د.نادية مضر الحلي Hypertensive Disorders of Pregnancy
Definition of Hypertension:
BP should be measured in the sitting position with a cuff that is large enough for the subject arm. Hypertension is defined as one of the following :
1. One measurement of diastolic BP of 110 mmHg or more; or
2. Two consecutive measurements of diastolic BP of ? 90 mmHg 4 hours or more apart.
Definition of proteinuria:
1. One 24-h urine collection with a total protein excretion of 300 mg or more; or
2. Two random clean-catch urine specimen with a 2+ or more on reagent strip.
Pre-eclampsia: is defined as hypertension associated with proteinuria arising de novo after the 20th week of gestation in a previously normotensive woman & resolving completely by the 6th postpartum week.
Eclampsia: is a serious life-threatening complication of pre-eclampsia when tonic-clonic convulsion occur in a woman with established pre-eclampsia, in the absence of any other neurological or metabolic cause.
Gestational hypertension: hypertension arising for the first time in the second half of pregnancy without the development of proteinuria, this usually have no important maternal or fetal consequences.
Chronic hypertension: hypertension which is apparent prior to, in the first half of, or persisting more than 6 weeks after pregnancy. superimposed pre-eclampsia in the presence of chronic hypertension is usually associated with worsening of the hypertension & the development, or worsening of proteinuria.
Incidence & Epidemiology:
Pre-eclampsia complicate about 3% of pregnancies. It is more common in primigravid women. There is genetic predisposition with a 3-4 fold increase in the incidence of pre-eclampsia in the first degree relatives of affected women. Risk factors for the development of pre-eclampsia include:
1. conditions in which the placenta is enlarged ( multiple gestation, diabetes, hydrops)
2. pre-existing hypertension or renal disease.
3. pre-existing vascular disease (as in diabetes or autoimmune vasculitis.
Aetiology:
During normal pregnancy, the cytotrophoblast invade the uterine spiral arteries & the inner part of the myometrium. Invasion of the spiral arteries is associated with degeneration of the tunica media & replacement by fibrinoid material resulting in marked dilatation of the spiral artery & increased intervillous blood flow.
In pre-eclampsia, trophoblast invasion is patchy & the spiral arteries retain their muscular walls which will prevent the development of high-flow, low-impedence uteroplacental circulation. Under-perfusion of the placenta causes it to release certain factors into the maternal circulation which target the vascular endothelium & cause dysfunction.
Pathophysiology:
The clinical picture of pre-eclampsia is due to activation or dysfunction of vascular endothelial cells. Normal pregnancy is characterized by marked peripheral vasodilatation resulting in a fall in total peripheral resistance. This peripheral vasodilatation is accomplished through a reduced vascular sensitivity to vasoconstrictors such as angiotensin. In pre-eclampsia the insensitivity to vasoconstrictors is lost. Vasospasm & endothelial cell dysfunction, with subsequent platelet activation & micro-aggregate formation, account for many pathological features of pre-eclampsia seen in every major organ system. These include:
Cardiovascular:
• Generalized vasospasm
• Increased peripheral resistance
Haematological
• Platelet activation & depletion
• Coagulopathy
• Decreased plasma volume
• Increased blood viscosity
Renal
• Proteinuria
• Decreased glomerular filtration rate
• Decreased uric acid excretion
Hepatic
• Periportal necrosis
• Subcapsular haematoma
Central nervous system
• Cerebral oedema
• Cerebral haemorrhage
Loss of endothelial cell integrity result in an increase in vascular permeability & contribute to the formation of generalized oedema. Dependent oedema of feet is common in normal pregnancy. However, rapidly progressing oedema of the face & hands is suggestive of pre-eclampsia.
Symptoms of pre-eclampsia:
• May be asymptomatic
• Headache
• Visual disturbance
• Epigastric & right upper abdominal pain
Signs of pre-eclampsia:
• Elevation of blood pressure
• Fluid retention ( non-dependant oedema)
• Ankle clonus(more than three beats) in severe disease.
• Uterus & fetus may feel small for gestational age
Screening tests: many tests have been tried to predict PE in those at risk , yet no blood test found to be specific & sensitive. Doppler ultrasound of the uterine artery waveform analysis has been used in pregnant women at risk of PE because of their medical or past obstetrical history. In pregnancies with inadequate or incomplete trophoblast invasion of the spiral arteries, a characteristic notch can be seen in the waveform pattern.
The most commonly used preventive therapy is low-dose aspirin (75 mg daily). Aspirin inhibits the synthesis of prostaglandins by inactivating cyclo-oxygenase, however, low dose aspirin will inhibit platelet activation & the release of vasoactive compounds such as thromboxane without impairing the synthesis of vasodilating prostaglandins (prostacyclin) produced by the vascular endothelium.
Management:
Women who have a diastolic blood pressure ? 90 mmHg need further assessment. The following investigations should be done:
• Urinalysis by dipstick
• 24-hour urine collection ( total protein & creatinine clearance)
• Full blood count ( platelet & haematocrit)
• Blood chemistry ( renal function, protein concentration)
• Plasma uric acid concentration
• Liver function test
• Coagulation profile
• Ultrasound assessment:
1. Fetal size
2. amniotic fluid volume
3. maternal & fetal Doppler
These investigations will be repeated at intervals depending on the overall picture.
A diagnosis of pre-eclampsia usually requires admission of the patient for more intensive investigations & monitoring of her condition. When the BP is only mildly elevated (diastolic BP 90-95 mmHg) & there is minimal proteinuria with normal haematological & biological parameters, it may be possible to monitor the patient as an outpatient, attending for regular fetal & maternal monitoring. However in more severe cases admission is mandatory.
Severe pre-eclampsia:
Criteria of severe pre-eclampsia are:
• BP of 160 mmHg systolic or 110 mmHg diastolic on at least two occasions at least 6 h apart with patient at rest.
• Proteinuria of 5 g per 24 h.
• Oliguria ( 400 ml in 24 h ).
• Cerebral or visual disturbance.
• Epigastric pain.
• Pulmonary oedema or cyanosis.
• Impaired liver function.
• Thrombocytopenia.
The mainstay of treatment of PE is by ending the pregnancy by delivering the fetus & placenta. This can be a significant problem for the baby if PE occurs at early gestation. The aim of antihypertensive therapy is to lower blood pressure & reduce the risk of maternal cerebrovascular accident without reducing uterine blood flow & compromising the fetus.
A variety of antihypertensives used in the management of PE:
• Hydralazine: arterial vasodilator used in acute treatment of severe hypertension, given in 5 mg intravenous boluses repeated every 20 minutes accordingly.
• Labetolol is an alpha & beta- blocking agent, can be given orally or intravenously & has good safety during pregnancy.
• Methyldopa is a centrally acting antihypertensive agent, safe during pregnancy but can be given orally only & takes up to 24 hours to take effect.
• Nifedipine is a calcium channel blocker with a rapid onset of action. It can cause severe headache which mimic worsening of disease.
patient with severe pre-eclampsia should be admitted & monitored closely because of the risk of developing eclampsia (imminent eclampsia), then acute treatment of severe hypertension, seizure prophylaxis with magnesium sulphate if imminent eclampsia & termination of pregnancy if indicated.
Management of labour & delivery:
Providing the maternal & fetal condition are satisfactory, expectant management should be continued to 37-38 weeks gestation. Deferring delivery beyond this gestation confers no benefit to the infant & increase the risk of deterioration in the maternal & fetal condition. Indication for preterm delivery are:
1. severe uncontrolled hypertension ( ? 160/110 mmHg)
2. haemolysis with thrombocytopenia & elevated ALT
3. progressive symptoms (headache, visual disturbance, epigastric pain)
4. pulmonary oedema
5. renal compromise with oliguria
6. eclampsia
7. fetal distress
The mode of delivery is determined by gestational age, the state of the cervix & fetal condition. The chances of successful induction of labour are low in primigravidae with unfavourable cervix. A high proportion of cases are delivered by caesarean section particularly when delivery need to be expedited because of concerns about maternal condition. Prolonged pushing should be avoided, ergometrine should not be used in the active management of the third stage because of the risk of dangerous hypertension, instead syntocinon should be administered. Fluid management is important in severe PE because the low plasma volume & cardiac output increase the possibility of fetal distress & oliguria. However, endothelial damage, low oncotic pressure & excessive fluid administration increase the risk of pulmonary oedema, so, accurate recording of fluid balance is required with administration of fluid maintenance ( 1 litre Ringer lactate / 12 h).The use of diuretics should be confined to women with pulmonary oedema.
Postnatal councelling: women who developed PE are at increased risk of recurrence in the next pregnancy. The risk of recurrence is increased with increased severity of PE. Those women are at increased risk of death from cardiovascular disease in the future particularly in those who remain hypertensive in the puerperium. Measurement of remote postnatal BP is therefore important. If BP returns to normal there is no contraindication to oral contraceptive.