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Sex Differences in the Association of Pretransfusion Hemoglobin Levels with Brain Structure and Function in the
Amanda Benavides1, Edward F Bell2, Amy L Conrad2
1Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA.
Insights
Red blood cell transfusions in preterm infants show sex-specific brain development differences. Higher pretransfusion hemoglobin levels correlate with lower white matter volume in males and poorer motor function in females.
Area of Science:
- Neonatal neuroscience
- Pediatric neurology
- Hematology
Background:
- Preterm infants often require red blood cell (RBC) transfusions due to anemia.
- Early brain development is crucial for long-term outcomes in preterm infants.
- Sex-specific differences in brain structure and function are increasingly recognized.
Purpose of the Study:
- To investigate sex-specific associations between pretransfusion hemoglobin (ptHb) levels and neonatal brain structure.
- To assess sex-specific relationships between ptHb and neurodevelopmental outcomes at 12 months corrected age.
- To evaluate the impact of RBC transfusions on brain development in preterm infants, considering sex.
Main Methods:
- A cohort of preterm infants (birth weight <1000 g, gestational age 22-29 weeks) was studied.
- Longitudinal ptHb measurements were collected as a marker of anemia severity.
- Neonatal brain volumes (MRI) and 12-month corrected age neurodevelopmental function (Bayley Scales) were assessed.
Main Results:
- Higher ptHb was associated with increased neonatal cerebral white matter volume in males, but not females.
- Females with higher ptHb showed significantly lower gross motor and pooled mean scores on the Bayley-III.
- Males did not exhibit significant associations between ptHb and neurodevelopmental scores.
Conclusions:
- This study reveals sex-specific associations between anemia markers, RBC transfusion status, and brain development in preterm infants.
- Neonatal white matter volume and 12-month cognitive function are differentially affected by ptHb levels based on sex.
- Findings highlight the importance of considering sex when evaluating the impact of transfusion practices on preterm infant neurodevelopment.
Objective:
To assess sex-specific differences in early brain structure and function of preterm infants after red blood cell (RBC) transfusions.
Study Design:
A single-center subset of infants with a birth weight <1000 g and gestational age 22-29 weeks were enrolled from the National Institute of Child Health and Human Development's Neonatal Research Network Transfusion of Prematures Trial. Hemoglobin (Hb) concentration obtained directly before each transfusion (pretransfusion Hb [ptHb]) was obtained longitudinally throughout each infant's neonatal intensive care unit stay and used as a marker of degree of anemia (n = 97). Measures of regional brain volumes using magnetic resonance imaging were obtained at ∼40 weeks postmenstrual age or at hospital discharge, if earlier (n = 29). Measures of brain function were obtained at 12 months corrected age using the Bayley Scales of Infant & Toddler Development, 3rd Edition (n = 34).
Results:
PtHb was positively correlated with neonatal cerebral white matter volume in males (B = +0.283; P = .006), but not females (B = -0.099; P = .713), resulting in a significant sex interaction (P = .010). Bayley-III gross motor scores and a pooled mean score were significantly lower in association with higher ptHb in females (gross motor score: B = -3.758; P = .013; pooled mean score: B = -1.225; P = .030), but not males (gross motor score: B = +1.758; P = .167; pooled mean score: B = +0.621; P = .359). Higher ptHb was associated with descriptively lower performance on multiple Bayley-III subscales in females, but not in males.
Conclusions:
This study demonstrates sex-specific associations between an early marker of anemia and RBC transfusion status (ie, ptHb) with both neonatal white matter volume and early cognitive function at age 12 months in preterm infants.
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