HypertensiHypertensive Disorders ve Disorders in Pregnancyin Pregnancy

Aleksandra Rajewska PhDAleksandra Rajewska PhDChair and Department of ObstetricsChair and Department of Obstetrics

and Gynecologyand Gynecology

Hypertensive disordersHypertensive disorders (HD) (HD)in pregnancyin pregnancy

Affects 7 – 10% pregnanciesAffects 7 – 10% pregnancies Increased perinatal morbidity & mortalityIncreased perinatal morbidity & mortality

Mild hypertension in pregnancy:Mild hypertension in pregnancy:

33% preterm delivery; 11% SGA neonates33% preterm delivery; 11% SGA neonates

Severe hypertension in pregnancy:Severe hypertension in pregnancy:

62 –62 – 70% preterm delivery; 40% SGA neonates70% preterm delivery; 40% SGA neonates

Hypertensive disorders in pregnancy: Hypertensive disorders in pregnancy: classificationclassification

1.1. Pregnancy Induced Hypertension (PIH) or Pregnancy Induced Hypertension (PIH) or Gestational Hypertension (GH) or Transient Gestational Hypertension (GH) or Transient HypertensionHypertension

2.2. PreeclampsiaPreeclampsia3.3. EclampsiaEclampsia4.4. Chronic hypertensionChronic hypertension5.5. Preeclampsia superimposed on chronic Preeclampsia superimposed on chronic

hypertensionhypertension

Maternal & fetal consequences of Maternal & fetal consequences of HDHD

Maternal Maternal DICDIC Cerebral hemorrhageCerebral hemorrhage Retinal hemorrhageRetinal hemorrhage Liver insufficiencyLiver insufficiency Acute renal failureAcute renal failure Cardiac insufficiencyCardiac insufficiency Pulmonary edemaPulmonary edema Placental abruptionPlacental abruption

Fetal Fetal IUGRIUGR Low birth weightLow birth weight OligohydramniosOligohydramnios Preterm deliveryPreterm delivery Neonatal prematurity Neonatal prematurity Intrauterine hypoxiaIntrauterine hypoxia Intrauterine fetal deathIntrauterine fetal death Placental abruptionPlacental abruption

EthiologyEthiology

Incomplete trophoblastic invasion of uterine vessels:Incomplete trophoblastic invasion of uterine vessels: Uteroplacental blood flow impairmentUteroplacental blood flow impairment Diminished placental perfusionDiminished placental perfusion Immunological factors:Immunological factors: Microscopic changes: acute graft rejectionMicroscopic changes: acute graft rejection Impairment of blocking antibodies formationImpairment of blocking antibodies formation ThTh11/Th/Th22 imbalance imbalance Anticardiolipin antibodiesAnticardiolipin antibodies

Spiral arteries modificationSpiral arteries modification

EthiologyEthiology

Vasculopathy & inflammatory changesVasculopathy & inflammatory changes Placental ischemia: released factors provoke Placental ischemia: released factors provoke

endothelial injuryendothelial injury Oxidative stress: formation of self-propagating Oxidative stress: formation of self-propagating

lipid peroxideslipid peroxides Nutritional factorsNutritional factors Antioxidants deficiencyAntioxidants deficiency Obesity & atherosclerosisObesity & atherosclerosis Genetic factors: primipaternity?Genetic factors: primipaternity?

Pathogenesis Pathogenesis

VasospasmVasospasm Endothelial cell activationEndothelial cell activation Increase pressor responseIncrease pressor response Coagulation promotionCoagulation promotion

Pregnancy Pregnancy IInduced nduced HHypertensionypertension (PIH) (PIH) 6 – 17% of primiparas6 – 17% of primiparas 2 – 4% of multiparas2 – 4% of multiparas Blood pressure Blood pressure ≥ 140/90 mmHg ≥ 140/90 mmHg

occurring for first time during occurring for first time during pregnancypregnancy

Blood pressure returns to normal Blood pressure returns to normal < 12 weeks postpartum< 12 weeks postpartum

No proteinuriaNo proteinuria Edema is not a PIH criterion any Edema is not a PIH criterion any

more!more! Final diagnosis Final diagnosis – – postpartumpostpartum

PreeclampsiaPreeclampsia (PE) (PE)

2 – 7% of primiparas2 – 7% of primiparas 14% of twin pregnancies14% of twin pregnancies 18% with PE in previous 18% with PE in previous

pregnancypregnancy

Minimum criteriaMinimum criteria BP BP ≥ 140/90 mmHg ≥ 140/90 mmHg

after 20 weeks’ gestationafter 20 weeks’ gestation Proteinuria ≥ 300 mg/24 Proteinuria ≥ 300 mg/24

hours or ≥ 1+ dipstickhours or ≥ 1+ dipstick

Increased certaintyIncreased certainty BP BP ≥ 160/110 mmHg≥ 160/110 mmHg Proteinuria ≥ 2.0 g/24 hours Proteinuria ≥ 2.0 g/24 hours

or ≥ 2+ dipstickor ≥ 2+ dipstick Serum creatinine >1,2 mg/dLSerum creatinine >1,2 mg/dL Persistent headache or other Persistent headache or other

cerebral or visual cerebral or visual disturbancesdisturbances

Persistent epigastric painPersistent epigastric pain

Preeclampsia (PE)Preeclampsia (PE)

Pregnancy-specific syndrome of Pregnancy-specific syndrome of reduced reduced organ perfusionorgan perfusion secondary to placental secondary to placental hypoperfusion, vasospasm and endothelial hypoperfusion, vasospasm and endothelial activationactivation

Risk factors: nulliparity, multifetal Risk factors: nulliparity, multifetal gestation, maternal age >35 years, obesity, gestation, maternal age >35 years, obesity, ethnicityethnicity

PreeclampsiaPreeclampsia (PE) (PE)

Preventive factors: placenta previa, Preventive factors: placenta previa, smokingsmoking

Histopathology: glomerular lesionHistopathology: glomerular lesion

In severe cases proteinuria may fluctuate In severe cases proteinuria may fluctuate over any 24-hours periodover any 24-hours period

EclampsiaEclampsia

Generalized tonic-clonic convulsions Generalized tonic-clonic convulsions (beginning about facial muscles)(beginning about facial muscles)

with subsequent comawith subsequent coma

in a woman with preeclampsiain a woman with preeclampsia

EclampsiaEclampsia

Typically in the third trimesterTypically in the third trimester Prognosis always seriousPrognosis always serious Preventable!Preventable! Fatal coma without convulsions – dgn. Fatal coma without convulsions – dgn.

controversialcontroversial

Eclampsia Eclampsia

Antepartum 38 – 53%Antepartum 38 – 53% Intrapartum 18 – 36%Intrapartum 18 – 36% Postpartum 11 – 44%Postpartum 11 – 44% Life threatening for mother & fetus!Life threatening for mother & fetus! Maternal mortality: 1,8 – 14%Maternal mortality: 1,8 – 14% Fetal/neonatal mortality: the earlier in Fetal/neonatal mortality: the earlier in

pregnancy E occurs the higherpregnancy E occurs the higher

Eclampsia: sequelsEclampsia: sequels

Transient diaphragm fixation: respiratory arrestTransient diaphragm fixation: respiratory arrest Continuous convulsions: Continuous convulsions: „status epilepticus”„status epilepticus” Placental abruptionPlacental abruption DICDIC Massive cerebral hemorrhageMassive cerebral hemorrhage Neurological deficitsNeurological deficits

Eclampsia: sequelsEclampsia: sequels

Aspiration pneumoniaAspiration pneumonia Pulmonary edemaPulmonary edema Cardiopulmonary arrestCardiopulmonary arrest Acute renal failureAcute renal failure Maternal deathMaternal death

Eclampsia: differential diagnosisEclampsia: differential diagnosis

Exclude:Exclude: EpilepsyEpilepsy EncephalitisEncephalitis MeningitisMeningitis Cerebral tumorCerebral tumor CysticercosisCysticercosis Ruptured cerebral aneurysmRuptured cerebral aneurysm

Eclampsia: treatmentEclampsia: treatment

1.1. Loading dose of magnesium sulfate i.v.Loading dose of magnesium sulfate i.v.**

2.2. Continuous infusion of magnesium sulfate i.v. or Continuous infusion of magnesium sulfate i.v. or periodic i.m. injectionsperiodic i.m. injections

3.3. Antihypertensive medication (i.v. or oral) if diastolic Antihypertensive medication (i.v. or oral) if diastolic pressure > 100 mmHgpressure > 100 mmHg

4.4. Avoid diuretics and limitations of fluid administration!Avoid diuretics and limitations of fluid administration!

5.5. DELIVERYDELIVERY

* Magnesium sulfate in eclampsia is given as anticonvulsant* Magnesium sulfate in eclampsia is given as anticonvulsant,, not not as as hypertension treatment!hypertension treatment!

Chronic hypertensionChronic hypertension

Blood pressure Blood pressure ≥ 140/90 mmHg before ≥ 140/90 mmHg before pregnancy or diagnosed before 20 weeks’ pregnancy or diagnosed before 20 weeks’ gestationgestationoror

Hypertension first diagnosed after 20 weeks’ Hypertension first diagnosed after 20 weeks’ gestationgestationor or

HypertensionHypertension persistent after 12 weeks’ persistent after 12 weeks’ postpartumpostpartum

Superimposed preeclampsiaSuperimposed preeclampsia

New-onset proteinuria New-onset proteinuria ≥ 300 mg/24 hours≥ 300 mg/24 hours

in hypertensive womanin hypertensive woman

A sudden increase in proteinuria or blood pressure A sudden increase in proteinuria or blood pressure in woman with hypertension and proteinuria in woman with hypertension and proteinuria before 20 weeks’ gestationbefore 20 weeks’ gestation

Superimposed preeclampsiaSuperimposed preeclampsia

Often develops earlier in pregnancy and gets Often develops earlier in pregnancy and gets more severe than „pure” preeclampsiamore severe than „pure” preeclampsia

All chronic hypertensive disorders predispose All chronic hypertensive disorders predispose to development of superimposed preeclampsia to development of superimposed preeclampsia and eclampsia!and eclampsia!

Pathophysiology: cardiovascular system Pathophysiology: cardiovascular system

Increased cardiac afterload caused by Increased cardiac afterload caused by hypertensionhypertension

Cardiac preload affected by hypovolemiaCardiac preload affected by hypovolemia Hemoconcentration: a consequence of general Hemoconcentration: a consequence of general

vasoconstriction and vascular permeabilityvasoconstriction and vascular permeability Excessive reaction to even normal blood loss at Excessive reaction to even normal blood loss at

deliverydelivery

Patophysiology: blood & coagulationPatophysiology: blood & coagulation

Acute thrombocytopenia < 100 000/Acute thrombocytopenia < 100 000/µµLL Fragmentation hemolysis (microangiopathic h.): Fragmentation hemolysis (microangiopathic h.):

elevated serum lactate dehydrogenase levelselevated serum lactate dehydrogenase levels HELLPHELLP syndrome syndrome: : HHemolysisemolysis, , ELELevated liver evated liver

transaminase enzymestransaminase enzymes, , LLow ow PPlateletslatelets 0,2 – 0,6% of all pregnancies0,2 – 0,6% of all pregnancies 4 – 12% of pregnancies complicated by PE or E4 – 12% of pregnancies complicated by PE or E But 15% of pregnancy without hypertension or But 15% of pregnancy without hypertension or

proteinuria!proteinuria!

Patophysiology: volume homeostasisPatophysiology: volume homeostasis

Decrease in renin, angiotensin II & Decrease in renin, angiotensin II & aldosterone activityaldosterone activity

Paradoxical sodium retentionParadoxical sodium retention Expanded volume of extracellular fluid:Expanded volume of extracellular fluid: Endothelial injuryEndothelial injury Reduced plasma oncotic pressure Reduced plasma oncotic pressure

(proteinuria)(proteinuria)

Pathophysiology: kidneyPathophysiology: kidney

Reduced renal perfusionReduced renal perfusion

Reduced glomerular filtrationReduced glomerular filtration

Elevated plasma uric acid concentrationElevated plasma uric acid concentration

Proteinuria: albumins, globulins, hemoglobin & Proteinuria: albumins, globulins, hemoglobin & transferrin transferrin

Pathophysiology: kidneyPathophysiology: kidney

In mild to moderate PE: elevated plasma In mild to moderate PE: elevated plasma creatinine valuescreatinine values

Severe PE: intrarenal vasospasm & oliguriaSevere PE: intrarenal vasospasm & oliguria Intensive intravenous fluid therapy Intensive intravenous fluid therapy

contraindicated!contraindicated! Intravenous dopamine infusion recommended!Intravenous dopamine infusion recommended!

Patophysiology: liverPatophysiology: liver

Most common in Most common in HELLPHELLP syndrome syndrome

Periportal hemorrhage described by Virchow Periportal hemorrhage described by Virchow in 1856in 1856

Focal hemorrhages can cause hepatic rupture Focal hemorrhages can cause hepatic rupture or subcapsular hematomaor subcapsular hematoma

Patophysiology: brainPatophysiology: brain

Gross Gross hemorrhagehemorrhage due to ruptured arterie due to ruptured arteriess caused by severe hypertension: most common in caused by severe hypertension: most common in women with underlying chronic hypertension; women with underlying chronic hypertension; PE is not necessary!PE is not necessary!

Hyperemia, ischemias, thrombosis & Hyperemia, ischemias, thrombosis & hemorrhage: common in PE, universal with hemorrhage: common in PE, universal with eclampsiaeclampsia

Patophysiology: brainPatophysiology: brain

Doppler findings in eclampsia: cerebral Doppler findings in eclampsia: cerebral hyperperfusion similar to hypertensive hyperperfusion similar to hypertensive encephalopathyencephalopathy

Cerebral edemaCerebral edema

Pathophysiology: placentaPathophysiology: placenta

Uteroplacental perfusion compromised from Uteroplacental perfusion compromised from vasospasmvasospasm

Most common in HELLP syndrome Most common in HELLP syndrome

Doppler velocimetryDoppler velocimetry!!

Prediction Prediction

Uric acidUric acid FibronectinFibronectin Coagulation activationCoagulation activation Oxidative stressOxidative stress CytokinesCytokines Placental peptidesPlacental peptides Fetal DNAFetal DNA Uterine artery Doppler velocimetryUterine artery Doppler velocimetry

Management: prevention?Management: prevention?

Low-dose AspirinLow-dose Aspirin

AntioixdantsAntioixdants

No salt intake restrictionsNo salt intake restrictions

No slimming dietNo slimming diet!!

Management: antepartum Management: antepartum hospitalizationhospitalization

Detailed examination and daily scrutiny for: Detailed examination and daily scrutiny for: headache, visual disturbances, epigastric pain headache, visual disturbances, epigastric pain and rapid weight gainand rapid weight gain

Everyday weight admittanceEveryday weight admittance

Analysis for proteinuria (every 2 days)Analysis for proteinuria (every 2 days)

Management: antepartum Management: antepartum hospitalizationhospitalization

Blood pressure readings (every 4 hours)Blood pressure readings (every 4 hours)

Measurements of plasma creatinine, Measurements of plasma creatinine, hematocrit, platelets, serum liver enzymeshematocrit, platelets, serum liver enzymes

Frequent evaluation of fetal size and Frequent evaluation of fetal size and amniotic fluid volumeamniotic fluid volume

Management: conservative Management: conservative antihypertensive therapyantihypertensive therapy

Aim: to prolong pregnancy and/or modify Aim: to prolong pregnancy and/or modify perinatal outcomesperinatal outcomes

α – metyldopaα – metyldopa: central & peripheral action; : central & peripheral action; no compromise of fetal hemodynamicsno compromise of fetal hemodynamics

LabetalolLabetalol: αβ – blocker: αβ – blocker

Management: conservative Management: conservative antihypertensive therapyantihypertensive therapy

Nifedipine, werapamilNifedipine, werapamil: Ca channel blockers: Ca channel blockers Contraindicated in I trimester! Contraindicated in I trimester! Contraindicated if high risk of eclampsia Contraindicated if high risk of eclampsia

(magnesium sulfur administration causes (magnesium sulfur administration causes hypotony)hypotony)

Dihydralazin: in severe hypertensionDihydralazin: in severe hypertension

Management: termination of Management: termination of pregnancypregnancy

Delivery is the cure for preeclampsia!Delivery is the cure for preeclampsia! Mild PE + fetal prematurity: Mild PE + fetal prematurity: temporizingtemporizing Moderate to severe PE: Moderate to severe PE: labor preinduction & labor preinduction &

inductioninduction Severe PE or unfavorable cervix: Severe PE or unfavorable cervix: elective elective

caesarian sectioncaesarian section SubarachnoidSubarachnoid analgesia recommended analgesia recommended

Hypertensive disordersHypertensive disordersin puerperiumin puerperium

PIH: recovery in few daysPIH: recovery in few days

Hypotensive agents: 3 – 4 weeks postpartumHypotensive agents: 3 – 4 weeks postpartum

PE/E: continue magnesium sulfate PE/E: continue magnesium sulfate administrationadministration 24 hours postpartum24 hours postpartum

and hypotensive agentsand hypotensive agents

Hypertensive disordersHypertensive disordersin puerperiumin puerperium

Eclampsia in puerperiumEclampsia in puerperium – most common in – most common in firstfirst 48 hours postpartum; incidentally up to 4 48 hours postpartum; incidentally up to 4 weeks postpartumweeks postpartum

Chronic hypertension – risk of cardiac failure, Chronic hypertension – risk of cardiac failure, pulmonary edema, renal failure, pulmonary edema, renal failure, eencephalopathyncephalopathy

Thank youThank you