The objective of the NeoPlaTT trial is to test whether, among extremely preterm infants born at 23 0/7 to 26 6/7 weeks' gestation, a lower platelet transfusion threshold, compared to a higher threshold, improves survival without major or severe bleeding up to 40 0/7 weeks' postmenstrual age (PMA).

Thrombocytopenia, defined as a platelet count <150 x 10^9/L, is a common neonatal problem that affects 22% to 35% of infants admitted to the neonatal intensive care unit. Platelets are important for primary hemostasis to prevent blood extravasation after vascular injury. Based on the role of platelets in hemostasis, prophylactic platelet transfusions are routinely administered to preterm infants with thrombocytopenia to prevent bleeding. The incidence of thrombocytopenia and administration of platelet transfusion are both inversely related to the gestational age at birth. Currently, there is uncertainty regarding the optimal platelet transfusion threshold, particularly among the most immature infants in the first week of life, which represents the period of highest bleeding risk.

The NeoPlaTT trial was designed to address this pressing uncertainty in the highest risk population (<27 weeks GA). It will test whether a threshold of 20x10^9/L could be safely used after the first week of life, when the risk of serious bleeding is significantly lower, and reduce the need for platelet transfusion altogether. The results of this study have a potential to change clinical practice and improve outcomes in this vulnerable population, while also decreasing costs and resource utilization.

This is a randomized trial with 1:1 allocation to parallel arms. Infants, inborn or outborn, who are admitted to participating NICUs, and who meet the inclusion and exclusion criteria, will be invited to enroll into the trial for platelet count monitoring. Only consented and enrolled infants meeting the additional platelet count trigger of < 50 x 10^9/L (postnatal days 1-7) or <35 x 10^9/L (8 or more postnatal days) will be randomized. Postnatal day 1 starts at birth. Randomization will be allowed to occur up to 36 6/7 weeks' PMA; subjects will be monitored through 40 0/7 weeks PMA. Approximately 30% of consented and enrolled infants are expected to meet the platelet count threshold for randomization.

Inclusion Criteria:

• Gestational age of 23 0/7 to 26 6/7 weeks
• Postnatal age of < 48 hours

Exclusion Criteria:

• Comfort care or withdrawal of care planned
• Neonatal alloimmune thrombocytopenia or suspected/confirmed congenital platelet or bleeding disorder
• Receipt of platelet transfusion
• No receipt of Vitamin K
• Parents/guardian decline consent

NIH has had a long-standing policy to share and make available to the public the results and accomplishments of the activities that it funds. The NRN plans to share de-identified data after final publication in an NIH supported data repository such as the NICHD Data and Specimen Hub (https://dash.nichd.nih.gov).

There will be no blinding/masking of the treatment group allocation to providers or parents to ensure providers are aware of treatment allocation to guide platelet transfusions. This is necessary to ensure adherence to the treatment arms. However, a standard tool will be used to assess bleeding as described below and grading of the severity of bleeding will be performed centrally. In addition, radiologists interpreting cranial ultrasound findings will be blinded to treatment arm allocation.