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

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

• Preeclampsia

• Superimposed preeclampsia

• Chronic hypertension

• Gestational hypertension

Classification (NHBPEP-2000)

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

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

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

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

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

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%

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

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

Symptoms of Preeclampsia

• may be asymptomatic

• headache

• visual disturbance

• epigastric and right upper abdominal pain

• oedema

• Systolic blood pressure 140–159 mmHg

• Diastolic blood pressure 90–109 mmHg

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

Criteria for Mild Preeclampsia

• 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

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

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.

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

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.

Antihypertensive Medicaments in

Preeclampsia (4)

Other antihypertensive medicaments:

• cardioselective -blockers,

• - and -adrenoreceptor blocker (labetalol),

• urapidil,

• ketanserin,

• prazosin.

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

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

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

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

• 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

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)

Histopathology

• Fibrin thrombi in portal vessels

and periportal sinusoids

• Parenchymal haemorrhage

• Hepatocellular necrosis

MAHA

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)

cholelythiasis peptic ulcer

cholecystitis pancreatitis

viral infection kidney stones

appendicitis pyelonephritis etc.

Imitators of HELLP syndrome: TTP, HUS, AFLP

Differential Diagnosis of HELLP syndrome

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

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)

Termination of pregnancy (SC)

Corticosteroids

Abrasion

Plasmapheresis

Hysterectomy

Management of HELLP syndrome

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