RBC transfusion and necrotizing enterocolitis in very preterm infants: a multicenter observational study

Abstract

The causal relationship between Packed red blood cell (RBC) transfusion and necrotizing enterocolitis (NEC) remains uncertain. This study aims to provide an exploration of transfusion and NEC in very preterm infants. Using data from the Chinese Neonatal Network cohort study between 2019 and 2021, the analysis focused on very preterm infants (with a birth weight of < 1500 g or a gestational age of < 32 weeks) who developed NEC after receiving transfusions. The time interval between the prior transfusion and NEC was analyzed. An uneven distribution of the time interval implies an association of transfusion and NEC. Additionally, multivariable logistic analysis was conducted to detect the prognosis of defined transfusion-associated NEC(TANEC). Of the 16,494 infants received RBC transfusions, NEC was noted in 1281 (7.7%) cases, including 409 occurred after transfusion. Notably, 36.4% (149/409) of post-transfusion NEC occurred within 2 days after transfusion. The time interval distribution showed a non-normal pattern (Shapiro-Wilk test, W = 0.513, P < 0.001), indicating a possible link between transfusion and NEC. TANEC was defined as NEC occurred within 2 days after transfusion. Infants with TANEC had a higher incidence of death (adjusted OR 1.69; 95% CI 1.08 to 2.64), severe bronchopulmonary dysplasia (adjusted OR 2.03; 95% CI 1.41 to 2.91) and late-onset sepsis (adjusted OR 2.06; 95% CI 1.37 to 3.09) compared with infants without NEC after transfusion. Unevenly high number of NEC cases after RBC transfusions implies transfusion is associated with NEC. TANEC is associated with a poor prognosis. Further research is warranted to enhance our understanding of TANEC.

Keywords: Preterm infants; Prognosis; Red blood cell transfusion; Transfusion-associated necrotizing enterocolitis.

Figure 1

Flow chart of preterm infants with transfusion. CHNN Chinese Neonatal Network, NEC necrotizing enterocolitis, No-NEC infants without NEC, UNTA-NEC preterm infants with NEC prior to all transfusion or NEC occurred beyond 2 days after transfusion, TANEC NEC occurred within 2 days after transfusion, Ud-NEC undefined NEC was defined as NEC that transfusion and NEC occurred on the same day and the onset of NEC (before or after transfusion) was ambiguous.

Figure 2

Distribution of time interval between transfusion and NEC. NEC necrotizing enterocolitis.

Figure 3

Outcomes of TANEC infants. BPD bronchopulmonary dysplasia, ROP retinopathy of prematurity, PVL periventricular leukomalacia. TANEC vs No-NEC: adjusted for gestational age, placental transfusion, age at first feed in days ≤ 3, PDA; TANEC vs UNTA-NEC: adjusted for gestational age, endotracheal incubation during resuscitation, age at first feed in days ≤ 3, inborn, low 5-min Apgar score ≤ 7, duration of antibiotic therapy in 1st 7 days of life in days > 4.