Obstetric disorders

Definitions

Hypertension in pregnancy is defined as a systolic pressure above 140mmHg or a diastolic pressure above 90mmHg on two or more occasions at least 4 hours apart. Diastolic pressure is taken at the fifth Korotkoff sound. At times in pregnancy, there is no fifth sound; in these circumstances, it is necessary to use the fourth sound.

Some definitions of hypertension also include reference to a rise in systolic pressure of at least 30mmHg or a rise in diastolic pressure of at least 15mmHg. There is no evidence that these women have adverse outcomes if the systolic BP remains less than 140 mmHg or diastolic less than 90 mmHg.

Proteinuria is defined as the presence of urinary protein in concentrations greater than 0.3g/L in a 24-hour collection or in concentrations greater than 1g/L on a random sample on two or more occasions at least 6 hours apart.

Oedema is defined as the development of pitting oedema or a weight gain in excess of 2.3kg in a week. Oedema occurs in the limbs, particularly in the feet and ankles and in the fingers, or in the abdominal wall and face ( Fig. 8.1 ). Oedema is very common in otherwise uncomplicated pregnancies. This is the least useful sign of hypertensive disease. It has therefore been dropped from many classifications of pregnancy-induced hypertension.

Classification

The various types of hypertension are classified as follows:

• Gestational hypertension is characterized by the new onset of hypertension without any features of pre-eclampsia after 20 weeks of pregnancy or within the first 24 hours postpartum. Although by definition the blood pressure should return to normal by 12 weeks after pregnancy; it usually returns to normal within 10 days after delivery.

• Pre-eclampsia is the development of hypertension with proteinuria after the twentieth week of gestation. It is more commonly a disorder of women in their first pregnancy.

• Eclampsia is defined as the development of convulsions secondary to pre-eclampsia in the mother.

• Chronic hypertensive disease is the condition in which hypertension has been present before pregnancy and may be due to various pathological causes.

• Superimposed pre-eclampsia or eclampsia is the development of pre-eclampsia in a woman with chronic hypertensive disease or renal disease.

• Unclassified hypertension includes those cases of hypertension arising in pregnancy on a random basis where there is insufficient information for classification.

Pathogenesis and pathology of pre-eclampsia and eclampsia

The exact nature of the pathogenesis of pre-eclampsia remains uncertain. Nearly every major system in the body is affected by the advanced manifestations of the condition. Therefore, every system that is studied appears to show changes without necessarily doing more than manifesting secondary effects.

The pathophysiology of the condition, as outlined in Figure 8.2 , is characterized by the effects of:

• Arteriolar vasoconstriction, particularly in the vascular bed of the uterus, placenta and kidneys

• DIC

Blood pressure is determined by cardiac output (stroke volume × heart rate) and peripheral vascular resistance. Cardiac output increases substantially in normal pregnancy, but blood pressure normally falls in the mid-trimester. Thus, the most important regulatory factor is the loss of peripheral resistance that occurs in pregnancy. Without this effect, all pregnant women would presumably become hypertensive!

As sympathetic tone appears to remain unchanged, peripheral resistance is determined by the balance between humoral vasodilators and vasoconstrictors. In pregnancy, there is a specific loss of sensitivity to angiotensin II, which normally counters the effect of locally active vasodilator prostaglandins, resulting in systemic vasodilatation. However, any factors that increase the activity of the renin–angiotensin system or reduce the activity of tissue prostaglandins will result in raising of the BP, thus countering the normal pregnancy changes.

Pre-eclamptic women appear to retain some sensitivity to infused angiotensin II, and there is evidence that platelet AII receptors are increased, all of which increases the chance of vasoconstriction and platelet aggregation.

Current evidence also suggests that pre-eclampsia is a disease of endothelial dysfunction. Nitric oxide (NO) or endothelial-derived relaxing factor (EDRF) is a potent vasodilator. In pre-eclampsia, NO synthesis is reduced, possibly because of an inhibition of NO synthetase activity.

A further area of consideration is the damaging effect of lipid peroxides on the endothelium. Normally, the production of antioxidants limits these effects, but in pre-eclampsia, antioxidant activity is decreased and endothelial damage occurs throughout the body, resulting in fluid loss from the intravascular space. All these changes occur in the second trimester long before a rise in BP is measurable in the mother.

Once vasoconstriction occurs in the placental bed, it results in placental damage and the consequent release of trophoblastic material into the peripheral circulation. This trophoblastic material is rich in thromboplastins, which precipitate variable degrees of DIC. This process gives rise to the pathological lesions, most notably in the kidney, liver and placental bed. The renal lesion results in sodium and water retention, with most of this fluid moving to the extracellular space due to vascular endothelial damage which permits fluid extravasation. In fact, the intravascular space is reduced in severe pre-eclampsia as plasma volume diminishes. At the same time, increased sodium retention results in increased vascular sensitivity to vasoconstrictor influences, which promotes further vasoconstriction and tissue damage in a vicious circle of events that may ultimately result in acute renal failure with tubular or cortical necrosis, hepatic failure with periportal necrosis, acute cardiac failure and pulmonary oedema, and even cerebral haemorrhage as BP becomes uncontrolled.

As the vasoconstriction progresses, the placenta becomes grossly infarcted, and this results in intrauterine growth restriction, increased risk of abruption and sometimes fetal death.

Why do some women develop pre-eclampsia and others do not? Is there a genetic predisposition in some women? The answer to this second question is almost certainly yes. Longitudinal studies in the United States, Iceland and Scotland have shown that the daughters of women who have suffered from pre-eclampsia or eclampsia have themselves a one in four chance of developing the disease, a risk that is 2.5 times higher than in the daughters-in-law of such women. The data suggest that a single recessive maternal gene is associated with pre-eclampsia. However, the data could also support a hypothetical model of dominant inheritance with partial penetrance. Although various gene loci have been proposed, further long-term studies are ongoing to try and identify the correct candidate gene. It is in fact unlikely that there is a single pre-eclampsia gene; it is probable that there are interactions between several genes, with external environmental factors enhancing this predisposition. These factors include autoimmune conditions, diseases that increase venous and arterial thromboembolic disease (thrombophilias) and the existence of underlying chronic renal disease or essential hypertension. Dietary intake may also be a factor.

The renal lesion

The renal lesion is, histologically, the most specific feature of pre-eclampsia ( Fig. 8.3 ). The features are:

• Swelling and proliferation of endothelial cells to such a point that the capillary vessels are obstructed.

• Hypertrophy and hyperplasia of the intercapillary or mesangial cells.

• Fibrillary material (profibrin) deposition on the basement membrane and between and within the endothelial cells.

The characteristic appearance is therefore one of increased capillary cellularity and reduced vascularity. The lesion is found in 71% of primigravid women who develop pre-eclampsia but in only 29% of multiparous women. There is a much higher incidence of women with chronic renal disease in multiparous women.

The glomerular lesion is always associated with proteinuria and with reduced glomerular filtration resulting in a raised serum creatinine. Decreased renal blood flow and proximal tubular changes result in impaired uric acid secretion, leading to hyperuricaemia.

Placental pathology

Placental infarcts occur in normal pregnancy but are considerably more extensive in pre-eclampsia. The characteristic features in the placenta ( Fig. 8.4 ) include:

• increased syncytial knots or sprouts

• increased loss of syncytium

• proliferation of cytotrophoblast

• thickening of the trophoblastic basement membrane

• villous necrosis

In the uteroplacental bed, the normal invasion of extravillous cytotrophoblast along the luminal surface of the maternal spiral arterioles does not occur beyond the deciduomyometrial junction, and there is apparent constriction of the vessels between the radial artery and the decidual portion ( Fig. 8.5 ). These changes result in reduced uteroplacental blood flow and in placental hypoxia.

Other associations with pregnancy hypertension

It has been postulated that pre-eclampsia may be due to an abnormality of the maternal host response to placentation. There is a lower incidence of pre-eclampsia in consanguineous marriages and an increased incidence of hypertension in first pregnancies of second marriages. Levels of human leukocyte antigen (HLA)-G are altered in pre-eclamptic women.

Indices of cell-mediated immune response have also been shown to be altered in severe pre-eclampsia. However, there are many other factors that operate independently from any potential immunological factors, such as race, climatic conditions and genetic or familial factors. One of these includes raised free fatty acids found in pre-eclampsia and their possible causative role in the increased incidence of pre-eclampsia in women with diabetes and obesity.

Management of gestational hypertension and pre-eclampsia

The object of management is to prevent the development of eclampsia and to minimize the risks of the condition to both the mother and the fetus. The achievement of these objectives depends on careful scrutiny of the condition of both the mother and the fetus and timely intervention to terminate the pregnancy when the risks of continuation outweigh the risks of intervention.

Laboratory investigations

• Full blood count with particular reference to platelet count and haemolysis.

• Tests for renal and liver function.

• Uric acid measurements: a useful indicator of progression in the disease.

• Clotting studies where there is severe pre-eclampsia and/or thrombocytopaenia.

• Catecholamine measurements in the presence of severe hypertension, particularly where there is no proteinuria, to rule out phaeochromocytoma.

Case study

Mrs F was pregnant with her first child after a long history of subfertility. She had been admitted to hospital before her pregnancy for tubal evaluation by dye laparoscopy, but at no time then or subsequently during her pregnancy had she shown any evidence of hypertension. At 32 weeks’ gestation, she was admitted to hospital at 10 pm with acute headache and severe hypertension, with a BP reading of 220/140 mmHg. There was no proteinuria and no hyper-reflexia. There was no evidence of fetal growth restriction. Despite initial attempts to control her BP with intravenous hydralazine and labetalol, and despite delivery of the fetus, her hypertension remained severe and uncontrollable and she went into high-output cardiac failure and died at 7 am the following morning. Autopsy revealed a large phaeochromocytoma in the right adrenal gland.

This is an extremely rare form of hypertension in pregnancy. It has an appalling prognosis unless it is detected early and the tumour removed. In this case, it presented late. All other antenatal recordings of BP had been normal. Although it would not have helped in this case as the BP readings were always normal, where hypertension is severe and presents early in pregnancy, it is always worth checking urinary catecholamines.

Fetoplacental investigations

Pre-eclampsia is an important cause of fetal growth restriction and perinatal death, and it is therefore essential to monitor fetal wellbeing using the following methods:

• Serial ultrasounds for:

  • Measurements of fetal growth every 2 weeks. Parameters measured are fetal biparietal diameter, head circumference, abdominal circumference and femur length.

  • Measurements of liquor volume and fetal Doppler studies up to twice weekly.

  • Daily cardiotocography (CTG) in advanced cases close to requiring delivery.

Doppler flow studies

• The use of serial Doppler waveform measurements in the fetus with every assessment of liquor is an essential part of assessment of the fetal wellbeing/oxygenation status. The resistance to flow in the umbilical artery is a measure of placental blood vessel integrity, with raised resistance being a measure of small-vessel disease. The fetal middle cerebral artery normally has a high resistance pattern, and a fall in resistance relates to vasodilatation and fetal hypoxia. Where the resistance in the umbilical vessels exceeds that in the middle cerebral vessels (cerebral/placental ratio (CPR) is less than 1), the fetus is at significant risk of morbidity associated with hypoxia. Consideration must be given to very close observation or delivery of these pregnancies, regardless of the fetal growth parameters, albeit that fetuses that are growth restricted from maternal pre-eclampsia are more likely to have an abnormal CPR than an appropriately grown fetus. At any time, absent or reverse flow in diastole in the umbilical artery of the fetus indicates severe vessel disease, with probable severe fetal compromise, and delivery of the fetus must be considered if the CTG is abnormal.

• As a single investigation, doppler ultrasound of maternal vessels after 14 weeks has not been shown to add to the ability to effectively treat maternal pre-eclampsia.

• Antenatal CTG measured daily in admitted cases of pre-eclampsia: CTG recordings are used in conjunction with Doppler assessment. The measurement of the antenatal CTG (fetal heart rate in relation to uterine activity) provides a useful tool in the detection of fetal wellbeing. A normal reactive trace is an assurance of a non-hypoxic fetus. A trace with recurrent decelerations and a loss of baseline variability is a strong indication of fetal metabolic acidaemia. Lesser anomalies on CTG trace can be over-interpreted, leading to an over-diagnosed fetal compromise. The CTG recording must therefore be interpreted with care.

A summary of the various management strategies for pregnancy-related hypertension is shown in Figure 8.6 . This flow diagram shows the various pathways of progression and their management. An initial presentation of mild hypertension may improve with conservative management, or it may progress rapidly to the severe forms of pre-eclampsia and ultimately eclampsia.

Prevention of pre-eclampsia

There is no doubt that careful management and anticipation can largely prevent the occurrence of eclampsia, but preventing pre-eclampsia should be the gold standard of care.

The first opportunity to prevent pre-eclampsia is at the 12-week scan. In the mother, the finding of increased resistance in the uterine arteries at 12 weeks, along with a finding of maternal hypertension and low pregnancy-associated plasma protein – A (PAPP-A) and Placental Growth Factor (PlGF) levels, has been associated with poor pregnancy outcome, in particular early-onset pre-eclampsia (significant pre-eclampsia before 32 weeks). Treatment with aspirin 100–150 mg has been shown to improve the pregnancy outcome by delaying the need for fetal delivery to close to term.

There is some evidence that calcium supplements may reduce the risk of pre-eclampsia in the general population, but only in women who have dietary deficiency.

In women with essential hypertension and those with pre-eclampsia in previous pregnancies, aspirin has been shown to reduce the incidence of pre-eclampsia in subsequent pregnancies.

In women who have had severe pre-eclampsia in the previous pregnancy, a thrombophilia screen should be undertaken postnatally, as there is an incidence of underlying thrombotic tendencies that may also benefit from the use of low-molecular-weight heparin therapy in addition to aspirin in a subsequent pregnancy.

Symptoms of pre-eclampsia and eclampsia

Pre-eclampsia is commonly an asymptomatic condition. However, there are symptoms that must not be overlooked, and these include frontal headache, blurring of vision, sudden onset of vomiting and right epigastric pain. Of these symptoms, the most important is the development of epigastric pain – either during pregnancy or in the immediate puerperium ( Fig. 8.7 ).

Where a woman presents with headache, markedly raised BP and hyperreflexia, and has blood testing confirming severe pre-eclampsia, delivery of the fetus must be considered. The initial treatment is to control the BP with IV medication and prevention of seizures with an infusion of magnesium sulphate 4 g IV over 20 minutes with 1 g/h until the risk of seizures has ceased 24 hours after delivery (see also Eclampsia later).

Induction of labour

In a pregnancy complicated by hypertensive disease, delivery of the fetus should be considered for the following maternal and/or fetal/placental reasons:

• maternal

  • gestation >37 weeks

  • uncontrollable BP

  • HELLP syndrome

  • rising liver dysfunction

  • falling platelets

  • falling haemoglobin due to haemolysis

  • deteriorating renal function (creatinine >90mmol/L)

  • eclampsia

  • acute pulmonary oedema

• fetal/placental

  • fetal compromise on CTG tracing

  • absent or reversal of end diastolic flow in the umbilical artery

  • abnormal cerebro/placental ratio on Doppler scanning of the fetal vessels

  • no fetal growth over more than 2 weeks on ultrasound

  • placental abruption with fetal compromise

If the decision has been made to proceed to delivery, the choice will rest with either the induction of labour or delivery by caesarean section. This decision will be determined by the seriousness of the clinical situation. If there is time, antenatal steroids should be given for gestations of less than 34 weeks to minimize neonatal morbidity. In an extreme situation like eclampsia or severe fetal compromise, delivery should not be delayed in order to administer steroids. Similarly, where a fetus is to be delivered at a gestation of less than 30 weeks, a loading dose and infusion of magnesium sulphate should be considered in the hour before delivery by lower uterine segment caesarean section (LUSCS) or during an induced labour, as it provides neuroprotection for the neonatal brain. Where an infusion of magnesium sulphate is being used as prophylaxis against maternal seizures (eclampsia), this infusion acts to protect the neonatal brain and no further dosing is required.

If the cervix is unsuitable for surgical induction (Bishop score of less than 7), it can often be ripened by the introduction of a prostaglandin E preparation into the posterior fornix of the vagina or the use of a mechanical balloon catheter (Foley catheter) through the cervix.

If the cervix has a Bishop score of greater than 7, labour is induced by artificial rupture of membranes and oxytocin infusion (see Chapter 11).

Complications

Complications can be grouped as follows:

• fetal

  • growth restriction, hypoxia, death

• maternal

  • severe pre-eclampsia is associated with a fall in blood flow to various vital organs. If the mother is inadequately treated and/or the fetus is not delivered in a timely manner, complications include renal failure (raised creatinine/oliguria/anuria), hepatic failure, intrahepatic haemorrhage, seizures, DIC, adult RDS (ARDS), cerebral haemorrhage/infarction and heart failure

• placental

  • infarction, abruption

Eclampsia

The onset of convulsions in a pregnancy complicated by pre-eclampsia denotes the onset of eclampsia. Eclampsia is a preventable condition, and its occurrence often denotes a failure to recognize the early worsening signs of pre-eclampsia. Although it is more common in primigravid women, it can occur in any pregnancy during the antepartum, intrapartum or postpartum period. It carries serious risks of intrauterine death for the fetus and of maternal death from cerebral haemorrhage and/or renal and hepatic failure.

All cases must be managed in hospital and preferably in hospitals with appropriate intensive care facilities. Any woman admitted to hospital with convulsions during the course of pregnancy or who is admitted in a coma associated with hypertension should be considered to be suffering from eclampsia until proved otherwise.

Case study

Not all women admitted with seizures in pregnancy are eclamptic. Marilyn D was a single mother who was brought into an accident and emergency department by two friends with a statement that she had fitted on two occasions. She was booked for confinement at the same hospital, and her antenatal records showed that her pregnancy had so far been uncomplicated. She was 34 weeks pregnant, and on admission her BP was 140/90 mmHg. There was a trace of protein in the urine. She was brought into hospital on a Saturday night, and her friends stated that they had stopped the car on the way into hospital and laid Marilyn down on the pavement by the roadside because of the violence of her seizure.

After careful assessment of the BP that settled to 110/75 mmHg and normal biochemical testing, it was decided to proceed with observation, and within 24 hours, there were no further fits. Further discussion with Marilyn revealed that she had taken a mixture of illicit drugs, including amphetamines: a diagnosis that was suggested by one of the medical students!

Management of eclampsia

The three basic guidelines for management of eclampsia are:

• Control the fits.

• Control the BP.

• Deliver the infant.

Management after delivery

The risks of eclampsia do not stop with delivery, and the management of pre-eclampsia and eclampsia continues for up to 7 days after delivery, although if a seizure occurs for the first time 48 hours after delivery, alternative diagnoses such as epilepsy or intracranial pathology such as cortical vein thrombosis must be considered. Up to 45% of eclamptic fits occur after delivery, including 12% after 48 hours.

The following points of management should be observed:

• Maintain the patient in a quiet environment under constant observation.

• Maintain appropriate levels of pain relief. If the mother has been treated with magnesium sulphate, continue the infusion for 24 hours after the last fit or until a diuresis is seen.

• Continue antihypertensive therapy until the BP has returned to normal. This will usually involve transferring to oral medication, and although there is usually significant improvement after the first week, hypertension may persist for the next 6 weeks.

Case study

Mrs T was a 28-year-old primigravida and the wife of one of the junior medical staff. Her pregnancy was uneventful until 37 weeks, when she developed hypertension and was admitted to hospital for bed rest. Her BP stayed around 140/90 and there was a trace of protein in the urine. At 38 weeks’ gestation, labour was induced and she had a normal delivery of a healthy male infant. The following day she was fully mobile but complained to the midwifery staff that she had a frontal headache and indigestion, with epigastric discomfort. She was given paracetamol and an antacid, but the symptoms persisted. Her hypertension also persisted, with the highest reading being 145/98 mmHg. Later that day she had a seizure. Unfortunately, she fell against the side of her bed and fractured her zygoma. Although she had not had a fit before delivery, it is important to remember that symptoms of severe pre-eclampsia in a postnatal woman are as significant after delivery as they are antenatally.

• Strict fluid balance charts should be kept and BP and urine output observed on an hourly basis during the day and 2-hourly at night. Biochemical and haematological indices should be made on a daily basis until the values have stabilized or started to return to normal.

Although most mothers who have suffered from pre-eclampsia or eclampsia will completely recover and return to normal, it is important to review all such women at 6 weeks after delivery. If the hypertension or proteinuria persists at this stage, they should be investigated for other factors such as underlying renal disease. Women should also be investigated for the possibility of an autoimmune, thrombophilic or antiphospholipid cause of her disease. Long term, women with severe pregnancy-induced hypertension have been found to have a higher rate of hypertension and cardiovascular disease later in life.

Placenta praevia

The placenta is said to be praevia when all or part of the placenta implants in the lower uterine segment and therefore lies beside or in front of the presenting part of the fetus ( Fig. 8.8 ).

Symptoms and signs

The main symptom of placenta praevia is painless vaginal bleeding. There may sometimes be lower abdominal discomfort where there are minor degrees of associated placental separation (abruption).

The signs of placenta praevia are:

• vaginal bleeding

• malpresentation of the fetus

• normal uterine tone

The bleeding is unpredictable and may vary from minor – common with the initial bleed – to massive and life-endangering haemorrhage.

Case study

Jane T was admitted to hospital at 28 weeks’ gestation with a painless vaginal haemorrhage of approximately 100mL in her first pregnancy. The presenting part was high but central, and the uterine tone was soft. A diagnosis of a grade III anterior placenta praevia was made on ultrasound, and the fetus showed no sign of compromise. Given the site of the placenta and the risk of a further and more substantial bleed, Jane was advised to stay in hospital under observation until delivery. The bleeding settled, and at 32 weeks’ gestation, she asked to go home to marry her partner. As this necessitated a 1-hour flight, she was strongly advised against this action so her partner flew to Janet instead, and the wedding was arranged in a church close to the hospital. At the wedding, Janet had a further substantial bleed as she walked down the aisle and was rushed back into hospital. On admission the bleeding was found to be settling and the fetus was not compromised. Given the gestation was less than 35 weeks, management was to observe and attempt to prolong the gestation to improve neonatal outcome. At 35 weeks’ gestation Janet had a massive haemorrhage in the ward to the extent that blood soaked her bed linen and flowed over the side of the bed. The resident staff inserted two IV lines and she was rushed to theatre. She was shocked and hypotensive, and it was extremely difficult to maintain her BP. The fetal heart showed hypoxic decelerations and finally a bradycardia associated with poor placental perfusion. A ‘crash section’ was performed, and the diagnosis of grade III placenta praevia was confirmed. A healthy male infant was delivered. Janet was resuscitated with over 10 units of blood and blood product. Had Janet been at home at the time of the bleed, it is possible that neither she nor her baby would have survived.