Transfusing to keep hemoglobin levels higher does not improve premature baby outcomes

Very small premature infants are at a high risk for anemia and often need blood transfusions to survive. Doctors use varying blood counts or hemoglobin levels to determine when a baby should be transfused with red blood cells. A study funded by the National Institutes of Health suggests that keeping the hemoglobin level higher in the first weeks of life offers no advantage in survival or brain development for extremely low birth weight infants.

This large, multicenter randomized controlled trial was conducted by Haresh Kirpalani, MD of the University of Pennsylvania, Edward Bell, MD of the University of Iowa, and colleagues of the NIH Neonatal Research Network. The study appears in the December 31 issue of The New England Journal of Medicine and is the largest study to date to compare thresholds for blood transfusions in premature babies. Other University of Iowa authors are Karen Johnson, RN, and John Widness, MD.

Very premature infants are at high risk for anemia because of their early stage of development, reduced ability to produce red blood cells, and need for blood sampling as part of their intensive medical care. Previous studies suggest that anemic infants who received transfusions at a higher hemoglobin threshold within the currently accepted range would have a lower risk of death or developmental problems. Measuring hemoglobin, a protein produced in red blood cells, indirectly indicates the proportion of red cells in the blood and the blood’s ability to carry oxygen to the body’s tissues.

NIH trial, largest study to-date compares thresholds for blood transfusions in premature babies, offers guidance for health care providers

1824 infants born with birth weights of 1000 grams or less were randomly assigned to be transfused when their hemoglobin levels (blood counts) fell below specific higher or lower thresholds. 1692 surviving infants were examined at 2 years. Of 845 infants assigned to the higher hemoglobin threshold, 50.1% died or survived with a neurodevelopmental impairment compared to 49.8% of 847 infants assigned to a lower threshold. When the two component outcomes were evaluated separately, the two groups also had similar rates of death (16.2% vs 15.0%) and of survival with neurodevelopmental impairment (39.6% vs 40.3%). The authors concluded that a higher hemoglobin threshold increased the number of transfusions but did not improve the chance of survival without neurodevelopmental impairment.

Notably, 53 infants from Duke participated in the study, and 154 infants participated from the Duke site as a whole, which also includes infants enrolled from the University of North Carolina, Chapel Hill and WakeMed, Duke’s satellite sites.

According to Bell, “The results of the TOP Trial suggest that, within the bounds of the transfusion thresholds used in the trial, there is no advantage for extremely low birth weight infants to routinely keeping their hemoglobin levels higher during the first weeks of life by using higher hemoglobin transfusion thresholds.”

The babies in this study are currently being seen at five years of age for continued assessment to check for long-term differences in the higher and lower threshold groups. This follow-up study is led by Amy Conrad, MD and Peg Nopoulos, MD of the University of Iowa and Sara DeMauro, MD of the University of Pennsylvania and is funded by the National Heart, Lung, and Blood Institute.

“The NICHD Neonatal Research Network’s TOP trial provides evidence for transfusion guidelines and thresholds for extremely premature infants,” said C. Michael Cotton, MD, professor of pediatrics and chief of the Division of Neonatology at Duke University Medical Center. “Infants and families from the Duke Intensive Care Nursery contributed significantly to the success of the study and continue to participate in the school age follow up portion to determine developmental and health outcomes for participants at 5-6 years of age. Examination of these school age outcomes will provide additional insights into the impact of higher versus lower transfusion thresholds in extremely premature infants.”

The Transfusion of Prematures (TOP) Trial was supported by grants from the National Heart, Lung, and Blood Institute to Haresh Kirpalani, Edward Bell, and Abhik Das of RTI International; and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development to the Neonatal Research Network center investigators, including Edward Bell. The National Heart, Lung, and Blood Institute (NHLBI), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Center for Research Resources (NCRR), and the National Center for Advancing Translational Sciences (NCATS) provided grant support for the TOP Trial through cooperative agreements.