hypertensive disorders of pregnancy · hypertensive disorders of pregnancy affect 10-20% of...

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Attila Molvarec, MD, PhD 1st Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary Hypertensive Disorders of Pregnancy

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Page 1: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

Attila Molvarec, MD, PhD

1st Department of Obstetrics and Gynecology, Semmelweis

University, Budapest, Hungary

Hypertensive Disorders of Pregnancy

Page 2: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

Hypertensive disorders of pregnancy

Affect 10-20% of pregnancies

Increasing incidence (increase in maternal age,

obesity, multiple pregnancies, chronic diseases)

Major causes of maternal and perinatal morbidity and

mortality

15% of preterm deliveries (In Hungary: 1200 preterm

births/year)

30% of maternal deaths

Page 3: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

• Preeclampsia

• Superimposed preeclampsia

• Chronic hypertension

• Gestational hypertension

Classification (NHBPEP-2000)

Page 4: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

HYPERTENSION IN PREGNANCY

hypertension after

midpregnancy with or w/o

proteinuria

=

gestational hypertension

preeclampsia

hypertension

already present before

pregnancy or diagnosed in

the first half of pregnancy

=

chronic hypertension

Page 5: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

Causes of

Chronic Hypertension in Pregnancy

• Chronic essential hypertension (90%)

• Renal

– Acute and chronic glomerulonephritis

– Interstitial nephritis

– Diabetic glomerulosclerosis

– Renal artery stenosis

– Polycystic kidney disease

– Renal transplant

• Endocrine

– Cushing’s disease and syndrome

– Hyperaldosteronism

– Pheochromocytoma

• Other

– Coarctation of the aorta

– Collagen vascular disease

Page 6: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

Etiology of Preeclampsia

Disease of theories

• „X” factor

• abnormal lipid metabolism

• reduced antioxidant status

• reduced production of nitric oxide

• abnormal immune response to pregnancy

• dietary calcium, magnesium, selenium content

Page 7: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

Etiology of Preeclampsia

Disturbed interaction between NK cells and extravillous

cytotrophoblast

• HLA-E: inhibit cytolytic activity through CD94/NKG2A

• HLA-G: stimulate angiogenic cytokine (VEGF, PlGF,

angiopoietin-2) production through KIR2DL4

• HLA-C: regulate cytokine production

KIRA: inhibitory KIRB: stimulatory

HLA-C2 + KIRAA

Page 8: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

HELLP syndrome, DIC

Eclampsia

Abruptio placentae

Pulmonary oedema

Acute renal failure

Liver failure or haemorrhage

Hypertensive encephalopathy, stroke

Death

Long-term cardiovascular morbidity

Maternal complications

Page 9: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

Causes of Maternal Mortality in

Preeclampsia

Cerebral haemorrhage 30–40%

Pulmonary oedema 30–38%

Cerebral oedema 19%

Renal failure 10%

Coagulopathy 9%

Airway obstruction 6%

Page 10: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

Preterm delivery

Fetal growth restriction (IUGR)

Hypoxia-neurologic injury

Perinatal death

Long-term cardiovascular morbidity

associated with low birtweight (fetal origin

of adult diseases)

Perinatal complications

Page 11: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

Organ-specific Changes

Associated with Preeclampsia

• Cardiovascular: generalized vasospasm, increased peripheral

resistance

• Central nervous: cerebral oedema and haemorrhages

• Hepatic: periportal necrosis, subcapsular haematoma

• Renal: proteinuria, decreased GFR rate and urate excretion

• Haematological:

– platelet activation and depletion, coagulopathy

– decreased plasma volume

Page 12: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

Symptoms of Preeclampsia

• may be asymptomatic

• headache

• visual disturbance

• epigastric and right upper abdominal pain

• oedema

Page 13: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

• Systolic blood pressure 140–159 mmHg

• Diastolic blood pressure 90–109 mmHg

• Proteinuria >300 mg/day but <5 g/day

Criteria for Mild Preeclampsia

Page 14: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

• Blood pressure readings with the patients at rest, of at least

160 mmHg systolic or 110 mmHg diastolic on two occasions

at least 6 h apart,

• Proteinuria levels of at least 5 g in a 24 h urine collection,

• Impaired liver function,

• Thrombocytopenia (PLT <100 000/L),

• Oliguria 24 urine output <400 ml,

• Visual disturbances, headache, epigastric pain

• Pulmonary oedema or cyanosis

Criteria for Severe Preeclampsia

Page 15: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

Investigations for Preeclampsia

(prenatal care)

• BP and pulse rate controll

• 24 h urine collection (total protein)

• Full blood count (Hb, Htk, PLT)

• Liver and renal function

• Obs. subjective signs of preeclampsia

• Haemodynamic controll

• Ultrasound assessment

• NST

Page 16: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

Antihypertensive Medicaments

in Preeclampsia (1)

Methyldopa:

• it has been extensively studied,

• its safe use is well established,

• it reduces systemic vascular resistance,

• peak plasma concentration reached 2 hours,

• maximum fall in arterial pressure occurs 4–8 hours

after an oral dose,

• doses: 500–3000 mg in two to four divided doses.

Page 17: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

Antihypertensive Medicaments in

Preeclampsia (2)

Calcium channel blockers:

• nifedipine for acute and chronic treatment,

• it may be given as second-line treatment or in

combination with methyldopa or a -blocker,

• with magnesium-sulphate may result profound

hypotension,

• it does not affect on uteroplacental blood flow

Page 18: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

Antihypertensive Medicaments in

Preeclampsia (3)

Hydralazine:

• for the acute management of hypertensive

emergencies,

• it reduces blood pressure by lowering systemic

vascular resistence,

• it has variable effect on uteroplacental blood flow,

• after volume expansion fetal distress does not occur.

Page 19: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

Antihypertensive Medicaments in

Preeclampsia (4)

Other antihypertensive medicaments:

• cardioselective -blockers,

• - and -adrenoreceptor blocker (labetalol),

• urapidil,

• ketanserin,

• prazosin.

Future: NO donors (?), prostacyclin (?)

Page 20: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

ACE inhibitors (Angiotensin II receptor blockers)

• 1st trimester

• Cardiovascular malformations

(RR: 3,72 95% CI: 1,89 -7,30)

• Central nervous system malformations (RR: 4,39 95% CI: 1,37-14,02)

• 2nd-3rd trimester

• Fetal hypotension, renal tubular dysplasia, anuria-

oligohydramnios, pulmonary hypoplasia, IUGR

• Hypocalvaria

• Intrauterine death

Drugs contraindicated in pregnancy

Page 21: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

Indications for Delivery in

Patients with Preeclampsia

Maternal indications: (One or more of following)

• Uncontrolled severe hypertension (RR>160/110 mmHg despite

max. recommended doses of two antihypertensive medications)

• Eclampsia

• GOT or GPT > 2x upper limit of normal with epigastric pain

• Platelet count < 100 000/L

• Persistent severe headache or visual changes

• Pulmonary oedema

• Compromised renal function

• Abruptio placentae

Page 22: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

Indications for Delivery in

Patients with Preeclampsia

Fetal indications:

• Severe growth retardation (fetal weight < 5th percentile)

• Pathologic NST

• Pathologic fetal or umbilical blood flow

• Biophysical profile < 6

• Severe oligohydramnios (AF index < 2)

• Gestational age > 37 weeks in mild preeclampsia

> 34 weeks in severe preeclampsia

Page 23: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

• Decreased plasma colloid oncotic pressure

1. Used of large amount of crystalloids

2. Loss of albumin in urine and interstitium

3. Blood loss during and after delivery

• Increased capillary wedge pressure

1. Iatrogenic fluid overload

2. Postpartum mobilization of extravascular fluid

3. Impaired renal function or renal failure

• Capillary endothelial damage

1. Increased permeability

2. Increased interstitial oncotic pressure

• Left ventricular dysfunction

Mechanisms Associated with

Pulmonary Oedema in Preeclampsia

Page 24: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

H = hemolysis

• abnormal peripheral smear

• lactate dehydrogenase (LDH) > 600 U/L

EL = elevated liver enzymes

• serum aminotransferases (AST, ALT) > 70 U/L

• lactate dehydrogenase (LDH) > 600 U/L

LP = low platelets

• platelet count < 150 000/L (Mississippi I:<50, II: 51-100,

III: 101-150)

EPIGASTRIC PAIN in 90%

HELLP syndrome (Weinstein 1982)

Page 25: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

Histopathology

• Fibrin thrombi in portal vessels

and periportal sinusoids

• Parenchymal haemorrhage

• Hepatocellular necrosis

Page 26: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

MAHA

Page 27: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

Frequency: 10–15 % in severe preeclampsia

Clinical symptoms:

Malaise 100%

Nausea (with or without vomiting) 100%

Epigastric pain 90%

Right upper–quadrant tenderness on palpitation 100%

Oedema 69%

Weinstein – HELLP syndroma (n=29)

Page 28: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

cholelythiasis peptic ulcer

cholecystitis pancreatitis

viral infection kidney stones

appendicitis pyelonephritis etc.

Imitators of HELLP syndrome: TTP, HUS, AFLP

Differential Diagnosis of HELLP syndrome

Page 29: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

Thrombotic microangiopathies

• Frequency: 1/25000 (as in non-pregnant women)

• Pregnancy does not predispose, in the 3rd trimester or postpartum

• Thrombotic thrombocytopenic purpure (TTP): MAHA, thrombocytopenia,

neurological disturbances, renal dysfunction and fever

ADAMTS13 activity<10% (ADAMTS13 gene mutations, autoantibodies,

drugs)

• Hemolytic uremic syndrome: renal failure is dominant, neurological

symptoms are rare

Shiga- and verocytotoxin producing bacteria, pneumococcus sepsis,

complement regulatory defects (hereditary or acquired)

• Therapy: corticosteroids, plasmapheresis, IVIG, transfusion, dialysis

Page 30: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

DIC 21%

Abruptio placentae 16%

Acute renal failure 8%

Severe ascites 8%

Pulmonary oedema 6%

Below 5%:

Subcapsular liver hematoma, ARDS,

cerebral oedema

Maternal letality: 1–24%

Maternal Complications

in 442 Patients with HELLP syndromes (Sibai BM: Am J Obstet Gynecol 1993; 169: 1000–1006)

Page 31: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

Termination of pregnancy (SC)

Corticosteroids

Abrasion

Plasmapheresis

Hysterectomy

Management of HELLP syndrome

Page 32: Hypertensive Disorders of Pregnancy · Hypertensive disorders of pregnancy Affect 10-20% of pregnancies Increasing incidence (increase in maternal age, obesity, multiple pregnancies,

There is no reliable early biochemical marker (sFlt-1,

PlGF?)

Uterine artery doppler: in high-risk population

Low dose aspirin: in high-risk women

LMWH: in thrombophilias

Calcium supplementation: at high risk with low dietary

calcium intake

Not recommended: antioxidant vitamins (C, E), fish oil

Prediction and prevention of preeclampsia