Recent prospective studies gave reassuring data for women with immune thrombocytopenia (ITP) who want to become pregnant and their neonates.1, 2 Risk of neonatal ITP (NITP) is close to 30%, but NITP is severe in only 10% of neonates (platelet count 3 months) and 34 pregnant women with newly diagnosed ITP during pregnancy, neonatal platelet counts were available for 137 and 31 neonates, with NITP prevalence of 27.7% (37/137) and 25.8% (8/31) respectively. In addition, one neonate from a mother with newly diagnosed ITP and who was not tested at birth was diagnosed at 1 month with NITP (Figure S1). Data on the neonatal period were prospectively collected from 2013 to 2018, and physicians and mothers were contacted from December 2023 to October 2024 to monitor the long-term evolution, in particular, the emergence of chronic ITP or another autoimmune disease in neonates. NITP was defined as mild with nadir neonate platelet count 50–100 × 109/L, moderate 30–49 × 109/L and severe 100 × 109/L, respectively, during follow-up. The neonatal outcome description included platelet count nadir, age at nadir, occurrence of bleeding event, treatment if needed and time to remission. Severe bleeding events were defined as organ or life-threatening bleeding. We also assessed the potential impact of breastfeeding on the duration of NITP and time to response to intravenous immunoglobulin (IVIg). The study was approved by the institutional review board and ethics committee of Bicêtre Hospital (PP13-013, 15 May 2013) and was conducted in accordance with the Declaration of Helsinki. Continuous variables were compared by Mann–Whitney test and categorical variables by Fisher exact test. Data are presented as median (interquartile range IQR, first quartile–third quartile or range minimum–maximum) for continuous variables, number (%) for categorical variables and odds ratio (OR) and 95% confidence interval (CI). Analyses involved using R 4.0.3 (R Foundation for Statistical Computing). All tests were significant at two-sided p < 0.05. We included 46 neonates with NITP (Figure S1). Their characteristics are summarized in Table 1. Seven (15.2%) neonates were moderate to late preterm and 1 (2.2%) was born very preterm. In total, 29 (63.0%) neonates were born by vaginal delivery with the use of instrument (i.e. use of vacuum extraction, forceps or spatulas) for 19% (4/21; data missing for 8) and 17 (37%) were born by C section. Twenty-six (56.5%) neonates were breastfed. A total of 39 (84.8%) neonates had a platelet count the first day of life. The median (range) initial platelet count was 78 × 109/L (6–245) and was normal in 19 (41.3%) neonates, including 8 (29.6%) with subsequent moderate to severe NITP. Platelet count nadir was reached after a median (range) time of 3 (0–7) days. NITP was mild in 9 (41.3%) patients, moderate in 7 (15.2%) and severe in 20 (43.5%). Figure S2 shows the evolution of platelet count over time. Overall, 5 (10.9%) neonates experienced bleeding events: 4 (8.7%) had non-severe bleeding and 1 (2.2%) neonate had intracranial haemorrhage (ICH). All neonates with bleeding events had moderate to severe NITP with a platelet count nadir (range) at 20 × 109/L (6–31). For the neonate with ICH, the condition was diagnosed in utero and he died at birth (platelet count 6 × 109/L). Four neonates had non-severe bleeding events, manifesting as minor cutaneous bleeding or subconjunctival haemorrhage with platelet count nadir from 19 to 31 × 109/L. None of the bleeding events occurred after the initiation of IVIg. In total, 27/45 (60.0%) neonates received at least one treatment (18/19 with severe NITP, all 7 with moderate NITP and 2/19 with mild NITP; the neonate who died at birth was excluded for the analysis): 14/45 (31.1%) received IVIg alone (seven had severe, five moderate and two mild NITP), 11/45 (24.4%) received IVIg and platelet transfusions (all with severe NITP) and 2/45 (4.4%) received platelet transfusions alone (all with moderate NITP and platelet count nadir at 31 and 44 × 109/L). One neonate with severe NITP (platelet count nadir at 20 × 109/L) and no haemorrhage did not receive any treatment. Overall, the dose of IVIg was 1 g/kg body weight/day for 1–3 days (2 days for 16/25 64% neonates) (Table S1). Of 11 neonates, 9 (81.8%) received a single platelet transfusion (data were missing for two). None of the neonates experienced any treatment-related adverse event. Apart from receiving IVIg and platelet transfusions, none of the neonates received any other ITP therapy, including glucocorticoids. Besides the neonate who died at birth and one neonate with mild NITP (platelet count 55 × 109/L) for whom no platelet count control was available after the first day of life, all other neonates achieved complete remission during follow-up, after a median (range) of 7 (1–33) days (timing of remission is missing for 10 neonates). Among neonates with severe NITP, the median (range) time to remission (partial or complete) after IVIg treatment alone or in combination with platelet transfusions was 3 (1–8) days (data were missing for two neonates). None of the neonates required a second course of IVIg. Breastfed neonates (N = 26) and non-breastfed neonates (N = 19 after exclusion of the neonate who died at birth) did not differ in duration of NITP (median range: 6.5 1–33 vs. 7.0 2–12 days, p = 0.757; Figure 1), incidence of bleeding events (11.5% vs. 5.3%; OR 2.31, 95% CI 0.17–129.9, p = 0.627) and time to first response in IVIg-treated neonates with moderate to severe NITP (median IQR: 3 1–3.5 vs. 2 2–3, p = 0.91, data were missing for one patient in each group). Long-term follow-up (over 1 year) was available for 36 neonates (Figure 2; Figure S1). After a median (range) follow-up of 7.9 (5.2–9.9) years, none of the neonates experienced thrombocytopenia relapse or another autoimmune disease. This is the first prospective study of autoimmune NITP with long-term follow-up. We included a large series of patients from several centres of the French ITP reference centre network. The platelet count nadir in NITP was reached at a median of 3 days of life. Notably, a substantial proportion of neonates had a normal platelet count at birth, including nine neonates (29.6%) who subsequently developed moderate to severe NITP. This finding confirms the importance of systematically controlling platelet count at birth and, if normal at birth, between 3 and 5 days of life in neonates of mothers with ITP. Severe bleeding events were rare, observed only in one neonate with severe NITP in whom ICH had been diagnosed in utero and who died at birth, for whom an alloimmune thrombocytopenia could not be formally excluded as no specific test was performed at birth. Although current international guidelines were mostly applied to neonates with severe NITP (all but one received IVIg), all neonates with moderate NITP and no bleeding event received treatment (IVIg or platelet transfusions), which is not in line with these guidelines.5 This study was a prospective observational study; management decision was left to clinician's judgement who did not have to justify treatment decision. Most treated neonates received only one or two infusions of IVIg, with a median time to remission of 3 days. We did not observe any negative effect of breastfeeding on the severity or duration of NITP. Nevertheless, we cannot formally exclude that, in some specific cases, breastfeeding may play a role in the delayed remission of neonates, as previously reported.6, 8 In such cases, which appear to be rare, discontinuation of breastfeeding for a few days should be considered so as to determine any impact on neonate platelet count. Finally, after a long-term follow-up of several years, data are reassuring with no ITP relapse. Our study has some limitations. Time to complete remission was missing for several neonates, mostly in the mild NITP group. These neonates with mild NITP and no bleeding events may have been discharged from hospital after several days of monitoring and their platelet counts subsequently controlled in primary care centres as suggested by the last available median (IQR) platelet count that was 67.5 × 109/L (64–86.8). Furthermore, the occurrence of NITP may have led to prolonged hospitalization, but we cannot confirm this. In conclusion, this study strengthens our knowledge of NITP, particularly regarding the importance of controlling platelet count in neonates after several days of life, the rare occurrence of severe bleeding events and rapid complete remission at a median age of 7 days with the use of IVIg or platelet transfusion only in case of moderate or severe NITP. It also provides reassuring data on both the long-term follow-up and the impact of breastfeeding in neonates with NITP. B.S. and S.G. designed the study and initiated this work; B.S., B.A and S.G. extracted the data; B.S. performed statistical analyses; B.S. and S.G. analysed the data; B.S. and S.G. wrote the manuscript; S.G. and B.G. supervised the project; all authors participated to patient recruitment and reviewed the manuscript. Open access publication funding provided by COUPERIN CY26. This work was supported by grants (PHRC; AOM12206) from the French health ministry. The sponsor was Assistance Publique—Hôpitaux de Paris (APHP) (délégation à la Recherche Clinique et à l'Innovation). B.G. served as an expert for Amgen, Novartis, Grifols and Sobi; the other authors have no conflicts of interest to declare. The study was approved by the institutional review board and ethics committee of Bicêtre Hospital (PP13-013, 15 May 2013) and was conducted in accordance with the Declaration of Helsinki. Written information was delivered by the investigators and oral consent was obtained from the patient or his/her legal guardian in accordance with French law for non-interventional study. Data are available upon reasonable request. Supporting Information has been supplied by the author(s). Data S1. Data S2. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Sorin et al. (Wed,) studied this question.