Hypertension_during_pregnancy

Hypertension during pregnancy

Dr. Yosra Tahir
Ninevah College of Medicine

Learning outcomes

After completing this lecture you should know:
• What blood pressure changes occur during a normal pregnancy
2. How to diagnose hypertension in pregnancy
3. How to diagnose and manage pre-eclampsia
4. When to start antihypertensive treatment
5. What antihypertensive drugs are suitable during pregnancy and breast feeding.

Introduction

Hypertension is the most common medical problem seen in pregnancy and is an important cause of morbidity and mortality for the mother and fetus.
It complicates about 15% of pregnancies and causes about 25% of all antenatal admissions, and is a marker for future cardiac and metabolic disease.

• The hypertensive disorders of pregnancy cover a spectrum of conditions, of which pre-eclampsia poses the greatest risk. Pre-eclampsia is one of the most common causes of maternal death. 17.6% of the causes of maternal death is due to pregnancy induced hypertension
• About one in two thousand women will have an eclamptic convulsion but the associated maternal mortality is 2%


Normal changes in blood pressure during pregnancy
Early in the first trimester there is a fall in blood pressure caused by vasodilation. This is caused by local mediators, such as prostacyclin and nitric oxide.

This reduction in blood pressure primarily affects the diastolic pressure, and a drop of 10 mm Hg is usual by 13-20 weeks' gestation.

Blood pressure continues to fall until 22-24 weeks. After this, there is a gradual increase in blood pressure until term, when blood pressure returns to the level it was before pregnancy. Immediately after delivery blood pressure usually falls and then increases over the next five days.

Even women whose blood pressure was normal throughout pregnancy may experience transient hypertension in the early period post partum. This perhaps reflects a degree of vasomotor instability.

Definition of hypertension in pregnancy and blood pressure measurement

You can diagnose hypertension in pregnancy from an absolute rise in blood pressure or from a relative rise above measurements obtained at booking (around 12 weeks).
The definition for a relative rise in blood pressure incorporates a rise in systolic pressure of >30 mm Hg or a rise in diastolic pressure of >15 mm Hg above blood pressure at booking.

Blood pressure must be elevated on at least two occasions and measurements should be made with the woman seated and using the appropriate cuff size. Late in the second trimester and in the third trimester, the pregnant uterus may obstruct venous return. If you take the woman's pressure while she is lying down, she should be lying on her side.

You should use Korotkoff V (disappearance) rather than phase IV (muffling) because it is more reproducible and shows better correlation with true diastolic blood pressure in pregnancy. If phase V is not present, you should record phase IV.
Automated systems for measuring blood pressure are unreliable in severe pre-eclampsia and they tend to under-record the true value

Definitions

The conventional definition of hypertension in pregnancy is:
• Diastolic BP ≥ 110 mmHg on any one occasion OR
• Diastolic BP ≥ 90 mmHg on 2 or more consecutive occasions ≥4 h apart
C. Systolic pressure >140 mm Hg on 2 or more consecutive occasions ≥4 h apart


But remember that blood pressure changes with normal pregnancy.

Proteinuria in pregnancy:

A. One 24 h collection with total protein excretion ≥300 mg per 24 h OR
B. Two ‘clean-catch – midstream’ or catheter specimens of urine collected ≥4 h apart with ≥2 + on reagent strip

Pathophysiology

poor trophoblast invasion in the myometrium, this results in maternal spiral arteries being hampered in their normal physiological vasodilatation this impairs intervillous blood flow and results in inadequate perfusion and ischaemia in the second half of pregnancy. This probably results in the production of reactive oxygen species and a condition of oxidative stress exists

Classification of hypertensive disorders of pregnancy

There are four types of hypertensive disorders:
A. Gestational or pregnancy induced hypertension and /or proteinuria developing during pregnancy, labour or the puerperium in a previously normotensive /nonproteinuric woman
• Gestational hypertension (without proteinuria)
• Gestational proteinuria (without hypertension)
• Gestational proteinuric hypertension (pre-eclampsia)

Classification of hypertensive disorders of pregnancy

B. Chronic hypertension (before the 20th week of pregnancy) and chronic renal disease (proteinuria before the 20th week of pregnancy)
• Chronic hypertension (without proteinuria)
• Chronic renal disease (proteinuria with or without hypertension)
• Chronic hypertension with superimposed pre-eclampsia (new onset proteinuria)
C. Unclassified hypertension and/or proteinuria
D. Eclampsia


Pre-existing hypertension
Pre-existing hypertension complicates 3-5% of pregnancies, although this figure may rise with the trend for women to postpone childbirth into their 30s and 40s.
You can diagnose someone with pre-existing hypertension if they have:
A known history of hypertension pre-pregnancy or
An elevated blood pressure ≥140/90 mm Hg before 20 weeks' gestation

Women with pre-existing hypertension that has not been diagnosed may appear normotensive in early pregnancy because of the normal fall in blood pressure starting in the first trimester. This may mask the pre-existing hypertension, and when you find hypertension later in the pregnancy you may interpret this as gestational
Sometimes the diagnosis only comes to light several months after the birth, when the blood pressure fails to return to normal as you would expect with gestational hypertension
Pre-eclampsia can occasionally present before 20 weeks' gestation: you may then misinterpret it as pre-existing hypertension

The presence of mild pre-existing hypertension approximately doubles the risk of pre-eclampsia and increases the risk of abruption of the placenta and restriction of growth in the fetus.
when pre-existing hypertension is severe (diastolic blood pressure >110 mm Hg before 20 weeks' gestation) the risk of pre-eclampsia is as high as 46%

Gestational hypertension

Gestational hypertension without proteinuria is hypertension occurring in the second half of pregnancy complicates 6-7% of pregnancies and resolves after the birth.
The risk of superimposed pre-eclampsia is 15-26%. But when gestational hypertension starts after 36 weeks of pregnancy, the risk falls to 10%.
With gestational hypertension, blood pressure usually returns to normal by six weeks after birth.

Pre-eclampsia and eclampsia

Pre-eclampsia usually occurs after 20 weeks' gestation and is a multisystem disorder. It is a disease of primigravida
It was classically defined as a triad of:
Hypertension
Oedema
Proteinuria.
But a more modern definition of pre-eclampsia concentrates on a rise in blood pressure during pregnancy together with >0.3 g proteinuria in 24 hours. Oedema is no longer included because it is not specific.
Pre-eclampsia may be associated with fetal growth restriction.


Pre-eclampsia and eclampsia
Eclampsia is the occurrence of a grand mal seizure in association with pre-eclampsia, although it may be the first presentation of the condition.
The incidence of pre-eclampsia is influenced by the presence of existing hypertension, although there are other risk factors.

Risk factors for developing pre-eclampsia

• Nulliparity, maternal age more than 40
Multiple pregnancy, raised diastolic pressure more than 80
Family history of pre-eclampsia
Pre-existing hypertension
Diabetes
Increased insulin resistance
Increased body mass index
Renal disease even without significant impairment
Antiphospholipid syndrome (acquired thrombophilia)
Previous pre-eclampsia
Hydatidiform mole
Black race

pre-eclampsia complicates 5-6% of pregnancies, but this figure increases to up to 25% in women with pre-existing hypertension. Eclampsia complicates 1-2% of pre-eclamptic pregnancies.
An estimated 50 000 women die each year from pre-eclampsia worldwide. Morbidity includes:
Placental abruption
Intra-abdominal haemorrhage from rupture liver
Cardiac failure
Multiorgan failure.
The most common cause of death is due to intracranial hemorrhage.


The risks to the fetus from pre-eclampsia
include:
Growth restriction secondary to placental insufficiency
Preterm delivery. pre-eclampsia is one of the most common causes of preterm delivery (accounting for 25% of all infants with very low birth weight, <1500 g).

Managing hypertension in pregnancyPre-pregnancy counselling

In women with pre-existing hypertension, assessment before conception allows:
Exclusion of secondary causes of hypertension (for example, renal and endocrine causes)
Optimal blood pressure control
Discussion of the increased risks of pre-eclampsia
Education about drug alterations that should be made prior to pregnancy or in the first trimester if the woman becomes pregnant.

Most women with controlled chronic hypertension will, under close supervision and management, have a successful outcome. Poorly controlled hypertension in the first trimester significantly increases maternal and fetal morbidity and mortality.
Most of the many antihypertensive drugs used in routine practice have not been shown to be teratogenic and women can safely conceive while taking medication. You should withdraw ACE inhibitors and angiotensin receptor blockers pre-pregnancy or early in the first trimester because they are teratogenic and fetotoxic.

Women who have experienced poor obstetric outcomes in previous pregnancies because of severe pre-eclampsia, and those at particular risk, should receive counselling about the condition, and you should also offer prophylactic treatment with low dose aspirin

Antenatal careGeneral maternal care

Checking for hypertension and proteinuria is the cornerstone of antenatal screening of all pregnant women for pre-eclampsia. Part of the assessment should include:
Doppler ultrasound of the uterine arteries around the time of the fetal anomaly scan at 20-22 weeks
Blood tests.

Laboratory tests

Full blood count
Thrombocytopenia, or haemoconcentration, or both suggest severe pre-eclampsia
Urea and electrolytes
Urea and creatinine are reduced in uncomplicated pregnancy. "Normal" values may indicate renal impairment
Liver function tests
Transaminase concentrations increase in pre-eclampsia and are always elevated in HELLP (haemolysis, elevated liver enzymes, and low platelets) syndrome (a variant of pre-eclampsia)
Urate
Levels rise in pre-eclampsia, largely due to reduced renal excretion
Clotting screen
When the platelet count <100 x 109/l
Blood film
Microangiopathic haemolytic anaemia may occur in patients with severe pre-eclampsia

Depending on the severity of maternal symptoms, the clinical findings, and the fetal growth pattern, consider referring patients to a day assessment unit to allow regular review as an outpatient. Alternatively, consider admitting the patient. New onset proteinuria and hypertension is an indication for immediate referral.
Many women are initially asymptomatic or report malaise. But headache, visual disturbance, and abdominal pain are well recognised signs of severe pre-eclampsia and imminent eclampsia


Surveillance of the fetus
In women with either pre-existing hypertension or pre-eclampsia, the fetus is at risk of intrauterine growth restriction. You should offer these women regular ultrasound scans to assess fetal growth, liquor volume, and blood flow through the umbilical artery.
When pre-eclampsia is severe, and there is a significant risk of delivery before 34-36 weeks' gestation, the steroid betamethasone should be given intramuscularly to the mother to enhance fetal lung maturity in anticipation of preterm delivery.

When to treat hypertension during pregnancy

Significant hypertension must be treated in its own right, regardless of the assumed underlying pathology, largely to reduce the incidence of maternal intracranial haemorrhage.
The level at which you should start antihypertensive treatment for non-severe hypertension is controversial. Most doctors start antihypertensives when:
Systolic blood pressure is >140-160 mm Hg or
Diastolic pressure is >90-110 mm Hg.
Treatment is mandatory for severe hypertension (when the blood pressure is ≥160/110 mm Hg).

The blood pressure you should aim to achieve is also controversial, but many practitioners would treat to keep the mean arterial pressure <125 mm Hg - for example, a blood pressure of < 150/100 mm Hg.
Lowering the blood pressure too much may lead to placental hypoperfusion because placental blood flow is not autoregulated. This will affect the fetus.
there is no evidence that treating chronic or gestational hypertension protects against the development of pre-eclampsia. There is no evidence that changes in diet or bed rest benefit the mother or fetus

Drug treatment

All antihypertensive drugs cross the placenta and reach the fetal circulation. Most of the antihypertensive agents in routine use are not teratogenic, although ACE inhibitors and angiotensin receptor blockers are, and should be avoided.
The objective of treating hypertension in pregnancy is to protect the woman from dangerously high blood pressure and to permit continuation of the pregnancy and growth of the fetus

Mild to moderate hypertension

Treating mild to moderate pre-existing hypertension in pregnancy benefits the mother, but there is no clear evidence of an enhanced outcome for the baby.
Some women with mild treated pre-existing hypertension are able to stop their medication in the first half of pregnancy because of the physiological fall in blood pressure during this period. But this is usually temporary, and women should be monitored and treatment restarted as soon as necessary


First line drugsMethyldopa
Methyldopa is a centrally acting agent and is the drug of first choice for treating hypertension in pregnancy. It is the most thoroughly assessed antihypertensive in randomised trials and has the longest safety track record. Long term use has not been associated with fetal or neonatal problems. 250 mg tab.tds
You should warn women that it can cause sedation; this can limit the dose used. The drug may cause liver transaminases to rise (in up to 5% of women) or a positive Coomb's test (although haemolytic anaemia is uncommon). You should not give methyldopa to women with a prior history of depression, because of the increased risk of postnatal depression

Second line drugs

You should use these drugs when monotherapy with methyldopa is insufficient or when women cannot tolerate methyldopa.
Nifedipine
Nifedipine is popular for treating hypertension in pregnancy. It is safe at any stage of gestation. You should avoid sublingual nifedipine to minimise the risk of sudden maternal hypotension and fetal distress, caused by placental hypoperfusion.
Giving concomitant magnesium sulphate can exacerbate abrupt hypotension.

Oral labetalol

This is used by some as a first line agent. It is a combined alpha and beta blocker and appears safe in pregnancy. Since beta blockers have been associated with growth restriction when used from the first trimester, the preference is to avoid labetalol until later in pregnancy.
Oral hydralazine 25mg tab
Hydralazine is safe throughout pregnancy, although there have been reports of lupus-like syndromes in the mother and neonate.
Hydralazine is more frequently used as an infusion for treating acute severe hypertension

Third line drugsAlpha and beta adrenergic blockers

you should avoid beta adrenergic blockers in the first half of pregnancy because of concerns about growth restriction.
Prazosin is safe and effective in pregnancy.
Thiazide diuretics
These drugs do not appear to be teratogenic. Although they reduce the expansion in plasma volume associated with normal pregnancy, this has not been proved to impair fetal growth.
They are usually avoided in the treatment of hypertension in pregnancy, their use is reserved for cardiac disease and pulmonary oedema.


Severe hypertension
Because of the reduction in the circulating plasma volume, women may be very sensitive to relatively small doses of antihypertensive agents (and diuretics), risking abrupt reductions in blood pressure.
Good control of hypertension in severe pre-eclampsia does not halt the progression of the disease, only delivery can do this, but it can reduce the incidence of complications such as cerebral haemorrhage.
Managing severe hypertension involves adequately controlling the blood pressure, often using parenteral agents and "expectant" management by trying to prolong the pregnancy without unduly risking the mother or fetus. In patients with severe hypertension you may gain only hours or days

Different units have their preferences for intravenous hydralazine or labetalol, which are equally effective, but the latter has fewer side effects. Oral nifedipine may also be used.
You should give hydralazine only after giving intravenous fluid: this reduces the reflex tachycardia, and abrupt hypotension, precipitated by vasodilation. Dose is 20 mg in slow iv infusion
These women are high risk and should be managed in a intensive care unit. They are sensitive to being overloaded with fluid and are at risk of developing non-cardiac pulmonary oedema, through capillary leak.

You should admit patients with severe forms of pre-eclampsia to intensive care, especially if they develop respiratory failure or the severe systemic inflammatory response syndrome.
Seizure prophylaxis, with intravenous magnesium sulphate, should be given to those with symptoms and signs of severe pre-eclampsia and those with eclampsia.

Treatment of eclamptic fit

first ABC.
An eclamptic fit is usually self-limiting; however, anticonvulsive therapy should be given to abort it when possible. Magnesium sulphate can be used to control such a fit (up to 8 g given by slow intravenous infusion).
in preventing further fits Magnesium sulphate is given in a 2 g intravenous loading dose in an infusion of 1 g/h.

Antihypertensive drugs to avoid in pregnancy

ACE inhibitors and angiotensin receptor blockers are teratogenic and fetotoxic.
In some women of childbearing age, for example those with renal disease and heavy proteinuria, these drugs are of particular benefit. Women may conceive while taking these agents provided they are discontinued as soon as pregnancy is confirmed in the early first trimester.
Although the greatest risk to the fetus appears to be associated with exposure in the third trimester, the earlier the drugs are withdrawn, the better. All women of childbearing age treated with ACE inhibitors or angiotensin receptor blockers should be informed to stop them as soon as pregnancy is detected


ACE inhibitors and angiotensin receptor blockers can cause:
Oligohydramnios
Fetal growth restriction
Contractures of the joints
Pulmonary hypoplasia
Cardiovascular and central nervous system malformations
Incomplete ossification of the fetal skull
Fetal renal tubular dysplasia
Neonatal renal failure.

Antihypertensive treatment post partum and during breast feeding

Hypertension is common post partum. Blood pressure typically rises after delivery over the first five days. Therefore, women who experienced hypertension during pregnancy may be normotensive immediately after the birth, but then become hypertensive again in the first postnatal week. The need to get blood pressure under control may delay discharge.
You should avoid methyldopa post partum because of the risk of postnatal depression. first line agent is atenolol, plus nifedipine or an ACE inhibitor if another agent is required.
Women with gestational hypertension or pre-eclampsia are usually able to stop all antihypertensives within six weeks after birth. Women with pre-existing hypertension can resume the drugs they were taking before they became pregnant. But women who want to breast feed should avoid diuretics because they can increase thirst

Proteinuria in pre-eclamptic women will usually resolve by three months post partum if there is no underlying renal abnormality. You should refer patients with persistent proteinuria to a nephrologist for further investigations.
Breast feeding
You can give most antihypertensive drugs used in routine practice to women who are breast feeding.

Risk of recurrence of hypertensive disorders in a subsequent pregnancy

Women who experience hypertension in a first pregnancy have a higher risk of hypertension in a subsequent pregnancy.
Factors influencing this risk include:
Stage at onset - the earlier the onset of hypertension in the first pregnancy, the greater the risk of recurrence
Type of hypertensive disorder.
One study reported a risk of recurrence of:
19% for gestational hypertension
32% for pre-eclampsia
46% for pre-eclampsia superimposed on pre-existing chronic hypertension
In addition, severe isolated fetal growth restriction is a risk factor for developing hypertension in a subsequent pregnancy.


Long term consequences of pregnancy induced hypertension
Women who develop gestational hypertension or pre-eclampsia are at increased risk of hypertension and stroke in later adult life. Furthermore, there is evidence of an increased risk of ischaemic heart disease in women who have experienced pre-eclampsia or isolated fetal growth restriction.
An association between pre-eclampsia and an increased risk of ischaemic heart disease in later adult life. Both conditions are associated with dyslipidaemia, insulin resistance, and endothelial dysfunction.
the lipid abnormalities that occur in pre-eclampsia (raised low density lipoprotein, very low density lipoprotein, free fatty acid, and triglyceride values) pre-date the clinical appearance of the condition.
Women who have hypertension during pregnancy should subsequently have their blood pressure measured annually.