ΕΓΚΥΜΟΣΥΝΗ ΕΓΚΥΜΟΣΥΝΗ ΚΑΙ ΥΠΕΡΤΑΣΗΚΑΙ ΥΠΕΡΤΑΣΗ

Ανδρέας ΠιτταράςΚαρδιολόγος

Hypertension specialist ESHΥπερτασικό Ιατρείου Τζάνειο νοσοκομείο

Υπερηχοκαρδιογραφικό εργαστήριο ΝΜΥΑ ΙΚΑ

Hypertensive disorders in pregnancy:Hypertensive disorders in pregnancy:

maternalmaternal

fetalfetal

neonatal neonatal morbidity and mortalitymorbidity and mortality

a major causea major cause ofof

Pregnant women with hypertensionPregnant women with hypertensionat higher risk forat higher risk for

abruptio placentaeabruptio placentae

cerebrovascular eventscerebrovascular events

organ failureorgan failure

DICDIC

Fetus at higher risk forFetus at higher risk for

intrauterine growth retardationintrauterine growth retardation

prematurityprematurity

intrauterine death intrauterine death

WHO definition of hypertensionWHO definition of hypertensionin pregnancyin pregnancy

1. SBP 1. SBP >> 140 mmHg or DBP 140 mmHg or DBP >> 90 mmHg 90 mmHg

2. Rise in SBP 2. Rise in SBP >> 25 mmHg or rise in DBP 25 mmHg or rise in DBP >> 15 mmHg compared to pre-pregnancy 15 mmHg compared to pre-pregnancy values or those in the first trimestervalues or those in the first trimester

Definition of hypertensionDefinition of hypertensionin pregnancyin pregnancy

SBP SBP >> 140 mmHg or DBP 140 mmHg or DBP >> 90 mmHg 90 mmHg

Cardiovascular changes in pregnancyCardiovascular changes in pregnancy

SBPSBP

DBPDBP

MAPMAP

HRHR

SVSV

COCO

4-6 mmHg4-6 mmHg

8-15 mmHg8-15 mmHg

6-10 mmHg6-10 mmHg

12-18 BPM12-18 BPM

10-30%10-30%

33-45%33-45%

All bottom at 20-24 wks, then riseAll bottom at 20-24 wks, then rise

gradually to pre-pregnancy values at gradually to pre-pregnancy values at

termterm

Early 2nd trimester, then stableEarly 2nd trimester, then stable

Early 2nd trimester, then stableEarly 2nd trimester, then stable

Peaks in early 2nd trimester, then Peaks in early 2nd trimester, then

until termuntil term

Parameter TimingParameter Timing

Main DM, Main EK: Obstetrics and Gynecology, 1984Main DM, Main EK: Obstetrics and Gynecology, 1984

Definition CHS NHBPEPWG WHODefinition CHS NHBPEPWG WHO

Hypertension,Hypertension,mmHgmmHg

Severe Severe hypertensionhypertension

DBP DBP >> 90 90

DP DP >> 110 110

BP BP >> 140/90 140/90

DP DP >> 110 or 110 orSP SP >> 160 160

BP BP >> 140/90 140/90or or riseriseSP SP >> 25 and/or 25 and/orDP DP >> 15 mmHg 15 mmHg

DP DP >> 110 110SP SP >> 160 160

CHS = Canadian Hypertension SocietyCHS = Canadian Hypertension Society

NHBEPWG = National High Blood Pressure Education Program Working Group (US)NHBEPWG = National High Blood Pressure Education Program Working Group (US)

WHO = World Health OrganizationWHO = World Health Organization

Definition ISSH ASSH ACOGDefinition ISSH ASSH ACOG

Hypertension,Hypertension,mmHgmmHg

Severe Severe hypertensionhypertension

DP DP >> 90 90

DP DP >> 110 110

DP DP >> 90 and/or 90 and/orSP SP >> 140, 140, oror rise risein SP of in SP of >> 25 and 25 andin DP of in DP of >> 15 15

DP DP >> 110 and/or 110 and/orSP SP >> 170 170

DP DP >> 90 90or SP or SP >> 140 140

DP DP >> 110 110SP SP >> 160-180 160-180

ISSH = International Society for Study of HypertensionISSH = International Society for Study of Hypertension

ASSH = Australian Society for Study of HypertensionASSH = Australian Society for Study of Hypertension

ACOG = American College of Obstetricians and GynecologistsACOG = American College of Obstetricians and Gynecologists

Criterion CHS NHBPEPWG WHOCriterion CHS NHBPEPWG WHO

KorotkoffKorotkoffsoundsound

Severe proteinuriaSevere proteinuria(24-h urine(24-h urine collection, g/d)collection, g/d)

IVIV

>> 3 3

VV

>> 2 2

IVIV

--

CHS = Canadian Hypertension SocietyCHS = Canadian Hypertension Society

NHBEPWG = National High Blood Pressure Education Program Working Group (US)NHBEPWG = National High Blood Pressure Education Program Working Group (US)

WHO = World Health OrganizationWHO = World Health Organization

Criterion ISSH ASSH ACOGCriterion ISSH ASSH ACOG

IVIV

>> 3 3

KorotkoffKorotkoffsoundsound

Severe proteinuriaSevere proteinuria(24-hr urine(24-hr urine collection, g/d)collection, g/d)

IVIV

>> 0.3 or positive 0.3 or positivedipstick result ofdipstick result of>> 2+ 2+

--

> 5> 5

ISSH = International Society for Study of HypertensionISSH = International Society for Study of Hypertension

ASSH = Australian Society for Study of HypertensionASSH = Australian Society for Study of Hypertension

ACOG = American College of Obstetricians and GynecologistsACOG = American College of Obstetricians and Gynecologists

Measurement of BPMeasurement of BP

Mercury sphygmomanometerMercury sphygmomanometer

Both Phases IV and V to be recordedBoth Phases IV and V to be recorded

Phase IV should be used for initiating Phase IV should be used for initiating clinical investigation and managementclinical investigation and management

Classification of hypertensionClassification of hypertensionin pregnancyin pregnancy

pre-existing hypertensionpre-existing hypertension

gestational hypertensiongestational hypertension pre-existing hypertension pluspre-existing hypertension plus superimposed gestational hypertensionsuperimposed gestational hypertension with proteinuriawith proteinuria

antenatally unclassifiable hypertensionantenatally unclassifiable hypertension

Pre-existing hypertensionPre-existing hypertension

1-5% of pregnancies1-5% of pregnancies

BP > 140/90 mmHg BP > 140/90 mmHg predates pregnancypredates pregnancy or develops beforeor develops before 20 weeks20 weeks of gestation of gestation

In most cases, hypertension In most cases, hypertension persists morepersists more than 42 days post partum,than 42 days post partum, it may be it may be associated with proteinuriaassociated with proteinuria

Gestational hypertensionGestational hypertension

Pregnancy-induced hypertension withPregnancy-induced hypertension withor without proteinuriaor without proteinuria

Hypertension develops Hypertension develops after 20 weeks´after 20 weeks´gestation,gestation, in most cases, in most cases, it resolves withinit resolves within42 days post partum42 days post partum

Poor organ perfusionPoor organ perfusion

Pre-existing hypertension plusPre-existing hypertension plussuperimposed gestational hypertensionsuperimposed gestational hypertension

with proteinuriawith proteinuria

Further worsening of BP and Further worsening of BP and proteinproteinexcretion > 3 g/dayexcretion > 3 g/day in 24-hour urine collection in 24-hour urine collection after 20 weeks´ gestationafter 20 weeks´ gestation

Previous terminology Previous terminology “chronic hypertension“chronic hypertension with superimposed pre-eclampsia“with superimposed pre-eclampsia“

Antenatally unclassifiable hypertensionAntenatally unclassifiable hypertension

Hypertension with or without systemicHypertension with or without systemicmanifestationmanifestation

BP BP first recorded after 20 weeks´ gestation,first recorded after 20 weeks´ gestation,re-assessment necessary at or after 42 daysre-assessment necessary at or after 42 dayspost partumpost partum

Pre-eclampsiaPre-eclampsia

Gestational hypertension associated Gestational hypertension associated with with significant proteinuriasignificant proteinuria

300 mg/l or300 mg/l or 500 mg/24 h or500 mg/24 h or dipstick 2+ or moredipstick 2+ or more

Poor organ perfusionPoor organ perfusion

Basic laboratory tests for monitoringBasic laboratory tests for monitoringhypertension in pregnancyhypertension in pregnancy

Hemoglobin and hematocritHemoglobin and hematocrit Platelet countPlatelet count Serum AST, ALT, LDH Serum AST, ALT, LDH Proteinuria (24-h urine collection)Proteinuria (24-h urine collection) UrinalysisUrinalysis Serum uric acid Serum uric acid Serum creatinineSerum creatinine

HemoglobinHemoglobin

and hematocritand hematocrit

Platelet countPlatelet count

Hemoconcentration supports diagnosis of gestationalHemoconcentration supports diagnosis of gestational

hypertension with or without proteinuria. It indicateshypertension with or without proteinuria. It indicates

severity.severity. Levels may be low in very severe cases Levels may be low in very severe cases

because of because of hemolysis.hemolysis.

Low levels < 100,000 x 10Low levels < 100,000 x 1099/L may suggest consumption/L may suggest consumption

in the microvasculature. Levels correspond to severityin the microvasculature. Levels correspond to severity

and are predictive of recovery rate in post-partumand are predictive of recovery rate in post-partum

period, especially for women with period, especially for women with HELLPHELLP syndrome.* syndrome.*

Basic laboratory tests for monitoring Basic laboratory tests for monitoring hypertension in pregnancyhypertension in pregnancy

** HELLP – Hemolysis, Elevated Liver enzyme levels and Low Platelet count HELLP – Hemolysis, Elevated Liver enzyme levels and Low Platelet count

Basic laboratory tests for monitoring Basic laboratory tests for monitoring hypertension in pregnancyhypertension in pregnancy

Serum uric Serum uric acidacid

SerumSerumcreatininecreatinine

Elevated levelsElevated levels aid in differential diagnosis of aid in differential diagnosis of

gestational hypertension and gestational hypertension and may reflect severity.may reflect severity.

Levels drop in pregnancy. Levels drop in pregnancy. Elevated levelsElevated levels suggest suggest

increasing severity of hypertensionincreasing severity of hypertension;; assessment assessment

of 24-h creatinine clearance may be necessary.of 24-h creatinine clearance may be necessary.

Basic laboratory tests for monitoring Basic laboratory tests for monitoring hypertension in pregnancyhypertension in pregnancy

Serum AST,Serum AST,

ALTALT

Serum LDHSerum LDH

Elevated levels suggest Elevated levels suggest hepatic involvement.hepatic involvement. Increasing levels suggest Increasing levels suggest worsening severity.worsening severity.

Elevated levels are associated with Elevated levels are associated with hemolysis hemolysis and and hepatic involvement.hepatic involvement. May reflect May reflect severityseverity and may and may predict potential for recovery post partum, predict potential for recovery post partum, especially for women with HELLP* syndrome.especially for women with HELLP* syndrome.

** HELLP – Hemolysis, Elevated Liver enzyme levels and Low Platelet count HELLP – Hemolysis, Elevated Liver enzyme levels and Low Platelet count

Basic laboratory tests for monitoring Basic laboratory tests for monitoring hypertension in pregnancyhypertension in pregnancy

UrinalysisUrinalysis

ProteinuriaProteinuria

(24-h urine(24-h urine

collection)collection)

Dipstick test for proteinuria has significant Dipstick test for proteinuria has significant false-positivefalse-positive

and and false-negativefalse-negative rates. If dipstick results are positive rates. If dipstick results are positive

((>> 1), 24-h urine collection is needed to confirm 1), 24-h urine collection is needed to confirm

proteinuria. Negative dipstick results do not rule outproteinuria. Negative dipstick results do not rule out

proteinuria, especially if DBP proteinuria, especially if DBP >> 90 mmHg. 90 mmHg.

Standard to quantify proteinuria. If in excess of 2g/day,Standard to quantify proteinuria. If in excess of 2g/day,

very close monitoring is warranted. If in excess of 3g/day,very close monitoring is warranted. If in excess of 3g/day,

delivery should be considered.delivery should be considered.

Management of hypertension in pregnancyManagement of hypertension in pregnancy

depends on depends on

BP levels BP levels gestational agegestational age associated maternal and fetal risk factorsassociated maternal and fetal risk factors

Non-pharmacologic managementNon-pharmacologic management

SBP 140-149 mmHg orSBP 140-149 mmHg or

DBP 90-99 mmHgDBP 90-99 mmHg

activity, bed rest (left lateral position)activity, bed rest (left lateral position)

AVOID :AVOID : weight reduction and salt restriction weight reduction and salt restriction

Emergency management of hypertensionEmergency management of hypertension in pregnancyin pregnancy

SBP ≥ 170 or DBP ≥ 110 mmHgSBP ≥ 170 or DBP ≥ 110 mmHg

hydralazine, labetalol, methyldopa or nifedipinehydralazine, labetalol, methyldopa or nifedipine

Thresholds for drug treatment initiationThresholds for drug treatment initiation

BP > 140/90 mmHg in women BP > 140/90 mmHg in women with gestational hypertension without proteinuria or with gestational hypertension without proteinuria or pre-existing hypertension before 28 weeks' gestation orpre-existing hypertension before 28 weeks' gestation or gestational hypertension and proteinuria or symptoms at any time orgestational hypertension and proteinuria or symptoms at any time or pre-existing hypertension and TOD orpre-existing hypertension and TOD or pre-existing hypertension and superimposed gestational hypertensionpre-existing hypertension and superimposed gestational hypertension

BP > 150/95 mmHgBP > 150/95 mmHg In all other circumstancesIn all other circumstances methyldopa, labetalol, calcium antagonists, and beta-blockersmethyldopa, labetalol, calcium antagonists, and beta-blockers

AVOID: ACE inhibitors, AIIA, diureticsAVOID: ACE inhibitors, AIIA, diuretics

magnesium sulfate:magnesium sulfate: eclampsia, treatment and prevention of seizures eclampsia, treatment and prevention of seizures

Br J Obstet Gynaecol 1998;105:718-22Br J Obstet Gynaecol 1998;105:718-22

Antihypertensive drugs used in pregnancyAntihypertensive drugs used in pregnancy

Women with pre-existing hypertension are advisedWomen with pre-existing hypertension are advised

to continue their current medication except for ACEto continue their current medication except for ACE

inhibitors and AIIAinhibitors and AIIA

Antihypertensive drugs used in pregnancyAntihypertensive drugs used in pregnancy

Central alfaCentral alfa

agonistsagonists

Beta-blockersBeta-blockers

Alfa-/beta-Alfa-/beta-

blockersblockers

MethyldopaMethyldopa is the is the drug of choice.drug of choice.

Atenolol Atenolol and and metoprolol metoprolol appear to be safe and effectiveappear to be safe and effective

in late pregnancy.in late pregnancy.

LabetalolLabetalol has comparable efficacy with methyldopa, has comparable efficacy with methyldopa,

in case of severe hypertension, it could be givenin case of severe hypertension, it could be given

intravenously.intravenously.

Antihypertensive drugs used in pregnancyAntihypertensive drugs used in pregnancy

Calcium-Calcium-

channel blockerschannel blockers

ACE inhibitors,ACE inhibitors,

angiotensin IIangiotensin II

antagonistsantagonists

Oral nifedipine or i.v. isradipine could be givenOral nifedipine or i.v. isradipine could be given

in hypertensive emergencies. Potential synergismin hypertensive emergencies. Potential synergism

with magnesium sulfate may induce hypotension.with magnesium sulfate may induce hypotension.

Fetal abnormalitiesFetal abnormalities including death can be caused including death can be caused

and these drugs should not be used in pregnancy.and these drugs should not be used in pregnancy.

Antihypertensive drugs used in pregnancyAntihypertensive drugs used in pregnancy

DiureticsDiuretics

DirectDirect

vasodilatorsvasodilators

Diuretics are recommended for chronic hypertensionDiuretics are recommended for chronic hypertension

if prescribed before gestation or if patients appear toif prescribed before gestation or if patients appear to

be salt-sensitive. They are not recommended inbe salt-sensitive. They are not recommended in

pre-eclampsia.pre-eclampsia.

Hydralazine Hydralazine is no longer the parenteral drug of choiceis no longer the parenteral drug of choice;;

perinatal adverse effects. perinatal adverse effects.

Breast-feedingBreast-feeding

Does not increase BP in nursing mothersDoes not increase BP in nursing mothers

All antihypertensive agents taken by the nursing All antihypertensive agents taken by the nursing mother are excreted into breast milk; however, mother are excreted into breast milk; however, most of them are present at very low concentrations, most of them are present at very low concentrations, except for propranolol and nifedipine concentrations, except for propranolol and nifedipine concentrations, which are similar to maternal plasmawhich are similar to maternal plasma

Implications of hypertension in pregnancy

Pathophysiologic factors involved in preeclampsia

Chronic hypertension     BP 140/90 mm Hg before the 20th week of gestationPreeclampsia     Elevated BP ( 140/90 mm Hg) in a patient who was normotensive before 20 weeks of gestation, accompanied by     Urinary excretion of 0.3 g of protein in a 24-h collectionOther features that increase the certainty of the diagnosis of preeclampsia     BP 160/110 mm Hg     Proteinuria 2.0 g/24 h that appears initially during pregnancy and regresses postpartum     Newly-elevated serum creatinine concentration ( 1.2 mg/dL)     Platelet count 100,000/mm3 and/or evidence of microangiopathic hemolytic anemia     Elevated hepatic enzymes (ALT or AST)

Classification of hypertensive disorders of pregnancy

Preeclampsia superimposed upon chronic hypertension (which

carries a worse prognosis than either condition alone) is more likely with

one or more of the following:

     New onset proteinuria ( 0.3 g/24 h)

     Hypertension and proteinuria before 20 weeks of gestation

     Sudden increase in proteinuria

     Sudden increase in BP, despite previous good control

     Thrombocytopenia (platelets 100,000 mm3)

     Increase in ALT or AST to abnormal levels

Classification of hypertensive disorders of pregnancy

Eclampsia    Occurrence of seizures that cannot be attributed to other causes

in a patient with preeclampsia

Gestational hypertension     Transient hypertension of pregnancy (if preeclampsia is not

present at time of delivery and BP returns to normal by 12 weeks

postpartum)

     Chronic hypertension (if the elevated BP seen during pregnancy

persists longer than 12 weeks postpartum)

Classification of hypertensive disorders of pregnancy

Management of hypertension in pregnancy

RecommendedMethyldopa initial drug of choice against which all other antihypertensive agents must be tested; used for the longest time in the treatment of hypertension in pregnancy, so it has the best long-term follow-up data supporting its lack of toxicity; also lowers the number of midtrimester abortions in hypertensive women compared with placeboHydralazine used extensively, usually with methyldopa, and considered safe for mother and fetus by most obstetricians -blockers (typically atenolol or labetalol) used with caution and concern about growth retardation, fetal bradycardia, and the ability of the fetus to withstand hypoxic stressNifedipine teratogenic in rats (at 30 the recommended dose in humans); sometimes acutely used in preterm labor, but without FDA approval

Drug therapy for hypertension in pregnancy

Drug therapy for hypertension in pregnancy

Not recommended

Diuretics cause volume depletion, which has been associated with

poor fetal outcomes

Contraindicated

ACE inhibitors or angiotensin II receptor antagonists associated

with lethal acute renal failure in neonates of women treated in the

third trimester

Relative risk of preeclampsia: calcium supplementation vs placebo

INCIDENCE OUTCOME ANTIPLT. AGENTS VS PLCB RR(95% CI)

Pregnancy-induced hypertension 795/8464 (9.4%) 810/8450 (9.6%) 0.96 (0.88 1.05)

Proteinuric preeclampsia 951/13,991 (6.8%) 1110/13,973 (7.9%) 0.85 (0.79 0.93)

Preterm delivery 1772/13,473 (13.1%) 1928/13,534 (14.2%) 0.92 (0.87 0.97)

Fetal, neonatal, or infant death 361/14,325 (2.5%) 407/14,353 (2.8%) 0.88 (0.77 1.01)

Small for gestational age 668/9439 (7.1%) 701/9448 (7.4%) 0.94 (0.85 1.04)

Preeclampsia: efficacy of anti-platelet agents vs placebo