Association of Treatments for Myeloproliferative Neoplasms During Pregnancy With Birth Rates and Maternal Outcomes A Systematic Review and Meta-analysis

IMPORTANCE Myeloproliferative neoplasms (MPNs) are increasingly being identified in women of childbearing potential. Pregnancy in women with MPNs is associated with maternal thrombosis, hemorrhage, and placental dysfunction leading to fetal growth restriction or loss. OBJECTIVE To evaluate the association between the use of aspirin, heparin, interferon, or combinations and live birth rate and adverse maternal outcomes in pregnant women with MPNs. DATA SOURCES Systematic searches of MEDLINE, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and the MEDLINE Epub Ahead of Print and In-Process and Other Non-Indexed Citations from inception to July 19, 2018, with no language restrictions, was conducted. Key search terms included myeloproliferative disorders, polycythemia vera, essential thrombocythemia, and primary myelofibrosis. STUDY SELECTION A study was eligible if it included pregnant patients with MPNs; interventions included aspirin, heparin, and/or interferon; there was a comparison group in which patients did not receive the intervention; the study reported on at least 1 of the study outcomes; and it was a randomized, case-control, or cohort study or series of at least 10 pregnancies. Data were extracted in duplicate; 0.5% of identified studies met selection criteria. DATA EXTRACTION AND SYNTHESIS The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and reported in accordance with Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Data were pooled using the Mantel-Haenszel approach. MAIN OUTCOMES AND MEASURES Outcomes were the number of live births and maternal complications, specifically, arterial or venous thrombosis, hemorrhage, and preeclampsia. RESULTS Twenty-two studies reporting on 1210 pregnancies were included. The live birth rate was 71.3%(95% CI, 65.1%-77.6%). Use of aspirin (11 studies, 227 patients; unadjusted odds ratio, 8.6; 95% CI, 4.0-18.1) and interferon (6 studies, 90 patients; unadjusted odds ratio, 9.7; 95% CI, 2.3-41.0) were associated with higher odds of live birth. Addition of heparin to aspirin was not associated with higher odds of live birth (6 studies, 96 patients; unadjusted odds ratio, 2.1; 95% CI, 0.5-9.0). The most common adverse maternal event was preeclampsia, with an incidence of 3.1% (95% CI, 1.7%-4.5%). CONCLUSIONS AND RELEVANCE Most studies reported on pregnancy with essential thrombocythemia. Few studies reported on pregnancy with polycythemia vera and none with myelofibrosis met the inclusion criteria. Most studies were retrospective and early pregnancy losses may have been underreported. Moderate-quality evidence suggests that aspirin or interferon is associated with higher odds of live birth in pregnant women with MPN.