Chike Onwuneme

The Association of Vitamin D Status with Acute Respiratory Morbidity in Preterm Infants

OBJECTIVE To assess the association between serum 25-hydroxyvitamin D (25OHD) levels and outcomes in preterm infants (<32 weeks gestation). STUDY DESIGN Serum 25OHD was measured in mothers and their infants within 24 hours of birth, before the start of enteral vitamin D supplementation, and at discharge from the neonatal intensive care unit. We evaluated the associations between vitamin D status and various early preterm outcomes. RESULTS Ninety-four preterm infants and their mothers were included; 92% of the infants had a 25OHD level≤50 nmol/L (20 ng/mL), and 64% had a 25OHD level<30 nmol/L (12 ng/mL). A low 25OHD level (<30 nmol/L) in preterm infants at birth was associated with increased oxygen requirement (P=.008), increased duration of intermittent positive-pressure ventilation during resuscitation at delivery (P=.032), and greater need for assisted ventilation (P=.013). CONCLUSION We observed a high prevalence of low 25OHD (<30 nmol/L), and found an association between vitamin D status and acute respiratory morbidity in preterm infants after birth.

Vitamin D and neonatal immune function.

Abstract Vitamin D deficiency is widespread in the neonatal and paediatric population of northern latitudes, particularly in children of African, Middle Eastern and Asian ethnicity. This is associated with diminished immune function and increases the risk of Th1 autoimmune diseases like type 1 diabetes. Epidermiological studies have also shown a link between vitamin D deficiency in children and a more severe course of illness with lower respiratory tract infection or Respiratory Syncitial Virus (RSV) bronchiolitis. The mechanism by which vitamin D enhances immunity is complex. It acts through the innate immune system by inducing antimicrobial peptides in epithelial cells, neutrophils and macrophages. The role of Vitamin D in neonatal and paediatric immunomodulation requires further study.

Inadequate vitamin D levels are associated with culture positive sepsis and poor outcomes in paediatric intensive care

This study aimed to assess vitamin D status, and its determinants, in paediatric patients with suspected sepsis who were admitted to a paediatric intensive care unit (PICU). We also investigated the association between vitamin D status and clinical outcomes.

Vitamin D Status in Irish Children and Adolescents: Value of Fortification and Supplementation

Background. Vitamin D has important skeletal and extraskeletal roles but those living at northerly latitudes are at risk of suboptimal levels because of reduced sunlight exposure. Aim. To describe the vitamin D status of Irish children and identify factors predictive of vitamin D status. Methods. A prospective cross sectional study was undertaken over a 12 month period. Two hundred and fifty two healthy children attending for minor medical or surgical procedures were recruited. All had 25-hydroxyvitamin D (25OHD), parathyroid hormone and bone profiles measured. Results. The mean (standard deviation) for 25OHD was 51(25) nmol/L (20.4 (10) ng/mL). Forty-five percent had levels >50 nmol/L (20 ng/mL). The following variables were significantly associated with 25OHD levels >50 nmol/L (20 ng/mL): sample drawn in April-September, use of vitamin D supplements, consumption of formula milk, and non-African ethnicity. Conclusion. More than half of the children in this study had 25OHD levels less than 50 nmol/L (20 ng/mL). Vitamin D status was significantly improved by augmented oral vitamin D intake.

Towards evidence based medicine for paediatricians. Question 2. What is the ideal dose of vitamin D supplementation for term neonates

During a well-baby check, a mother asked for the consultants recommendation on the ideal dose and type of vitamin D formulation for her infant. She intends to breastfeed her baby exclusively. Her baby was born at 39 weeks gestation by spontaneous vaginal delivery. In a normal term neonate [patient], what is the optimal dose of vitamin D supplementation [intervention] to prevent vitamin D deficiency and rickets [outcome]? ### Primary sources MEDLINE was searched via PubMed from 1990 to July 2011. The advanced search mode was used with the terms ‘vitamin D’ and ‘neonates’ and ‘supplementation’. ### Secondary sources A search of the Cochrane Library was conducted using the search terms ‘vitamin D’ and ‘infants’. Vitamin D is essential for good bone health and insufficient levels are linked to rickets in children.1 5 A resurgence of vitamin D insufficiency and nutritional rickets has been reported across many countries.1 Studies in infants and children are also exploring the association between vitamin D insufficiency and type 1 diabetes mellitus as well as inflammatory diseases.1 2 There …

Perinatal Asphyxia and Erythropoietin and VEGF: Serial Serum and Cerebrospinal Fluid Responses.

Background: Infants with neonatal encephalopathy (NE) of hypoxic-ischaemic origin are at risk of oxidative and ischaemia-reperfusion injury, which may induce abnormal inflammatory responses involving excessive cytokine production and release in serum and cerebrospinal fluid (CSF). Systemic inflammation is found in infants with NE, and we therefore were interested in cytokines associated with hypoxia, including vascular endothelial growth factor (VEGF) and erythropoietin (Epo). Objective: To investigate the relationship between Epo, VEGF levels, brain injury and outcome in a group of term infants exposed to perinatal asphyxia (PA) compared to controls. Methods: Serum and CSF biomarkers associated with hypoxia (VEGF, Epo) were serially measured using multiplex immunoassays over days 1-4 in term infants exposed to PA including infants with NE and controls. Results were compared to severity of encephalopathy, MR brain imaging and mortality. Results: Ninety-four infants had 247 serum samples collected (n = 12 controls, 82 exposed to PA with 34 CSF samples), and 4 infants died. Controls had significantly lower serum Epo levels on days 1 and 2 compared to those exposed to PA (p = 0.02). Grade II/III NE was significantly associated with elevated day 2 Epo and decreased day 1 VEGF (p < 0.05; day 2 Epo AUC = 0.74, cut-off 10.05 IU/ml). Elevated serum Epo was associated with severely abnormal MRI. Mortality was associated with elevated day 3 Epo and decreased day 1 VEGF. CSF levels were all after hypothermia and were not significantly associated with outcome. Conclusion: Serum Epo and VEGF may be markers of severity of hypoxia-ischaemia and brain injury as they are closely related to hypoxic exposure.

Renal Function and Novel Urinary Biomarkers In Infants with Neonatal Encephalopathy

Perinatal asphyxia is associated with multi‐organ injury including acute kidney injury (AKI). New urinary biomarkers may detect more subtle renal injury.

Neutrophil and monocyte Toll-Like Receptor 4, CD11b and Reactive Oxygen Intermediates and Neuroimaging Outcomes in Preterm Infants

Background:Activated leukocytes and infection are implicated in neonatal brain injury. Leukocyte surface receptors are increased in stroke models and may be targets for future adjunctive therapies.Methods:Serial blood samples were analyzed from preterm infants (n = 51; <32 wk gestation) on days 0, 1, 2, and 7 of life. Monocyte and neutrophil activation were evaluated via flow cytometry at baseline and following endotoxin stimulation ex vivo by measuring CD11b (activation), toll-like receptor 4 (TLR-4; endotoxin recognition) expression, and intracellular reactive oxygen intermediate (ROI) production (function).Results:Control preterm infants with normal neuroimaging had elevated baseline CD11b and TLR-4 expression and ROI production compared with adults as well as a robust immune response following endotoxin stimulation. Preterm infants with abnormal neuroimaging had increased neutrophil TLR-4 and ROI compared with all controls.Conclusion:Preterm infants have a robust immune response compared with adults. Increased TLR-4 expression in preterm infants with abnormal neuroimaging is similar to findings in adult stroke. In addition, ROI production may cause tissue injury. The modulation of these responses may be beneficial in preterm inflammatory disorders.

Vitamin D enhances reactive oxygen intermediates production in phagocytic cells in term and preterm infants

Background:Newborn infants are endotoxin tolerant which may be responsible for their increased susceptibility to bacterial sepsis. Vitamin D has an immunomodulatory effect and newborn infants are at risk of vitamin D deficiency. We examined the in vitro effect of 1, 25-dihydroxyvitamin D (1,25OHD) on whole blood phagocytic toll-like receptor 4 (TLR4), CD11b, and reactive oxygen intermediates (ROIs) in newborn infants during sepsis.Methods:Whole blood from preterm infants <32-wk gestation, control term neonates, and adults were sampled for phagocytic expression of ROI, TLR4, CD11b in response to lipopolysaccharide (LPS), and 1,25OHD using flow cytometer.Results:ROI production from newborn phagocytes incubated with LPS alone was decreased. Pretreatment with 1,25OHD demonstrated increased (P = 0.001) phagocytic ROI production in newborns but not in adults. 1,25OHD did not have any effect on TLR4 and CD11b in both newborns and adults. Pretreatment with ROI inhibitors (apocynin (APO) and diphenyleneiodonium), phosphoinositide 3-kinase (PI3K) inhibitor, and p38 inhibitor blocked neutrophil ROI production.Conclusion:Neonatal phagocytic cells had diminished ROI production in the presence of LPS, however, pretreatment with 1,25OHD reversed this hyporesponsiveness. This action by 1,25OHD was mediated by activation of nicotinamide adenine dinucleotide phosphate oxidase system through PI3K signaling enzymes.

PS-108 Urinary Biomarkers May Help Predict Outcome In Neonatal Encephalopathy

Background Following a perinatal hypoxic-is chaemic insult, term infants are at risk of multi-organ injury including AKI. Infants with NE experience up-regulation of urinary cytokines which may reflect severity of brain injury. Objective To investigate the association between novel urinary biomarkers and outcome in a group of term infants with NE compared to controls. Methods Levels of urinary biomarkers [Albumin, B2M, Cystatin-C, EGF, NGAL, Osteopontin, Uromodulin] were serially measured over day 1–11 in a group of term newborns with NE and controls. These values were compared to grade of encephalopathy defined by Sarnat score. Results Ten control and 82 cases had urine samples collected (Grade 0 NE = 7, Grade I NE = 22, Grade II NE = 42, Grade III NE = 11). Thirty-nine infants underwent TH, 4 infants died. Control infants had significantly lower B2M on day 1, NGAL on day 1–2 and significantly higher urinary EGF on day 2–3 and Uromodulin on day 3, compared with cases (p-values Conclusion Infants with NE have elevated urinary biomarkers compared to controls. Abnormal grade of encephalopathy is best predicted by day 2 urinary Cystatin-C and day 3 NGAL. Urinary biomarkers may have a role in long term outcome prediction following NE.