Preeclampsia:

Classification, Diagnosis, and

Management Update

dr. Rima Irwinda, SpOG (K)

Divisi Fetomaternal
Dept Obstetri dan Ginekologi
FKUI-RSCM
 The revised classification for hypertensive
disorders in pregnancy
Chronic hypertension
Gestational hypertension
Preeclampsia de novo or superimposed on chronic hypertension
White coat hypertension

ISSHP does not advocate for any clinical distinction between

mild and severe preeclampsia in usual clinical practice.

The classification, diagnosis and management of the hypertensive disorders of pregnancy: A revised
statement from the ISSHP. Pregnancy Hypertension: An International Journal of Womens Cardiovascular
Health 4 (2014) 97104
 Diagnosis?
The terminology is inconsistent
Several systems of nomenclature are in use around the world

There is a general consensus that the factors determining severity

and indication to expedite delivery are the difficulty in controlling
blood pressure and the deteriorating clinical conditions (HELLP
syndrome, impending eclampsia, worsening thrombocytopenia, or
worsening fetal growth restriction)

Andrea L. Tranquilli, Mark A. Brown, Gerda G. Zeeman, Gustaaf Dekker, Baha M. Sibai. The definition
of severe and early-onset preeclampsia. Statements from the International Society for the Study of
Hypertension in Pregnancy (ISSHP)
 The revised ISSHP definition preeclampsia
(2014)
Hypertension developing after 20 weeks gestation and the
coexistence of one or more of the following new onset conditions:
1. Proteinuria
2. Other maternal organ dysfunction:
Renal insufficiency (creatinine >90 umol/L)
Liver involvement (elevated transaminases and/or severe right upper
quadrant or epigastric pain)
Neurological complications
Haematological complications
3. Uteroplacental dysfunction
Fetal growth restriction
The classification, diagnosis and management of the hypertensive disorders of pregnancy: A revised
statement from the ISSHP. Pregnancy Hypertension: An International Journal of Womens Cardiovascular
Health 4 (2014) 97104
 Blood pressure Statements of ISSHP
Considered severely elevated: >160
mmHg systolic or >110 mmHg diastolic.
Not to rely on a single reading,
appropriate-sized cuff
In the case of severely elevated BP not to
wait for 6 h apart, but in 15-30 m
Suggest mercury sphygmomanometry or
sphygmomanometry using a liquid crystal
device. If an automated device is to be
used then it should have been validated
for use in pregnancy.

Andrea L. Tranquilli, Mark A. Brown, Gerda G. Zeeman, Gustaaf Dekker, Baha M. Sibai. The definition
of severe and early-onset preeclampsia. Statements from the International Society for the Study of
Hypertension in Pregnancy (ISSHP)
 Proteinuria for the diagnosis of preeclampsia

Does not predict clinical outcome

A spot urine protein/creatinine ratio > 30 mg/mmol
There is no clear consensus on the amount of proteinuria to
be considered severe (between >3 and 5 g/l)
NOT CONSIDER PROTEINURIA FOR DEFINING SEVERE
PREECLAMPSIA

Andrea L. Tranquilli, Mark A. Brown, Gerda G. Zeeman, Gustaaf Dekker, Baha M. Sibai. The definition
of severe and early-onset preeclampsia. Statements from the International Society for the Study of
Hypertension in Pregnancy (ISSHP)
Camille E. Powe, AB; Richard J. Levine; S. Ananth Karumanchi. Circulation. 2011;123:2856-2869
 Two-stage model of development of preeclampsia

CHRISTOPHER W.G. REDMAN, IAN L. SARGENT AND ROBERT N. TAYLOR. Immunology of Normal Pregnancy
and Preeclampsia. Chesleys Hypertensive Disorder in Pregnancy
 Four-stage model of development of preeclampsia

CHRISTOPHER W.G. REDMAN, IAN L. SARGENT AND ROBERT N. TAYLOR. Immunology of Normal Pregnancy
and Preeclampsia. Chesleys Hypertensive Disorder in Pregnancy
Anne Cathrine Staff, et al. Redefining Preeclampsia Using Placenta-Derived Biomarkers. Hypertension. 2013;61:932-942
 Poor ability to Predict Pre-Eclampsia
Test No of studies No of women Sn (95% CI) Sp (95% CI)
BMI>34 2 16200 18 (15 - 21) 93 (87 - 97)
BMI>29 8 410823 23 (15 - 33) 88 (80 - 93)
BMI>24.2 9 440214 41 (29 - 53) 75 (62 - 84)
BMI<19.8 7 152720 11 (8 - 16) 80 (73 - 86)
AFP 12 137097 9 (5 - 16) 96 (94 - 98)
Fibronectin cellular 2 135 50 (30 - 70) 96 (79 - 99)
Fibronectin total 3 373 65 (42 - 83) 94 (86 - 98)
Foetal DNA 3 351 50 (31 - 69) 88 (80 - 93)
HCG 16 72732 24 (16 - 35) 89 (86 - 92)
Oestriol 3 26811 26 (9 - 56) 82 (61 - 93)
Serum uric acid 5 514 36 (22 - 53) 83 (73 - 90)
Urinary calcium excretion 4 705 57 (24 - 84) 74 (69 - 79)
Urinary calcium/creatinine ratio 6 1345 50 (36 - 64) 80 (66 - 89)
Total proteinuria 4 2228 35 (13 - 68) 89 (79 - 94)
Total albuminuria 2 88 70 (45 - 87) 89 (79 - 94)
Microalbuminuria 2 190 62 (23 - 90) 68 (57 - 77)
Microalbumin/creatinine ratio 1 1422 19 (12 - 28) 75 (73 - 77)
Kallikreinuria 1 307 83 (52 - 98) 98 (98 - 100)
SDS Page proteinuria 1 153 100 (88 - 100) 69 (60 - 77)
Doppler any/unilateral notching 19 14345 63 (51 - 74) 82 (74 - 87)
Doppler bilateral notching 21 29331 48 (34 - 62) 92 (87 - 95)
Doppler other ratios 8 2619 55 (37 - 72) 80 (73 - 86)
Doppler pulsatility index 8 14697 48 (29 - 69) 87 (75 - 94)
Doppler resistance index 29 7982 66 (54 - 76) 80 (74 - 85)
Doppler combinations of FVW 25 22896 64 (54 - 74) 86 (82 - 90)

0 20 40 60 80 100 0 20 40 60 80 100

Source: Meads CA, 2008. Sensitivity Specificity

Risk Factor Risk Ratio
Nulliparity 3
Age>40 years 3
African-american race 1.5
Family history of pregnancy induced hypertension 5
Chronic hypertension 10
Chronic renal disease 20
Antiphospholipid syndrome 10
Diabetes mellitus 2
Twin gestation 4

Revised from ACOG. Hypertension in pregnancy

 Primary Prevention of PE
Intervention No of RCTs No of women RR (95% CI)
Ambulatory BP 0 0
Bed rest for high BP 1 228 0.98 (0.80, 1.20)
Exercise 2 45 0.31 (0.01, 7.09)
Rest alone for normal BP 1 32 0.05 (0.00, 0.83)
Altered dietary salt 2 631 1.11 (0.46, 2.66)
Antioxidants 7 6082 0.61 (0.50, 0.75)
Calcium 12 15206 0.48 (0.33, 0.69)
Nutritional advice 1 136 0.98 (0.42, 1.88)
Balanced protein/energy intake 3 512 1.20 (0.77, 1.89)
Isocaloric balanced protein supplementation1 782 1.00 (0.57, 1.75)
Energy/protein restriction 2 284 1.13 (0.59, 2.18)
Garlic 1 100 0.78 (0.31, 1.93)
Magnesium 2 474 0.87 (0.57, 1.32)
Marine oils 4 1683 0.86 (0.59, 1.27)
Antihypertensives v none 19 2402 0.99 (0.84, 1.18)
Antiplatelets 43 33439 0.81 (0.75, 0.88)
Diuretics 4 1391 0.68 (0.45, 1.03)
Nitric oxide donors and precursors 4 170 0.83 (0.49, 1.41)
Progesterone 1 128 0.21 (0.03, 1.77)

0.01 0.1 0.2 0.5 1 2 5 10

Relative Risk (95% Confidence Interval)
 SEIZURE PROPHYLAXIS AND TREATMENT
In the Magpie study, 10,000 preeclamptic women were randomized
to receive magnesium sulfate or placebo.
Magnesium sulfate clearly reduced the risk of eclampsia in this trial,
and it was shown to be superior to other prophylactic medications,
including phenytoin, and diazepam.

RCT of MgSO4 prophylaxis with placebo or active drug in women with gestational hypertension

JAMES M. ALEXANDER AND F. GARY CUNNINGHAM. Clinical Management. . Chesleys Hypertensive

Disorder in Pregnancy
 Randomized comparative trials of Magnesium Sulfate
with Another Anticonvulsant to Prevent Recurrent
Eclamptic Convulsions

JAMES M. ALEXANDER AND F. GARY CUNNINGHAM. Clinical Management. . Chesleys Hypertensive

Disorder in Pregnancy
 In women with normal renal function, the half-time for excretion is
about 4 hours.
Because excretion depends on delivery of a filtered load of
magnesium that exceeds the Tmax, the half-time of excretion is
prolonged in women with a decreased GFR

Magnesium slows or blocks neuromuscular and cardiac

conducting system transmission, decreases smooth muscle
contractility, and depresses central nervous system irritability
 Magnesium sulfate and uterine effect

Inhibition of uterine contractility is magnesium dose

dependent
Serum levels of at least 8-10 mEq/L are necessary to inhibit
uterine contractions (Watt-Morse, 1995)

Therapeutic dose of MgSO4 as anticonvulsant prophylaxis does

not inhibit uterine contraction

JAMES M. ALEXANDER AND F. GARY CUNNINGHAM. Clinical Management. . Chesleys Hypertensive

Disorder in Pregnancy
 Hypertensive
Crisis
Hypertensive urgency
SBP > 180 mmHg and/or DBP > 120
mmHg may have severe headache or
dyspnea, but no progressive end
organ damage
Reduce blood pressure over 2448 h
The Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure
Hypertensive emergency
Pre-eclampsia/eclampsia AND
SBP > 160 mmHg and/or DBP > 110
mm Hg
OR
Markedly elevated BP (DBP > 120
mmHg) AND progressive acute end-
organ damage (aortic dissection,
acute myocardial infarction,
pulmonary edema, and respiratory
failure)
Immediate: decrease mean arterial
pressure by 1525% Target: SBP 140
150 mmHg, DBP 90100 mmHg
 Autoregulation of Cerebral Blood Flow
is Affected by Hypertension

Cerebral
Cerebral Blood Flow

Risk of
Loss
Loss of
of Autoregulation
hypertensive
encephalopathy
Normotensive

Poorly controlled
Risk of
ischemia hypertensive

50 100 150 200 250

Mean Arterial Pressure (MAP)

Adapted with permission from Varon J, Marik PE. Chest. 2000;118:214-227.

 Antihypertensive Drugs
Regulation of Blood Pressure
Blood pressure = Cardiac output x Systemic vascular resistance

Cardiac
Cardiac factors
factors Circulating
Circulating volume
volume
Heart
Heart rate
rate Salt
Salt
Contractibility
Contractibility Aldosterone
Aldosterone
Drugs Drugs
1. Beta-blokers 1. ACE inhibitors
2. Calcium channel blokers 2. Diuretics
3. Centrally acting adrenergics

Peripheral
Peripheral sympathetic
sympathetic CNS Lokal
Hormones
Hormones CNS Lokal
receptors
receptors
Vasodilators
Vasodilators Constrictors
Constrictors 1. Centrally acting 1. Peripherally
Vasoconstrictors
Vasoconstrictors Dilators
Dilators adrenergics acting adrenergics
1. Vasodilators Receptors
2. Prostaglandins
3. ACE inhibitors
4. Calcium channel blokers Alpha Beta
5. Angiotensin II blokers 1. Alpha1-blokers 1. Beta-blokers

Normal regulation of blood pressure and corresponding medications. ACE = Angiotensin-coonverting en-zyme; CNS = central nervous system.

Mosby items and derived items 2007, 2005, 2002 by Mosby. Inc. , an affiliate of Elsevier Inc.
 Treatment of Mild-Moderate Hypertension

JASON G. UMANS, EDGARDO J. ABALOS AND F. GARY CUNNINGHAM. Antihypertensive treatment. Chesleys
Hypertensive Disorder in Pregnancy
 Randomized Placebo-Controlled Trials of Antihypertensive Therapy for Early
Mild Hypertension During Pregnancy

JASON G. UMANS, EDGARDO J. ABALOS AND F. GARY CUNNINGHAM. Antihypertensive treatment. Chesleys Hypertensive Disorder in
Pregnancy
 DRUGS FOR TREATMENT OF SEVERE HYPERTENSION IN PREGNANCY

Drug Dose Onset Duration Adverse Effects

Hydralazine 510 mg IV q 20 min 1020 min 36 h Tachycardia, headache, flushing,

aggravation of angina

Labetalol 2040 mg IV q 10 min 1 1020 min 36 h Scalp tingling, vomiting, heart block
mg/kg as needed

Nifedipine 1020 mg PO q 2030 min 1015 min 45 h Headache, tachycardia, synergistic

interaction with magnesium sulfate

Nicardipine 515 mg/h IV 510 min 14 h Tachycardia, headache, phlebitis

Sodium 0.255 g/kg/min IV Immediate 12 min Nausea, vomiting, muscle twitching,

nitroprusside thiocyanate and cyanide intoxication

Nitroglycerin 5100 g/min IV 25 min 35 min Headache, methemoglobinemia,

tachyphylaxis
 INDICATIONS FOR DELIVERY OF THE FETUS IN SEVERE
PREECLAMPSIA
ABSOLUTE RELATIVE
MATERNAL
Convulsion Severe hypertension
Cerebral irritability Right upper quadrant
Heart failure Abdominal pain
Oliguria with urine output<20mL/hr Heavy proteinuria
Uncontrollable hypertension
Rising serum creatinine (>50%)
Thrombocytopenia
Disseminated intravascular coagulation
Clinical placental abruption

FETAL
Fetal distress Intrauterine growth retardation

Modified from Gallery EDM: Hypertension in pregnancy. Practical management recommendations. Drugs 1995;49:4:561.
 ACTIVE OR EXPECTANT?

Lower SGA, Higher HMD and admission to SCBU

Eclampsia is lower with Magnesium Sulphate
 Long term consequences?

Bellamy L et al. BMJ 2007;335:974

 Preeclampsia & Ischemic heart disease

Bellamy L et al. BMJ 2007;335:974

2007 by British Medical Journal Publishing Group

 Bellamy L et al. BMJ 2007;335:974

2007 by British Medical Journal Publishing Group

 Bellamy L et al. BMJ 2007;335:974

2007 by British Medical Journal Publishing Group

Thank You