Introduction
Methods of review
Clinical headache phenotypes and observational studies in pregnancy
Primary headaches
Author | Study design | Sample size | Improvement or remission (%) | Unchanged (%) | Worsening (%) | Extra data |
---|---|---|---|---|---|---|
Migraine without aura | ||||||
Granella et al. [8] | R | 571 | 67.3 | 29.2 | 3.5 | Full sample size: 1300 women; 943 had had pregnancies; 571 women with migraine before first pregnancy |
Scharff et al. [9] | P | 19 | 56.7 | 36.6 | 6.7 | Full sample size: 30; 11/30 with headache onset during pregnancy |
Maggioni et al. [5] | R | 81 | 89.5 | 7.7 | 2.5 | Full sample size: 430 women, interviewed 3 days after delivery; among them, 81 MO, 12 MA, 33 TTH |
Marcus et al. [10] | P | 49 | 40.8 | 51 | 8.2 | 16 M, 16 TTH, 15 M + TTH. Headache recorded daily during pregnancy and 3 months post-partum |
Granella et al. [11] | R | 200 | 76.8 | 22.2 | 1 | 100 MA and 200 MO as controls |
Mattsson [12] | R | 728 | 81.4 | 17.6 | 1 | Full sample size: 728; full information available for 102 women |
Sances et al. [13] | P | 47 | 87.2 | 12.8 | 0 | Full sample size 49: 2 MA, 47 MO |
Kelman [14] | R | 504 | 38.2 | 27.8 | 34 | Greater improvement in MO patients rather than MA patients |
Ertresvåg et al. [15] | P | 410 | 65.9 | 19.8 | 14.4 | Full sample size: 1361 women. 410 with M. |
Melhado et al. [16] | P | 737 | 65 | 26.1 | 8.9 | Full sample size: 1101 women. 737 with M. Data partially derived from graphics |
Summary | 3346 | 66.9 | 25.8 | 8 | ||
Migraine with aura | ||||||
Maggioni et al. [5] | R | 12 | 83.4 | 16.6 | 0 | 430 women 3 days after delivery; among them, 81 MO, 12 MA, 33 TTH |
Granella et al. [11] | R | 100 | 43.6 | 48.7 | 7.7 | 100 MA and 200 MO as controls |
Mattsson [12] | R | 728 | 78.3 | 4.3 | 17.4 | Full sample size: 728; full information available for 23 women |
Summary | 840 | 68.4 | 23.2 | 8.4 | ||
Tension-type Headache | ||||||
Maggioni et al. [5] | R | 33 | 82,1 | 17,9 | 0 | Full sample size: 430 women, interviewed 3 days after delivery; among them, 81 MO, 12 MA, 33 TTH |
Melhado et al. [16] | P | 112 | N/A (≈ 60) | N/A (≈ 35) | N/A (≈ 5) | Full sample size: 1101 women. 112 with TTH. Data derived from graphics |
Summary | 145 | – | – | – | ||
Cluster Headache | ||||||
Van Vliet et al. [31] | R | 53 | 69,9 | 20,7 | 9,4 | Full sample size: 196 CH; 53 had their first attack before the first pregnancy. 23% of episodic CH patients reported that an “expected” cluster period did not occur during pregnancy. Here improvement includes 8 patients who had a cluster period within 1 month after delivery. |
Migraine
Tension-type headache
Cluster headache
Secondary headaches
1. | Headache that peaks in severity in less than five minutes |
2. | New headache type versus a worsening of a previous headache |
3. | Change in previously stable headache pattern |
4. | Headache that changes with posture (e.g. Standing up) |
5. | Headache awakening the pregnant |
6. | Headache precipitated by physical activity or Valsalva manoeuvre (e.g. Coughing, laughing, straining) |
7. | Thrombophilia |
8. | Neurological symptoms or signs |
9. | Trauma |
10. | Fever |
11. | Seizures |
12. | History of malignancy |
13. | History of HIV or active infections |
14. | History of pituitary disorders |
15. | Elevated blood pressure |
16. | Recent travel at risk of infective disease |
Secondary headaches during pregnancy | |
---|---|
Arterial dissection | Intracranial hypotension |
Arteriovenous malformation | Ischemic stroke |
Brain tumors | Meningitis/encephalitis |
Cerebral venous thrombosis (CVT) | Pituitary adenoma |
Choriocarcinoma | Pituitary apoplexy |
Cranial neuralgias | Pituitary meningioma |
Dehydration | Reversible posterior leukoencephalopathy syndrome (PRES) |
Eclampsia and pre-eclampsia | Reversible vasoconstriction syndrome (RCVS) |
Head trauma | Sinusitis |
Idiopathic intracranial hypertension (IIH) | Subarachnoid haemorrhage (SAH) |
Intracranial haemorrhage (ICH) | Vasculitis |
Cerebral venous thrombosis
Pre-eclampsia and eclampsia
Ischaemic stroke
Subarachnoid haemorrhage
Arterial dissection
Reversible cerebral vasoconstriction syndrome
Posterior reversible encephalopathy syndrome
Idiopathic intracranial hypertension
Pituitary apoplexy
Treatment of headaches in pregnancy and breastfeeding women
Medication | Adverse effects | Concerns | Comments |
---|---|---|---|
Paracetamol | – | Possible increased risk for asthma, ADHD | Preferred acute treatment |
Nsaids (non-selective): ibuprofen, naproxen, diclofenac, indomethacin | - TR1: miscarriage - TR3: premature closure ductus arteriosus, impaired renal function, cerebral palsy, intraventricular haemorrhage | TR1: possible associated CM | - can be used safely during TR2 - avoid in TR3 - selective COX-inhibitors contra-indicated |
Triptans: sumatriptan, zolmitriptan, eletriptan, rizatriptan | No major congenital defects | TR1: possible link with behavioral problems | Appropriate if benefit outweighs risk |
Aspirin (ASA) | > 100 mg/d or TR3: premature closure of ductus arteriosus, oligohydramnios, neonatal bleeding | – | - < 100 mg/day seems safe - caution in TR1 and TR2 - avoid in TR3 |
Caffeine | – | Moderate to high daily doses: possible association with miscarriage, low birth weight, preterm delivery | – |
Combined preparations: paracetamol, aspirin and caffeine | – | – | Not recommended |
High flow oxygen | – | – | Preferred acute treatment in CH |
Lidocaine | – | – | - second line acute treatment in CH - intranasal formulation preferred |
Corticosteroids: prednisone, prednisolone | – | Possible early lung maturation | - avoid during first semester - low doses recommended - reserved for CH or status migrainosus |
Weak opioids: tramadol, codeine | - MOH - withdrawal symptoms and respiratory depression in the newborn | – | - not considered first line treatment in primary headaches - caution in TR1 and TR2 - avoid in TR3 |
Ergots/Ergots Alkaloids | - uterotonic and vasoconstrictive effect - fetal distress - CM | – | Avoid in any trimester |
Β-blockers: metoprolol, propranolol | Neonatal bradycardia, hypotension, hypoglycaemia when exposed in TR3 | - intrauterine growth retardation - preterm birth - respiratory distress | - first line migraine prophylaxis - if possible tapper off TR3 - monitor newborn exposed in TR3 |
ACE- I, ARB | CM | – | Avoid in any trimester |
Verapamil | – | – | First line CH profylaxis |
TCA | – | - possible CM (not confirmed) - withdrawal symptoms in the newborn | - second line migraine prophyaxis when β-blocker ineffective/contra-indicated - amytriptiline preferred |
Venlafaxine | CM | – | Should be avoided |
Duloxetine | – | – | No reported AE |
Valproate | Neural tube defects, cardiac defects, urinary tract defects, cleft palate, lower IQ scores | – | Avoid in any trimester |
Topiramate | Cleft lip/palate, low birth weight | – | Avoid in any trimester |
Gabapentin | – | Osteological deformities | Limited data |
Lamotrigine | No major congenital defects | Increased occurrence of autism/dyspraxia | Safest antiepileptic drug |
Magnesium | - high dose I.V.: bone abnormalities - possible transient neurological symptoms and hypotonia after delivery | Possible bone abnormalities in lower dosage or when taken orally | - appropriate in any trimester; caution directly before delivery - chronic use of oral magnesium: controversial |
Coenzyme Q10 | – | – | No reported AE |
Feverfew, butterbur, high dosed riboflavine | – | Possible CM | Not recommended |
Flunarizine | – | – | Not recommended (no data available) |
Lithium | - congenital cardiac malformations and cardiac arrhythmias - anomalies of the CNS and endocrine system - polyhydramnios - stillbirth | – | Not recommended but can be considered in uncontrolled CH refractory to Verapamil |
Botulinum toxin A | – | – | No reported AE when injected correctly |
Nerve blocks | – | – | - no reported AE when injected correctly - preferred agent: lidocaine |
Medication | Adverse effects | Comments |
---|---|---|
Paracetamol | – | Preferred acute treatment |
Nsaids (Non-selective): Ibuprofen, naproxen, indomethacin | Aggravation of jaundice | Ibuprofen preferred |
Triptans | – | - sumatriptan: no need to ‘pump and dump’ - less evidence on the other triptans: avoid nursing for 24 h after use of triptan as extra safety measurement |
Aspirin (ASA) | Reye’s syndrome | Not recommended |
Caffeine | – | Moderate dosage |
High flow oxygen | – | Preferred acute treatment in CH |
Lidocaine | – | - second line acute treatment in CH - intranasal formulation preferred |
Corticosteroids: prednisone, prednisolone | Prolonged high-dosed therapy: infant growth and development can be affected | Intravenously: delay breastfeeding for 2-8 h |
Weak opioids: tramadol, codeine | Sedation and respiratory depression in the infant | Not considered first line treatment in primary headaches |
Ergots/Ergots Alkaloids | - vomiting, diarrhea, convulsions - decrease of prolactine in the mother | Avoid in any trimester |
Β-blockers: metoprolol, propranolol | - hypotension, bradycardia - weakness | - metoprolol preferred - avoid in children with astma |
ACE-I, ARB | Impact on kidney development | Probably compatible (limited data) |
Verapamil | – | First line CH profylaxis |
TCA | – | No reported AE |
Venlafaxine | – | No reported AE |
Duloxetine | – | No reported AE |
Valproate | Interfere with liver and platelet function | Avoid in women of child-bearing age |
Topiramate | - sedation, irritability - poor suckling, diarrhea | – |
Gabapentin | – | No reported AE |
Lamotrigine | – | No reported AE |
Magnesium, Riboflavine | – | No reported AE |
Flunarizine | – | Not recommended: no data available |
Lithium | Renal toxicity | Not recommended, but can be considered in uncontrolled CH, refractory to Verapamil |
Botox | – | No reported AE when injected correctly |
Nerve blocks | – | No reported AE when injected correctly |