Vitamin D Supplementation: Association With Serum Cytokines in Pediatric Hematopoietic Stem Cell Transplantation.

Vitamin D deficiency is prevalent in pediatric patients presenting for hematopoietic stem cell transplantation (HSCT) and has been linked to poor clinical outcomes. Using the data from a randomized control trial, in this paper we explore the effects of vitamin D supplementation on circulating cytokine levels during pediatric HSCT (www.clinicaltrials.gov as NCT03176849). A total of 41 children, 20 received Stoss therapy and 21 children received standard of care vitamin D supplementation. Levels of 25(OH)D and 20 cytokines were assessed at baseline and day +30. Significantly (P < 0.05) higher levels of mostly proinflammatory cytokines, FGF, GCSF, TNFα, IL-2, IL-6, IP10 were detected pre-transplant for patients with low compared to those with normal vitamin D levels. In sex stratified models that compare changes in cytokines between Stoss vs. standard of care, females in the Stoss group show greater changes in mostly pro -inflammatory cytokines- IP-10 (P = 0.0047), MIG (P = 0.009), and RANTES (P = 0.0047), IL-2R (P = 0.07) and IL-6(P = 0.069). Despite a small sample size, these findings suggest vitamin D deficiency affects the pre-transplant cytokine milieu and higher doses of vitamin D (Stoss therapy) appears to influence proinflammatory cytokine responses in a sex specific manner during pediatric HSCT. Larger clinical trials are warranted to validate these results.

Impact of Adequate Day 30 Post-Pediatric Hematopoietic Stem Cell Transplantation Vitamin D Level on Clinical Outcome: An Observational Cohort Study.

This prospective observational study evaluated the impact of adequate vitamin D levels by day +30 after vitamin D supplementation on early post-HSCT outcomes, including acute graft-versus-host disease (aGVHD), immune recovery, infection rates, and overall survival. Forty children (age 2 to 16 years) undergoing hematopoietic stem cell transplantation (HSCT) were given vitamin D supplementation, were followed prospectively from day +30 post-transplantation, and had day +30 vitamin D levels measured. Thirty patients with normal vitamin D levels (≥30 ng/mL) were compared with 10 patients with low day +30 vitamin D levels (<30 ng/mL). The times to neutrophil and platelet engraftment was similar in both day +30 vitamin D groups (P = .13 and .32, respectively). At day +100, slower immune recovery in CD4+ cells (P = .027), CD19+ cells (P = .024), and natural killer cells (P = .042) was observed in the patients with a low vitamin D level (<30 ng/mL), and no between-group differences were detected in the incidence of infection (P = .72) or grade II-IV aGVHD (P = .46). Our findings show that patients with adequate vitamin D levels during transplantation had faster immune recovery and better overall survival. Vitamin D deficiency does not appear to impact engraftment or the risk of aGVHD and infection in pediatric HSCT.

Lower Maternal Chronic Physiological Stress and Better Child Behavior at 18 Months: Follow-Up of a Cluster Randomized Trial of Neonatal Intensive Care Unit Family Integrated Care.

OBJECTIVE: To assess whether Family Integrated Care (FICare) in the neonatal intensive care unit improves maternal chronic physiological stress and child behavior at 18 months of corrected age for infants born preterm. STUDY DESIGN: Follow-up of a multicenter, prospective cluster-randomized controlled trial comparing FICare and standard care of children born at <33 weeks of gestation and parents, stratified by tertiary neonatal intensive care units, across Canada. Primary outcomes at 18 months of corrected age were maternal stress hormones (cortisol, ie, hair cumulative cortisol [HCC], dehydroepiandrosterone [DHEA]) assayed from hair samples. Secondary outcomes included maternal reports of parenting stress, child behaviors (Internalizing, Externalizing, Dysregulation), and observer-rated caregiving behaviors. Outcomes were analyzed using multilevel modeling. RESULTS: We included 126 mother-child dyads from 12 sites (6 FICare sites, n = 83; 6 standard care sites, n = 43). FICare intervention significantly lowered maternal physiological stress as indicated by HCC (B = -0.22 [-0.41, -0.04]) and cortisol/DHEA ratio (B = -0.25 [-0.48, -0.02]), but not DHEA (B = 0.01 [-0.11, 0.14]). Enrollment in FICare led to lower child Internalizing (B = -0.93 [-2.33, 0.02]) and Externalizing behavior T scores (B = -0.91 [-2.25, -0.01]) via improvements to maternal HCC (mediation). FICare buffered the negative effects of high maternal HCC on child Dysregulation T scores (B = -11.40 [-23.01, 0.21]; moderation). For mothers reporting high parenting stress at 18 months, FICare was related to lower Dysregulation T scores via maternal HCC; moderated mediation = -0.17 (-0.41, -0.01). CONCLUSIONS: FICare has long-term beneficial effects for mother and child, attenuating maternal chronic physiological stress, and improving child behavior in toddlerhood. CLINICAL TRIAL REGISTRATION: NCT01852695.

Stoss therapy is safe for treatment of vitamin D deficiency in pediatric patients undergoing HSCT.

Vitamin D deficiency remains common among pediatric patients undergoing hematopoietic stem cell transplant (HSCT) despite both aggressive and standard of care strategies. This study examined the safety and efficacy of single high-dose oral vitamin D therapy (Stoss therapy) for treatment of vitamin D deficiency in HSCT recipients. Patients ages 1-21 years presenting for HSCT were randomized to receive either Stoss regimen plus weekly/daily supplementation or standard of care, per US Endocrine Society guidelines. Among the total 48 subjects, 22 (46%) were randomized to Stoss and 26 (54%) to control arms. Baseline 25-hydroxyvitamin D (25-OHD) levels were insufficient/deficient in total of 34 (71%) patients, without difference between treatment groups. The Stoss regimen was well tolerated and no toxicity was observed. At Day +30, mean 25-OHD levels were significantly higher (P = 0.04) with Stoss (42.3 ± 12 µg/l) compared to controls (35.6 ± 14.3 µg/l), and a higher proportion of Stoss patients had adequate vitamin D levels than controls (85% vs 65%). Stoss therapy is a safe and efficacious treatment option for vitamin D deficiency in children undergoing HSCT and may achieve sufficient levels more rapidly than standard of care. This trial was registered at www.clinicaltrials.gov as NCT03176849.

Vitamin D deficiency and outcomes in pediatric hematopoietic stem cell transplantation.

BACKGROUND: Pediatric patients undergoing hematopoietic stem cell transplantation (HSCT) are frequently diagnosed with vitamin D deficiency, which may impact outcomes. OBJECTIVES: To estimate the prevalence of vitamin D deficiency and examine its association with short-term survival in pediatric HSCT patients. METHODS: Patients undergoing HSCT at Phoenix Children's Hospital were retrospectively identified. Routine serum 25-hydroxyvitamin D measurements were described prior to transplant and at 100 days and 1-year post-HSCT. Associations of pre-HSCT vitamin D groups (i.e., normal ≥30 ng/ml, insufficient 20-29 ng/ml, and deficient <30 ng/ml) with demographics, clinical factors, and outcomes were examined using nonparametric tests and Cox proportional hazards analyses. RESULTS: Among 72 study subjects, the median vitamin D pre-HSCT was 26 ng/ml (range: 19-34 ng/ml). Levels were insufficient and deficient in 25 (35%) and 20 (28%) patients, respectively, with only two (3%) patients on supplemental therapy pre-HSCT. Despite supplemental therapy provided to 46 (74%) subjects, insufficient/deficient rates did not significantly change between pre-HSCT and 100 days post-HSCT, but mean vitamin D levels significantly increased by 1-year post-HSCT (P = 0.01).Vitamin D pre-HSCT was not associated with the development of acute or chronic graft-versus-host disease (GVHD) or delayed engraftment. Overall 1-year survival was significantly lower for patients with deficient (65%) compared to normal (93%) pre-HSCT vitamin D (P = 0.001). CONCLUSION: Suboptimal vitamin D levels are common in pediatric patients scheduled to receive HSCT and are associated with lower overall 1-year survival. Further study is warranted to delineate the mechanisms underlying the role of vitamin D in successful HSCT.

Asthma treatment and outcomes for children in the emergency department and hospital.

OBJECTIVE: To describe and compare the treatment of acute asthma exacerbations in children given in the emergency department (ED) and admitted to acute care floor in the hospital or intensive care unit (ICU). METHODS: A retrospective chart review of visits for acute exacerbation of asthma treated at Phoenix Children's Hospital between January 1, 2014 and December 31, 2016. RESULTS: A total of 287 asthma exacerbation cases were identified including 106 (37%) ED visits, 134 (47%) hospital floor and 47 (16%) ICU admissions. A history of a previous ED visit (ED 88%, Floor 60% and ICU 68%; p < 0.0001) and prior pulmonology inpatient consultation (ED 30%, Floor 19% and ICU 15%; p = 0.05) varied significantly. Pulmonology inpatient consultations were performed more frequently in the ICU than on the hospital floor (54% versus 8%; p < 0.0001). Although overall 145 (51%) of the cases were already on inhaled corticosteroids (ICS) at the time of visit with no differences across locations, ICS initiation/step-up was greater in the ICU (72%) than on the hospital floor (54%) and ED (2%) (p < 0.0001). A recommendation given to the family for follow-up with pulmonology was more frequent for patients who had been admitted to the ICU (68%) as compared to those only admitted to the floor (31%) or ED (4%) (p < 0.0001). Readmission rates were similar for patients previously admitted to the hospital (Floor 42%; ICU 40%), but significantly higher for previous ED visits (77%) (p < 0.0001). CONCLUSIONS: Physicians in the ED have an opportunity to provide preventative care in the acute care setting and should be encouraged to initiate treatment with ICS. Consideration should be given to develop a program or clinical pathway focused on long-term asthma management and maintenance to reduce readmissions and long hospital stays.