Table 2.

Results of selected studies on brain injury and development.

References	Study design, No. infants	GA/BW	Study population	Outcome measure	RBC transfusion practice	Hb-/Ht-level	Brain injury and development
Kirpalani et al. (17)	RCT, n = 1,824	<1,000 g and >22 to <29 wks	Preterm infants in liberal and restrictive RBC-tx group	Brain ultrasound	15 ml/kg	Pre-transfusion mean Hb differed between groups by 1.9 g/dL	No difference in percentage of infants with moderate or severe IVH, or PVL between infants randomized to liberal and restrictive transfusion thresholds
Fontana et al. (50)	Case-Control study, n = 178/182	<1,500 g and ≤ 32 wks	Transfused and non-transfused preterm infants	Brain ultrasound	10–15 ml/kg in 4 h	NA	Transfused infants showed a higher incidence of severe IVH and PVL
Franz et al. (18)	RCT, n = 1,013	>400 to <999 g and <30 wks	Preterm infants in liberal and restrictive RBC-tx group	Brain ultrasound	20 ml/kg	Mean Ht during 1st week was 39.5% (restrictive group) vs. 41.9% (liberal group); During 2nd week this was 36.2 vs. 39.5%	No difference in percentage of infants with moderate or severe IVH, or PVL between infants assigned to liberal and restrictive transfusion thresholds
Benavides et al. (51)	Follow-up study, n = 25	>500 to <1,300 g	Female liberal and restrictive transfusion threshold infants at school age	Brain MRI	15 ml/kg in 5 h	Mean Ht was 35.7% (restrictive group) vs. 44.3% (liberal group)	Liberal RBC-tx practice was associated with deficit of WM brain structure, with decreased temporal lobe and caudate structure
Morris et al. (52)	Cohort study, n = 21	<1,500 g	Anemic preterm infants; 34–37 wks PMA	Brain MRI	NA	Mean Ht was 31.3%	Higher CBF in infants with lowest Ht; Elevated oxygen extraction was associated with worsening anemia
McCoy et al. (53)	Follow-up study, n = 26	>500 to <1,300 g	Liberal transfusion threshold infants at school age	Brain MRI	15 ml/kg in 5 h	NA	Possible adverse effect of high RBC-tx thresholds in which females had decreased temporal lobe WM, related to poor verbal fluency
Nopoulos et al. (54)	Case-Control follow-up study, n = 44/40	>500 to <1,300 g	Liberal and restrictive transfusion threshold infants at school age; healthy term controls at school age	Brain MRI	15 ml/kg in 5 h	Mean Ht was 36.5% (restrictive group) vs. 44.8% (liberal group)	Liberal RBC-tx group had greatest brain structure abnormalities with decrements in ICV; Cerebral WM was more substantially reduced in liberal group; Liberal group girls had most abnormalities; Cerebral WM volume was inversely correlated with Ht-level
Chen et al. (55)	RCT, n = 36	<1,500 g	Preterm infants in liberal and restrictive RBC-tx group	Brain ultrasound	10 ml/kg	Mean Hb and Ht on day 30 after birth were similar between groups; 10.4 g/dL and 29.9%	No differences in percentage of infants with moderate or severe IVH
Kirpalani et al. (19)	RCT, n = 451	<1,000 g and <31 wks	Preterm infants in liberal and restrictive RBC-tx group	Brain ultrasound	15 ml/kg	Mean Hb during 1st week was 14.3 g/dL (restrictive group) vs. 14.9 g/dL (liberal group); During 2nd week this was 11.9 vs. 13.1 g/dL	Brain injury slightly favored the low threshold group non-significantly
Bell et al. (20)	RCT, n = 100	>500 to <1,300 g	Preterm infants in liberal and restrictive RBC-tx group	Brain ultrasound	15 ml/kg in 5 h	Mean Hb and Ht were 8.3 g/dL and 26% (restrictive group) vs. 11.0 g/dL and 32% (liberal group)	Restrictive RBC-tx group included more infants with IVH gr 4, and more infants suffering severe adverse brain events (IPL, PVL)

GA, gestational age; BW, birth weight; RBC-tx, red blood cell transfusion; NA, not applicable; PMA, postmenstrual age; Ht, hematocrit; CBF, cerebral blood flow; WM, white matter; ICV, intracranial volume; RCT, randomized controlled trial; IVH, intraventricular hemorrhage; IPL, intraparenchymal brain hemorrhage; PVL, periventricular leukomalacia.