Pregnancy Outcomes in Patients with Myeloproliferative Neoplasms in the United Kingdom
Authors: Alimam Samah , Chappell Lucy , Knight Marian , Bewley Susan , Gray Garbriella , Harrison Claire N. , Robinson Susan 
Published: October 2019

Abstract
Introduction
Philadelphia negative myeloproliferative neoplasms (MPNs) are associated with an increased incidence of haemorrhagic and thromboembolic complications as well as progression to myelofibrosis and acute myeloid leukaemia. MPNs have a peak incidence in 6th and 7th decade of life. However, they can occur in younger age groups and women of child bearing age.
Pregnant women with MPN are at an increased risk of maternal thrombosis and haemorrhage and also of impaired uterine blood flow, placental dysfunction, fetal growth restriction, pre-term delivery and fetal loss. There are no prospective studies of pregnancy outcome in the literature.
Method
A national prospective cohort was established to describe the maternal and fetal outcomes of pregnancy in women with MPN in the United Kingdom (UK). Data were collected using the UK Obstetric Surveillance System (UKOSS) between January 2010 and December 2012 (UKOSS methodology described by Knight et al, 2005). UK hospitals with a consultant led maternity unit identified pregnant woman with a MPN and provided detailed data on antenatal, maternal and fetal outcomes. Pregnancy outcome data were compared with that reported by the UK Office of National Statistics (ONS) in 2011.
Results
58 women were identified: 47 with Essential Thrombocythaemia (81%), 5 with Polycythaemia Vera (8.6%), 5 with Myelofibrosis (8.6%) and 1 with JAK2 positive MPN unspecified (1.7%). The incidence of MPN in pregnancy was 6.4/100,000 maternities.
The median age was 33 years (range 16-42), compared to average national age during 2011 of 29.7 years. There were 58 live births (56 singleton, 2 twin), one miscarriage and one stillbirth (at 37 weeks) with a miscarriage rate of 1.8% and the perinatal mortality rate of 17/1000 live and stillbirths. The national rates reported by ONS in 2011 were 6.4 miscarriages/100 pregnancies and of 5.2 stillbirths/1000 live and stillbirths. The incidence of pre-eclampsia was 8.8% (n=5/57), compared to 3.4% as reported by Ananth et al 2013. The majority 78.9% (n = 45/57) of women laboured; 42.1% (n = 24/57) underwent induction and spontaneous vaginal delivery occurred in 39% (n = 22/57) of women. Caesarean section (CS) was performed in 42.1% (n = 24/57). Most of the caesareans were performed pre-labour, with an elective CS rate of 24.6% (n = 14/57), and emergency CS rate of 17.5% (n = 10/57). The UK average CS rate in 2011 was 24.8%.
Most (86%; 49/57) women delivered at term (>37 weeks). The incidence of preterm (< 37 weeks) and very preterm (<32 weeks) birth was 7.0% (n = 4/59) and 3.5% (n =2/59) respectively; ONS 2011 UK averages were 10.7% and 5.3% respectively. The median birth weight was 3150g (range 720 - 4700g); 13.6% (n = 8/59) of neonates had a low birth weight (<2500g) and 5.1% (n=3) had a very low birth weight (<1500g). 5% of births in 2011 were documented to be below 2500g according to ONS.
There was considerable variation amongst clinicians in the management of MPNs. Only 50% (n = 29/58) of women were in receipt of aspirin therapy prior to the index pregnancy. This increased during pregnancy with over 88% (n = 51/58) prescribed aspirin; 38% (n = 22/58) were on both aspirin and low molecular weight heparin. Cytoreductive therapy was used in 43% (n=25/58) of the women prior to index pregnancy (including hydroxyurea (HU), anagrelide (ANA) and interferon). During the index pregnancy, 7 women continued cytoreductive therapy, switching to interferon when prior HU or ANA were used. One woman with ET was initiated on interferon.
Conclusion
This first prospective analysis of maternal and fetal outcomes in women showed an incidence of MPN in pregnancy of 6.4/100,000 maternities which is consistent with previous reports. The increased occurrence of pre-eclampsia and fetal growth restriction might explain the higher rates of induction and caesarean section. The majority (87%) of babies were delivered at term.Although this was a small sample, it was reassuring there were no maternal deaths or admissions to intensive care, and only one perinatal death, as previous retrospective data has reported worse outcomes. The clinician variability in the approach to the management of women with MPNs in pregnancy suggests further improvements may be possible.

Disclosures
Harrison: Shire: Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; Sanofi: Honoraria, Speakers Bureau; Gilead: Honoraria; CTI Biopharma: Consultancy, Honoraria, Speakers Bureau.