Infants
The median completed gestation was 39/40 (IQR 38 - 40) and birthweight 3325g (IQR 3060-3645). Infant diagnosis was not performed or missing in 44 pregnancies with a further 3 having genetic testing outstanding. When women with Type 1 VWD and females born to women with Haemophilia were excluded this reduced to 15 pregnancies with 6 of these infants born to women with an inherited platelet disorder. Of the infants who were tested 22% were found to be affected. Testing was initially performed on cord blood. Formal venepuncture was performed to confirm the diagnosis if the cord blood result was abnormal.
Over half (56%) of the affected infants received Vitamin K and their hepatitis B vaccine intramuscularly, all without documented complication.
Discussion
Major findings
PPH, both primary and secondary, occurred more frequently in women with inherited bleeding disorders compared to the general Australian obstetric population with observed prevalence of 20% and 2% respectively. In comparison, national estimates for primary PPH are 4.7-8.3%(6, 7) and 1% for secondary PPH(8). Most striking, almost half of these PPHs resulted in an estimated blood loss greater than 1000ml, consistent with the definition of major PPH. The increased prevalence of PPH, in particular primary PPH, in women with IBD is reflected in other published reports with previous studies capturing HA carriers, HB carriers, women with VWD and RBD estimating the prevalence of primary PPH to be 14-22% and secondary PPH to be 2-29%(9-12). In our cohort, PPH was experienced in women who had both “normalised” their haemostatic potential throughout pregnancy and in those who received replacement at the time of birth in a relatively even distribution. This raises the question of whether thresholds recommended in current guidelines, which are based on non-pregnant individuals are truly relevant in pregnant women with IBD. This is further supported, by the now well established evidence, that fibrinogen levels increase in pregnancy with fibrinogen levels ranging between 4-6g/L(6) in pregnancy compared to 1.5-4g/L in non-pregnant healthy individuals. Furthermore levels <2g/L are thought to be associated with increased risk of PPH. This increased bleeding risk may be intrinsic to the reproductive tract as neuraxial analgesia was provided at the same threshold without any documented complication.
Any increase in factor levels achieved during pregnancy tend to return to baseline approximately 1-2 weeks post partum(4) resulting in an increased risk of secondary post-partum haemorrhage in women with IBD. Hawke et al(13) have demonstrated the protective nature of prophylactic tranexamic acid in the post-partum period against secondary PPH in these women. Whilst the overall use of tranexamic acid in our study was low, the majority of women with more severe bleeding disorders were prescribed it in the post-partum period. In addition the study spanned the period of practice change, where in 2017(14) tranexamic acid became standard of post-partum care for women with IBD.
Neuraxial analgesia was administered without complication in women with a diverse range of inherited bleeding disorders who achieved factor levels above those recommended in the guidelines, either through natural increases in pregnancy or administration of factor replacement. Unfortunately 3% (4) of eligible women who requested neuraxial analgesia were denied it. It should be noted that due to the paucity of safety data and in consultation with National and International Haemophilia physicians, all women with Hypofibrinogenaemia were counselled against neuraxial analgesia4. Whilst the numbers in our study are small, in conjunction with other published reports, these findings add weight to the safety of neuraxial analgesia in this population.
Neonatal outcomes were excellent with no documented bleeding complications despite interventions such as vacuum extraction and scalp electrodes being utilised in a very small number of births. When low risk neonates were excluded, including those born to women with Type 1 VWD and females born to mothers with Haemophilia, diagnosis at the time of birth was available in the majority of newborns. Recommendations for oral vitamin K and subcutaneous immunisations were poorly adhered to and highlights the need to improve communication between maternity and neonatal caregivers.
Strengths
Our study describes the real-life management and bleeding complications of one of the largest cohorts of pregnant women with IBD and encompasses a broad range of diagnoses, managed across several tertiary health care services in Australia.
Limitations
The major limitations of this study are the retrospective nature and method of data collection, with some missing data. The study also did not capture fertility issues including miscarriage.
Interpretation (in light of other evidence)
Our findings support previously published reports that women with IBD experience higher rates of PPH compared to the general population. The higher rate and volume of PPH suggest that target “acceptable” factor levels for safe birth, as published in current guidelines, are likely inadequate. This is further supported by the recognition that fibrinogen levels at birth are greater than in the non-pregnant population. Viscoelastic haemostatic assays, which are currently being explored in monitoring of haemostasis in PPH, may play a role in assessing haemostatic potential.
Conclusion:
This retrospective analysis demonstrates that women with IBD can deliver safely, with mode of birth dictated by obstetric indications or maternal choice, and receive neuraxial analgesia without complication when adhering to best practices.
PPH occurred at significantly higher rates and is associated with larger volumes than the general obstetric population despite adhering to current guidelines. These findings raise concern over the current definition of “adequate” factor levels at the time of birth. We feel that further study of ideal coagulation factor levels in pregnancy in normal women and those with inherited bleeding disorders are recommended.
Disclosures of interest.
Nil.
Contribution to authorship.
LJC collected data, analysed the data and wrote the manuscript.
JC critically appraised the manuscript.
BC collected data and critically appraised the manuscript.
BR collected data and critically appraised the manuscript
GKG conceived the idea, collected data and critically appraised the manuscript.
Ethics
Ethics approval was obtained through the human research ethics committee (SESLHD HREC 15/294).
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