Seizures in pregnancy

A seizure in pregnancy is a paroxysmal event with altered awareness or convulsive movements occurring between conception and 6 weeks after birth. The main clinical point is that a new seizure after 20 weeks, or in the first 6 weeks after birth, is eclampsia until proved otherwise, and magnesium sulphate is the first drug. Other causes include epilepsy, cerebral venous thrombosis, stroke, infection, metabolic disturbance, drugs and tumours. The care of the mother comes first, then the foetus.

Clinical relevance. Eclampsia and status epilepticus carry a high risk of maternal death, hypoxic brain injury and foetal death. Epilepsy in pregnancy needs drug choice that balances seizure control against teratogenicity.

Physiology. Pregnancy lowers the seizure threshold through sleep loss, vomiting, missed drugs, and increased drug clearance (lamotrigine, levetiracetam and phenytoin levels fall). Hypoxia and acidosis in the mother quickly affect the foetus.

Mechanisms. Eclampsia results from cerebral endothelial dysfunction, loss of autoregulation, vasogenic oedema and focal ischaemia. Epileptic seizures arise from abnormal neuronal discharges. Symptomatic seizures follow structural, metabolic, toxic or infective insults.

Classification. By onset: first seizure in pregnancy or known epilepsy. By timing: antepartum, intrapartum, early postpartum (within 48 hours) and late postpartum (up to 6 weeks). By type: focal, generalised tonic clonic, absence, status epilepticus (seizure over 5 minutes, or repeated seizures without recovery). By cause: eclamptic, epileptic, provoked or non epileptic.

Key distinctions. Hypertension, proteinuria, headache and visual symptoms favour eclampsia, but a minority of women have normal blood pressure before the seizure. Onset under 20 weeks, after 48 hours postpartum, focal signs, fever, persistent confusion or normotension suggests another cause. Convulsive syncope and psychogenic events can mimic seizures.

History (from witnesses where possible)

• Event: onset, preceding aura, focal onset, duration, eye deviation, tongue bite, incontinence, post ictal state, injury.
• Prodrome: headache, visual disturbance, epigastric pain, vomiting, confusion.
• Gestation or days since birth; blood pressure and urine results at antenatal visits.
• Epilepsy: type, last seizure, drugs and doses, adherence, drug levels, triggers (sleep loss, vomiting, missed doses), folic acid use.
• Medical: diabetes, renal disease, hypertension, head injury, stroke, tumour, HIV, tuberculosis, meningitis, neurocysticercosis, alcohol, drug use, eclampsia in previous pregnancy.
• Drugs: antiepileptics, bupivacaine or lidocaine (local anaesthetic toxicity after epidural or block), theophylline, tramadol, bupropion, antibiotics (high dose penicillin, carbapenems), cocaine, amphetamines, alcohol and benzodiazepine withdrawal.
• Fever, rash, neck stiffness, travel (malaria), animal contact, immunosuppression.
• Obstetric: caesarean section, neuraxial anaesthesia, massive haemorrhage, amniotic fluid embolism.
• Social: alcohol, substances, intimate partner violence.

Examination

• Airway, breathing, circulation; level of consciousness (Glasgow Coma Scale), oxygen saturation, temperature, blood pressure (repeated), pulse, respiratory rate, glucose.
• Neurological: pupils, focal deficit, tone, reflexes (hyperreflexia and clonus in eclampsia), plantar response, fundi (papilloedema, retinal haemorrhage), neck stiffness, tongue bite.
• Cardiovascular and respiratory examination (pulmonary oedema, arrhythmia).
• Skin: rash, petechiae, injection marks.
• Obstetric: uterine tone and tenderness, vaginal bleeding, foetal heart, cardiotocography.
• Postpartum: wound, lochia, breasts, calves.

Red flags

• Seizure with blood pressure 140/90 mmHg or more, proteinuria, headache or visual disturbance.
• Seizure lasting over 5 minutes, repeated seizures, or no return to baseline (status epilepticus).
• Focal neurological deficit, persistent confusion, severe or thunderclap headache.
• Fever, neck stiffness, rash, immunosuppression, travel to malaria areas.
• Seizure before 20 weeks or after 48 hours postpartum.
• Hypoglycaemia, hyponatraemia, hypocalcaemia or hypoxia.
• Recent epidural or nerve block (local anaesthetic toxicity), peri arrest.
• Abnormal foetal heart or vaginal bleeding.

Special groups. Women with epilepsy: continue antiepileptic drugs and check levels; pregnancy changes drug requirements. Postpartum women: eclampsia, venous thrombosis, reversible vasoconstriction and post dural puncture complications are common causes. Region specific: cerebral malaria, neurocysticercosis, tuberculous meningitis and HIV related causes.

Organised by cause. Each cause is common unless marked serious or uncommon.

Hypertensive and pregnancy specific

• Serious: eclampsia (antepartum, intrapartum or postpartum).
• Serious: posterior reversible encephalopathy syndrome.
• Serious: reversible cerebral vasoconstriction syndrome.
• Serious: amniotic fluid embolism.
• Serious: thrombotic thrombocytopenic purpura.
• Peripartum angiopathy.

Epilepsy

• Known epilepsy: breakthrough from missed drugs, vomiting, sleep deprivation or increased clearance.
• New onset focal or generalised epilepsy.
• Juvenile myoclonic epilepsy and other generalised syndromes.

Cerebrovascular

• Serious: cerebral venous thrombosis.
• Serious: ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage.
• Arteriovenous malformation and cavernoma (bleeding risk increased in pregnancy).
• Cerebral vasculitis.

Metabolic

• Hypoglycaemia, hyperglycaemia and ketoacidosis.
• Hyponatraemia (water intoxication, syndrome of inappropriate antidiuretic hormone, oxytocin infusion), hypernatraemia.
• Hypocalcaemia (hypoparathyroidism), hypomagnesaemia, hypophosphataemia.
• Uraemia, hepatic encephalopathy, hypoxia, hypothyroid or thyroid storm, Wernicke encephalopathy.

Infection and inflammation

• Serious: bacterial meningitis, herpes simplex encephalitis, cerebral abscess.
• Serious: cerebral malaria.
• Neurocysticercosis, tuberculoma, toxoplasmosis, HIV related opportunistic infection, neurosyphilis.
• Autoimmune encephalitis, systemic lupus erythematosus, antiphospholipid syndrome.

Structural

• Brain tumour (meningioma, glioma, metastasis, pituitary), choriocarcinoma metastasis.
• Head injury and subdural haematoma, including intimate partner violence.
• Idiopathic intracranial hypertension.

Drugs and toxins

• Local anaesthetic toxicity (bupivacaine, lidocaine), cocaine, amphetamines, theophylline, tramadol, isoniazid, penicillins, carbapenems, ciprofloxacin, bupropion.
• Alcohol and benzodiazepine withdrawal, organophosphate poisoning.

Non epileptic events

• Convulsive syncope, cardiac arrhythmia, hyperventilation, panic attack.
• Psychogenic non epileptic seizures.
• Movement disorders, rigors, eclamptic like shaking with magnesium toxicity or hypocalcaemia.

Stepwise reasoning

1. Stabilise airway, breathing and circulation and stop the seizure.
2. Check glucose and blood pressure at once.
3. If after 20 weeks or postpartum, presume eclampsia and give magnesium sulphate while looking for other causes.
4. Look for other causes by history, examination, bloods and imaging.
5. Assess the foetus after the mother is stable.

First line tests

• Capillary glucose (immediately), blood pressure, oxygen saturation, temperature.
• Blood gas with lactate, full blood count, urea, creatinine, electrolytes (sodium, calcium, magnesium, phosphate), liver function tests, lactate dehydrogenase, uric acid, coagulation screen with fibrinogen, haemolysis screen.
• Urine protein, pregnancy test (early pregnancy), toxicology screen and alcohol level.
• Malaria film or rapid test in endemic areas, HIV test.
• Antiepileptic drug levels (phenytoin, carbamazepine, valproate, lamotrigine) in women on treatment.
• Blood cultures and C reactive protein if febrile.
• Electrocardiogram.
• Cardiotocography after maternal stabilisation, and ultrasound for foetal well being and placental abruption.

Neuroimaging and further tests

• Indications for imaging: focal deficit, persistent altered consciousness, seizure despite adequate magnesium, atypical timing (under 20 weeks, over 48 hours after birth), normal blood pressure, fever, thunderclap headache, previous cancer, head injury, new seizure type in epilepsy, or first seizure in a woman without clear cause.
• CT head (foetal dose negligible) when MRI is not immediately available or haemorrhage is suspected.
• MRI brain with MR venography (no gadolinium) for posterior reversible encephalopathy syndrome, cerebral venous thrombosis, stroke, and tumour.
• Lumbar puncture after imaging for suspected meningitis or encephalitis; do not delay antibiotics.
• Electroencephalography for non convulsive status, diagnosis of epilepsy syndrome, and unexplained altered consciousness.

Limitations. Eclampsia may occur with normal blood pressure and no proteinuria. Hyponatraemia can result from oxytocin infusion. Antiepileptic drug levels need trimester specific interpretation, and free levels are preferred for phenytoin. Magnesium sulphate does not stop non eclamptic seizures reliably.

Immediate steps. Call for help. Protect from injury, place in the left lateral position (or manual uterine displacement) after 20 weeks, clear and protect the airway, give oxygen 10 to 15 L/min by reservoir mask, establish intravenous access, check glucose, and monitor oxygen saturation, blood pressure and pulse. Do not restrain. Note the time.

Eclampsia: magnesium sulphate

• 4 g intravenously over 5 to 15 minutes (in 100 mL sodium chloride 0.9%), then 1 g/h for 24 hours after birth or the last seizure. For a recurrent seizure give 2 g over 5 minutes.
• Monitor respiratory rate (over 12 breaths/min), oxygen saturation, patellar reflexes and urine output (over 0.5 mL/kg/h) hourly. In renal impairment reduce the maintenance to 0.5 g/h and measure serum magnesium (therapeutic 2 to 4 mmol/L; loss of reflexes about 3.5 to 5 mmol/L; respiratory depression about 6 to 7 mmol/L).
• Antidote for toxicity: calcium gluconate 10% 10 mL (1 g) intravenously over 10 minutes.
• Where pumps are unavailable: 4 g intravenously over 5 to 10 minutes plus 10 g intramuscularly (5 g into each buttock), then 5 g intramuscularly every 4 hours into alternate buttocks if reflexes are present, respiratory rate is over 16 breaths/min and urine output is over 100 mL in 4 hours.
• Magnesium sulphate reduces recurrence better than diazepam or phenytoin.
• Control severe hypertension (160/110 mmHg or more) to systolic 140 to 150 mmHg and diastolic 90 to 100 mmHg with labetalol 200 mg orally repeated once after 30 minutes, or 20 mg intravenously then 40 mg, 80 mg and 80 mg at 10 minute intervals (total 220 mg); or nifedipine immediate release 10 mg orally repeated after 30 minutes (maximum 30 mg in the first hour); or hydralazine 5 mg intravenously (maximum 20 mg).
• Restrict fluids to about 80 mL/h. Manage pulmonary oedema with furosemide 40 mg intravenously.
• Plan delivery once stable. Do not deliver during the seizure. Vaginal birth is acceptable if favourable; caesarean section for obstetric indications or maternal or foetal deterioration. Neuraxial anaesthesia if platelets are 75 x 10^9/L or more and coagulation is normal; general anaesthesia carries risk of hypertensive response at intubation (give labetalol 20 mg or alfentanil beforehand).
• Intensive care for recurrent seizures, coma, pulmonary oedema, stroke or HELLP syndrome.

Seizure lasting over 5 minutes or recurring despite magnesium (status epilepticus)

• Lorazepam 4 mg intravenously (0.1 mg/kg to a maximum of 4 mg a dose), repeated once after 10 minutes if seizures continue; or midazolam 10 mg intramuscularly (over 40 kg) or 10 mg buccally; or diazepam 10 mg intravenously over 2 minutes (repeat once; or 10 to 20 mg rectally). Monitor for respiratory depression.
• Second line: levetiracetam 60 mg/kg intravenously (maximum 4500 mg) over 10 to 15 minutes; or phenytoin 20 mg/kg intravenously (maximum 2000 mg) at not more than 50 mg/min with continuous electrocardiogram and blood pressure monitoring (risk of hypotension and arrhythmia); or sodium valproate 40 mg/kg (maximum 3000 mg) is avoided in pregnancy and used only if there is no alternative.
• Refractory status: general anaesthesia with propofol, midazolam or thiopental in an intensive care setting, with continuous electroencephalogram monitoring, and delivery decision made with the obstetric and anaesthetic teams (maternal stability determines timing).
• Check and correct glucose: if glucose is under 4 mmol/L give dextrose 10% 150 mL intravenously (or 50% 50 mL via a large vein), with thiamine 100 mg intravenously first in women with vomiting, alcohol use or malnutrition.

Treat the cause

• Hyponatraemia with seizure: 3% sodium chloride 150 mL intravenously over 20 minutes, repeated up to twice, aiming for a rise of 4 to 6 mmol/L; limit correction to 10 mmol/L in 24 hours.
• Hypocalcaemia: calcium gluconate 10% 10 to 20 mL intravenously over 10 minutes, then an infusion.
• Hypomagnesaemia: magnesium sulphate 2 g intravenously over 15 minutes, repeated as directed by serum levels.
• Cerebral venous thrombosis: therapeutic enoxaparin 1 mg/kg subcutaneously every 12 hours (reduce to once daily for creatinine clearance under 30 mL/min) through pregnancy and for at least 6 weeks after birth (minimum total 3 to 6 months); levetiracetam 500 mg orally twice daily (maximum 3 g daily).
• Meningitis and encephalitis: ceftriaxone 2 g intravenously every 12 hours with amoxicillin 2 g intravenously every 4 hours (covers Listeria) and dexamethasone 10 mg intravenously every 6 hours for 4 days; aciclovir 10 mg/kg intravenously every 8 hours (adjusted to renal function) for suspected herpes encephalitis.
• Cerebral malaria: artesunate 2.4 mg/kg intravenously at 0, 12 and 24 hours, then daily until oral treatment is possible, with glucose monitoring.
• Local anaesthetic toxicity: stop the injection, airway and oxygen, benzodiazepine for seizure, and 20% lipid emulsion 1.5 mL/kg intravenously over 1 minute then 15 mL/kg/h infusion (maximum 12 mL/kg total), with early cardiac support; deliver by caesarean section if cardiac arrest.
• Intracranial haemorrhage or tumour: neurosurgical care.
• Posterior reversible encephalopathy syndrome and reversible vasoconstriction: control blood pressure, stop vasoactive drugs, magnesium sulphate for eclampsia.
• Alcohol or benzodiazepine withdrawal: diazepam 10 mg intravenously or orally, repeated, with thiamine 200 to 300 mg intravenously daily.

Epilepsy in pregnancy

• Continue antiepileptic drugs. Do not stop abruptly. Lamotrigine and levetiracetam are preferred. Avoid valproate (neural tube defects, neurodevelopmental effects), topiramate, phenobarbital and, where possible, phenytoin; carbamazepine has a moderate risk and is used if it is the only effective drug. Avoid polytherapy. Switch only before conception if possible, with specialist advice.
• Folic acid 5 mg orally daily before conception and until at least 12 weeks.
• Monitor levels (free levels for phenytoin) at booking, each trimester, and after birth. Lamotrigine clearance rises up to 300%; increase the dose by 25 to 50%, adjusted to levels or symptoms, and return to the pre pregnancy dose over the first 3 weeks after birth to avoid toxicity. Levetiracetam levels also fall; monitor and adjust.
• Vitamin K 10 mg orally daily from 36 weeks has been used for enzyme inducing drugs (evidence limited); all newborns receive vitamin K 1 mg intramuscularly.
• Women on enzyme inducing drugs need contraception that remains effective (levonorgestrel intrauterine system, copper intrauterine device, medroxyprogesterone acetate depot).
• Counsel about triggers, sleep, bathing and baby care safety; give a seizure plan for family and midwives.
• Anomaly scan at 18 to 20 weeks, and growth scans in women on drugs that restrict growth.
• Labour: continue drugs; deliver in hospital; avoid pethidine; use benzodiazepines for prolonged seizures. Breastfeeding is generally compatible with antiepileptic drugs, with infant observation for sedation.

Foetal care. Continuous cardiotocography after the seizure and when the mother is stable. Transient bradycardia and late decelerations are common and usually recover; persistent abnormality after maternal stabilisation needs urgent obstetric decision. Betamethasone 12 mg intramuscularly twice, 24 hours apart, for gestation under 34 weeks when birth is likely within 7 days; magnesium sulphate for neuroprotection is covered by the eclampsia dose before 30 weeks.

Non epileptic events. Treat the underlying cause, avoid unnecessary antiepileptic drugs, and refer for psychological care.

Special groups. Women with HIV on antiretroviral therapy: interactions with enzyme inducers lower antiretroviral levels (efavirenz, dolutegravir); seek specialist advice. Women with renal impairment: reduce magnesium maintenance. Adolescents: confidentiality and child protection. Region specific: eclampsia care at first level facilities (magnesium sulphate, antihypertensives, oxygen, transfer) is life saving.

Monitoring. Continuous monitoring for the first hours: oxygen saturation, blood pressure, pulse, respiratory rate, level of consciousness, urine output hourly, reflexes, fluid balance, and glucose. Repeat bloods at 6 hours and daily (platelets, creatinine, liver tests). Foetal monitoring as appropriate.

Referral and escalation. Call the consultant obstetrician, anaesthetist and neurologist for any seizure. Refer to critical care for status epilepticus, recurrent seizures, coma, HELLP syndrome or pulmonary oedema. Refer to neurology for epilepsy care and new neurological findings, to neurosurgery for structural lesions, and to the neonatal team.

Admission criteria. All women with a seizure in pregnancy or the first 6 weeks after birth, at least until the cause is known and the woman is stable. Critical care for eclampsia, status epilepticus or reduced consciousness.

Discharge and follow up. Discharge when seizure free, the cause is treated or understood, the foetal state is reassuring and a follow up plan exists. After eclampsia: review at 6 weeks with blood pressure, renal function, urine, and counselling on recurrence risk and aspirin in the next pregnancy. Neurology follow up for epilepsy, with dosing plan after birth.

Safety netting. Return at once for any further seizure, severe headache, visual disturbance, confusion, weakness, vomiting, or missed antiepileptic doses because of vomiting; women with epilepsy should avoid bathing alone and should not drive until cleared.