Preeclampsia

Preeclampsia is a multisystem disorder specific to pregnancy, defined by new-onset hypertension developing after 20 weeks' gestation together with evidence of maternal end-organ dysfunction — most classically proteinuria, but proteinuria is not required for the diagnosis if another marker of end-organ involvement is present. It complicates roughly 2-8% of pregnancies globally and is one of the leading causes of maternal and perinatal death, both directly (eclampsia, stroke, HELLP syndrome, placental abruption) and through the downstream effects of medically indicated preterm delivery.^[1] Preeclampsia sits within a broader family of hypertensive disorders of pregnancy — chronic hypertension, gestational hypertension, preeclampsia, and chronic hypertension with superimposed preeclampsia — that share overlapping management principles (see Recognize the Condition).

For a community or prenatal pharmacist, the single highest-yield interaction with this condition is low-dose aspirin prophylaxis: a large proportion of pregnant patients meet at least one risk-factor threshold for aspirin, the drug is available without a prescription, and the timing window (started by 16 weeks, ideally by 12 weeks) is easy to miss if it is not raised proactively at an early prenatal counselling visit. The second major pharmacist-relevant thread in this chapter is recognizing that ACE inhibitors and ARBs are contraindicated in pregnancy — a genuinely common and dangerous prescribing/dispensing error when a patient with treated chronic hypertension becomes pregnant.^[2]

Often silent until a routine check finds it

Mild-to-moderate preeclampsia is frequently asymptomatic — it is found on a routine blood pressure check or routine prenatal urinalysis, not because the patient feels unwell. Symptoms, when present, more often signal progression toward severe disease (see Red Flags & Refer) than early or mild disease, so a well-appearing, asymptomatic patient cannot be assumed to be at low risk on that basis alone.

Symptoms that suggest progression toward severe disease

• New, persistent headache unresponsive to usual-dose acetaminophen.
• Visual disturbances — blurred vision, scotomata (flashing lights or spots), or transient vision loss.
• Right-upper-quadrant or epigastric pain, with or without nausea and vomiting — easy to mistake for heartburn or gallbladder pain in the third trimester, but a genuine red flag in this context.
• Shortness of breath, or rapidly worsening edema out of proportion to normal late-pregnancy swelling.
• Hyperreflexia or clonus on examination.

High-risk factors

Any single high-risk factor is enough on its own to recommend low-dose aspirin prophylaxis (see Choose Initial Treatment).

• Preeclampsia in a previous pregnancy, especially when it was accompanied by an adverse outcome (early-onset disease, preterm delivery, growth restriction).
• Multifetal gestation (twins or higher order).
• Chronic hypertension.
• Pregestational diabetes mellitus (type 1 or type 2).
• Renal disease.
• Autoimmune disease associated with an elevated preeclampsia risk — systemic lupus erythematosus, antiphospholipid antibody syndrome.

Moderate-risk factors

More than one moderate-risk factor is needed before aspirin prophylaxis is recommended — evidence does not clearly separate individual moderate factors from one another, but risk rises with the number present.

• Nulliparity.
• Obesity (pre-pregnancy BMI over 30 kg/m²).
• Family history of preeclampsia (mother or sister).
• Maternal age 35 years or older.
• Personal history factors — a previous low-birth-weight or small-for-gestational-age infant, a previous adverse pregnancy outcome, or a pregnancy interval of more than 10 years.
• Assisted reproductive technology.
• Obstructive sleep apnea.

Low risk

A previous uncomplicated full-term delivery, on its own, does not warrant aspirin prophylaxis.

Diagnostic criteria for preeclampsia

Or, in the absence of proteinuria, new-onset hypertension together with any one of the following new findings after 20 weeks:

• Thrombocytopenia — platelet count under 100 × 10⁹/L.
• Renal insufficiency — serum creatinine over 97 μmol/L (1.1 mg/dL), or a doubling of the serum creatinine in the absence of other renal disease.
• Impaired liver function — liver transaminases elevated to twice the upper limit of normal.
• Pulmonary edema.
• New-onset headache unresponsive to usual-dose acetaminophen and not accounted for by an alternative diagnosis, or new visual disturbances.

Severe features

Any one of the following, present alongside the diagnosis above, makes this preeclampsia with severe features — a materially higher-risk state that changes management (see Choose Initial Treatment):

• Systolic BP ≥160 mmHg or diastolic BP ≥110 mmHg on 2 occasions at least 4 hours apart (unless antihypertensive therapy was already started, in which case the interval requirement is relaxed).
• Thrombocytopenia — platelet count under 100 × 10⁹/L.
• Impaired liver function not accounted for by an alternative diagnosis — liver transaminases more than twice the upper limit of normal, or severe, persistent right-upper-quadrant or epigastric pain unresponsive to medication.
• Renal insufficiency — serum creatinine over 97 μmol/L (1.1 mg/dL), or a doubling of the serum creatinine, in the absence of other renal disease.
• Pulmonary edema.
• New-onset headache unresponsive to usual-dose acetaminophen and not accounted for by an alternative diagnosis.
• Visual disturbances.

HELLP syndrome

Diagnosed with all 3 of: hemolysis (abnormal peripheral blood smear, elevated LDH ≥600 IU/L, or elevated bilirubin), elevated liver enzymes (AST or ALT more than twice the upper limit of normal), and thrombocytopenia (platelet count under 100 × 10⁹/L). Deteriorates in an insidious, sometimes atypical pattern — as noted in Recognize the Condition, up to 15% of cases lack hypertension or proteinuria at presentation, so maintain suspicion in any pregnant or postpartum patient with new right-upper-quadrant pain and malaise even with a reassuring blood pressure.^[1]

Distinguishing superimposed preeclampsia from worsening chronic hypertension

In a patient with pre-existing chronic hypertension, suspect superimposed preeclampsia when any of the following develops after 20 weeks: new proteinuria (or a sudden increase in previously stable proteinuria), a sudden increase in blood pressure that had previously been well controlled, new thrombocytopenia, or a new rise in liver enzymes. Because both conditions share the same baseline finding — hypertension — this diagnosis rests on a genuine change from the patient's own baseline, not on an isolated reading.

Investigations

• CBC with platelet count.
• Serum creatinine.
• AST and ALT.
• LDH and uric acid if HELLP or hepatic involvement is suspected.
• Urinalysis and a urine protein-to-creatinine ratio (or 24-hour urine collection where a rapid ratio is not available).
• Fetal assessment — ultrasound for growth and amniotic fluid volume, and antenatal fetal testing, guided by gestational age and severity.

• Prevent progression to eclampsia, stroke, HELLP syndrome, placental abruption, and pulmonary edema.
• Control severe-range blood pressure promptly enough to prevent maternal stroke and cardiac complications, without lowering it so aggressively that placental perfusion is compromised.
• Prevent an eclamptic seizure in every patient with severe features, using magnesium sulfate — and treat one promptly if it occurs.
• Support a safely timed delivery — the only definitive treatment for preeclampsia — balancing maternal risk of continuing the pregnancy against fetal risk of early delivery.
• In patients at increased risk, reduce the incidence and severity of preeclampsia in the first place through correctly timed aspirin prophylaxis.
• Provide adequate postpartum surveillance and treatment, since preeclampsia and eclampsia can newly appear or worsen after delivery.
• Counsel every affected patient on the associated long-term cardiovascular risk once the pregnancy has ended.

• Bed rest, with or without hospitalization, has not been shown to reduce the risk or severity of preeclampsia and should not be routinely recommended.
• Sodium restriction has not been shown to reduce preeclampsia risk and is not routinely recommended for this purpose.
• For patients with low dietary calcium intake, calcium supplementation of at least 1 g/day reduces the risk of preeclampsia and related hypertensive complications — the benefit is most pronounced in populations with low baseline calcium intake.^[2]
• Vitamins C and E, fish oil, garlic, vitamin D, and folic acid supplementation have not shown sufficient evidence of benefit for preeclampsia prevention specifically and should not be recommended for this indication.^[1]
• Educate every patient — at the first prenatal visit, and again at every visit thereafter — on the warning symptoms in Red Flags & Refer, and to seek care immediately if any occur, including in the postpartum period.
• For gestational hypertension or preeclampsia without severe features managed as an outpatient, arrange frequent blood pressure and symptom checks (a combination of in-clinic and home monitoring, at least once weekly in-clinic) and serial laboratory monitoring — this is not a "wait until the next routine visit" condition.
• Smoking cessation and standard healthy-pregnancy counselling (diet, weight management as appropriate) remain relevant for overall pregnancy risk, though neither has been shown to specifically prevent preeclampsia.

Postpartum

Continue magnesium sulfate for 24 hours after delivery (or 24 hours after the last seizure) in every patient who required it antepartum or intrapartum — stopping early raises the risk of a postpartum eclamptic seizure.^[1]

Preeclampsia and eclampsia can develop for the first time after delivery, most often within the first week postpartum, and a patient with no antepartum hypertension is not exempt. Take new severe headache, visual change, epigastric pain, or hypertension seriously in any postpartum patient, not only those with a known antepartum diagnosis.

NSAIDs are preferred over opioids for routine postpartum analgesia, even in patients with preeclampsia with severe features — randomized and cohort data have not shown that NSAID use lengthens the duration of severe-range blood pressure or changes antihypertensive requirements in the postpartum period, so avoiding NSAIDs on this basis alone is outdated practice.^[1]

Blood pressure follow-up: check BP within 72 hours of delivery (inpatient if the patient is still admitted, or a dedicated office/virtual visit if already discharged), and again at 7-10 days postpartum — blood pressure typically falls in the first 48 hours after delivery but rebounds around days 3-6, which is exactly the window a standard 6-week postpartum visit would miss entirely. Support home blood pressure monitoring in between these visits and give explicit written warning-symptom education at discharge.^[6]

HELLP syndrome

Delivery is generally recommended regardless of gestational age once HELLP syndrome is diagnosed, given its progressive and sometimes sudden clinical course; patients remote from term should be cared for at a centre with neonatal and obstetric intensive-care resources. Monitor platelet count and liver enzymes at least every 12 hours until a clear improving trend is established — the platelet nadir typically occurs about 23 hours after delivery, and a rebound thrombocytosis by day 4-7 postpartum is a normal recovery pattern, not a new problem.^[1]

Breastfeeding

Labetalol, nifedipine extended-release, methyldopa, and magnesium sulfate are all considered compatible with breastfeeding.

Renal impairment

In mild renal impairment (serum creatinine 88-133 μmol/L [1.0-1.5 mg/dL]) or oliguria (urine output under 30 mL/hr for more than 4 hours), give the standard magnesium sulfate loading dose but reduce the maintenance infusion to 1 g/hour, and check serum magnesium levels every 4 hours — magnesium is cleared almost entirely by the kidney, so impaired clearance raises toxicity risk substantially at a standard maintenance rate.^[1]

Obesity / higher body mass index

A higher volume of distribution in patients with a BMI over 35 kg/m² can leave magnesium levels subtherapeutic for several hours after a standard loading dose — some protocols use a higher loading dose (e.g., 4.5 g followed by a 1.8 g/hr maintenance infusion) in this group; follow local hospital protocol.^[1]

When IV access is difficult

Magnesium sulfate can be given intramuscularly: 4 g IV as a loading dose, immediately followed by 10 g IM (5 g deep IM into each buttock), then 5 g IM every 4 hours. Mixing the IM dose with 1 mL of 2% lidocaine reduces injection-site pain; the IM route carries a higher rate of local adverse effects than the IV route.^[1]

During a magnesium sulfate infusion: assess deep tendon reflexes, respiratory rate, and urine output at least hourly. Loss of deep tendon reflexes is the earliest clinical sign of impending toxicity and should prompt an immediate serum magnesium level and consideration of stopping the infusion.

Deep tendon reflexes are lost before respiratory depression occurs at a higher level still — provided reflexes are present, more serious toxicity has been avoided. If renal function is impaired, levels rise faster and monitoring should be more frequent (see Special Populations).^[1]

Blood pressure and severity monitoring: for hospitalized severe disease, monitor blood pressure and symptoms continuously through labour and delivery, and immediately postpartum, watching specifically for progression to severe features. For outpatient gestational hypertension or preeclampsia without severe features, weekly platelet count, creatinine, and liver enzymes, with blood pressure and symptom checks in-clinic at least weekly supplemented by home monitoring.^[1]

Long-term: counsel every patient with a history of preeclampsia that it roughly doubles the future risk of cardiovascular disease (hypertension, myocardial infarction, heart failure, stroke), with a graded relationship — the more severe the preeclampsia, the higher the later cardiovascular risk. Recommend ongoing primary-care follow-up and cardiovascular risk-factor management well beyond the postpartum period, not only the standard 6-week check.^[1]

1. Blood pressure not controlled despite an adequate dose of the first-line agent: add a second agent from a different class rather than pushing a single drug to its maximum dose, and reassess urgency — persistent severe-range BP despite treatment is itself an indication precluding expectant management (see Choose Initial Treatment).
2. Eclamptic seizure occurs: call for help, protect the airway, place the patient in the lateral decubitus position, prevent injury, and give supplemental oxygen. Most eclamptic seizures are self-limited — magnesium sulfate is given to prevent recurrence, not to abort the seizure itself. Start (or continue) the standard magnesium sulfate loading dose and maintenance infusion.^[1]
3. Seizure recurs despite magnesium sulfate: give an additional 2-4 g IV bolus over 5 minutes.
4. Refractory to magnesium — still seizing 20 minutes after the bolus, or 2 or more recurrences: this needs specialist/ICU-directed second-line anticonvulsant therapy (e.g., phenytoin or a benzodiazepine per institutional protocol), consideration of intubation, and consideration of head imaging, since most magnesium-refractory eclampsia has an abnormal finding on brain imaging.^[1]
5. Signs of magnesium toxicity (absent deep tendon reflexes, respiratory depression, or a serum level in the toxic range): stop the infusion immediately, give calcium gluconate 10 mL of 10% solution IV over 3 minutes, and support respiration (supplemental oxygen, assisted ventilation, or intubation as needed) until the level falls.
6. HELLP syndrome develops or worsens: this is itself an indication for delivery regardless of gestational age (see Choose Initial Treatment) — do not continue expectant management on the assumption the lab picture will stabilize on its own.
7. New severe symptoms or hypertension in the postpartum period: treat with the same urgency as antepartum severe preeclampsia — do not assume that delivery has already resolved the risk.

• Continuing an ACE inhibitor or ARB after conception, or failing to switch a patient with treated chronic hypertension before a planned pregnancy — genuinely contraindicated, not merely "preferably avoided."
• Missing the aspirin-prophylaxis window — starting after 16 weeks meaningfully reduces the benefit on severe and preterm preeclampsia compared with starting before 16 weeks.^[3]
• Treating non-severe hypertension in pregnancy toward an aggressively low target — over-lowering blood pressure can compromise placental perfusion; the target is roughly 120-140/80-90 mmHg, not the tightest number achievable.
• Assuming magnesium sulfate is an antihypertensive — it prevents and treats seizures only; blood pressure still needs separate, active management.
• Stopping a magnesium sulfate infusion before the full 24-hour postpartum course is complete, particularly around the stress of a caesarean delivery, when the seizure threshold may be lowest.
• Missing HELLP syndrome because hypertension or proteinuria is absent — up to 15% of cases present without either, with right-upper-quadrant pain and malaise as the dominant symptoms instead.
• Withholding NSAIDs from a postpartum patient with a history of severe features out of outdated concern — current evidence supports their preferential use over opioids for postpartum analgesia in this group.
• Discharging a patient with a hypertensive disorder of pregnancy without a scheduled blood pressure check in the 72-hour and 7-10-day window, missing the well-documented days-3-to-6 rebound in blood pressure.
• Treating delivery as the end of the condition — new-onset postpartum preeclampsia and eclampsia are real, and long-term cardiovascular risk counselling is easy to skip once the pregnancy itself has ended.
• Not keeping calcium gluconate readily available at the bedside whenever a magnesium sulfate infusion is running.

How to use this table: doses are adult obstetric doses for preeclampsia specifically and require patient-specific confirmation. Drug pricing is intentionally omitted. Select any drug name to open its complete Pharmasist Drug Database page.

Aspirin — Preeclampsia Prophylaxis

The only prevention strategy with strong supporting evidence in patients meeting the risk-factor threshold.^[3]

Oral Antihypertensives — Non-Severe Hypertension Maintenance Therapy

1st-line maintenance options once BP is sustained over 140/90 mmHg; target roughly 120-140/80-90 mmHg.^[2]

Parenteral / Acute-Onset Antihypertensives — Severe Hypertension (≥160/110 mmHg)

Treat within 30-60 minutes of confirming persistent severe-range BP.^[1]

Magnesium Sulfate — Eclamptic Seizure Prophylaxis and Treatment

The drug of choice for preventing and treating eclamptic seizures — more effective than phenytoin, diazepam, or nimodipine for this purpose.^[4]

Contraindicated in pregnancy

Evidence note: drug inventory, dosing, adverse effects, and comments reflect standard Canadian obstetric practice, cross-checked against current SOGC and ACOG guidance.^[2][1]