Anna Ravn Landtblom, Therese M-L Andersson, Anna L. V. Johansson, Frida E. Lundberg, Jan Samuelsson, Magnus Björkholm & Malin Hultcrantz
Abstract
Myeloproliferative neoplasms (MPN) are associated with inferior pregnancy outcome, however, little is known about fertility and childbearing potential in women with MPN. In this study we aimed to describe reproductive patterns, as well as to quantify risk of miscarriage and stillbirth. Women aged 15–44 years with an MPN diagnosis 1973–2018, were identified in Swedish health care registers, and age-matched 1:4 to population controls. We identified 1141 women with MPN and 4564 controls. Women with MPN had a lower rate of childbirth (hazard ratio [HR] with 95% confidence interval was 0.78 (0.68–0.90)). Subgroup analysis showed that the rate was not significantly reduced in essential thrombocythemia, HR 1.02 (0.86–1.22) while the HR was 0.50 (0.33–0.76) in PV and 0.45 (0.28–0.74) in PMF. The risk of miscarriage was not significantly increased before MPN diagnosis, the HR during follow-up after diagnosis was 1.25 (0.89-1.76). Women with MPN were more likely to have had a previous stillbirth. Women with MPN had fewer children at diagnosis, and fewer children in total. In conclusion, the childbirth rate was lower among women with MPN than controls, but not among women with essential thrombocythemia.
Anna Ravn Landtblom, Therese M-L Andersson, Anna L. V. Johansson, Frida E. Lundberg, Jan Samuelsson, Magnus Björkholm & Malin Hultcrantz
Abstract
Myeloproliferative neoplasms (MPN) are associated with inferior pregnancy outcome, however, little is known about fertility and childbearing potential in women with MPN. In this study we aimed to describe reproductive patterns, as well as to quantify risk of miscarriage and stillbirth. Women aged 15–44 years with an MPN diagnosis 1973–2018, were identified in Swedish health care registers, and age-matched 1:4 to population controls. We identified 1141 women with MPN and 4564 controls. Women with MPN had a lower rate of childbirth (hazard ratio [HR] with 95% confidence interval was 0.78 (0.68–0.90)). Subgroup analysis showed that the rate was not significantly reduced in essential thrombocythemia, HR 1.02 (0.86–1.22) while the HR was 0.50 (0.33–0.76) in PV and 0.45 (0.28–0.74) in PMF. The risk of miscarriage was not significantly increased before MPN diagnosis, the HR during follow-up after diagnosis was 1.25 (0.89-1.76). Women with MPN were more likely to have had a previous stillbirth. Women with MPN had fewer children at diagnosis, and fewer children in total. In conclusion, the childbirth rate was lower among women with MPN than controls, but not among women with essential thrombocythemia.
Whilst MPN are traditionally considered diseases of adults in their sixth or seventh decade these conditions do occur in young patients for example for essential thrombocythaemia in particular there is a second peak in women of reproductive age. Pregnancy therefore is an uncommon but not rare occurrence and clinical challenge in some scenarios. Here we discuss in detail our local approach to the management of pregnancy in MPN patients taking a case-based approach. We take time to include relevant updates in the field and point to a future research strategy which should be internationally focused in order to obtain as much information in as short a time as possible.
Are use of aspirin, heparin, interferon, or combinations associated with live birth rate and adverse maternal outcomes in pregnant women with myeloproliferative neoplasms?
Findings
In this systematic review and meta-analysis of 22 studies, reporting on 1210 pregnancies, the live birth rate was 71.3%; most studies reported on pregnancy with essential thrombocythemia. The use of aspirin and interferon—but not heparin—was associated with higher odds of live birth.
Meaning
Moderate-quality evidence suggests that treatment with aspirin or interferon is associated with higher odds of live birth in pregnant patients with myeloproliferative neoplasms.
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.
