Maternal and fetal risks in pregnancy with MPN

Diagnoses of myeloproliferative neoplasms (MPN) in pregnancy are very rare, occurring in ~3.2 cases per 100,000 pregnancies per year; equivalent to ~24 patients diagnosed with MPN while pregnant over the course of one year.¹ Such diagnoses present unique clinical challenges for both the mother and fetus.

Complications associated with the mother include venous and arterial thromboembolism and hemorrhage, while common fetal complications include blood loss, pre-eclampsia, eclampsia, and intrauterine growth retardation.¹ Due to the presence of the fetus, standard MPN therapies such as hydroxyurea and ruxolitinib are not suitable for the treatment of pregnant mothers.¹ As a result, clinicians currently rely on aspirin, low molecular weight heparin, and pegylated interferon to control any potential complications and maximize the chances of a healthy birth.¹

During a 2023 Global MPN Scientific Foundation (GMPNSF) Educational Symposium, Ellis presented findings from a recent systematic review and meta-analysis investigating whether treatment with aspirin, heparin, interferon, or a combination of treatments is associated with live birth rates and reduced adverse maternal outcomes. Below, we summarize the key findings.

Results

• A total of 1,210 pregnant patients with MPN were enrolled in the review.
• The rate of pregnancy loss was 28.7% overall, including
  • 28.9% loss in patients with essential thrombocythemia; and
  • 33.3% loss in patients with polycythemia vera.
• The highest percentage of patients experienced a pregnancy loss in the first trimester (Figure 1).

Figure 1. Rates of pregnancy loss in each trimester* 

*Adapted from Ellis.¹

• Aspirin alone was statistically favored for increasing live birth rate compared with observation alone (hazard ratio [HR], 8.55; confidence interval [CI], 4.03–18.12)
• IFN alone was statistically favored for increasing live birth rate compared with observation alone (HR, 9.72); however, the CI was questionable (2.31–41.01)
• Aspirin plus heparin was favored for increasing live birth rate compared with aspirin alone (HR, 2.13); however, the CI was questionable (0.50–9.03)
• For placenta related complications, aspirin was favored for reducing these events compared with observation alone (HR, 0.59; CI, 0.19–1.84)
• In contrast, aspirin plus heparin compared with observation alone showed no statistical advantage in the use of either treatment approach to reduce the rate of associated complications (HR, 1.07; CI, 0.27–4.28)

Conclusion

Overall, the analysis showed that the live birth rate increased 8–10-fold with aspirin or IFN treatment compared with observation alone. Placenta complications were lower than previously reported. Maternal thrombosis remained uncommon and was unaffected by aspirin or IFN treatment. These findings indicate that the management of pregnancy in MPN patients should remain multidisciplinary, with increased emphasis on the use of uterine artery flow patterns to detect potential abnormalities.

Further investigation into the mechanisms of placenta-mediated complications, different treatment options, and consideration of women with previous pregnancy loss or placenta complications will be important to improving outcomes for these patients.