Urinary neutrophil gelatinase-associated lipocalin is an early predictor of acute kidney injury in premature infants.

Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is produced in response to tubular epithelial injury and is a biomarker of tubulointerstitial injury. The aim of the present study was to examine whether acute kidney injury (AKI) could be predicted by measuring uNGAL in very low-birth weight (VLBW) infants. Forty VLBW infants with birthweight below 1,500 g were enrolled in the present study. uNGAL and serum creatinine (sCre) were measured daily from postnatal days 0 to 8. Infants with sCre ≥1.2 mg/dl were diagnosed with AKI. The relationship of uNGAL with sCre was measured on the day after uNGAL measurement (next-day sCre) was examined. The results showed that 16 infants had sCre ≥1.2 mg/dl in this period. Logistic regression analysis revealed that uNGAL on postnatal days 2, 3, 4, 5 and 6 was correlated with next-day sCre (P<0.05). uNGAL corrected by urinary Cre (uCre) (uNGAL/uCre) was only correlated with an increase in next-day sCre on postnatal days 5 and 6 (P<0.05). For the logistic analysis, subjects with high and low uNGAL levels based on the median value for each day, uNGAL on postnatal days 2, 3 and 6 in the high uNGAL group was correlated with an increase in next-day sCre. Thus, AKI may be predicted by measuring uNGAL in VLBW infants. This measurement was non-invasive, and is potentially useful for the evaluation of renal function in VLBW infants.

Safety of lipid emulsion in very low-birthweight infants according to cytokine level.

BACKGROUND: The aim of this study was to verify whether lipid emulsion treatment aggravates infection and inflammation in very low-birthweight (VLBW) infants. STUDY DESIGN: Very low-birthweight (<1500 g) infants born at <32 weeks gestational age between October 2013 and October 2014 at Dokkyo Medical University Hospital (Mibu, Tochigi, Japan) were treated with or without i.v. nutrition with a lipid emulsion. Infants were excluded who had congenital abnormalities, could not receive i.v. nutrition because of poor general condition, or on physician decision. Lipid emulsion with purified soybean oil was initiated at 0.5 g/kg/day on postnatal day 1. The dose was increased to 1 g/kg/day, and then to 1.5 g/kg/day (maximum dose). Blood tests were performed before (day 1) and after (day 8) initiation of lipid emulsion treatment. Interleukin (IL)-6, IL-8, monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), total bilirubin (T-Bil), direct bilirubin (D-Bil) and insulin were measured. Changes in respiratory condition, amount of oxygen used, and phototherapy duration were investigated. RESULTS: A total of 17 treated and 15 untreated VLBW infants were enrolled. IL-6, IL-8, MCP-1, TNF-α, CRP, T-Bil, D-Bil and insulin on days 1 and 8; respirator or surfactant use; amount of oxygen used; and phototherapy duration were not significantly different between the two groups. CONCLUSIONS: Lipid emulsion treatment did not increase inflammatory cytokine levels or aggravate respiratory disorders. Lipid emulsions, if proven safe, could be used to treat VLBW infants soon after birth, which may prevent extrauterine growth restriction and improve intellectual development prognosis.

Thyroxine for transient hypothyroxinemia and cerebral palsy in extremely preterm infants.

BACKGROUND: The relationship of thyroxine supplementation for transient hypothyroxinemia of prematurity to the incidence of cerebral palsy (CP) in infants <28 weeks of gestation is unclear. METHODS: The incidence of CP at a corrected age of 18 months was compared between infants born in a 3-year period in which routine measurement of free T4 (FT4) in the blood was not performed (first period, n= 54), and those born in a later 3-year period in which FT4 was measured (second period, n= 60; mainly at 7 days old), and in which l-thyroxine 5-10 µg/kg per day (mean, 9 µg/kg/day) was administered for FT4 levels <0.8 ng/dL. Incidence of CP at 3 years of age was also compared between the same groups. RESULTS: Background clinical factors between the two groups were comparable except for prenatal steroid administration, which was reduced in the second period. Incidence of CP at a corrected age of 18 months was significantly lower in the second period (3.3%) than in the first period (16.6%). Incidence of CP at 3 years of age was also significantly lower in the second period. Multiple logistic regression analysis using factors except thyroxine supplementation, for the total of 114 infants from both groups, found no perinatal factors related to the development of CP at a corrected age of 18 months. CONCLUSIONS: Thyroxine supplementation for transient hypothyroxinemia of prematurity may reduce the incidence of CP in extremely preterm infants. Large-scale randomized controlled trials are essential to determine the effects of thyroxine supplementation in reducing the incidence of CP among extremely preterm infants.

Anti-apoptotic effect of nerve growth factor is lost in congenital insensitivity to pain with anhidrosis (CIPA) B lymphocytes.

Congenital insensitivity to pain with anhidrosis (CIPA) is identified as a genetic disorder of mutations in the human TrkA known as high affinity receptor of nerve growth factor (NGF). NGF signal through TrkA promotes anti-apoptotic activity in hematopoietic cells including B lymphocytes. Here we studied the effect of NGF on anti-apoptotic activity by using human EBV-immortalized B lymphoblastoid cell lines (EB-LCLs) derived from a patient with CIPA and the associated carriers of CIPA. The TrkA(mt/mt) EB-LCL derived from the CIPA patient and the TrkA(wt/mt) EB-LCL derived from the carrier with the heterozygous TrkA mutation did not show any responses to NGF on anti-apoptotic activity. We concluded that this phenomenon is one of the pathogeneses of CIPA.