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Neurology Today:
doi: 10.1097/01.NT.0000406015.68139.84
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Pregnancy-Related Strokes on the Rise Nationwide

Fitzgerald, Susan

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ARTICLE IN BRIEF

Investigators reported that pregnancy-related stroke hospitalizations increased by about 54 percent between 1994-1995 and 2006-2007; and the rates of hospitalization for stroke rose by about 83 percent among new mothers in the postpartum period.

AMONG PREGNANT WOMEN...
AMONG PREGNANT WOMEN...
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Strokes among pregnant women and new mothers have risen significantly, especially during the postpartum period, according to a new federal study that tracked trends from two decades.

The number of pregnancy-related stroke hospitalizations increased from about 4,100 in 1994-1995 to 6,300 in 2006-2007 — an increase of 54 percent. The rate of hospitalization for stroke rose markedly among new mothers in the postpartum period, increasing by 83 percent.

Increases in stroke occurred along with increases in the number of pregnant women who had hypertensive disorders and chronic heart disease, according to the study by the US Centers for Disease Control and Prevention, published in the July 28 online edition of Stroke.

Elena V. Kuklina, MD, PhD, an epidemiologist in the CDC Division of Heart Disease and Stroke Prevention and the study's lead author, told Neurology Today that the rise in obesity and high blood pressure in the population as a whole is likely helping to drive up the stroke rate among pregnant women, though this study did not look specifically at whether the women with stroke were obese.

DR. ELENA V. KUKLINA...
DR. ELENA V. KUKLINA...
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“Women who are intending to get pregnant should have a doctor's visit beforehand to get evaluated,” Dr. Kuklina said. “Obesity, high blood pressure, high cholesterol and diabetes are things you can address and have under control before pregnancy.”

Olajide Williams, MD, associate professor of neurology at Columbia University, who was not involved with the study, told Neurology Today that the increase in stroke described in the CDC study is alarming.

“It is a call to action for us to pay closer attention to stroke prevention efforts among women of child-bearing age, including improved identification of women at higher risk for pregnancy-related stroke,” said Dr. Williams, who is a spokesman for the American Heart Association. Good management and monitoring of blood pressure needs to be a top concern, he said, and lifestyle factors such as poor diet, smoking and inadequate exercise also should be addressed.

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RISK FACTORS ON THE RISE

Several population-based studies in the US have found a “growing proportion of pregnant women with risk factors for stroke, such as heart disease, hypertensive disorders, diabetes, and postpartum hemorrhage,” the investigators wrote. They noted that rising rates of obesity, multiple births, and maternal age “have adversely affected the health status of pregnant women in high-income countries,” including the United States and the United Kingdom. Also, better management of chronic conditions such as congenital heart defects and autoimmune diseases is allowing more high-risk women to pursue pregnancy.

The researchers analyzed data from the Nationwide Inpatient Sample, developed as part of the Healthcare Cost and Utilization Project sponsored by the Agency for Healthcare Research and Quality. Diagnostic codes were used to calculate rates of six types of stroke — subarachnoid hemorrhage, intracerebral hemorrhage, ischemic stroke, transient ischemic attack, cerebral venous thrombosis and unspecified stoke — among pregnant women and new mothers. They also checked diagnostic codes for chronic heart disease, hypertensive disorders (including preeclampsia and eclampsia but excluding gestational hypertension), diabetes, postpartum infection, and postpartum hemorrhage.

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POSTPARTUM PERIOD PROBLEMATIC

DR. OLAJIDE WILLIAMS...
DR. OLAJIDE WILLIAMS...
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The researchers found that hospitalizations for stroke during the antenatal period increased from 0.15 per 1,000 deliveries in 1994-1995 to 0.22 per 1,000 in 2006-2007 — an increase of 47 percent. The postpartum hospitalization rate for stroke increased from 0.12 per 1,000 deliveries in 1994-1995 to 0.22 per 1,000 in 2006-2007 — an increase of 83 percent. The rate of stroke at the time of delivery remained virtually unchanged at 0.27 per 1,000 deliveries.

“In 2006 to 2007, (approximately) 32 percent and 53 percent of antenatal and postpartum hospitalizations with stroke, respectively, had concurrent hypertensive disorders or heart disease,” according to the study.

The CDC researchers said it was difficult to compare the trends identified in their studies with previous studies because methodologies differed. Cheryl Bushnell, MD, associate professor of neurology at Wake Forest School of Medicine, who used the same database from 2000-2001 to analyze strokes trends in pregnancy, told Neurology Today in an e-mail that while she thought the CDC study was important, there are limitations to the research “that need to be considered when interpreting the results.”

She said her team's analysis did not include carotid stenosis diagnosis codes, as did the CDC study, because it was not necessarily linked to stroke. Her research also looked at migraine as it related to stroke in pregnant women and found a significant association between the two. She said the CDC study “seems liked a missed opportunity because of the unanswered questions related to migraine, stroke and other vascular diseases during pregnancy.”

She noted that the CDC study also did not break down data by race or ethnicity. “We found that African-American race was independently associated with risk of stroke during pregnancy,” Dr. Bushnell said.

Dr. Williams noted changes in clinical guidelines and improved stroke facilities might also account for the increase in the numbers. “During the two time periods studied — 1994-1995 and 2006-2007 — neuroimaging for acute stroke has evolved with increased use of MRI scans (including MRV) for stroke diagnosis; improved efficiency of stroke management due to the proliferation of certified stroke centers; and a new TIA definition published in 2002, which shifted TIA diagnosis from being time based (symptoms less than 24 hours) to tissue based (requiring brain imaging). These factors may introduce bias related to stroke identification and with that a possible artificial increase in prevalence between the two study periods, although I doubt that this would explain the sheer magnitude of the trends observed.”

Dr. Kuklina said that more research is needed into how best to identify risk factors for stroke during pregnancy as well as optimal preventive treatment for at-risk women or those who suffer a stroke during pregnancy. Her team noted in its published report that there is little in the medical literature to go on.

“The most current recommendations for clinical management of pregnant women at risk for stroke or with stroke are based on small and/or observational studies, with the benefits and risks remaining uncertain,” the CDC researchers noted in the report. For instance, “In a recent review of studies on stroke among pregnant women, only 11 patients treated with thrombolysis were identified in the literature.”

“In addition to the issues of the benefits, safety, and efficacy of anticoagulation and thrombolytic therapy in pregnancy, our results indicating a growing number of pregnancy hospitalizations with stroke highlighted other areas that demand attention of the clinical and research communities. They include monitoring the prevalence of pregnant women with indications for anticoagulation therapy; estimating physicians' compliance with and patients' adherence to current evidence-based recommendations for prevention and treatment of stroke and their effects on fetal, neonatal, and maternal outcomes; and identifying new, emerging risk factors for stroke among pregnant women,” the study said.

Dr. Williams said that “for ischemic stroke, secondary prophylaxis with low-dose aspirin can be used, although its safety during the first trimester has been challenged,” he said. “When anticoagulation is indicated, such as for patients with cerebral venous thrombosis, low molecular weight heparin can be used. Acute treatment with thrombolysis is contraindicated during pregnancy as its safety is unproven, although there are reports of its use.”

DR. CHERYL BUSHNELL ...
DR. CHERYL BUSHNELL ...
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Dr. Williams said both the mother's health and the baby's well being are at stake. “Stroke can threaten the lives of pregnant mothers and its complications injure the fetus — sometimes irreparably,” he said.

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CRITERIA FOR THE COUNT

* The CDC analysis included all pregnancy-related hospitalizations in 1994 to 2007, which were identified according to the ICD-9 CM diagnostic codes and classified hierarchically into delivery, postpartum, and antenatal hospitalizations.

* ICD-9-CM codes were used to identify six types of stroke hospitalizations: subarachnoid hemorrhage, intracerebral hemorrhage, ischemic stroke, transient ischemic attacks, and cerebral venous thrombosis.

* These comorbidities were also identified: chronic heart disease, hypertensive disorders, including preeclampsia and eclampsia but excluding transient [gestational diabetes], diabetes, and postpartum infection.

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REFERENCES:

Kuklina EV, Tong X, Callaghan WM, et al. Trends in pregnancy hospitalizations that included a stroke in the United States from 1994 to 2007: Reasons for concern? Stroke 2011;E-pub 2011 Jul 28.

James AH, Bushnell CD, Myers ER, et al. Incidence and risk factors for stroke in pregnancy and the puerperium. Obstet Gynecol 2005;106(3):509-516.

©2011 American Academy of Neurology

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