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Pregnancy in Women with Migraine: A Time of Increased Vascular Risk
Abstract & Commentary
By Dara Jamieson, MD, Associate Professor of Clinical Neurology, Weill Cornell Medical College. Dr. Jamieson reports she is a retained consultant for Boehringer Ingelheim, Merck, and Ortho-McNeil, and is on the speaker's bureau for Boehringer Ingelheim and Merck.
Synopsis: Peripartum migraine increases the risk of ischemic stroke, myocardial infarction, heart disease, and pulmonary embolus during pregnancy. Women with persistent migraines during pregnancy are at increased risk of gestational hypertension and pre-eclampsia.
Sources: Bushnell CD, Jamison M, James AH. Migraines during pregnancy linked to stroke and vascular diseases: US population-based case-control study. BMJ 2009;338:b664. doi: 10.1136/bmj.b664; Facchinetti F, Allais G, Nappi RE, et al. Migraine is a risk factor for hypertensive disorders in pregnancy: A prospective cohort study. Cephalalgia 2009;29: 286292.
Multiple studies confirm that migraine confers increased vascular risk, especially for women. Cheryl Bushnell and her colleagues have expanded their previously published work on risk factors for stroke during pregnancy, which included African-American race, age greater than 35 years, lupus, blood transfusion, and migraine headaches. In this large sample of pregnant women admitted to hospitals, they examined the association between migraine and vascular diseases during pregnancy, using a United States population-based case-control study (the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality). ICD-9 codes for migraine and vascular diseases were extracted from 18,345,538 pregnancy-related hospital discharges from 2000 to 2003. Diagnoses that were jointly associated with migraine codes during pregnancy (excluding pre-eclampsia) were stroke [odds ratio (OR) 15.05, 95% confidence interval (CI) 8.26 to 27.4], myocardial infarction/heart disease (OR 2.11, CI 1.76 to 2.54), pulmonary embolus/venous thromboembolism (OR 3.23, CI 2.06 to 7.07), and hypertension (OR 8.61, CI 6.43 to 11.54), as well as pre-eclampsia/gestational hypertension (OR 2.29, CI 2.13 to 2.46), smoking (OR 2.85, CI 2.53 to 3.21), and diabetes (OR 1.96, CI 1.64 to 2.35). Migraine was not associated with several vascular (cerebral venous thrombosis, subarachnoid hemorrhage) and non-vascular (pneumonia, transfusions, postpartum infection or hemorrhage) diagnoses. The study was not able to differentiate between migraine with and without aura, an important distinction in determining vascular risk. The study did not determine whether the migraine or the vascular condition came first, but concluded that active migraine during pregnancy was a potential marker of vascular disease.
Facchinetti et al assessed whether women suffering from migraine were at higher risk of developing hypertensive disorders in pregnancy. The prospective cohort study of 702 normotensive Northern Italian women with singleton pregnancy at 1116 weeks' gestation excluded women with a history of hypertension or hypertensive disorders in pregnancy. The main outcome measure was the onset of either gestational hypertension or preeclampsia in the 270 women (38.5%) who were diagnosed with migraine (68.1% with migraine without aura) according to the International Headache Society criteria. The risk of developing hypertensive disorders in pregnancy was higher in migraineurs (9.1%) compared with non-migraineurs (3.1%) (OR adjusted for age, family history of hypertension and smoking 2.85, 95% CI 1.40, 5.81). Women with migraine also showed a trend to increased risk for low birth weight infants compared to women without migraine (OR 1.97, CI 0.98, 3.98). Women whose migraine headaches did not improve during pregnancy had an increased risk of developing hypertensive disorders in pregnancy (P = 0.001).
These two studies determined vascular conditions (ischemic stroke, myocardial infarction, gestational hypertension, pre-eclampsia) found with increased frequency in pregnant women with migraine. Especially close monitoring of women with persistent migraine headaches during pregnancy may prevent some of these vascular complications of pregnancy. Further studies of the specific pattern of migraine headaches during pregnancy may stratify vascular risk. Most women have significant, albeit transient, relief of migraines during the last two trimesters of pregnancy; the increased risk with the persistence of migraines during pregnancy should be evaluated for ischemic stroke and myocardial infarction. These two studies were not able to differentiate risk with migraine with or without aura; but data on the increased vascular risk of non-pregnant women with migraine with aura could possibly be extrapolated to predict an even greater vascular risk in pregnant women with this less common migraine type.
Advising women with migraine with aura about their reproductive options can be complicated. There is an increased vascular risk with the use of oral contraceptives in women with migraine with aura; yet pregnancy also confers vascular risk in migraineurs. Reassuringly, the vascular risk for women of reproductive age who have migraine with aura is still extremely small and decisions about contraception and pregnancy should be based on personal preference, not fear of vascular events.