Predictors of Mortality and Functional Outcome in Pregnancy and Puerperium-Related Cerebral Venous Thrombosis

Abstract

<b><i>Introduction:</i></b> Cerebral venous thrombosis (CVT) associated with pregnancy and puerperium has long been recognized, with poor information in terms of functional outcomes. Our objective was to analyze risk factors, clinical, imaging, and laboratory variables to predict functional outcome and death in this population. <b><i>Methods:</i></b> CVT registries from three referral centers from Pakistan, Turkey, and Mexico, recruiting prospective cases, were combined for CVT associated with pregnancy or puerperium. Datasets and variables were standardized. Demographic characteristics, presentation, risk factors, and functional outcomes in pregnancy/puerperium-related CVT were analyzed. Binary logistic regression was used to assess predictors of outcome. The main outcome was modified Rankin score >2 at 30 days and mortality at 30 days. <b><i>Results:</i></b> Five hundred fifty-three cases (median age 28 years [IQR 23–34]) of CVT associated with pregnancy and puerperium were included; 439 cases (79.4%) happened in the puerperium and 20.6% during pregnancy (53.5% occurred during the first trimester). Anemia (36.7%) and dehydration (22.9%) were the commonest obstetric risk factors identified. Predictors of poor outcome (mRS >2) were encephalopathy (OR 12.8, <i>p</i> < 0.001), cases from Mexican origin (OR 3.1, <i>p</i> = 0.004), fever/puerperal infection (OR 2.7, <i>p</i> = 0.02), and anemia (OR 2.2, <i>p</i> = 0.01). Cases from Mexican origin (OR 12.0, <i>p</i> = 0.003) and Encephalopathy (OR 7.7, <i>p</i> < 0.001), presented with the highest mortality association in the final adjusted model. <b><i>Discussion/Conclusion:</i></b> In CVT associated with pregnancy and puerperium, encephalopathy, fever/puerperal infection, and anemia are associated with bad functional outcomes, meanwhile encephalopathy and cases from Mexican origin with higher mortality in the acute (30-days) of CVT onset. Anemia and infection are potential reversible predictors of poor outcome that clinicians should be aware of in order to prevent poor outcomes in these patients.

Diagnosis and Management of Cerebral Venous Thrombosis: A Scientific Statement From the American Heart Association

“…Approximately 80% of pregnancy-related CVT cases occur after delivery. 12 10 Overall, studies published since the prior scientific statement 1 have found that the prognosis for women with pregnancy-related CVT is better than or the same as that for patients with CVT in general. 71 VKAs, including warfarin, are associated with fetal embryopathy and bleeding in the fetus and neonate and thus are contraindicated in pregnancy.…”

“…Women with a history of VTE appear to have an increased risk of thrombotic events (ie, deep venous thrombosis, pulmonary embolism) in future pregnancies. 64 A systematic review comprising 17 studies and 393 pregnancies found a recurrence rate of 8 per 1000 pregnancies (95% CI, [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. The rate of noncerebral VTEs was 22 per 1000 pregnancies (95% CI, 11-43).…”

“…Approximately 80% of pregnancy-related CVT cases occur after delivery. 12 A case-control study found that the risk is increased only in the puerperium (OR, 10.6 [95% CI, 5.6–20.0]), whereas there was no statistically significant increased risk of CVT during pregnancy (OR, 1.2 [95% CI, 0.6–2.3]). 10 Cesarean delivery appears to be associated with a higher risk after adjustment for age, vascular risk factors, presence of infections, hospital type, and location (OR, 3.10 [95% CI, 2.26–4.24]).…”

“…10,11 Rates of CVT are highest in younger women, with both oral contraception and pregnancy/ puerperium being major risk factors. 12,13 Oral contraception and hormonal therapies 14 (primarily those containing estrogen-based formulations) may increase the odds of CVT nearly 8-fold, 11 with possible additional synergistic effects with obesity. 15 Other well-established risk factors include acquired thrombophilias such as antiphospholipid antibody syndrome, JAK2 mutations, malignancy, particularly myeloproliferative disorders, and autoimmune disease, including Behçet and inflammatory bowel disease.…”

“…74 According to the available evidence, CVT is not a contraindication for future pregnancies. 12,72,75 Considering the additional risk that pregnancy confers to women with a history of CVT, prophylaxis with LMWH during future pregnancies and the postpartum period is probably beneficial. 75…”