Libesman Sol, Seidler Anna Lene, Tan-Koay Ava G, Cunningham Peter S, Robledo Kristy, Cruise Sam, Wadsworth Makayla, Kluckow Martin, Gill Andrew W, de Waal Koert, Tarnow-Mordi William, Liley Helen G
NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia,
NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia.
Neonatology. 2025 Mar 28:1-9. doi: 10.1159/000545526.
Delaying clamping of the umbilical cord (deferred cord clamping [DCC]) in preterm infants reduces mortality and the need for blood transfusions. The mechanisms leading to these benefits are not well understood. The TITANS study investigates potential mediators of the reduction in blood transfusions in infants who received DCC.
Additional patient data was sourced from Australian and New Zealand sites from the Australian Placental Transfusion Study (APTS). APTS randomized preterm infants <30 weeks' gestation to receive DCC (60 s) or immediate cord clamping. We examined whether placental transfusion or initial severity of illness mediated the reduced requirement for blood transfusions for infants randomized to DCC. Peak hematocrit in the first 7 days (Hct) was used as an indicator of placental transfusion quantity. Cumulative blood sampled, mechanical ventilation, and arterial sampling lines were used as indicators of severity of illness. We quantified the natural indirect effect of peak Hct and then for all mediators in a joint model with sequential mediation.
Data from 1,260 (of 1,401) Australian and New Zealand APTS infants were obtained. The effect of DCC on subsequent blood transfusion was mediated through peak Hct (indirect effect OR = 0.85, 95% CI: 0.79-0.93; p < 0.001), which accounted for 37% of the total effect. Indicators of severity of illness did not mediate the effect independently of peak Hct.
Peak Hct mediated some, but not all, of the effect of DCC on blood transfusion, whereas markers of severity of illness were not independent mediators.
延迟结扎脐带（延迟脐带结扎[DCC]）可降低早产儿死亡率及输血需求。导致这些益处的机制尚不完全清楚。TITANS研究调查了接受DCC的婴儿输血减少的潜在介导因素。
额外的患者数据来自澳大利亚胎盘输血研究（APTS）在澳大利亚和新西兰的研究点。APTS将孕周<30周的早产儿随机分为接受DCC（60秒）或立即结扎脐带组。我们研究了胎盘输血或初始疾病严重程度是否介导了随机分配至DCC组的婴儿输血需求的降低。将出生后7天内的最高血细胞比容（Hct）用作胎盘输血量的指标。累积采血量、机械通气及动脉采样管路用作疾病严重程度的指标。我们在一个具有序贯中介作用的联合模型中对最高Hct以及所有中介因素的自然间接效应进行了量化。
获取了1401例澳大利亚和新西兰APTS婴儿中1260例的数据。DCC对后续输血的影响是通过最高Hct介导的（间接效应OR = 0.85，95%CI：0.79 - 0.93；p < 0.001），其占总效应的37%。疾病严重程度指标并未独立于最高Hct介导该效应。
最高Hct介导了DCC对输血影响的部分而非全部效应，而疾病严重程度标志物并非独立的介导因素。
