Migraine Linked To Preeclampsia, Other Pregnancy Complications

Migraine Linked To Preeclampsia, Other Pregnancy Complications

Pregnant women with a history of migraine are at elevated risk for gestational hypertension and preeclampsia, and of delivering their baby preterm, new research suggests.

In a large prospective study, researchers also found a link between migraine with aura and increased preeclampsia risk.

Dr Alexandra Purdue-Smithe

Overall, the findings suggest women with a history of migraine may benefit from enhanced monitoring during pregnancy, co-investigator Alexandra Purdue-Smithe, PhD, associate epidemiologist at Brigham and Women’s Hospital and instructor in medicine at Harvard Medical School, Boston, Massachusetts, told Medscape Medical News.

“Our results suggest that migraine history may be an important consideration in  obstetric risk assessment,” Purdue-Smithe added.

The findings, which have not yet been peer reviewed, will be presented at the American Academy of Neurology (AAN) 2022 Annual Meeting in April.

Common Neurovascular Disorder

Migraine is a common neurovascular disorder, affecting about 15% of adults. The condition carries “a pretty remarkable sex bias” as it affects up to three times more women than men, and about a quarter of women in the reproductive age bracket of 18-44 years, Purdue-Smithe noted.

Despite this, relatively little is known about migraine and pregnancy risks, she said.

What is known is that women with migraine have a higher burden of cardiovascular risk factors such as obesity and chronic hypertension; and these factors can also increase risk for pregnancy complications, she added.

In the study, researchers analyzed data on 30,555 pregnancies in about 19,000 women without a history of cardiovascular disease, type 2 diabetes, or cancer during a 20-year period ending in 2009.

The data came from the Nurses’ Health Study II, a large prospective cohort study established in 1989 when it enrolled women aged 25-42 years.

Participants in the ongoing study complete questionnaires every 2 years, reporting information on various health conditions as well as pregnancy and reproductive events.

The investigators estimated associations of physician-diagnosed pre-pregnancy migraine with preterm delivery, gestational diabetes, gestational hypertension, preeclampsia, and low birth weight (<2500 grams [5.5 lb]).

About 11% of the women in the study had migraine diagnosed by a physician before pregnancy.

Researchers adjusted for age at pregnancy, race/ethnicity, age at menarche, and pre-pregnancy chronic hypertension, body mass index, physical activity, smoking status, alcohol intake, history of infertility, parity, oral contraceptive use, and analgesic use.

“A Bit Surprising”

Results showed that compared with women without a history of migraine, those with such a history had higher risk for preterm delivery (relative risk [RR], 1.17; 95% CI, 1.05 – 1.30), gestational hypertension (RR, 1.28; 95% CI, 1.11 – 1.48), and preeclampsia (RR, 1.40; 95% CI, 1.19 – 1.65).

Pre-pregnancy migraine was not associated with low birth weight (RR, 0.99; 95% CI, 0.85 – 1.16) or gestational diabetes (RR, 1.05; 95% CI, .91 – 1.22).

It was a “bit surprising” that women with migraine had a higher risk for preterm delivery but their babies were not necessarily underweight — although some prior literature had similar findings, said Purdue-Smithe.

She noted that in her study the association was limited to moderate preterm delivery (gestational age, 32-37 weeks) and not with very preterm births (before 32 weeks).

Researchers also assessed adverse pregnancy outcomes by aura phenotype. “Women with migraine with aura have a higher risk of cardiovascular disease later in life, so we hypothesized that aura might be more strongly associated with adverse pregnancy outcomes with underlying vascular pathology,” Purdue-Smithe said.

Both women with and without aura had elevated risks for preterm delivery and gestational hypertension. Those with aura had a slightly higher risk for preeclampsia (RR, 1.51; 95% CI, 1.22 – 1.88) than those without aura (RR, 1.29; 95% CI, 1.04 – 1.61).

As the association between migraine and adverse pregnancy outcomes persisted after adjusting for established cardiovascular and obstetric risk factors, “this suggests there may be subclinical factors that are contributing to elevated risks of these outcomes in women with migraine,” said Purdue-Smithe.

Such factors could include platelet activation, chronic inflammation, and endothelial dysfunction, she added.

While findings of some previous case-control and retrospective studies suggested a possible link between migraine and adverse pregnancy outcomes, until now few large prospective studies have examined the association.

“Strengths of our study include its prospective design, very large sample size, and more complete adjustment for potential pre-pregnancy confounders,” Purdue-Smithe said.

Independent Risk Factor?

In the past, it has been somewhat unclear whether migraine is an independent risk factor for these complications or whether women with migraine just have greater risk factors for adverse pregnancy outcomes.

“Our preliminary findings suggest that migraine is independently associated with these adverse pregnancy outcomes, or at least that’s what it seems,” said Purdue-Smithe.

The new results could be used by clinicians to “flag” women who may be at risk for complications, she added. “These women may benefit from closer monitoring in pregnancy so that if issues arise, physicians can act quickly.”

She noted that preeclampsia “can come on suddenly and escalate rapidly,” and there are few interventions to treat it besides delivery.

However, low-dose aspirin may be worth investigating. Various healthcare groups and the US Preventive Services Task Force recommend pregnant women at high risk for preeclampsia take low-dose aspirin (81 mg/d) after 12 weeks’ gestation.

“It would be interesting to see if women with migraine who take aspirin in pregnancy can reduce their risk of preeclampsia, and future research should address this question,” said Purdue-Smithe.

Additional testing showed that associations with preeclampsia and gestational hypertension did not vary according to age and other obstetrical risks.

The Nurses’ Health Study II did not have information on number and severity of migraine attacks, so the researchers were unable to determine if these factors affect pregnancy outcomes.

“Understanding whether specific migraine features, such as attack frequency, are associated with adverse pregnancy outcomes will be an important area for future research,” said Purdue-Smithe. She noted prior studies showed the frequency of migraine attacks is related to ischemic stroke and other cardiovascular outcomes.

The authors acknowledged a limitation for the current study: Although migraine history was reported prior to pregnancy, information on migraine aura was collected after most of the pregnancies in the cohort were over. So the findings for migraine aura may have been influenced by participants’ ability to accurately remember their experiences.

Collaboration Key

Commenting for Medscape Medical News, Nina Riggins, MD, PhD, director of the Headache and Traumatic Brain Injury Center, Department of Neurosciences, University of California San Diego, said the study “stands out” because it distinguishes pregnancy complications between those with and without aura among women with migraine. 

Riggins noted the investigators found the risk of preeclampsia, which on average occurs in about 3% to 5% of pregnancies, is higher among women with migraine with aura.  

“The good news is that treatments are available,” she said. “Preconception planning should include this discussion for patients living with migraine.”

However, the study did not compare risks for patients who have frequent migraine attacks vs episodic migraine, Riggins noted. 

“We need to learn more about whether any treatments can be safe and effective to decrease risks of complications during pregnancy in this population,” she said.

“I believe, ultimately, what this study reveals is that collaboration among primary care, ob/gyn, maternal–fetal medicine specialists, and neurologists will likely benefit pregnant patients with migraine,” Riggins said.

The study received funding from the National Institutes of Health. Purdue-Smithe has disclosed no relevant financial relationships.

American Academy of Neurology (AAN) 2021 Annual Meeting. Abstract 412. To be presented April 3, 2022.

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