618 - Relationship of Vitamin E and Vitamin A Levels at One Month After Birth with In-Hospital Adverse Neonatal Outcomes Among Very Preterm Infants

Publication Number: 1595.618

Sandy Huang, University of Washington School of Medicine, Sammamish, WA, United States; Olivia C. Brandon, University of Washington School of Medicine, Seattle, WA, United States; Clara G.. McAdams, University of Washington School of Medicine, Tacoma, WA, United States; Sophia Rodriguez, University of Washington School of Medicine, Kirkland, WA, United States; Virginia Higgins, University of Washington School of Medicine, Edina, MN, United States; Ineeya Senthilnathan Kayal, University of Washington School of Medicine, Seattle, WA, United States; Natalie Chapkis, Seattle Children's/ University of Washington, Seattle, WA, United States; Jill Irvine, university of washington medical center, seattle, WA, United States; Rebecca Hoban, Seattle Children's, Seattle, WA, United States; Katie M.. Strobel, University of Washington School of Medicine, Seattle, WA, United States; Krystle Perez, University of Washington School of Medicine, Snohomish, WA, United States; Sarah Kolnik, University of Washington - Seattle Children's Hospital, Seattle, WA, United States; Gregory C. Valentine, University of Washington School of Medicine, Tacoma, WA, United States

Background: Very preterm (VP; born at ≤32 weeks gestational age [GA]) infants are at increased risk for deficiencies of essential fat-soluble vitamins, including Vitamins E and A, which are important for health and immune function. While low vitamin E and A levels have been linked to neonatal complications such as bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP), findings remain unclear.

Objective: To assess associations between vitamin E and A levels at 1 month of age and adverse neonatal outcomes among very preterm infants admitted to a level IV neonatal intensive care unit (NICU).

Design/Methods: We retrospectively reviewed infants born ≤32 weeks' GA who had vitamin measurements available and remained in-NICU and survived for at least 1 month. Our Level IV NICU protocol recommends obtaining vitamin E and A levels 1 month after birth, although in practice, the first recorded vitamin measurements ranged from 21-35 days. Locally estimated scatterplot smoothing (LOESS) curves examined associations between vitamin levels and BPD, ROP, or length of stay (LOS). Univariate and multivariate logistic and linear regression models assessed associations between vitamin levels and in-hospital outcomes. Descriptive statistics utilized Fisher's exact test, Kruskal-Wallis, and Wilcoxon rank sum tests.

Results: Among n=286 neonates, baseline characteristics did not differ between those with < 5mg/L (deficient) and ≥5mg/L (adequate) vitamin E levels (Table 1). Vitamin E and A levels showed no significant differences across categorized GA groups (Table 1). There was a trend toward increasing vitamin E level by gestational age category ( < 28 weeks: 13.1 (8.2-18.9); 28- < 32 weeks: 15.3 (9.2, 20.4); 32- < 33 weeks: 18.0 (13.0, 21.4), p=0.062). In unadjusted analyses, higher vitamin E and A levels at 1 month did not show associations with BPD or ROP nor duration of LOS (Figure 1). In both univariate (unadjusted) analyses and multivariate (adjusted) analyses, 1-month vitamin E and A levels showed no significant associations with in-NICU outcomes (Figure 2).

Conclusion(s): One month of age, postnatal vitamin E and A levels were not associated with adverse in-hospital neonatal outcomes. These findings suggest that assessing vitamin E and A levels at 1 month of age may have limited clinical utility for discerning risk of in-NICU morbidity. Future analyses are needed to examine longitudinal trends in vitamin levels by GA strata, to clarify potential subgroup effects and inform supplementation strategies.

Table 1: Maternal and Infant Characteristics by Vitamin E Deficient versus Adequate at 1 month
*Fisher's exact test and Wilcoxon rank sum test for categorical and continuous variables, respectively. Continuous data is presented as median (IQR) and categorical data as n (%). Abbreviations: NICU, neonatal intensive care unit; NPO, nil per os (nothing by mouth). Necrotizing enterocolitis was defined as Bell's stage IIA or higher. Bronchopulmonary dysplasia was defined as oxygen or positive pressure support at 36 weeks post-menstrual age. Small for gestational age was defined as birthweight <10th percentile for gestational age using Fenton growth standards.

Figure 1: Locally estimated scatterplot smoothing (LOESS) curves showing the relationship between early postnatal vitamin E levels (top row; A-C) and vitamin A levels (bottom row; D-F) with neonatal outcomes: (A, D) bronchopulmonary dysplasia (BPD), (B, E) any retinopathy of prematurity (ROP), and (C, F) length of stay (LOS).
Curves were relatively flat across the observed vitamin E (0-40 mg/L) and vitamin A (100-400 mcg/L) levels, indicating no clear associations, which is consistent with univariate and multivariate analyses. Gray shaded areas represent the 95% confidence intervals of the mean. Points at y=1 represent babies with BPD or ROP, while points at y=0 represent babies without BPD or ROP.

Figure 2: Forest plot of univariate (unadjusted; shown in brown) and multivariate (adjusted; shown in purple) associations between vitamin E levels (Plot A) and vitamin A levels (Plot B) with neonatal outcomes, including length of stay (LOS), bronchopulmonary dysplasia (BPD), and retinopathy of prematurity (ROP).
Linear regression was used for LOS (estimate and 95% confidence interval shown), and logistic regression was used for BPD and ROP (odds ratio and 95% confidence interval shown). Adjustments include antenatal corticosteroid exposure, inborn/outborn status, small-for-gestational age status, vasopressor use in the first week after birth, sex, and gestational age. Neither vitamin E nor vitamin A shows any significant associations with in-hospital outcomes. Odds ratios are shown per 1 mg/L increase in vitamin E and per 50 mcg/L in vitamin A.