Hypertension specialist ESH

Hypertensive disorders in pregnancy:

maternal
fetal
neonatal morbidity and mortality
a major cause of
Pregnant women with hypertension
at higher risk for
abruptio placentae
cerebrovascular events
organ failure
DIC
Fetus at higher risk for
intrauterine growth retardation
prematurity
intrauterine death
WHO definition of hypertension
in pregnancy
1. SBP > 140 mmHg or DBP > 90 mmHg

2. Rise in SBP > 25 mmHg or rise in DBP
> 15 mmHg compared to pre-pregnancy
values or those in the first trimester
Definition of hypertension
in pregnancy
SBP > 140 mmHg or DBP > 90 mmHg
Cardiovascular changes in pregnancy
SBP
DBP
MAP
HR
SV
CO
4-6 mmHg
8-15 mmHg
6-10 mmHg
12-18 BPM
10-30%
33-45%
All bottom at 20-24 wks, then rise
gradually to pre-pregnancy values at
term
Early 2nd trimester, then stable
Early 2nd trimester, then stable
Peaks in early 2nd trimester, then
until term
Parameter Timing
Main DM, Main EK: Obstetrics and Gynecology, 1984
Definition CHS NHBPEPWG WHO
Hypertension,
mmHg



Severe
hypertension
DBP > 90




DP > 110
BP > 140/90




DP > 110 or
SP > 160
BP > 140/90
or rise
SP > 25 and/or
DP > 15 mmHg

DP > 110
SP > 160
CHS = Canadian Hypertension Society
NHBEPWG = National High Blood Pressure Education Program Working Group (US)
WHO = World Health Organization
Definition ISSH ASSH ACOG
Hypertension,
mmHg



Severe
hypertension
DP > 90




DP > 110
DP > 90 and/or
SP > 140, or rise
in SP of > 25 and
in DP of > 15

DP > 110 and/or
SP > 170
DP > 90
or SP > 140



DP > 110
SP > 160-180
ISSH = International Society for Study of Hypertension
ASSH = Australian Society for Study of Hypertension
ACOG = American College of Obstetricians and Gynecologists
Criterion CHS NHBPEPWG WHO
Korotkoff
sound

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


> 3
V


> 2
IV


-
CHS = Canadian Hypertension Society
NHBEPWG = National High Blood Pressure Education Program Working Group (US)
WHO = World Health Organization
Criterion ISSH ASSH ACOG
IV


> 3
Korotkoff
sound

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


> 0.3 or positive
dipstick result of
> 2+
-


> 5
ISSH = International Society for Study of Hypertension
ASSH = Australian Society for Study of Hypertension
ACOG = American College of Obstetricians and Gynecologists
Measurement of BP
Mercury sphygmomanometer

Both Phases IV and V to be recorded

Phase IV should be used for initiating
clinical investigation and management
Classification of hypertension
in pregnancy
pre-existing hypertension
gestational hypertension
pre-existing hypertension plus
superimposed gestational hypertension
with proteinuria
antenatally unclassifiable hypertension
Pre-existing hypertension
1-5% of pregnancies

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

In most cases, hypertension persists more
than 42 days post partum, it may be
associated with proteinuria
Gestational hypertension
Pregnancy-induced hypertension with
or without proteinuria

Hypertension develops after 20 weeks
gestation, in most cases, it resolves within
42 days post partum
Poor organ perfusion
Pre-existing hypertension plus
superimposed gestational hypertension
with proteinuria
Further worsening of BP and protein
excretion > 3 g/day in 24-hour urine collection
after 20 weeks gestation

Previous terminology chronic hypertension
with superimposed pre-eclampsia
Antenatally unclassifiable hypertension
Hypertension with or without systemic
manifestation

BP first recorded after 20 weeks gestation,
re-assessment necessary at or after 42 days
post partum
Pre-eclampsia

Gestational hypertension associated
with significant proteinuria
300 mg/l or
500 mg/24 h or
dipstick 2+ or more

Poor organ perfusion
Basic laboratory tests for monitoring
hypertension in pregnancy
Hemoglobin and hematocrit
Platelet count
Serum AST, ALT, LDH
Proteinuria (24-h urine collection)
Urinalysis
Serum uric acid
Serum creatinine
Hemoglobin
and hematocrit



Platelet count
Hemoconcentration supports diagnosis of gestational
hypertension with or without proteinuria. It indicates
severity. Levels may be low in very severe cases
because of hemolysis.

Low levels < 100,000 x 10
9
/L may suggest consumption
in the microvasculature. Levels correspond to severity
and are predictive of recovery rate in post-partum
period, especially for women with HELLP syndrome.*
Basic laboratory tests for monitoring
hypertension in pregnancy
* HELLP Hemolysis, Elevated Liver enzyme levels and Low Platelet count
Basic laboratory tests for monitoring
hypertension in pregnancy
Serum uric
acid

Serum
creatinine
Elevated levels aid in differential diagnosis of
gestational hypertension and may reflect severity.

Levels drop in pregnancy. Elevated levels suggest
increasing severity of hypertension; assessment
of 24-h creatinine clearance may be necessary.
Basic laboratory tests for monitoring
hypertension in pregnancy
Serum AST,
ALT

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

Elevated levels are associated with hemolysis and
hepatic involvement. May reflect severity and may
predict potential for recovery post partum,
especially for women with HELLP* syndrome.
* HELLP Hemolysis, Elevated Liver enzyme levels and Low Platelet count
Basic laboratory tests for monitoring
hypertension in pregnancy
Urinalysis





Proteinuria
(24-h urine
collection)
Dipstick test for proteinuria has significant false-positive
and false-negative rates. If dipstick results are positive
(> 1), 24-h urine collection is needed to confirm
proteinuria. Negative dipstick results do not rule out
proteinuria, especially if DBP > 90 mmHg.

Standard to quantify proteinuria. If in excess of 2g/day,
very close monitoring is warranted. If in excess of 3g/day,
delivery should be considered.
Management of hypertension in pregnancy

depends on
BP levels
gestational age
associated maternal and fetal risk factors
Non-pharmacologic management
SBP 140-149 mmHg or
DBP 90-99 mmHg

activity, bed rest (left lateral position)

AVOID : weight reduction and salt restriction
Emergency management of hypertension
in pregnancy


SBP 170 or DBP 110 mmHg
hydralazine, labetalol, methyldopa or nifedipine
Thresholds for drug treatment initiation

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

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

AVOID: ACE inhibitors, AIIA, diuretics

magnesium sulfate: eclampsia, treatment and prevention of seizures
Br J Obstet Gynaecol 1998;105:718-22
Antihypertensive drugs used in pregnancy
Women with pre-existing hypertension are advised
to continue their current medication except for ACE
inhibitors and AIIA
Antihypertensive drugs used in pregnancy
Central alfa
agonists

Beta-blockers


Alfa-/beta-
blockers
Methyldopa is the drug of choice.


Atenolol and metoprolol appear to be safe and effective
in late pregnancy.

Labetalol has comparable efficacy with methyldopa,
in case of severe hypertension, it could be given
intravenously.
Antihypertensive drugs used in pregnancy
Calcium-
channel blockers


ACE inhibitors,
angiotensin I I
antagonists
Oral nifedipine or i.v. isradipine could be given
in hypertensive emergencies. Potential synergism
with magnesium sulfate may induce hypotension.

Fetal abnormalities including death can be caused
and these drugs should not be used in pregnancy.
Antihypertensive drugs used in pregnancy
Diuretics




Direct
vasodilators
Diuretics are recommended for chronic hypertension
if prescribed before gestation or if patients appear to
be salt-sensitive. They are not recommended in
pre-eclampsia.

Hydralazine is no longer the parenteral drug of choice;
perinatal adverse effects.
Breast-feeding


Does not increase BP in nursing mothers

All antihypertensive agents taken by the nursing
mother are excreted into breast milk; however,
most of them are present at very low concentrations,
except for propranolol and nifedipine concentrations,
which 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 gestation
Preeclampsia
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 collection
Other 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/mm
3
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 mm
3
)
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
Recommended
Methyldopa 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 placebo
Hydralazine 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 stress
Nifedipine 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