Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by immune-mediated destruction of platelets, leading to isolated thrombocytopenia and the potential for bleeding complications.1 Despite a wealth of research in this area, the impact of ITP on pregnancy and neonatal outcomes has not been well studied. Current guidelines are based on expert opinion and data from retrospective studies, some of which suggest that treatment modification to optimize platelet counts is often required in patients with ITP during pregnancy.2,3
In the recently published study by Dr. Stéphanie Guillet and colleagues, the investigators designed a nationwide, prospective, multicenter, observational exposed-nonexposed cohort study that aimed to assess the clinical course of patients with ITP in pregnancy relative to a matched nonpregnant ITP population. Patients with a diagnosis of ITP who were older than 18 years were included in the study and separated into exposed and nonexposed groups based on pregnancy status. The primary outcome was occurrence of ITP worsening during 1) pregnancy and the six-month postpartum period for exposed (pregnant) women and 2) the 15-month follow-up period for nonexposed (nonpregnant) women. ITP worsening was defined as occurrence of a new bleeding event, occurrence of severe thrombocytopenia, or ITP treatment initiation or modification (except when used to optimize platelet count for delivery). Secondary outcomes included pregnancy and birth outcomes including pre-term delivery, development of gestational diabetes, obstetric complications, and neonatal outcomes including neonatal thrombocytopenia. Of the original 348 ITP patients, 314 (158 exposed, 156 nonexposed) had complete follow-up, and 262 (131 in each group) were matched based on history of splenectomy, ITP duration (<12 months vs. chronic), and ITP status (reflecting severity of their disease based on platelet count).
This study produced some interesting findings. First, there was no statistically significant difference between the two groups with respect to overall ITP worsening (HR, 1.35; 95% CI, 0.89-2.03; p = 0.16), incidence of severe thrombocytopenia (HR, 1.13; 95% CI, 0.71-1.82; p = 0.61), or incidence of bleeding events (HR, 1.54; 95% CI, 0.87-2.73; p = 0.13). It is worth noting however that the difference in the incidence of bleeding events may have approached statistical significance if the trial had more statistical power, as the target of 150 patients was not reached. Despite the overall absence of difference in these clinically important outcomes, ITP treatment initiation and modification were notably more frequent for pregnant women than nonpregnant women with ITP (HR, 1.73; 95% CI, 1.06-2.82; p = 0.03). Pregnant and nonpregnant women had a similar platelet count nadir within the month before ITP treatment change (16 × 109/L and 17 × 109/L, respectively), suggesting this difference was not explained by providers using a higher platelet count as a trigger for treatment. This variation in practice between the two groups may have been the result of closer monitoring (the exposed group had a median number of medical visits of 10 vs. 5 for the nonexposed group) and/or patient and physician anxiety regarding thrombocytopenia. Further studies are required to better understand the factors contributing to this variability in practice.
The study also demonstrated that pregnant women were more likely than nonpregnant women to have multiple events of severe thrombocytopenia and treatment modification (HR, 2.71; 95% CI, 1.41-5.23; p = 0.003; vs. HR, 2.01; 95% CI, 1.14-3.57; p = 0.017; respectively). There was, however, no difference in severity of bleeding events. One reassuring finding for patients and providers alike was that overall ITP status was not different between the two matched groups when comparing platelet counts at the beginning and end of the 15-month follow-up period.
With respect to other secondary outcomes, the study found no significant difference in obstetric complications. A clear majority (69%) of pregnant patients with ITP received epidural analgesia at the time of delivery. The investigators shed light on neonatal ITP (NITP) and demonstrated a similar incidence of NITP to what has been previously reported.2,4-6 The association of NITP with history of splenectomy, as has been reported in previous studies,6-8 was interestingly not observed in this study. The investigators did however find that a maternal platelet count less than 50 ×109/L in the last three months of pregnancy was associated with NITP, as was having a sibling with a history of NITP, which has been corroborated by previous studies.4-6
This is the first prospective cohort study of ITP in pregnancy, addressing an important gap in the literature. These findings provide some reassurance that, with close follow-up, ITP does not adversely affect pregnancy outcomes. We may also tentatively conclude that the overall clinical course of ITP may not be adversely impacted by pregnancy, with the important caveat that there was a trend toward increased bleeding events that may have reached statistical significance with a larger cohort size. The finding that the pregnant patients in the study were more likely to experience treatment modification than the nonpregnant patients is interesting. It is not possible to determine based on this study design whether this was an artifact of closer patient follow-up (as the authors speculate), or an indication of more aggressive disease that was “rescued” by provider intervention. Further research, including studies using qualitative or mixed methods, could clarify this observation. This study also adds to our current understanding of risk factors associated with NITP. Strengths of the study include its prospective design, the well-matched cohorts, and assessment of many clinically important outcomes. The study is limited by the small sample size, which affects generalizability of the results. Larger studies to replicate and explain these findings will be provide much-needed information and further inform care for this important patient population.
Dr. Ladha and Dr. Scott indicated no relevant conflicts of interest.