Randomized Controlled Trial of Enteral Vitamin D Supplementation (ViDES) in Infants <28 Weeks Gestational Age or <1000 Grams Birth Weight: Study Protocol.

Background: Vitamin D is necessary to develop healthy lungs and other organs early in life. Most infants born before 28 weeks' gestation have low vitamin D levels at birth and a limited intake during the first month. Enteral vitamin D supplementation is inexpensive and widely used. The appropriate supplementation regimen for extremely preterm infants is controversial, and the effect of different regimens on their blood levels and outcomes is unclear. Methods: Randomized, blinded comparative effectiveness trial to compare two vitamin D supplementation regimens for inborn infants <28 weeks gestation or <1000 grams birth weight at a large academic center in the United States.Infants are stratified by birth weight and randomized within 96 hours after birth to either routine supplementation (400 IU/day with established feedings) or increased supplementation (800 IU/day with any feedings) during the first 28 days after birth.We hypothesize that the higher and early vitamin D dose (800 IU/d with early feeding) compared to placebo plus routine dose (400 IU/d with established feeding) will substantially increase total 25-hydroxyvitamin D3 levels measured as state-of-art at one month, reduce respiratory support at 36 weeks' postmenstrual age (on an ordinal scale predictive of later adverse outcomes) and improve or at least not worsen other important secondary outcomes. The infants in the study will follow up at 22-26 months' corrected age (~2 years) with blinded certified examiners to evaluate neurodevelopmental outcomes.The sample size of a minimum of 180 infants provides >90% power to detect a >95% posterior probability of a 33% increase in serum 25-hydroxy vitamin D3 and >80% power to detect a >80% posterior probability of a relative risk decrease of 20% of reducing respiratory support by intention-to-treat Bayesian analyses using a neutral prior probability. Discussion: Our study will help clarify the uncertain relationship of vitamin D supplementation and its associated serum metabolites to clinical outcomes of extremely preterminfants. Confirmation of our hypotheses would prompt reconsideration of the supplementation regimens used in extremely preterm infants and justify a large multicenter study to verify the generalizability of the results. Trial registration: ClinicalTrials.gov registered on July 14, 2022 (NCT05459298).

Randomized controlled trial of enteral vitamin D supplementation (ViDES) in infants <28 weeks gestational age or <1000 g birth weight: study protocol.

BACKGROUND: Vitamin D is necessary to develop healthy lungs and other organs early in life. Most infants born before 28 weeks' gestation have low vitamin D levels at birth and a limited intake during the first month. Enteral vitamin D supplementation is inexpensive and widely used. The appropriate supplementation regimen for extremely preterm infants is controversial, and the effect of different regimens on their blood levels and outcomes is unclear. METHODS: Randomized, blinded comparative effectiveness trial to compare two vitamin D supplementation regimens for inborn infants <28 weeks gestation or <1000 g birth weight at a large academic center in the United States. Infants are stratified by birth weight and randomized within 96 h after birth to either routine supplementation (400 IU/day with established feedings) or increased supplementation (800 IU/day with any feedings) during the first 28 days after birth. We hypothesize that the higher and early vitamin D dose (800 IU/day with early feeding) compared to placebo plus routine dose (400 IU/day with established feeding) will substantially increase total 25-hydroxyvitamin D3 levels measured as state-of-art at 1 month, reduce respiratory support at 36 weeks' postmenstrual age (on an ordinal scale predictive of later adverse outcomes), and improve or at least not worsen other important secondary outcomes. The infants in the study will follow up at 22-26 months' corrected age (~2 years) with blinded certified examiners to evaluate neurodevelopmental outcomes. The sample size of a minimum of 180 infants provides >90% power to detect a >95% posterior probability of a 33% increase in serum 25-hydroxy vitamin D3 and >80% power to detect a >80% posterior probability of a relative risk decrease of 20% of reducing respiratory support by intention-to-treat Bayesian analyses using a neutral prior probability. DISCUSSION: Our study will help clarify the uncertain relationship of vitamin D supplementation and its associated serum metabolites to clinical outcomes of extremely preterm infants. Confirmation of our hypotheses would prompt reconsideration of the supplementation regimens used in extremely preterm infants and justify a large multicenter study to verify the generalizability of the results. TRIAL REGISTRATION: ClinicalTrials.gov NCT05459298. Registered on July 14, 2022.

Hospital-Level NICU Capacity, Utilization, and 30-Day Outcomes in Texas.

Importance: Risk-adjusted neonatal intensive care unit (NICU) utilization and outcomes vary markedly across regions and hospitals. The causes of this variation are poorly understood. Objective: To assess the association of hospital-level NICU bed capacity with utilization and outcomes in newborn cohorts with differing levels of health risk. Design, Setting, and Participants: This population-based retrospective cohort study included all Medicaid-insured live births in Texas from 2010 to 2014 using linked vital records and maternal and newborn claims data. Participants were Medicaid-insured singleton live births (LBs) with birth weights of at least 400 g and gestational ages between 22 and 44 weeks. Newborns were grouped into 3 cohorts: very low birth weight (VLBW; <1500 g), late preterm (LPT; 34-36 weeks' gestation), and nonpreterm newborns (NPT; ≥37 weeks' gestation). Data analysis was conducted from January 2022 to October 2023. Exposure: Hospital NICU capacity measured as reported NICU beds/100 LBs, adjusted (ie, allocated) for transfers. Main Outcomes and Measures: NICU admissions and special care days; inpatient mortality and 30-day postdischarge adverse events (ie, mortality, emergency department visit, admission, observation stay). Results: The overall cohort of 874 280 single LBs included 9938 VLBW (5054 [50.9%] female; mean [SD] birth weight, 1028.9 [289.6] g; mean [SD] gestational age, 27.6 [2.6] wk), 63 160 LPT (33 684 [53.3%] female; mean [SD] birth weight, 2664.0 [409.4] g; mean [SD] gestational age, 35.4 [0.8] wk), and 801 182 NPT (407 977 [50.9%] female; mean [SD] birth weight, 3318.7 [383.4] g; mean [SD] gestational age, 38.9 [1.0] wk) LBs. Median (IQR) NICU capacity was 0.84 (0.57-1.30) allocated beds/100 LB/year. For VLBW newborns, NICU capacity was not associated with the risk of NICU admission or number of special care days. For LPT newborns, birth in hospitals with the highest compared with the lowest category of capacity was associated with a 17% higher risk of NICU admission (adjusted risk ratio [aRR], 1.17; 95% CI, 1.01-1.33). For NPT newborns, risk of NICU admission was 55% higher (aRR, 1.55; 95% CI, 1.22-1.97) in the highest- vs the lowest-capacity hospitals. The number of special care days for LPT and NPT newborns was 21% (aRR, 1.21; 95% CI,1.08-1.36) and 37% (aRR, 1.37; 95% CI, 1.08-1.74) higher in the highest vs lowest capacity hospitals, respectively. Among LPT and NPT newborns, NICU capacity was associated with higher inpatient mortality and 30-day postdischarge adverse events. Conclusions and Relevance: In this cohort study of Medicaid-insured newborns in Texas, greater hospital NICU bed supply was associated with increased NICU utilization in newborns born LPT and NPT. Higher capacity was not associated with lower risk of adverse events. These findings raise important questions about how the NICU is used for newborns with lower risk.