Pre-eclampsia/hypertension in pregnancy

Hypertensive disorders of pregnancy affect approximately 5–10% of pregnancies in Australia, and are associated with both maternal and fetal morbidity and mortality. Delivery is the only definitive cure for pre-eclampsia, so the GP’s job is detection, risk stratification, aspirin prophylaxis and timely referral.

In a normal pregnancy, blood pressure falls in the first trimester. The fall reaches a maximum of 10–15 mmHg systolic in mid-pregnancy, and returns to pre-pregnancy levels by term. That physiological dip is why a booking BP can look deceptively normal in a woman with chronic hypertension.

Definitions

• Hypertension is a systolic blood pressure 140 mmHg or above, or diastolic blood pressure 90 mmHg or above. Confirm it over four hours with repeated measures, or after overnight rest.
• Severe hypertension is classified as a systolic blood pressure 160 mmHg or above, or a diastolic blood pressure 110 mmHg or above, and requires urgent management in hospital.
• Chronic hypertension predates the pregnancy or is first diagnosed before 20 weeks gestation.
• Gestational hypertension is the development of hypertension at or after 20 weeks gestation, in the absence of other features of pre-eclampsia.
• Pre-eclampsia is new-onset hypertension at or after 20 weeks with one or more organ-system features, and may also be superimposed on chronic hypertension.
• White-coat hypertension is a clinic BP of at least 140/90 mmHg with normal BP outside the clinic, diagnosed on 24-hour ambulatory or home monitoring.

Pre-eclampsia is a complex multisystem disorder of pregnancy arising from abnormal placentation, resulting in an imbalance of angiogenic and anti-angiogenic factors, oxidative stress and immunological involvement. Hypertension is usually, but not always, the first sign.

Risk assessment

Check every woman at the first antenatal visit.

High-risk factors: hypertensive disease in a previous pregnancy; chronic hypertension; chronic kidney disease; type 1 or type 2 diabetes; autoimmune disease (SLE, antiphospholipid syndrome).

Moderate-risk factors: booking BP 140/90 or above; first pregnancy; age 40 or over; interpregnancy interval over 10 years; BMI 35 or over at the first visit; family history of pre-eclampsia; multiple pregnancy; assisted reproduction.

Two local (HNE HealthPathways, from the SOMANZ 2023 guideline) differences worth knowing, because both widen who gets aspirin: the moderate-risk blood pressure trigger is systolic >130 and/or diastolic >80 rather than 140/90, and multifetal gestation counts as high risk, not moderate.

Chronic hypertension is not a benign background finding. Its pooled outcomes are superimposed pre-eclampsia 25%, preterm delivery 28%, fetal growth restriction 17% and perinatal death 4%. White-coat hypertension is not entirely benign either and is associated with an increased risk of pre-eclampsia of about 8%, though treatment is generally not required if the clinic BP is below 160/110 mmHg and out-of-office readings stay normal.

Gestational hypertension is associated with an increased risk of developing pre-eclampsia — up to 25%, depending on the gestation at presentation. Fetal growth restriction is not typically a feature of gestational hypertension itself.

First-trimester screening: the FMF algorithm

It is strongly recommended by the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) that routine screening in early pregnancy for preeclampsia is offered to all women.

Risk factors alone screen poorly. Risk factor–based screening has the poorest performance when compared with other approaches, only identifying 30% of cases, with a screen-positive rate of 10%. It is still the fallback when nothing else is available.

The Fetal Medicine Foundation (FMF) algorithm is better. In predicting preterm preeclampsia, the FMF algorithm had a detection rate (or sensitivity) of 82.4%, whereas the NICE guidelines had a detection rate of 40% (at the same screen- positive rate of 10%). RANZCOG endorses it. The calculator is free at fetalmedicine.org.

Its inputs, all collected at 11–14 weeks:

• maternal characteristics and medical and obstetric history
• mean arterial pressure (MAP) — validated automated device, both arms simultaneously, after 5 minutes’ rest, two sets of readings 1 minute apart
• uterine artery pulsatility index (UtPI) — add it to the request for the 11–14-week ultrasound
• placental growth factor (PlGF) and/or PAPP-A — add PlGF to the combined first trimester screening or NIPT request. PAPP-A is already part of CFTS.

PlGF is not covered by the Medicare Benefits Schedule and costs an out-of-pocket fee of $50–$100. If some inputs are missing, run the algorithm anyway. A limited model still beats risk factors alone: maternal factors plus UtPI detects 62%, plus PlGF 59%, plus MAP 49%.

A risk above 1 in 100 is high risk and needs aspirin.

Aspirin prophylaxis

Offer low-dose aspirin to anyone at high risk on the FMF algorithm. Where it isn’t available, offer it to any woman with one high-risk factor or two or more moderate-risk factors.

• Aspirin 100–150 mg daily, ideally before 16 weeks gestation and as early as 12 weeks.
• Prefer 150 mg at night. RANZCOG recommends a dose of at least 100 mg to be effective at preventing preeclampsia. In practice that is half a 300 mg tablet, or one and a half 100 mg tablets.
• When to stop differs between guidelines. NICE and ACOG recommend prescribing low-dose aspirin from 12 weeks gestation until birth, which supersedes their previous statement of continuing until 36 weeks gestation. The FMF/RANZCOG approach, following the ASPRE trial protocol, stops at 36 weeks.
• Contraindications: aspirin or NSAID allergy, aspirin-sensitive asthma, active bleeding, erosive gastritis, severe liver or kidney disease, and bleeding disorders.
• The ASPRE trial used combined first trimester screening and found a 62% reduction in preterm pre-eclampsia at less than 37 weeks gestation in women who took aspirin 150 mg daily.
• Aspirin reduces the risk of preterm birth, fetal growth restriction and fetal death, but may increase postpartum bleeding. Other evidence finds low-dose aspirin does not increase the risk of placental abruption or postpartum haemorrhage.
• Aspirin is often not started until the second or early third trimester in Australia, once an obstetric specialist is involved. That is contrary to evidence-based best practice — start it in general practice.
• Women with inadequate dietary calcium should aim for the recommended daily allowance of 1000 mg daily through diet or supplementation to reduce risk. The calcium benefit was shown in women with low dietary intake, which may not be applicable to the general Australian population.
• Prenatal exercise has also been shown to reduce the odds of preeclampsia in a systematic review of 3322 women (odds ratio 0.59, 95% CI: 0.37–0.90), although data are limited.

Assessment at each antenatal visit

Blood pressure technique. Seated, legs on a flat surface, cuff at heart level, with a large cuff if arm circumference exceeds 32 cm. Measure both arms at the first visit; a difference under 10 mmHg is normal. Systolic is the first Korotkoff sound (K1); diastolic is disappearance (K5), or muffling (K4) if K5 is absent. Use an automated office or liquid crystal sphygmomanometer where possible; home BP monitoring can form part of the assessment.

Features of pre-eclampsia:

• Renal — proteinuria with a spot urine protein:creatinine ratio 30 mg/mmol or more; acute kidney injury with serum creatinine above 90 micromol/L; oliguria under 80 mL in 4 hours; sudden facial, hand or foot swelling.
• Haematological — thrombocytopenia with a platelet count under 100,000 per microlitre, haemolysis, disseminated intravascular coagulation.
• Hepatic — raised serum transaminases (ALT or AST above 40 IU/L); severe right upper quadrant or epigastric pain.
• Neurological — eclamptic convulsion; sustained clonus (hyperreflexia alone is common and not diagnostic); severe headache; visual disturbance such as photopsia, scotomata or cortical blindness; stroke.
• Pulmonary oedema.
• Uteroplacental — fetal growth restriction, abnormal umbilical artery Doppler, stillbirth, placental abruption.

Also assess fetal movements and growth at every visit.

Investigations

For a woman with chronic hypertension the initial recommended tests are full blood count; urea, creatinine and electrolytes; liver function tests; uric acid; urinalysis and microscopy; urine protein:creatinine ratio to establish a baseline; and an ECG.

Dipstick urinalysis is the usual screening test for proteinuria; a negative or trace result sits within the normal range. One plus or more on dipstick is sensitive but inaccurate and should be further evaluated with a spot urine protein:creatinine ratio. Add a renal ultrasound for new-onset hypertension, and remember that routine testing for secondary causes is not recommended in pregnancy but should be considered postpartum.

Referral

Urgent maternity referral, even with mild BP elevation, for any of: severe hypertension; suspected pre-eclampsia; neurological symptoms; significant epigastric or right upper quadrant pain; new proteinuria or oedema; abnormal UEC, LFT or platelets; BP persisting at 140–160/90–100 mmHg despite treatment; or high pre-eclampsia risk needing a medication plan.

Routine maternity referral for new-onset hypertension after 20 weeks with no other pre-eclampsia features, and by 20 weeks for two or more moderate risk factors.

Antihypertensive drug choice

Avoid or stop: ACE inhibitors and angiotensin receptor blockers are contraindicated — teratogenic in the second and third trimesters, causing fetal anuria, oligohydramnios, hypocalvaria, intrauterine growth restriction, patent ductus arteriosus and death. Stop ideally before conception or at diagnosis of pregnancy. Avoid diuretics (maternal hypovolaemia, fetal electrolyte disturbance), beta blockers other than labetalol (fetal bradycardia, growth restriction with atenolol), and calcium channel antagonists other than nifedipine and diltiazem.

Safe oral agents in pregnancy, with usual dose ranges:

• Labetalol 100 mg twice a day to 400 mg three times a day. Exclude asthma first; it can blunt hypoglycaemia awareness in insulin-treated diabetes. Adverse effects: bradycardia, bronchospasm, headache.
• Nifedipine controlled release 30 mg daily to 60 mg twice a day. Adverse effects: first-dose headache, flushing, tachycardia, peripheral oedema.
• Methyldopa 250 mg twice a day to 750 mg three times a day. Adverse effects: depression, dry mouth, sedation, rarely haemolysis and hepatitis.
• Hydralazine 25 mg three times a day to 50 mg three times a day.
• Prazosin 0.5 mg twice a day to 5 mg three times a day.

Aim for a blood pressure around 110–140/85 mmHg rather than simply “under 140/90” — over-treatment matters too. The physiological first-trimester fall often allows a reduction or cessation of antihypertensive therapy.

Severe hypertension, pre-eclampsia and eclampsia

Management should occur at a specialist centre with the required protocols and expertise, because inpatient care is usually required. Severe hypertension needs drugs that rapidly lower blood pressure — intravenous hydralazine or labetalol, or oral nifedipine — and magnesium sulphate infusion should be considered, since it reduces the rate of seizure by 50%. The first choice for seizure prophylaxis in patients with pre-eclampsia with severe features is intravenous magnesium sulfate therapy. These are inpatient regimens; the GP’s role is recognition and immediate transfer.

Delayed delivery in the late preterm period increases the risk of severe hypertension, with severe consequences such as eclampsia, HELLP syndrome, pulmonary oedema, myocardial infarction, stroke, renal and retinal injury, and fetal complications including growth restriction, placental abruption, or fetal or maternal death. Hypertensive disorders of pregnancy constitute a leading cause of maternal and perinatal mortality worldwide.

Postpartum

After delivery, hypertension typically resolves within 12 weeks for women with gestational hypertension or pre-eclampsia. If it does not, investigate for primary or secondary hypertension.

• Monitor BP regularly postnatally and down-titrate antihypertensives when the systolic BP drops below 120 mmHg, reviewing weekly and withdrawing the most frequently dosed drug first.
• Check BP two weeks after stopping medication, and investigate persisting proteinuria for underlying renal disease.
• The antihypertensive drugs that are safe in pregnancy are also safe in breastfeeding.
• Methyldopa is associated with a 30% risk of depression, so it is usually stopped postpartum.
• ACE inhibitors, particularly enalapril, have very low concentrations in breast milk and are often used during lactation, whereas angiotensin receptor blockers are not recommended because safety information is lacking.
• After severe pre-eclampsia, arrange a thrombophilia screen at three months postpartum.

Long-term follow-up

Gestational hypertension and pre-eclampsia are associated with a two- to fourfold increase in the future risk of cardiovascular disease, including hypertension, stroke, diabetes, venous thromboembolic disease and chronic kidney disease, sometimes presenting in middle age.

Women with a history of hypertension in pregnancy require indefinite follow-up, with annual reviews of blood pressure, fasting lipids and blood glucose, plus lifestyle counselling on diet, BMI, smoking cessation and exercise. Pre-eclampsia also recurs, so offer preconception counselling and plan early aspirin before the next pregnancy.