ΕΓΚΥΜΟΣΥΝΗ ΚΑΙ ΥΠΕΡΤΑΣΗ Ανδρέας Πιτταράς...
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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
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