635 - Elemental micronutrients in very preterm infants and associations with brain development

Publication Number: 635.4764

Christopher M. Elitt, Boston Children's Hospital, Boston, MA, United States; Amy Cheng, Boston Children's Hospital, Boston, MA, United States; Jianlin Wang, Boston Children’s Hospital, Newton, MA, United States; Sara Cherkerzian, Harvard Medical School, Boston, MA, United States; Madeline Ross, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States; Katherine Bell, Brigham and Women’s Hospital, Boston, MA, United States; Zhigang He, Boston Children's Hospital, Boston, MA, United States; Terrie Inder, Childrens Hospital of Orange County, Orange, CA, United States; Helen Christou, Brigham and Women's Hospital, Boston, MA, United States; Mandy Belfort, Harvard Medical School, Boston, MA, United States; Paul A.. Rosenberg, Boston Children's Hospital, Boston, MA, United States

Background: Little is known about associations between micronutrient blood content and brain development or the extent to which preterm infant micronutrient content differs from full-term infants.

Objective: To 1) determine longitudinal changes in whole blood micronutrient content among hospitalized, very preterm infants, 2) compare to healthy, full-term infants at birth, and 3) determine associations of blood micronutrient content and brain size.

Design/Methods: We studied 43 very preterm infants (VPT, gestational age [GA] 24-30 weeks) and 15 full-term infants (FT, GA 37-39 weeks). Inductively coupled plasma-mass spectrometry was used to measure iron (Fe), zinc (Zn), copper (Cu), selenium (Se) and rubidium (Rb) content in whole blood samples from VPT at 4 time points (birth, 2 weeks, 1 month, discharge) and in cord blood from FT at birth. Content distributions were plotted at each time point and changes assessed using mixed effects modeling (MEM) and Sidak’s multiple comparisons test. Differences between VPT at discharge and FT at birth were tested using Mann-Whitney U. VPT brain metrics at term equivalent were head circumference (HC) z-score and MRI-based measurements (interhemispheric distance; bifrontal, biparietal, and cerebellar diameters). The associations of VPT brain metrics with mean micronutrient levels over time were analyzed using MEM.

Results: Demographic and clinical characteristics of the VPT and FT are shown in Table 1. VPT content for Se (p < 0.0001), Fe (p < 0.0091) and Rb (p < 0.0036) all were decreased from birth to DOL30 (Fig 1). Zn and Cu remained unchanged (Fig 1). Compared to FT cord blood, VPT at discharge had higher Cu (p < 0.0001) but lower Se (p < 0.0001), Fe (p < 0.0001) and Rb (p < 0.0001) content (Fig 1). VPT with biparietal diameter (BPD) in the top tertile had higher Se content over the course of the hospitalization compared to VPT with BPD in the bottom tertile (Fig 2) (p=0.0345; MEM). We did not observe associations of HC z-score or other brain metrics with Cu, Zn, Fe, Se or Rb content. GA was similar in the top and bottom tertile groups.

Conclusion(s): Se, Fe and Rb content in VPT at discharge were lower than in FT at birth raising concern for nutritional deficiency despite supplementation. Larger BPD was associated with higher selenium content during the hospitalization, a finding that aligns with our prior observation that higher selenium intake from milk was associated with white matter development (Bell et al., PAS 2024, 2140.3). Given the importance of selenoproteins in myelination, supplementation with selenium may be beneficial for brain development in VPT.

TABLE 1. Demographic and clinical characteristics by term status
TABLE 1.pdf

Figure 1: Distributions of whole blood micronutrient content in preterm and full term infants.
Figure 1 PAS2025d.pdfA) Se content at birth (n=30), DOL14 (n=17), DOL30 (n=18) and discharge (n=17) in preterm infants and in cord blood from full term infants (n=15). Se was decreased in preterm infants comparing birth with DOL14 (p=0.0295, t=3.4, df=12), with DOL30 (p < 0.0001, t=6.6, df=14), and discharge (p=0.0218, t=3.8 and df=10). Se was lower at discharge compared to full term infants at birth (p < 0.0001). B) Fe content at birth (n=30), DOL14 (n=20), DOL30 (n=24) and discharge (n=25) in preterm infants and in cord blood from full term infants (n=15). Fe was decreased in preterm infants comparing birth with DOL30 (p=0.0091, t=3.8, df=16). Fe was lower at discharge compared to full term infants at birth (p < 0.0001). C) Zn content at birth (n=29), DOL14 (n=20), DOL30 (n=19) and discharge (n=25) in preterm infants and in cord blood from full term infants (n=15). Zn was unchanged during the hospitalization in preterm infants. There was no difference in zinc content in preterm infants at discharge compared to full term infants at birth. D) Cu content at birth (n=33), DOL14 (n=20), DOL30 (n=25) and discharge (n=25) in preterm infants and in cord blood from full term infants (n=15). Cu was unchanged during the hospitalization in preterm infants. Cu was higher at discharge compared to full term infants at birth (p < 0.0001). E) Rb content at birth (n=25), DOL14 (n=16), DOL30 (n=16) and discharge (n=20) in preterm infants and in cord blood from full term infants (n=15). Rb was decreased in preterm infants comparing birth with DOL14 (p=0.0312, t=3.7, df=9), with DOL30 (p=0.0036, t=4.9, df=10), and discharge (p=0.0475, t=3.3, df=10). Rb was lower at discharge compared to full term infants at birth (p < 0.0001). All values mean +/- standard error. *p < 0.05 vs birth, ** <0.01 vs birth, ****p < 0.0001 vs birth. †††† p<0.0001 vs discharge.

Figure 2: Longitudinal trajectories of selenium content by biparietal diameter tertiles of preterm infants
Figure 2-selenium BPD top-bottom tertiles.pdfAssociation between BPD tertile and longitudinal selenium content using mixed effect model (fixed effects: BPD tertile (top vs bottom), time, group x time interaction). The top tertile of biparietal diameter in preterm infants (n=11) compared to the bottom tertile (n=11) had higher selenium content over the course of the hospitalization (p=0.0337, F(1, 20) = 5.197). Mean gestational age in weeks between the top tertile (29.10 +/- 0.51) and bottom tertile (28.91+/-0.52) were not different. All values mean +/- standard error. * p<0.05.