Risk of Midlife Stroke After Adverse Pregnancy Outcomes: The FinnGen Study

Abstract

BACKGROUND: Adverse pregnancy outcomes (APO) contribute to higher risk of maternal cerebrovascular disease, but longitudinal data that include APO and stroke timing are lacking. We hypothesized that APO are associated with younger age at first stroke, with a stronger relationship in those with >1 pregnancy with APO. METHODS: We analyzed longitudinal Finnish nationwide health registry data from the FinnGen Study. We included women who gave birth after 1969 when the hospital discharge registry was established. We defined APO as a pregnancy affected by gestational hypertension, preeclampsia, eclampsia, preterm birth, small for gestational age infant, or placental abruption. We defined stroke as first hospital admission for ischemic stroke or nontraumatic intracerebral or subarachnoid hemorrhage, excluding stroke during pregnancy or within 1 year postpartum. We used Kaplan-Meier survival curves and multivariable-adjusted Cox and generalized linear models to assess the relationship between APO and future stroke. RESULTS: We included 144 306 women with a total of 316 789 births in the analysis sample, of whom 17.9% had at least 1 pregnancy with an APO and 2.9% experienced an APO in ≥2 pregnancies. Women with APO had more comorbidities including obesity, hypertension, heart disease, and migraine. Median age at first stroke was 58.3 years in those with no APO, 54.8 years in those with 1 APO, and 51.6 years in those with recurrent APO. In models adjusted for sociodemographic characteristics and stroke risk factors, risk of stroke was greater in women with 1 APO (adjusted hazard ratio, 1.3 [95% CI, 1.2–1.4]) and recurrent APO (adjusted hazard ratio, 1.4 [95% CI, 1.2–1.7]) compared with those with no APO. Women with recurrent APO had more than twice the stroke risk before age 45 (adjusted odds ratio, 2.1 [95% CI, 1.5–3.1]) compared with those without APO. CONCLUSIONS: Women who experience APO have earlier onset of cerebrovascular disease, with the earliest onset in those with more than 1 affected pregnancy.

Opportunities in the Postpartum Period to Reduce Cardiovascular Disease Risk After Adverse Pregnancy Outcomes: A Scientific Statement From the American Heart Association

“…51 Women with a history of 1 or more APOs experience myocardial infarction and stroke at younger ages compared with those without APOs. 52,53 Early detection and treatment of hypertension after pregnancy thus may yield downstream benefits for prevention of myocardial infarction, heart failure, and stroke, especially among those who have experienced 1 or more APOs. A history of HDP and other APOs furthermore should be considered a strong risk factor in the evaluation of a young adult with cardiac or stroke-like symptoms; these symptoms are more likely to be misdiagnosed as mimics (eg, anxiety attack, complicated migraine) in young women.…”

Are fetal microchimerism and circulating fetal extracellular vesicles important links between spontaneous preterm delivery and maternal cardiovascular disease risk?

“…Observations from several groups suggest that fetal microchimerism occurs in the maternal brain, [145,146] and many have suggested roles similar [147] or related [148] to those discussed herein. In addition to heart disease, PTB is also associated with stroke risk, [3,149] but more analysis needs to be done to delineate the phenotype of PTB as being indicated, spontaneous, or preceded by spontaneous rupture of membranes. New data is emerging that links pregnancy disorders with long-term risk of vascular dementia, [150] and this will be an exciting area of research into the role of PTB and fetal microchimerism.…”

Addressing the Impact of Adverse Pregnancy Outcomes on Stroke Risk in Women: A Call for Comprehensive Strategies

“…The study conducted by Miller et al, 7 featured in this issue of Stroke, delves deeper into this relationship, offering additional insight into the impact of APO on the risk of cerebrovascular disease in women.…”