Neurology and Neurosurgery

Adverse Pregnancy Outcomes Linked to Midlife Stroke Risk

    A large observational study conducted by NewYork-Presbyterian/Columbia neurologists suggests there is a link between adverse pregnancy outcomes, such as preeclampsia and preterm birth, and the risk of early onset of stroke.

    The findings, which were first presented at the American Stroke Association’s International Stroke Conference in 2023, showed that a single pregnancy with an adverse outcome lowered the median age for first stroke from 59 years to 55 years, while additional pregnancies with adverse outcomes lowered the median age to 51 years.

    Dr. Eliza Miller

    “We found that the more pregnancies you had with adverse outcomes, the younger you were at the time of first stroke admission to the hospital. It was a very clear dose response,” explains Eliza C. Miller, MD, MS, an assistant professor of neurology in the division of stroke and cerebrovascular disease at NewYork-Presbyterian/Columbia.

    While there is an established increased risk of cardiovascular disease and stroke for women who experience adverse pregnancy outcomes, little is known about the timing of that risk. For the most part, stroke is an age-related disease that primarily affects people in their 60s or older, Dr. Miller says. When she began seeing women in their 40s and 50s coming to the hospital with acute stroke, she wondered what could be triggering the early onset.

    Dr. Miller, who conducts research on the epidemiology and pathophysiology of pregnancy-related stroke, began by asking these women about their pregnancy history. “I found that people would say yes, they have had three or four children and they were each born early, or they had hypertension during their pregnancies,” she says. “When you start hearing this kind of a pattern, you start asking what it’s all about.”

    As Dr. Miller examined the literature, it became clear that the cases of early stroke fit into a broader pattern of women with various adverse pregnancy outcomes experiencing a higher risk of developing cardiovascular disease. She set out to investigate whether having a history of an adverse pregnancy outcome would put someone at-risk for having a stroke earlier in life, and if the risk would increase with each pregnancy that included vascular-related complications.

    Pregnancy is a part of the medical history that is relevant to a woman’s health. It is something that all doctors should do, just as they ask about other aspects of the medical history, like smoking.

    — Dr. Eliza C. Miller

    MRI of the brain showing a stroke

    To do this, Dr. Miller and her colleagues partnered with researchers from Finland who had access to a nationwide longitudinal study with data from multiple national health registries and biobanks. They matched these records with pregnancy outcomes data and hospital stroke data spanning a 52-year period.

    Dr. Miller’s study included 130,764 women who had given birth at least once. Nearly 18 percent of the study cohort had experienced one or more adverse pregnancy outcomes, and about five percent of the women had been admitted to the hospital for stroke during the 52-year study period.

    The adverse pregnancy outcomes described in the study identified included:

    • Preterm birth (before 37 weeks gestation)
    • Gestational hypertension
    • Preeclampsia and eclampsia
    • Placental abruption
    • Stillbirth
    • Fetal growth restriction
    • Small for gestational age

    It was not uncommon for more than one of these conditions to occur within a single pregnancy, according to Dr. Miller.

    The researchers found that, compared with women who had uncomplicated pregnancies, those who had one pregnancy with an adverse outcome had 1.7 times the risk of having any type of stroke at age 45 years or earlier. Women who had two or more pregnancies with adverse outcomes had double the risk for stroke by age 45.

    The researchers found that, compared with women who had uncomplicated pregnancies, those who had one pregnancy with an adverse outcome had 1.7 times the risk of having any type of stroke at age 45 years or earlier. Women who had two or more pregnancies with adverse outcomes had double the risk for stroke by age 45.

    While Dr. Miller had expected to see the association, she says she was surprised by how young the women were when they had their first strokes. “The median age at the time for first stroke was 51 for those with recurrent adverse pregnancy outcomes, which means that half of the people who had a stroke had it before age 51,” Dr. Miller says.

    She adds that there’s a different type of impact when a stroke occurs in midlife. “Those are prime working years, earning years, and caregiving years. There’s a lot of stuff that you’re responsible for at that time in your life and so having a stroke at that age also has a completely different impact, regardless of anything else,” Dr. Miller says.

    These are critical issues because recent research shows that one in five women in the U.S. have some type of adverse pregnancy outcome.

    The study is also a call to action, Dr. Miller says, for physicians to routinely ask about pregnancy history. In 2021, the American Heart Association issued a scientific statement on cardiovascular disease prevention in women that urged health care providers to consider adverse pregnancy outcomes when evaluating cardiovascular disease risk in women.

    “Pregnancy is a part of the medical history that is relevant to a woman’s health. It is something that all doctors should do, just as they ask about other aspects of the medical history, like smoking,” Dr. Miller says. “If we don’t at least ask, we’re not going to be able to answer these important clinical and research questions.”

    For physicians who take care of women who have an adverse pregnancy outcome, the study findings point to the need for educating patients about their risks in the future and the need to be monitored and treated in a proactive way. “Stroke is an end-stage disease, but there are a lot of things that lead up to that,” Dr. Miller says.

    Going forward, Dr. Miller and her colleagues are continuing to look at research on the impact of pregnancy complications and stroke risk. In a prospective observational cohort study that has been ongoing for about 10 years, Dr. Miller and her research colleagues are following women from the beginning of their first pregnancy and performing cognitive assessments and brain MRIs to see what brain changes are happening over time. That, and other ongoing research, has the potential to answer further questions about the link between vascular changes in pregnancy and later stroke, and how these poor outcomes can be prevented in the future.

      Read More

      Temporal Trends in Adverse Pregnancy Outcomes in Birthing Individuals Aged 15 to 44 Years in the United States, 2007 to 2019. Freaney PM, Harrington K, Molsberry R, et al. J Am Heart Assoc. 2022;11(11):e025050. doi:10.1161/JAHA.121.025050.

      Adverse Pregnancy Outcomes and Cardiovascular Disease Risk: Unique Opportunities for Cardiovascular Disease Prevention in Women: A Scientific Statement From the American Heart Association. Parikh NI, Gonzalez JM, Anderson CAM, et al. Circulation. 2021;143(18):e902-e916. doi:10.1161/CIR.000000000000096.

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      image of Dr. Eliza Miller
      Dr. Eliza Miller
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