome

Others

ObesityBMI>35kg/m2

Psychologicalstress&strainSmoking

Previoushistoryofpreeclamsia

• Hyperhomocysteinemia ,

• Autoimmune disease

• Antiphospholipid antibodies,

• Thrombophilia

MILDPREECLAMPSIA

GESTATION ≥20WEEKS

SUSTAINEDHYPERTENSION(≥140/90)

Proteinuria(≥300mg/24hr)

SYMPTOMS

EXAMINATION

PATHO-PYSIOLOGY

NONE

NONE

DiffuseVasospasmCapillaryinjury

LABORATORY FINDINGS

MANAGEMENT

Proteinuria (1-2+)Hemoconcentration

< 36 wks Conservative>36 wks MgSO4 and

Delivery

GESTATIONALHYPERTENSION

GESTATION ≥20WEEKS

SUSTAINEDHYPERTENSION(≥140/90)

NOPROTEINURIA

MILDPREECLAMPSIA

SUSTAINEDHYPERTENSION( ≥140/90)

Proteinuria( ≥300mg/24hr)

GESTATION ≥ 20WEEKS

BLOODPRESSURE

PROTEINURIA

SYMPTOMS

≥160/110

≥ 5grams

1. Headache2. Epigastricpain3. Visualchanges

LABORATORYFINDINGS

SIGNS

DICElevatedLiverenzymes

1. Pulmonaryedema2. Oliguria3. cyanosis

• new onset of seizures or unexplained coma

during pregnancy in patients with pre-existing

preeclampsia and without pre-existing

neurological disorder.

• addition of convulsions in a womanwith preeclampsia

• occurs in 0.5-4% of deliveries

• 25% have eclamptic seizures before labour, 50% duringlabour, and 25% after delivery.

Eclampsia PreeclampsiaSeizure/

Convulsion/Coma

rebra

SYMPTOMS

PATHO-PYSIOLOGY

RISKFACTORS SameasPreeclampsia

Cerebralvasospasm,ischemiaandedema

Generalizedtonic-clonicSEIZURES

ECLAMPSIA

LABORATORYFINDINGS

MANAGEMENT

• Proteinuria• Hemoconcentration• DIC• ElevatedLiverenzymes

1. StopconvulsionswithMgSO42. Promptdeliveryatanygestational

age3. LowerdiastolicBP90-100mm/Hg

ECLAMPSIA

MANAGEMENT

IVMgSO4– Topreventconvulsions(continue24hrspost-partum)

LOWERB.P(hydralazineorlabetalol)

INDUCELABOR(IVoxytocin andamniotomy )

• Bloodpressure≥140/90before20weeksofgestation.

OR

• persistenceofhypertensionbeyond12weeksafterdelivery.

CHRONICHYPERTENSION

GESTATION<20WEEKSORPrepragnancy

SUSTAINEDHYPERTENSION(≥140/90)

+/- PROTEINURIA

GOODPROGNOSIS

POORPROGNOSIS

WORSTPROGNOSIS

B.P140/90to179/109Noendorgandamage

KIDNEYS:RenaldiseaseEYES:RetinopathyHEART:LeftVentricularHypertrophy(B.P>180/110)

UncontrolledHTNChronicHTN+SuperimposedPIH

MANAGEMENTOFCHRONICHYPERTENSION

Ifantihypertensivemedsneeded- Methyldopa isdrugofchoice(orlabetalol)

Serialultrasounds(increaseriskofIUGR>30weeks)

Inducelaboratterm

DCantihypertensivemeds(ifB.P>100mmHgdiastolic)

SerialB.Pandurineprotein(watchforsuperimposedpreeclampsia)

• New-onsetproteinuria> 300mg/24hrsinhypertensivewomenbutnoproteinuriabefore20wks gestation.

• Asuddenincreaseinproteinuriaorbloodpressureorplateletcount<100,000/cumminwomenwithhypertensionandproteinuriabefore20wksgestation.

CHRONICHTNSUPERIMPOSEDPIH

CHRONICHYPERTENSION

WorseningBLOODPRESSURE

Worseningproteinuria

MANAGEMENTofChronicHTNandsuperimposedPIH

MgSO4– Topreventconvulsions(continue24hrspost-partum)

LOWERB.P- Diastolic90-100mmHg(hydralazineorlabetalol)

INDUCELABOR(IVoxytocin andamniotomy )

• HTNpatientswithhemolysis (H),elevatedliverenzymes(EL),lowplatelet count(LP)

• 4-12% ofpt.withseverepreeclampsiaandeclampsiadevelopHELLPsyndrome

• cardiovascularstabilization,correctionofcoagulationabnormalities,anddelivery

• PLTtransfusionbeforeorafterdeliveryifPLTcountis<20,000/mm3 (advisedat<50,000/mm3 beforecesarean)• <32weeksgestation;steroidtherapy

mayhelpstabilizematernalPLTcount

• Complex disease• Appearstobetriggeredbytheplacenta• Canoccurinmolar

pregnancieswherefetusabsent

• Canalsooccurinabdominalpregnancy(pregnancynotinuterus)

Stage03-8weeks

Stage18-18weeks

Stage220weeksto

birth

PoorImmunoregulationInadequatetolerancetofeto-paternalantigensduring conceptionandimplantation

PoorPlacentationDeficienttrophoblast invasionandspiralarteryremodelling

ClinicalmanifestationOveractivationofmaternalendothelium andsystemicinflammatorynetwork

OxidativeStress

EndoplasmicreticulumStressInflammatory

Stress

invasivecytotrophoblasts offetalorigininvadethe

maternalspiralarteries

transformsthemfromsmall-caliber resistancevesselstohigh-calibercapacitance vessels

capableofprovidingplacentalperfusion

adequatetosustainthegrowingfetus

Normal Pregnancy

cytotrophoblasts failtoadoptaninvasiveendothelialphenotype

invasionofthespiralarteriesisshallowandtheyremainsmallcaliber,

resistancevessels

placentalischemia

Preeclampsia

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Defective implantation, poor Placentation

Successful implantation, but failed Placentation

Complete implantation failure Infertility

Miscarriage

Pre-eclampsia

Stage1:reducedplacentalperfusionAbnormalimplantation

Stage2:maternalsyndrome-hypertension-proteinuria-endothelialdysfunction

NORMALPREGNANCY

PREECLAMPSIA

Impair/inadequatetrophoblast invasiontothespiralarteries

Spiralarteriesretaintheircharecteristic (narrow,tortuous,highresistance)

Reducebloodsupplytoplacenta

Resultinplacentalhypoperfusion

AsacompensationHighBPinmaternal

Stage1:reducedplacentalperfusionAbnormalimplantation

Stage2:maternalsyndrome-hypertension-proteinuria-endothelialdysfunction

WHATGETSINTOMATERNALCIRCULATION???

ANTI-ANGIOGENICFACTORS

ANGIOGENICFACTORS

Vascularendothelialgrowth(VEGF)includingplacentalgrowthfactor

Transforminggrowthfactor- beta(TGF-B)

Look aftermaternalendothelium

Solubleendoglin (sEng)

SolubleFMS-liketyrosinekinase-1(sFlt-1)

Releasedfromdiseasedplacenta

• 1.vasodialator& vasoconstrictor.

• 2.angiogenic andantiangiogenic factors.

FetalSyndrome

MaternalSyndrome47

Inadequate trophoblast invasion and defect remodeling of spiral arteries

Placental ischemia and inflammation

Systemic inflammation Apoptosis Oxidative

stress

Relase of placental

factor

Endothelial dysfunction

Pre-eclampsia

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vasodialator

NO

PGI-2

vasoconstrictor

Angiotensin-II

Endothelin-I

ThromboxaneA2

placenta

Syncytiotrophoblast&endothelium

↓PGI2↑TXA2

VasoconstrictionPlateletaggregation↑Vasopressorresponse↑uterineactivity

Activatedendothelialcellspromotecoagulationandincreasevasopressorsensitivity

Widespreadcoagulationoccur(DIC)

Fibrindepositioninkidney&placenta

HPT&placentalinsufficiency

Cardiovascular

• Generalizedvasospasm• Increasedperipheralresistance• Reducedcentralvenous/

pulmonarypressure

Hematological

• Plateletactivationanddepletion• Coagulopathy• Decreasedplasmavolume• Increasedbloodviscosity

• Proteinuria• Decreasedglomerularfiltrationrate• Decreasedurateexcretion

Renal

Hepatic

• Periportalnecrosis• Subscapularhematoma

• Cerebraloedema• Cerebralhaemorrhages

CentralNervousSystem

OrganSpecificChangesassociatedwithPre-eclampsia

Organ Damage

utero-placenta IUGR

Hematological Epistaxis,DIClikefeatures,hemoconcentration

CNS Cerebraledema,cerebralhgeàseizures

Heart Subendothelial hge,focalnecrosis&hge,cardiomyopathy,heartfailure

Lungs Pulmonaryedema,hemorrhagicbrochopneumonia

Kidneys glomerularendotheliosis,oliguria

liver Subcapsular hge, ischaemiaàperiportalnecrosis,HELLP

Antihypertensivedrugsusedinpregnancyare

• Methyldopa

• Hydralazine

• labetalol

• RoutinelyusedinseverePE.

• Magnesiumsulphate:mostcommonlyused.

• Initiatedwithonsetoflabortill24hpostpsrtum.

• Forcaesarean,started2hrsbeforethesection

till12hrspostpartum.

itcanbegiveneitherIVorIM.IVhasgoodprognosis.

LoadingdoseforIVis4g.i.e.8mldilutedin12mlnormalsaline.This20mlisgivenin20minutes.

Maintenancedoseis20gi.e.40mldilutedin60mlnormalsalineandgivenatrateof1g/hr.

IMisalsoused.

LoadingdoseisasIV.

Maintenancedoseis5gevery4hrsinalternatebuttocksfor24hrs.

Mgso4actsonNMjunctionandinhibitentryofCa++ionsthusinhibitingexcitabilityofneurons.

• Maternal:flushingperspirationheadache,muscleweaknesspulmonaryoedema

• Neonatal:lethargyhypotoniarespiratorydepression

Management of MgSO4 Toxicity

Theonlydefinitivetreatment

Preeclampticpatientsdividedinto3categories

A- Preeclampsiafeaturesfullysubside

B- partialcontrol,butBPmaintainsasteadyhighlevel

C- persistentlyincreasingBPtosevereleveloraddition

ofotherfeatures

A:canwaittillspontaneousonsetoflabor

don’texceedExpectedDateofDelivery

B:>37wkterminatewithoutdelay

<37wk,expectantmanagementatleast

till34wks

C:terminateirrespectiveofPOG

startseizureprophylaxisandsteroidsif<34wks

Unlesscontraindicated:Eclampticwomenshouldundergonormalvaginaldelivery

Indicationsforcaesareansection-FetaldistressPlacentalabruptionUnfavourablecervixFailedinductionoflabourRecurrentseizures

• Urine:24hoururine,Proteinuria.

• Kidneyfunctions:serumcreatinine,urea,creatinineclearanceanduricacid.

• Liverfunctions:bilirubin,Enzymes

• Blood:CBC,HCt,HemolysisandPlateletcount(Thrombocytopenia).

• CoagulationProfile:Bleedingandclottingtime

• Convulsionsandcoma(eclampsia).• Cerebralhaemorrhage.• Renalfailure.• Heartfailure.• Liverfailure.• Disseminatedintravascularcoagulation.• Abruptio placentae.• Residualchronichypertensioninabout1/3ofcases.• Recurrentpre-eclampsia innextpregnancies.

a.Intrauterinegrowthretardation(IUGR).

b.Intrauterinefoetal death.

c.Prematurityanditscomplications.

• RegularAntenatalcheckup:rapidgaininweightrisingbloodpressureedemaproteinuria/derangedliverorrenalprofile• LowdoseAspirininHighriskgroup:↑PGsand↓TXA2• Calcium supplementation:noeffectsunlesswomenare

calciumdeficient• Antioxidants-VitaminC andE• Nutritionalsupplementation:zinc,magnesium,fishoil,

lowsaltdiet

v meningitisv encephalitisv spaceoccupyinglesionv electrolytedisturbancev vasculitisv amnioticfluidembolismv Medicationsv organfailurev stroke

N.B:Gradesofproteinuria (ing/L):Trace=0.1,1+=0.3,2+=1,3+=3,4+=10

Pregnancyinduced

Hypertension

GestationalHTN

● BP≥140/90mmHg●Noevidenceofunderlying

causeofHTN●Noassociatedsymptoms●Comestonormalwithin6

wksofdelivery

Pre-eclampsia

NonSevere Severe

Eclampsia

PreEclamsia+

Convulsion±

Coma

N.B:Pre-eclampsia isprincipallyasyndromeofsignsandwhensymptomsappearitis

usuallylate.Assessmentoftheseverityofpre-eclampsia

isgiveninthenextslide.

• ismostpromising,butcurrently,noneofthemiscompletelysuitableforclinicaluse.(Conde-Agudelo,2014;Kleinrouweler,2012;Myatt,2012a).

• Thesehavevalueforfetal-growthrestrictionbutnotpreeclampsia(ACOG,2013a).

• Asaresultofthesetrials,somemethodstopreventPreeclampsiahavebeentheorized…

UterineArteryDopplerVelocimetry(abnormalflowresistance/diastolicnotchin2nd/3rd

trimester)

Inpreeclampticmother:ShowingearlydiastolicNOTCHDecreasedEDF(due tohigh resistance)

Innormalmother

ABNORMALITIES NONSEVERE SEVEREBlood pressure ≥140/90mmHg but

<160/110mmHg≥160/110mmHg

Proteinuria ≤2+ ≥3+Oliguria Absent <400ml/dayHeadache Absent PresentVisual disturbances Absent PresentPlatelet count Normal Thrombocytopenia

(<100,000/mm3)HELLP syndrome Absent May be present

ALT,AST >70 IU/LLDH>600 IU/LBilirubin >1.2g/L

Serum transaminases(AST,ALT)

Normal (<40 IU/L) Elevated

Serum Creatinine Normal ElevatedEpigastric pain Absent PresentFetal growth restriction Absent ObviousPulmonary oedema Absent present

• Pre-eclampsia is a pregnancy specific

disorder .

• It can occur in absence of the fetus.

• The disease is cured by the removal of

the placenta .76

77

Genetic ModulatorsPre-existing

Vascular Pathology

Central players

Cytokines

Ros

78

q Hemoglobinandhematocritplateletcount:decreased,if<1lakhcoagulationprofile

q LFTs:indicatedinallpatientsq RFTs:raised(S.ureacreatinineisdecreasedinNormal

pregnancy)q UrineRoutine:proteinuria

OBSTETRICMANAGEMENT

1.Maternalevaluation

2.Fetalevaluation:

q Dailyfetalmovementcountq Ultrasoundq Dopplerultrasoundforfetalbloodflow

• Genetic factor• Immunologic factor• Endocrinologic factor• Nutritional factor• Infectious factor

Serious hypertension üBP ≥ 160/110mmHg for at least 12hüProtein in the urine is over 5g/24h or +++~++++ üCreatinine level increasesüFunction of liver impaired obviouslyüFunction of the placenta impaired üFetus IUGR, asphyxia and even death

• GestationalHTN• TransientHTNofpregnancy

• Preeclampsia• Mild

• Severe

• Eclampsia• ChronicHTNprecedingpregnancy

• ChronicHTNwithsuperimposedpregnancy-inducedhypertension• Superimposedpreeclampsia• Superimposedeclampsia

ClassificationoftheAmericanCollegeofObstetriciansandGynecologists

Endothelial Dysfunction/Oxidant

StressFeto-Placental unit

Endocrine Dysfunction

Renal Dysfuntion Misc

Placental Perfusion/ Vascular Resistance

related TestsUterine Artery Doppler

Velocimetry

AT- III

ANPFree fetal DNAAdapted from Conde-Agudelo and associates (2009)

NO

YES

Neither forced nor restricted

• Gestational HTN :onlyifsevereHTN

• Preeclampsia :ü If diastolic pressure≥ 100mmof Hg OR, there is proteinuria OR, there is fetal compromise.ü37 completed weeks of gestation.

HEMOLYSIS(due to

passage of RBCs

through partially

obstructed vessel)

s)HEPATIC

DYSFUNCTION(due to

intravascular fibrin

deposition & sinosoidal

obst.)

Decreased Liver blood

flow

HELLP

SyndromeTHROMBO-CYTOPENIA

(due to platelet

aggregation & dipositionin the sites of endothhelial

damage)

Prompt delivery of fetus to achieve cure

Avoidance of diuretics & hyper osmotic agents

Limitation of I.V fluid

Intermittent antihypertensive to control BP judiciously

Control of convulsion by MgSO4 (IM/IV route)

Protection & supporting care during convulsionProtection in a railed

cotProtection of airway & prevention of tongue

biteCorrection of hypoxia &

acidosis

Managed in Eclampsia room.

88

“It is the most effective drug to control even recurrent seizures without any central nervous system depression to mother & fetus”

89

Magnesium sulphate

90

• Notusedtolowerbp• Produceintravascularvolumedepletion• Worsenmaternalhemoconcentration• Useislimitedtopresenceofpulmonaryedema(FUROSEMIDE)• Maybeusedinpersistentseverepostpartumhypertension

Enviromental

Genetics

CVS and inflammatory

changes

Maternal immunological

intolerance

Abnormal placental

implantaion

• Totalproteinin24hoursurine>300mg

• Protein:Creatinineratioinrandomsample>0.1

• Newonsetofhypertensionafter20weeks ofgestationwithoutproteinuria,followedbyreturnofB.P.tonormalwithin12weekspost-partum.

• Newonsetofhypertensionafter20weeksofgestationalongwithproperlydocumentedproteinuria,followedbyreturnofB.P.tonormalwithin12weekspost-partum.

PreeclamsiaGestational Hypertensio

nProteinuria

• Generalizedtonic-clonicseizure inapatientwithPreeclampsianotattributedtoanyothercause.

Eclampsia Preeclampsia

Seizure/Convulsion

/Coma

• Hypertensionbeforepregnancy/Diagnosedbefore20weeksofpregnancynotduetogestationaltrophoblasticdisease.

• Hypertensiondiagnosedafter20weeksbutpersistentafter12weekspostpartum

• Newonset proteinuriainhypertensivewomenbutnoproteinuria before20weeks'gestation

• Asuddenincrease inproteinuriaorbloodpressureorplateletcount<100,000/Linwomenwithhypertensionandproteinuriabefore20weeks'gestation

Primiparity Immunologicfactors PreviouspregnancycomplicatedbyPreeclampsia/Eclampsia/HELLP

FamilyhistoryofPreeclampsia BMI Pregnancyrelatedconditions

Primipaternity Sexualco-habituation Maternalinfection

Gestationalageatdeliveryof1st Pregnancy Socioeconomic status Smoking

Angiogenicfactor

• VEGF• TFG-beta• PlGF

Antiangiogenicfactor

• sFlt-1• sEng

Ø HistoryofPreeclampsiainpreviouspregnancyØ AdvancedmaternalageØ FamilyhistoryofPreeclampsiaØ Historyofplacentalabruption,IUGR,fetaldeathØ Obesity,BMI>35doublestheriskØ HypertensionØ DiabetesØ ThromboticvasculardiseasesØ MultiplegestationØ MolarpregnancyØ Smoking

Ø Largeplacenta

Ø Prolongedpregnancy

Ø Placentalhydrops

Ø Chromosomalabnormality