• The primary diagnosis that must be ruled out in pregnancy >20 weeks gestation is preeclampsia as this often presents as a headache.
• Pregnancy confers a higher risk of central venous sinus thrombosis (CVST) and stroke due to due to a physiologic hypercoagulable state.
• Neuroimaging should be used judiciously but is indicated in pregnancy when required to rule out dangerous intracranial pathology.

Careful consideration of pharmaceutical therapy is indicated to avoid fetal harm.

History and Physical Exam

• Obtain a prenatal history and ensure adequate fetal movements.
• A thorough history and physical exam should be elicited in the same manner as it would for a headache in the non-pregnant adult.
• Always screen for red flags suggestive of serious underlying disease including neurologic changes, vascular compromise, increased intracranial pressure, infection, and mass effect.
• If previously diagnosed with a primary headache disorder (tension/cluster/migraine), determine if its characteristic has changed. Stable symptoms are reassuring, atypical presentations should raise suspicion for alternative etiology.
• Ruling out preeclampsia requires obtaining a reliable blood pressure. Also assess for visual changes, RUQ/epigastric pain, nausea/vomiting, peripheral edema, and pulmonary edema. Seizure is concerning for progression to eclampsia.

Laboratory Investigations

• Labs for headache are indicated in the same manner as in the non-pregnant adult.
• Any concern for preeclampsia should be evaluated with the following: CBC, serum creatinine, serum transaminases, and urine protein/creatine ratio.
• Lumbar punctures are not contraindicated in pregnancy and should be considered in the same manner as in the non-pregnant adult.

Imaging

• MRI itself does not expose the fetus to radiation and is safe. Gadolinium contrast may be associated with adverse fetal outcomes¹ and should generally be avoided unless the diagnostic benefit it confers is expected to significantly improve maternal or fetal outcomes².
• CT head involves minimal fetal exposure to radiation³. Contrast does cross the placenta but should be used when indicated as brief exposures are not known to be associated with adverse fetal outcomes⁴.

Diagnostic considerations

• MUST rule out preeclampsia in all pregnancies >20 weeks gestation. Hypertension (>140/90) in the context of proteinuria, thrombocytopenia, elevated serum creatinine, elevated transaminases, objective pulmonary edema, or visual changes meets diagnostic criteria for preeclampsia. Blood pressure increase in the context of chronic HTN should also be considered. Normotension excludes preeclampsia in most cases, although if signs/symptoms exist in the context of a headache it should still raise suspicion and warrants further investigation.
• Consider posterior reversible encephalopathy syndrome (PRES) and reversive cerebral vasoconstriction syndrome (RCVS) in the context of suspected preeclampsia².
• Consider CVST given the physiologic hypercoagulability of pregnancy, especially if headache is accompanied by papilledema, visual changes, seizure, neurological deficits, or mental status changes. Urgent neuroimaging with CT venogram or MR venogram is indicated when suspicion for this diagnosis is raised.
• Most headaches in pregnancy occur in those with a previous history of primary headache⁵. If preeclampsia has been ruled out and the presentation is consistent with this previous diagnosis, consider treating the likely etiology.
• Any new onset or atypical headache should be considered a secondary headache until proven otherwise and evaluated as it would be outside of pregnancy.
• Consider medication overuse headache as there is often a significant MSK pain burden associated with pregnancy.

Treatment

• Medications that are absolutely contraindicated in pregnancy include ergotamine and isomethemtene. In general, avoid teratogens, uterotonics and vasoconstrictors.
• Triptans pose a theoretical risk of uterotonicity and placental vasoconstriction. Limited evidence of sumatriptan exposure in pregnancy has not shown increased rates of adverse fetal outcomes⁶, it may be cautiously considered in refractory migraine².
• Acetaminophen is considered safe in pregnancy and should be considered 1^st line for migraine².
• Metoclopramide (10mg IV or enteral) with the addition of diphenhydramine (25-50mg IV or enteral) are reasonable additions for persistent headache².
• NSAIDS are associated with fetal risk. Consider as a second line agent, and limit to short courses (<48 hours) only in the second trimester². It is relatively contraindicated in early and late pregnancy.
• Consider opioids as a third line agent. The effects of opioids on the developing embryo are not fully understood and use in early pregnancy may be associated with a small risk of congenital anomaly⁷.
• Glucocorticoids may be considered as a third line agent for refractory migraine⁸. Prednisone (20mg PO QID for 2 days) or methylprednisone (4mg PO, 21 tabs over 6 days) are the preferred agents as the placenta metabolizes them into inactive forms. There is mixed evidence regarding the association of first trimester exposure and cleft lip/palate^2,8.
• Definitive preeclampsia treatment is delivery of the fetus and placenta, the timing of which primarily depends on the gestational age of the pregnancy. Obstetric consult is required. If severe hypertension, start antihypertensive therapy to reduce the risk of stroke or possible abruption. Consider IV labetalol or IV hydralazine. Consider magnesium sulfate to prevent eclamptic seizure.

Disposition

• Concern for preeclampsia requires an obstetric consult.
• Abnormal neurological findings or imaging results indicate a neurology / neurosurgery consult in the same manner as it would in the non-pregnant adult.

1. Committee Opinion No. 723: Guidelines for Diagnostic Imaging During Pregnancy and Lactation. Obstet Gynecol 2017; 130:e210.

   
   

2. ACOG Committee on Clinical Practice Guidelines–Obstetrics. Headaches in Pregnancy and Postpartum: ACOG Clinical Practice Guideline No. 3. Obstet Gynecol 2022; 139:944.

   
   

3. Goldberg-Stein SA, Liu B, Hahn PF, Lee SI. Radiation dose management: part 2, estimating fetal radiation risk from CT during pregnancy. AJR Am J Roentgenol 2012; 198:W352.

   
   

4. Rajaram S, Exley CE, Fairlie F, Matthews S. Effect of antenatal iodinated contrast agent on neonatal thyroid function. Br J Radiol 2012; 85:e238.

   
   

5. Melhado EM, Maciel JA Jr, Guerreiro CA. Headache during gestation: evaluation of 1101 women. Can J Neurol Sci 2007; 34:187.

   
   

6. Marchenko A, Etwel F, Olutunfese O, et al. Pregnancy outcome following prenatal exposure to triptan medications: a meta-analysis. Headache 2015; 55:490.

   
   

7. Broussard CS, Rasmussen SA, Reefhuis J, et al. Maternal treatment with opioid analgesics and risk for birth defects. Am J Obstet Gynecol 2011; 204:314.e1.

   
   

8. Lucas S. Medication use in the treatment of migraine during pregnancy and lactation. Curr Pain Headache Rep 2009; 13:392.