Risk of Midlife Stroke After Adverse Pregnancy Outcomes: The FinnGen Study
Authors: Miller Eliza C. , Kauko Anni , Tom Sarah E. , Laivuori Hannele , Niiranen Teemu , Bello Natalie A. , Palotie Aarno , Daly Mark , Riley-Gills Bridget , Jacob Howard , Paul Dirk , Matakidou Athena , Platt Adam , Runz Heiko , John Sally , Okafo George , Lawless Nathan , Salminen-Mankonen Heli , Plenge Robert , Maranville Joseph , McCarthy Mark , Hunkapiller Julie , Ehm Margaret G. , Auro Kirsi , Longerich Simonne , Fox Caroline , Mälarstig Anders , Klinger Katherine , Raipal Deepak , Green Eric , Graham Robert , Yang Robert , Donnell Chris O´ , Mäkelä Tomi P. , Kaprio Jaakko , Virolainen Petri , Hakanen Antti , Kilpi Terhi , Perola Markus , Partanen Jukka , Pitkäranta Anne , Raivio Taneli , Serpi Raisa , Laitinen Tarja , Kosma Veli-Matti , Laukkanen Jari , Hautalahti Marco , Tuovila Outi , Pakkanen Raimo , Waring Jeffrey , Riley-Gillis Bridget , Rahimov Fedik , Tachmazidou Ioanna , Chen Chia-Yen , Runz Heiko , Ding Zhihao , Jung Marc , Biswas Shameek , Pendergrass Rion , Hunkapiller Julie , Ehm Margaret G. , Pulford David , Raghavan Neha , Huertas-Vazquez Adriana , Sul Jae-Hoon , Mälarstig Anders , Hu Xinli , Klinger Katherine , Graham Robert , Green Eric , Mozaffari Sahar , Waterworth Dawn , Renaud Nicole , Obeidat Ma´en , Ripatti Samuli , Schleutker Johanna , Perola Markus , Arvas Mikko , Carpén Olli , Hinttala Reetta , Kettunen Johannes , Mannermaa Arto , Aalto-Setälä Katriina , Kähönen Mika , Laukkanen Jari , Mäkelä Johanna , Kälviäinen Reetta , Julkunen Valtteri , Soininen Hilkka , Remes Anne , Hiltunen Mikko , Peltola Jukka , Raivio Minna , Tienari Pentti , Rinne Juha , Kallionpää Roosa , Partanen Juulia , Abbasi Ali , Ziemann Adam , Smaoui Nizar , Lehtonen Anne , Eaton Susan , Runz Heiko , Lahdenperä Sanni , Biswas Shameek , Hunkapiller Julie , Bowers Natalie , Teng Edmond , Pendergrass Rion , Xu Fanli , Pulford David , Auro Kirsi , Addis Laura , Eicher John , Li Qingqin S , He Karen , Khramtsova Ekaterina , Raghavan Neha , Färkkilä Martti , Koskela Jukka , Pikkarainen Sampsa , Jussila Airi , Kaukinen Katri , Blomster Timo , Kiviniemi Mikko , Voutilainen Markku , Daly Mark , Abbasi Ali , Waring Jeffrey , Smaoui Nizar , Rahimov Fedik , Lehtonen Anne , Lu Tim , Bowers Natalie , Pendergrass Rion , McCarthy Linda , Hart Amy , Guan Meijian , Miller Jason , Kalpala Kirsi , Miller Melissa , Hu Xinli , Eklund Kari , Palomäki Antti , Isomäki Pia , Pirilä Laura , Kaipiainen-Seppänen Oili , Huhtakangas Johanna , Mars Nina , Abbasi Ali , Waring Jeffrey , Rahimov Fedik , Lertratanakul Apinya , Smaoui Nizar , Lehtonen Anne , Hochfeld Marla , Bowers Natalie , Pendergrass Rion , Esparza Gordillo Jorge , Auro Kirsi , Waterworth Dawn , Farias Fabiana , Kalpala Kirsi , Bing Nan , Hu Xinli , Laitinen Tarja , Pelkonen Margit , Kauppi Paula , Kankaanranta Hannu , Harju Terttu , Lahesmaa Riitta , Smaoui Nizar , Lassi Glenda , Eaton Susan , Chen Hubert , Pendergrass Rion , Bowers Natalie , Betts Joanna , Auro Kirsi , Mishra Rajashree , Mouded Majd , Ngo Debby , Vaura Felix , Salomaa Veikko , Metsärinne Kaj , Aittokallio Jenni , Kähönen Mika , Hernesniemi Jussi , Gordin Daniel , Sinisalo Juha , Taskinen Marja-Riitta , Tuomi Tiinamaija , Hiltunen Timo , Laukkanen Jari , Elliott Amanda , Pat Reeve Mary , Ruotsalainen Sanni , Challis Benjamin , Paul Dirk , Hunkapiller Julie , Bowers Natalie , Pendergrass Rion , Chu Audrey , Auro Kirsi , Reilly Dermot , Mendelson Mike , Parkkinen Jaakko , Miller Melissa , Meretoja Tuomo , Joensuu Heikki , Carpén Olli , Mattson Johanna , Salminen Eveliina , Auranen Annika , Karihtala Peeter , Elenius Päivi Auvinen Klaus , Schleutker Johanna , Pitkänen Esa , Mars Nina , Daly Mark , Popovic Relja , Waring Jeffrey , Riley-Gillis Bridget , Lehtonen Anne , Schutzman Jennifer , Hunkapiller Julie , Bowers Natalie , Pendergrass Rion , Kulkarni Diptee , Auro Kirsi , Porello Alessandro , Loboda Andrey , Lehtonen Heli , McDonough Stefan , Vuoti Sauli , Kaarniranta Kai , Turunen Joni A , Ollila Terhi , Uusitalo Hannu , Karjalainen Juha , Pitkänen Esa , Liu Mengzhen , Runz Heiko , Loomis Stephanie , Strauss Erich , Bowers Natalie , Chen Hao , Pendergrass Rion , Tasanen Kaisa , Huilaja Laura , Hannula-Jouppi Katariina , Salmi Teea , Peltonen Sirkku , Koulu Leena , Smaoui Nizar , Rahimov Fedik , Lehtonen Anne , Choy David , Pendergrass Rion , Waterworth Dawn , Kalpala Kirsi , Wu Ying , Pussinen Pirkko , Salminen Aino , Salo Tuula , Rice David , Nieminen Pekka , Palotie Ulla , Siponen Maria , Suominen Liisa , Mäntylä Päivi , Gursoy Ulvi , Anttonen Vuokko , Sipilä Kirsi , Pendergrass Rion , Kurra Venla , Kotaniemi-Talonen Laura , Heikinheimo Oskari , Kalliala Ilkka , Aaltonen Lauri , Jokimaa Varpu , Kettunen Johannes , Vääräsmäki Marja , Uimari Outi , Morin-Papunen Laure , Niinimäki Maarit , Piltonen Terhi , Kivinen Katja , Widen Elisabeth , Tukiainen Taru , Pat Reeve Mary , Daly Mark , Välimäki Niko , Laakkonen Eija , Tyrmi Jaakko , Silven Heidi , Sliz Eeva , Arffman Riikka , Savukoski Susanna , Laisk Triin , Pujol Natalia , Liu Mengzhen , Riley-Gillis Bridget , Pendergrass Rion , Kumar Janet , Auro Kirsi , Hovatta Iiris , Chen Chia-Yen , Isometsä Erkki , Ollila Hanna , Suvisaari Jaana , Damm Als Thomas , Mäkitie Antti , Bizaki-Vallaskangas Argyro , Toppila-Salmi Sanna , Willberg Tytti , Saarentaus Elmo , Aarnisalo Antti , Salminen Eveliina , Rahikkala Elisa , Kettunen Johannes , Aittomäki Kristiina , Åberg Fredrik , Kurki Mitja , Ripatti Samuli , Daly Mark , Karjalainen Juha , Havulinna Aki , Mehtonen Juha , Palta Priit , Hassan Shabbeer , Della Pietro , Parolo Briotta , Zhou Wei , Maasha Mutaamba , Hassan Shabbeer , Lemmelä Susanna , Rivas Manuel , Niemi Mari E. , Palotie Aarno , Liu Aoxing , Lehisto Arto , Ganna Andrea , Llorens Vincent , Tukiainen Taru , Pat Reeve Mary , Heyne Henrike , Mars Nina , Rämö Joel , Saarentaus Elmo , Ollila Hanna , Rodosthenous Rodos , Strausz Satu , Palotie Tuula , Palin Kimmo , Garcia-Tabuenca Javier , Siirtola Harri , Kiiskinen Tuomo , Lee Jiwoo , Tsuo Kristin , Elliott Amanda , Kristiansson Kati , Arvas Mikko , Hyvärinen Kati , Ritari Jarmo , Carpén Olli , Kettunen Johannes , Pylkäs Katri , Sliz Eeva , Karjalainen Minna , Mantere Tuomo , Kangasniemi Eeva , Heikkinen Sami , Mannermaa Arto , Laakkonen Eija , Pitkänen Nina , Lessard Samuel , Chatelain Clément , Terho Perttu , Soini Sirpa , Partanen Jukka , Punkka Eero , Serpi Raisa , Siltanen Sanna , Kosma Veli-Matti , Kuopio Teijo , Jalanko Anu , Shen Huei-Yi , Kajanne Risto , Aavikko Mervi , Palin Henna , Linna Malla-Maria , Kurki Mitja , Karjalainen Juha , Della Pietro , Parolo Briotta , Lehisto Arto , Mehtonen Juha , Zhou Wei , Kanai Masahiro , Maasha Mutaamba , Havulinna Aki , Lemmelä Susanna , Kiiskinen Tuomo , Elisa Lahtela L. , Kaunisto Mari , Kilpeläinen Elina , Sipilä Timo P. , Alexander Dada Oluwaseun , Ghazal Awaisa , Kytölä Anastasia , Weldatsadik Rigbe , Ruotsalainen Sanni , Donner Kati , Sipilä Timo P. , Loukola Anu , Laiho Päivi , Sistonen Tuuli , Kaiharju Essi , Laukkanen Markku , Järvensivu Elina , Lähteenmäki Sini , Männikkö Lotta , Wong Regis , Toivola Auli , Brunfeldt Minna , Mattsson Hannele , Kristiansson Kati , Lemmelä Susanna , Koskelainen Sami , Hiekkalinna Tero , Paajanen Teemu , Palta Priit , Pärn Kalle , Kals Mart , Luo Shuang , Laitinen Tarja , Pat Reeve Mary , Sampath Padmanabhuni Shanmukha , Niemi Marianna , Siirtola Harri , Gracia-Tabuenca Javier , Helminen Mika , Luukkaala Tiina , Vähätalo Iida , Pitkänen Jyrki , Hautalahti Marco , Mäkelä Johanna , Smith Sarah , Southerington Tom 
Published: May 2023

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.