By: Dr Nicolas Martinez-Majander, Department of Neurology, Helsinki University Hospital, Finland

Incidence of young-onset ischemic stroke is currently about 13/100 000 per year in high-income countries and has been increasing since 1980s. In young patients, stroke affects social life, family, and working ability for years after the event. In addition to well-known risk factors, such as diabetes mellitus, hypertension, and hypercholesterolemia, young patients also have unconventional, age-specific risk factors such as pregnancy and puerperium. However, there are still many unanswered questions in terms of risk factors for stroke in the young, and so far study results have been inconsistent.

Ischemic stroke during and after pregnancy

Both pregnancy and puerperium are associated with an increased risk of all stroke subtypes. In a single-center Canadian study, most ischemic strokes occurred during the third trimester, around delivery, or during postnatal period with an incidence of 18 strokes per 100.000 deliveries.1 Furthermore, of all thromboembolisms during pregnancy, stroke contributed to 12% of them.2 Up to 25% of ischemic strokes during pregnancy can be associated with eclampsia.3 Other risk factors for ischemic stroke during pregnancy include e.g. hypertension, diabetes, age over 35 years, black ethnicity, migraine headaches, thrombophilia, smoking, alcohol, and other substance abuse.4 Kittner et al. also showed that the relative risk of ischemic stroke was up to 8.7 (95% CI, 4.6-16.7) during puerperium.3

The choice of secondary prevention depends mostly on the stroke etiology and gestational age. Aspirin in low daily doses is usually the drug of choice especially during the second and third trimester, but there are inconsistent results regarding its teratogenic effects during the first trimester.5 If anticoagulation is indicated, e.g. in high-risk source of cardioembolism, then low-molecular-weight heparin would be recommended instead of novel anticoagulants or warfarin which crosses placenta and is found to be potentially teratogenic. A few case reports and retrospective studies have shown that in acute treatment, intravenous thrombolysis (rtPA) might be safe during pregnancy, but since these women were excluded from all the randomized clinical trials, pregnancy is still a formal contraindication of rtPA. The same applies to mechanical thrombectomy and treatment decisions should be made on an individual basis for each patient.

Pregnancy after ischemic stroke

Finally, there are only a few studies on the effect of ischemic stroke on future pregnancies, and previously the overall outcome was considered similar to those in the general population. However, two more recent studies showed a higher incidence for pregnancy- and delivery-related complications for mothers with a previous stroke. A prospective Dutch FUTURE study of young stroke patients reported higher rates of pregnancy loss throughout their lives. In addition, after the index stroke, young nulliparous women experienced serious pregnancy complication more frequently compared with the stroke-free population.6 Another case-control study from Finland also showed a higher incidence for pregnancy- and delivery-related complications for mothers with a previous stroke, although larger studies would be needed to verify these findings.7

In conclusion, the association between pregnancy, puerperium and stroke should be kept in mind, especially in women with other established risk factors for ischemic stroke, such as hypertension, diabetes, thrombophilia, or prior pregnancies with thromboembolic complications. However, further prospective studies on optimal antithrombotic treatment strategies, acute treatment options, and long-term outcome of these women are still warranted. One such study, SiPP (Stroke in Pregnancy and Postpartum) aims to give an insight into this topic.8

 

References:

  1. Jaigobin C, Silver FL. Stroke and pregnancy. Stroke 2000;31:2948-2951.
  2. Hogan MC, Foreman KJ, Naghavi M, et al. Maternal mortality for 181 countries, 1980-2008: a systematic analysis of progress towards Millennium Development Goal 5. Lancet 2010;375:1609-1623.
  3. Kittner SJ, Stern BJ, Feeser BR, et al. Pregnancy and the risk of stroke. N Engl J Med 1996;335:768-774.
  4. James AH, Bushnell CD, Jamison MG, et al. Incidence and risk factors for stroke in pregnancy and the puerperium. Obstet Gynecol 2005;106:509-516.
  5. van Alebeek ME, de Heus R, Tuladhar AM, et al. Pregnancy and ischemic stroke: a practical guide to management. Curr Opin Neurol 2018;31:44-51.
  6. van Alebeek ME, de Vrijer M, Arntz RM, et al. Increased Risk of Pregnancy Complications After Stroke: The FUTURE Study. Stroke 2018;49:877-883.
  7. Aarnio K, Gissler M, Grittner U et al. Outcome of pregnancies and deliveries before and after ischaemic stroke. Eur Stroke Journal 2017;2:4:346-355.
  8. Lorenzano S, Kremer C, Pavlovic A, et al. SiPP (Stroke in Pregnancy and Postpartum): A prospective, observational, international, multicentre study on pathophysiological mechanisms, clinical profile, management and outcome of cerebrovascular diseases in pregnant and postpartum women. Eur Stroke Journal Online First Dec 6, 2019