Outcome for Mothers and Neonates Among Pregnant Women with Von Willebrand Disease: A Prospective Nationwide Multicenter Study

Introduction

Von Willebrand disease (VWD) is the most common hereditary bleeding disorder characterized by defective platelet adhesion and aggregation. Women with VWD are at a greater risk of bleeding, which may affect the health of mothers and children during pregnancy and the intra- and postpartum periods. Given the wide heterogeneity of phenotypes and of the underlying pathophysiological mechanisms associated with the disorder, pregnancy and delivery in VWD represent a significant clinical challenge. There are only limited data on the outcomes of the mothers and the neonates among women with VWD during pregnancy and childbirth. In this study, we aimed to report the maternal and fetal outcomes of women with VWD and compare them with those of women without VWD.

Methods

This was a prospective nationwide multicenter observational study. We consecutively enrolled 210 pregnant women (302 pregnancies) with VWD from 18 academic tertiary centers in China from January 2013 to December 2023. Three controls were randomly selected for each VWD patient at the time of hospital admission (i.e., the control and case were hospitalized at approximately the same time). Finally, 302 pregnancies with VWD and 906 pregnancies without VWD were included in this prospective observational study. We compared outcomes for mothers and neonates in both groups. We also studied obstetrical complications in both groups. Logistic regression was used to compute odds ratios with 95% CIs.

Results

In total, 302 pregnancies of 210 patients were assessed (VWD type 1 n = 143, type 2A n = 18, type 2B n = 6, type 2M n = 5, type 2N n = 7, type 3 n = 1, subtype unidentified n = 30). The median age of patients at childbirth was 28 years. The patients’ median age at VWD diagnosis was 20 (16-30) years. 82 (39.0%) women had a history of first trimester miscarriage. The patients’ median ISTH bleeding score before pregnancy was 2 (0-11). Median gestational age at delivery was 38 (35-40) weeks.

Among 302 pregnancies with 314 fetuses (12 twins), 301 neonates were live births, and 13 were intrauterine deaths thought to be unrelated to VWD. Among 301 neonates, 24 were born preterm, and 277 were born at term. No differences in premature delivery were observed between patients with VWD and those without VWD (P = 0.287). The median Apgar score at 10 min was 10.0. No neonatal deaths were observed in this study. And there were no cases of neonatal intracranial hemorrhage. Among those cases, 56 involved cesarean section, and 233 involved vaginal delivery. Cesarean delivery was more common in pregnant patients with VWD (P = 0.016).

Pregnancy with VWD were more likely to experience postpartum hemorrhage compared with controls (22.3% vs. 3.2%, P < 0.001). Pregnancy with VWD were also more likely to experience antepartum bleeding (OR 8.2, 95% CI: 5.1-15.9). Intravenous desmopressin (DDAVP) was administered postdelivery in 92 (43.8%) patients, and IV human vWF was administered in 46 (21.9%) cases.

Pregnancy with VWD required more transfusions; specifically, 75 (24.8%) of 302 pregnancies required transfusions during pregnancy or childbirth. The OR of requiring transfusion was 5.2 (95% CI: 3.1-8.5) for women with VWD compared with women without VWD. There were no statistical differences in placental abruption, intrauterine fetal growth restriction, preeclampsia, eclampsia, gestational diabetes or hypertension between the two groups. Pregnancy with VWD for childbirth had more days of hospitalization compared with patients without VWD (5.2 vs. 2.1, P < 0.01).

For thrombotic events, 2 (0.7%) pregnancies experienced deep vein thrombosis (DVT), and no patient experienced pulmonary embolism. No patients experienced cerebral infarction or myocardial infraction. Pregnancy with VWD did not increase the incidence of venous thromboembolism (OR 1.1, 95% CI 0.61-2.35).

Conclusions

Pregnancy in women with VWD are at increased risk of antepartum and postpartum hemorrhage. No neonatal severe bleeding events occurred. Individualized treatment to restore hemostasis may achieve favorable outcomes for both mothers and their infants.