Immune thrombocytopenia and pregnancy: an exposed/nonexposed cohort study

Abstract

The risk of immune thrombocytopenia (ITP) worsening during pregnancy and neonatal ITP (NITP) have never been prospectively studied. We included 180 pregnant and 168 nonpregnant women with ITP in a prospective, multicenter, observational cohort study. A total of 131 pregnant women with ITP were matched to 131 nonpregnant women with ITP by history of splenectomy, ITP status (no response, response, complete response), and duration. Groups were followed for 15 months. The primary outcome was the first occurrence of ITP worsening defined by a composite end point including bleeding events and/or severe thrombocytopenia (<30 × 109/L) and/or ITP treatment modification. We also studied the recurrence of ITP worsening and the incidence of NITP and risk factors. The first occurrence of ITP worsening did not differ between pregnant and nonpregnant women with ITP (53.4 per 100 person-years [95% confidence interval {CI}, 40.8-69.9] vs 37.1 [95% CI, 27.5-50.0]; hazard ratio {HR}, 1.35 [95% CI, 0.89-2.03], P = .16). Pregnant women with ITP were more likely to have recurrence of severe thrombocytopenia and treatment modification (HR, 2.71 [95% CI, 1.41-5.23], P = .003; HR, 2.01 [95% CI, 1.14-3.57], P = .017, respectively). However, recurrence of severe bleeding events was not different between groups (P = .4). Nineteen (14%) neonates showed NITP <50 × 109/L. By multivariable analysis, NITP was associated with a previous offspring with NITP and maternal platelet count <50 × 109/L within 3 months before delivery (adjusted odds ratio, 5.55 [95% CI, 1.72-17.89], P = .004 and 4.07 [95% CI, 1.41-11.73], P = .009). To conclude, women with ITP do not increase their risk of severe bleeding during pregnancy. NITP is associated with NITP history and the severity of maternal ITP during pregnancy. These results will be useful for counseling women with ITP.

Graphical abstract

Figure 1.

Enrollment and outcomes. ∗Taken into account for frequency of miscarriage when it was the reason for the woman being lost to follow-up; n = 6/9 lost to follow-up after a miscarriage. In the other cases, reasons for the woman being lost to follow up were that she moved or was not seen at follow-up consultations or contacted by telephone. ITP, immune thrombocytopenia.

Figure 2.

Incidence of first immune thrombocytopenia (ITP) worsening during pregnancy among matched pregnant and nonpregnant women with ITP. First ITP worsening was evaluated by a composite end point, including first event of severe thrombocytopenia <30 × 10⁹/L and/or bleeding event and/or treatment modification/initiation. First event and multiple events were assessed. (A) ITP worsening-free probability (and 95% confidence interval [CI]) was estimated with the Kaplan-Meier method and compared in the 2 groups with the use of a Cox model with shared frailty. (B-D) Free probability of severe thrombocytopenia (platelet count <30 × 10⁹/L), bleeding event, and treatment modification/initiation (and 95% CI), respectively, was estimated with the Kaplan-Meier method and compared in the 2 groups with the use of a Cox model with shared frailty. ∗Except treatment to prepare delivery.

Figure 3.

Incidence of recurrent immune thrombocytopenia (ITP) worsening during pregnancy among matched pregnant and nonpregnant women with ITP. ITP worsening was evaluated by a composite end point including recurrences of severe thrombocytopenia <30 × 10⁹/L and/or bleeding event and/or treatment modification/initiation. (A) ITP worsening-free probability (and 95% confidence interval [CI]) was estimated with the Kaplan-Meier method and compared in the 2 groups with the use of an Anderson-Gill Cox model. (B-D) Free probability of severe thrombocytopenia (platelet count <30 × 10⁹/L), bleeding event, and treatment modification/initiation (and 95% CI), respectively, was estimated with the Kaplan-Meier method and compared in the 2 groups with the use of an Anderson-Gill Cox model. ∗Except treatment to prepare delivery.