High-Risk Pregnancy & Hypertensive Disorders

Obstetrics differs from every other clinical subject in having two patients whose interests can diverge, and in having one intervention that resolves almost everything for one of them while imposing all the risk on the other.

The organising tool has two parts. First, pre-eclampsia is a placental disease that presents as a maternal one, which is why the only cure is delivery. Second, every high-risk pregnancy decision reduces to one question: is the fetus safer inside or outside?

Almost every management question in this chapter is that second question in disguise. Continuing the pregnancy exposes the mother to a disease that can kill her; delivering exposes the baby to prematurity. The answer changes with gestation, and that is why gestational age appears in every management rule here.

1. The Placental Lesion

Pre-eclampsia begins long before the blood pressure rises, and it begins in the placenta rather than in the mother.

In normal pregnancy, extravillous trophoblast invades the spiral arteries of the decidua and myometrium and destroys their muscular walls, converting them from narrow high-resistance vessels into wide flaccid conduits that deliver a large, low-pressure flow to the intervillous space.

In pre-eclampsia this remodelling is incomplete. The spiral arteries retain their muscle, remain narrow and responsive to vasoconstriction, and the placenta is chronically underperfused.

The underperfused placenta releases antiangiogenic factors into the maternal circulation, principally soluble fms-like tyrosine kinase 1, which binds and neutralises vascular endothelial growth factor and placental growth factor.

Those factors cause generalised maternal endothelial dysfunction, and every clinical feature of pre-eclampsia follows from it. Endothelial dysfunction produces vasoconstriction and hypertension, glomerular endotheliosis and proteinuria, increased capillary permeability and oedema, platelet activation and thrombocytopenia, and hepatic sinusoidal injury with raised transaminases.

That single mechanism therefore explains a disease affecting the kidneys, liver, brain, blood and placenta simultaneously, and it explains the one certainty of management.

Delivery of the placenta removes the source of the antiangiogenic factors, which is why delivery is the only cure and why nothing else is more than temporising.

2. Definitions and Severe Features

The definitions matter because they are examined precisely and because one of them has changed.

Hypertension in pregnancy means a systolic pressure of 140 or more, or a diastolic of 90 or more, on two occasions at least four hours apart.

Proteinuria is no longer required to diagnose pre-eclampsia. In its absence the diagnosis is made when new hypertension is accompanied by thrombocytopenia, raised transaminases, renal impairment, pulmonary oedema, or new cerebral or visual symptoms.

That change matters clinically because a substantial minority of women who develop eclampsia never had significant proteinuria, and waiting for it delayed treatment.

Severe features are a systolic pressure of 160 or more or a diastolic of 110 or more, thrombocytopenia, impaired liver function or right upper quadrant pain, progressive renal insufficiency, pulmonary oedema, and cerebral or visual disturbance.

The degree of proteinuria is not itself a severe feature and does not determine management, which is a reversal of older teaching. Massive proteinuria with normal organ function is less concerning than modest proteinuria with a falling platelet count.

3. Predicting and Preventing

Risk factors divide usefully into high and moderate, and their presence determines who receives prophylaxis.

High-risk factors are previous pre-eclampsia, chronic hypertension, chronic kidney disease, pre-existing diabetes, and autoimmune disease including antiphospholipid syndrome.

Moderate-risk factors are nulliparity, age above 40, a pregnancy interval over 10 years, a body mass index above 35, a family history of pre-eclampsia, and multiple pregnancy.

Low-dose aspirin substantially reduces preterm pre-eclampsia and is the only effective prophylaxis. It is started between 12 and 16 weeks, before placentation is complete, and continued until near term.

Timing is critical, because aspirin works by improving placentation, and starting it after 16 weeks does not achieve that.

Dose matters too. The large randomised trial that established the benefit used 150 milligrams, and meta-analysis shows 150 to 162 milligrams outperforms 75 to 81 milligrams for preventing preterm pre-eclampsia.

Calcium supplementation reduces pre-eclampsia in populations with low dietary calcium intake, which makes it relevant in India.

4. Managing Pre-eclampsia

Management has three components: control the blood pressure, prevent seizures, and decide when to deliver.

Antihypertensives are given to prevent maternal stroke, not to treat the disease. They do not improve placental perfusion or alter the natural history, and lowering the pressure too aggressively can reduce placental flow further.

Labetalol, nifedipine and methyldopa are the accepted agents. Angiotensin converting enzyme inhibitors and receptor blockers are contraindicated because they cause fetal renal failure, oligohydramnios and skull hypoplasia.

Severe hypertension at 160 systolic or 110 diastolic is an emergency requiring treatment within an hour, because it is the level at which intracerebral haemorrhage occurs.

Delivery is decided by gestation and severity. At term, delivery is indicated. Before 37 weeks with stable disease, expectant management with close surveillance and corticosteroids for fetal lung maturity is reasonable.

Delivery is indicated regardless of gestation for uncontrollable hypertension, eclampsia, HELLP syndrome, pulmonary oedema, placental abruption, deteriorating renal or liver function, or a non-reassuring fetal state.

Pre-eclampsia can present or worsen after delivery, and postpartum eclampsia is well recognised, so monitoring continues for several days.

5. Eclampsia and Magnesium Sulphate

Eclampsia is a generalised tonic-clonic seizure in a woman with pre-eclampsia, and it may occur antepartum, intrapartum or postpartum.

Magnesium sulphate is the drug of choice for both treating and preventing eclamptic seizures, and it is superior to diazepam and to phenytoin. That superiority is established by large trials and is examined directly.

It acts as a cerebral vasodilator and a membrane stabiliser rather than as a conventional anticonvulsant, which is why drugs that are better anticonvulsants in other settings perform worse here.

The Pritchard regimen uses an intravenous and intramuscular loading dose followed by intramuscular maintenance, and the Zuspan regimen uses intravenous loading followed by an intravenous infusion.

Monitoring is clinical and is examined more often than the regimens. Toxicity is detected by loss of the patellar reflex, which occurs first, then respiratory depression, then cardiac arrest.

Urine output is monitored because magnesium is renally excreted, and oliguria causes accumulation. The antidote is intravenous calcium gluconate.

Management of an eclamptic fit is to protect the airway, place the woman in the left lateral position, give magnesium sulphate, control the blood pressure, and then deliver once she is stable.

Delivery follows stabilisation rather than preceding it, because operating on an unstabilised eclamptic woman is dangerous and the seizure itself is not an indication for immediate caesarean section.

6. HELLP Syndrome

HELLP is haemolysis, elevated liver enzymes and a low platelet count, and it is a severe variant of pre-eclampsia that can occur without marked hypertension.

Presentation is often with right upper quadrant or epigastric pain, nausea and malaise, and it is regularly misdiagnosed as gastritis or hepatitis in a pregnant woman.

Epigastric pain in a pregnant woman in the second half of pregnancy is HELLP until proved otherwise, and it reflects stretching of the liver capsule by subcapsular haemorrhage.

The feared complication is hepatic rupture, which carries very high mortality.

Blood film shows fragmented red cells, lactate dehydrogenase and bilirubin are raised, and the platelet count falls.

Management is stabilisation and delivery, with platelet transfusion for very low counts or before surgery. Corticosteroids improve the laboratory picture but do not clearly improve maternal or perinatal outcome.

7. Chronic Hypertension and What Changed

Women with chronic hypertension face increased risks of superimposed pre-eclampsia, fetal growth restriction, abruption and preterm birth.

Practice on treating mild chronic hypertension in pregnancy reversed following the CHAP trial. Previously, mild hypertension was left untreated for fear that lowering maternal pressure would reduce placental perfusion and restrict fetal growth.

CHAP randomised women with mild chronic hypertension to treatment at a threshold of 140 over 90 against no treatment until severe hypertension developed, and found that active treatment reduced the composite of severe pre-eclampsia, indicated preterm birth before 35 weeks, abruption and fetal or neonatal death.

Crucially, it did not increase small-for-gestational-age births, which was the harm the older approach was designed to avoid.

The recommendation is therefore now to treat chronic hypertension in pregnancy to a target below 140 over 90.

Methyldopa, labetalol and nifedipine remain the agents used, and angiotensin converting enzyme inhibitors are stopped before or as soon as pregnancy is confirmed.

8. Other High-Risk Conditions

Gestational diabetes is glucose intolerance first recognised in pregnancy, driven by the insulin resistance that placental hormones produce in the second half.

India uses a distinctive single-step approach. The DIPSI method gives a 75 gram oral glucose load irrespective of the last meal and diagnoses gestational diabetes at a two-hour value of 140 milligrams per decilitre or more, which is designed for a population that cannot easily return fasting.

Management is diet and exercise first, with insulin where targets are not met and metformin used in selected women. Complications include macrosomia with shoulder dystocia, polyhydramnios, neonatal hypoglycaemia and later maternal type 2 diabetes.

Pre-existing diabetes is a different and more dangerous problem, because hyperglycaemia at conception causes congenital malformation, particularly cardiac and neural tube defects, and caudal regression is the classically associated anomaly.

Anaemia is the dominant high-risk condition in Indian obstetrics, contributing substantially to maternal mortality, and it is developed alongside the national programmes in the Maternal-Child Health chapter.

Heart disease in pregnancy is dangerous because pregnancy increases cardiac output by around 40 per cent. Mitral stenosis is the classic Indian problem from rheumatic disease, and it decompensates because a fixed valve area cannot accommodate the increased output and the tachycardia shortens diastolic filling.

Hypothyroidism requires an increased levothyroxine dose in pregnancy and is screened for because untreated maternal hypothyroidism impairs fetal neurodevelopment.

9. Rhesus Isoimmunisation

Isoimmunisation occurs when a rhesus D negative mother is exposed to rhesus D positive fetal red cells, mounts an antibody response, and those antibodies cross the placenta in a later pregnancy and destroy fetal red cells.

The first affected pregnancy is usually not the sensitising one. The primary response produces immunoglobulin M, which does not cross the placenta, and the anamnestic immunoglobulin G response in a subsequent pregnancy is what causes haemolytic disease.

That single fact explains why prophylaxis works: preventing the primary response protects every future pregnancy.

Sensitising events are delivery, miscarriage, termination, ectopic pregnancy, antepartum haemorrhage, external cephalic version, amniocentesis and abdominal trauma.

Anti-D immunoglobulin is given routinely at around 28 weeks and again within 72 hours of delivery of a rhesus positive baby, and additionally after any sensitising event. It works by clearing fetal cells from the maternal circulation before the immune system can respond to them.

The Kleihauer test quantifies the volume of fetomaternal haemorrhage and determines whether more than the standard anti-D dose is required.

The indirect Coombs test detects maternal antibody and is the screening test. Once a mother is sensitised, anti-D is useless, and management shifts to surveillance: antibody titres, and middle cerebral artery peak systolic velocity on Doppler, which detects fetal anaemia non-invasively because anaemic blood is less viscous and flows faster.

Severe fetal anaemia is treated by intrauterine transfusion. Untreated, it progresses to hydrops fetalis.

10. Multiple Pregnancy

Twin pregnancy carries increased risk of essentially every obstetric complication, but the single most important determination is not the number of fetuses.

Chorionicity matters more than zygosity, because it decides whether the fetuses share a circulation. It is best determined by ultrasound in the first trimester, using the lambda sign for dichorionic and the T sign for monochorionic placentation.

Dizygotic twins are always dichorionic. Monozygotic twins may be dichorionic, monochorionic diamniotic or monochorionic monoamniotic depending on how late the split occurred, and the later the split, the more shared the structures.

Monochorionic twins share placental vascular anastomoses, which permits twin-to-twin transfusion syndrome, in which one twin becomes the donor with oligohydramnios and growth restriction and the other the recipient with polyhydramnios and circulatory overload.

It is treated by fetoscopic laser ablation of the connecting vessels, and untreated it has very high mortality. Monoamniotic twins additionally risk cord entanglement.

11. Fetal Growth and Surveillance

Fetal growth restriction means a fetus that has not achieved its growth potential, which is not the same as being constitutionally small.

Symmetrical restriction, affecting head and abdomen equally, suggests an early insult such as chromosomal abnormality or congenital infection. Asymmetrical restriction, sparing the head at the expense of the abdomen, suggests later placental insufficiency, because blood is redistributed to the brain.

That redistribution is the brain-sparing effect, and it is detectable on Doppler as reduced resistance in the middle cerebral artery.

Umbilical artery Doppler is the key surveillance tool in placental insufficiency. Rising resistance, then absent end-diastolic flow, then reversed end-diastolic flow, mark a worsening sequence, and reversed flow demands delivery.

Antenatal corticosteroids are given before 34 weeks and reduce respiratory distress syndrome, intraventricular haemorrhage and neonatal death. Magnesium sulphate given before very preterm birth is neuroprotective and reduces cerebral palsy, which is a second and separate indication from seizure prophylaxis.

12. Worked Examples

Example 1. A woman at 34 weeks has a blood pressure of 158 over 104, no proteinuria, a platelet count of 88,000 and transaminases twice the upper limit.

The absence of proteinuria does not exclude pre-eclampsia. New hypertension after 20 weeks with thrombocytopenia and impaired liver function establishes the diagnosis, and both of those are severe features.

She requires admission, antihypertensive treatment, magnesium sulphate for seizure prophylaxis, and corticosteroids, with delivery planned. Waiting for proteinuria would delay treatment in a woman who is already at risk of eclampsia.

Example 2. A woman with previous severe pre-eclampsia is seen at 11 weeks in her second pregnancy.

Previous pre-eclampsia is a high-risk factor and mandates aspirin prophylaxis, which should be started between 12 and 16 weeks and continued until near term.

The timing is essential, because aspirin works by improving trophoblastic invasion and spiral artery remodelling, and starting after 16 weeks misses the window. A dose of about 150 milligrams is supported by the trial evidence. Calcium supplementation is also worthwhile given typical Indian dietary intake.

Example 3. A woman receiving magnesium sulphate becomes drowsy, and the patellar reflex cannot be elicited.

This is magnesium toxicity, and loss of the patellar reflex is the earliest clinical sign, appearing before respiratory depression and well before cardiac arrest.

The infusion is stopped, the respiratory rate and urine output checked, and intravenous calcium gluconate given as the antidote. Reduced urine output is the usual precipitant, because magnesium is renally excreted and accumulates in oliguria.

Summary

• Pre-eclampsia is a placental disease presenting as a maternal one.
• Incomplete spiral artery remodelling leaves the placenta underperfused.
• The underperfused placenta releases antiangiogenic factors that injure maternal endothelium.
• One mechanism explains kidney, liver, brain, platelet and placental features.
• Delivery of the placenta is the only cure; everything else is temporising.
• Hypertension is 140 systolic or 90 diastolic on two occasions four hours apart.
• Proteinuria is no longer required for the diagnosis.
• Organ dysfunction in place of proteinuria establishes pre-eclampsia.
• The degree of proteinuria is not a severe feature and does not guide management.
• Severe features include 160 over 110, thrombocytopenia and cerebral symptoms.
• Aspirin is the only effective prophylaxis and must start before 16 weeks.
• A dose of about 150 milligrams outperforms 75 to 81 milligrams.
• Calcium supplementation helps where dietary intake is low, as in India.
• Antihypertensives prevent maternal stroke; they do not treat the disease.
• Angiotensin converting enzyme inhibitors are contraindicated in pregnancy.
• Severe hypertension must be treated within an hour.
• Delivery is decided by gestation and severity together.
• Pre-eclampsia can present or worsen after delivery.
• Magnesium sulphate beats diazepam and phenytoin for eclampsia.
• It acts as a cerebral vasodilator rather than a conventional anticonvulsant.
• Loss of the patellar reflex is the first sign of magnesium toxicity.
• Calcium gluconate is the antidote; oliguria causes accumulation.
• Stabilise before delivering; a seizure is not an indication for immediate caesarean.
• HELLP can occur without marked hypertension.
• Epigastric pain in late pregnancy is HELLP until proved otherwise.
• Hepatic rupture is the feared complication.
• CHAP reversed practice: treat mild chronic hypertension to below 140 over 90.
• Treatment did not increase small-for-gestational-age births.
• DIPSI uses a 75 gram load irrespective of meals, with a two-hour cut-off of 140.
• Pre-existing diabetes causes malformation; gestational diabetes causes macrosomia.
• Mitral stenosis decompensates because output rises and diastole shortens.
• The first affected pregnancy is not the sensitising one, because IgM does not cross.
• Anti-D is given at 28 weeks and within 72 hours of delivery.
• Kleihauer quantifies fetomaternal haemorrhage; indirect Coombs screens for antibody.
• Anti-D is useless once sensitisation has occurred.
• Middle cerebral artery peak velocity detects fetal anaemia non-invasively.
• Chorionicity matters more than zygosity and is determined in the first trimester.
• The lambda sign means dichorionic; the T sign means monochorionic.
• Monochorionic twins risk twin-to-twin transfusion, treated by laser ablation.
• Symmetrical growth restriction suggests an early insult; asymmetrical suggests placental failure.
• Reversed end-diastolic umbilical flow demands delivery.
• Corticosteroids before 34 weeks reduce respiratory distress and death.
• Magnesium before very preterm birth is neuroprotective, a separate indication.