Transcutaneous bilirubin measurement during phototherapy in term neonates.

BACKGROUND: We tested whether direct transcutaneous bilirubin (TcB) measurement from an area unexposed to phototherapy is reliable for estimation of total serum bilirubin (TSB) in neonates during phototherapy and whether it contributes to reduction in TSB blood sampling in phototherapy decision making. METHODS: This was a retrospective observational study of term neonates who received phototherapy in the mother's room. TSB and TcB from the neonate's sternum were measured before and during phototherapy and compared using linear regression analysis and Bland-Altman plot, respectively. Various cut-offs of TcB for estimating TSB during phototherapy at >72 h after birth were analyzed. RESULTS: There were moderate correlations between TSB and TcB before (r = 0.56) and during (r = 0.47) phototherapy in 125 neonates. The mean difference (TSB-TcB) before and during phototherapy was 1.2 ± 1.7 mg/dL and 1.0 ± 1.7 mg/dL, respectively. The 95% limits of agreement for the difference before and during phototherapy ranged from -2.1 to 4.5 and from -2.3 to 4.3 mg/dL, respectively. For TSB ≤18 mg/dL during phototherapy, a TcB cut-off of 14 mg/dL had a specificity of 1.0; with this method, 43% of the TSB measurements could have been avoided. CONCLUSIONS: Direct measurement of TcB during phototherapy using a bed-type device is a reliable method to estimate TSB in term neonates and would contribute to a reduction in blood sampling. It cannot, however, be used as a substitute for TSB measurement.

Prolonging in utero-like oxygenation after birth diminishes oxidative stress in the lung and brain of mice pups.

BACKGROUND: Fetal-to-neonatal transition is associated with oxidative stress. In preterm infants, immaturity of the antioxidant system favours supplemental oxygen-derived morbidity and mortality. OBJECTIVES: To assess if prolonging in utero-like oxygenation during the fetal-to-neonatal transition limits oxidative stress in the lung and brain, improving postnatal adaptation of mice pups. MATERIAL AND METHODS: Inspiratory oxygen fraction (FiO2) in pregnant mice was reduced from 21% (room air) to 14% (hypoxia) 8-12 h prior to delivery and reset to 21% 6-8 h after birth. The control group was kept at 21% during the procedure. Reduced (GSH) and oxidized (GSSG) glutathione and its precursors [γ-glutamyl cysteine (γ-GC) and L-cysteine (CySH)] content and expression of several redox-sensitive genes were evaluated in newborn lung and brain tissue 1 (P1) and 7 (P7) days after birth. RESULTS: As compared with control animals, the GSH/GSSG ratio was increased in the hypoxic group at P1 and P7 in the lung, and at P7 in the brain. In the hypoxic group a significant increase in the mRNA levels of NAD(P)H:quinone oxidoreductase 1 (noq1), Sulfiredoxin 1 (srnx1) and Glutathione Peroxidase 1 (gpx) was found in lung tissue at P1, as well as a significant increase in gpx in brain tissue at P7. CONCLUSIONS: Delaying the increase in tissue oxygenation to occur after birth reduces short-and-long-term oxidative stress in the lung. Similar yet more subtle effects were found in the brain. Apparently, the fetal-to-neonatal transition under hypoxic conditions appears to have protective qualities.

CaBP1, a neuronal Ca2+ sensor protein, inhibits inositol trisphosphate receptors by clamping intersubunit interactions.

Calcium-binding protein 1 (CaBP1) is a neuron-specific member of the calmodulin superfamily that regulates several Ca(2+) channels, including inositol 1,4,5-trisphosphate receptors (InsP3Rs). CaBP1 alone does not affect InsP3R activity, but it inhibits InsP3-evoked Ca(2+) release by slowing the rate of InsP3R opening. The inhibition is enhanced by Ca(2+) binding to both the InsP3R and CaBP1. CaBP1 binds via its C lobe to the cytosolic N-terminal region (NT; residues 1-604) of InsP3R1. NMR paramagnetic relaxation enhancement analysis demonstrates that a cluster of hydrophobic residues (V101, L104, and V162) within the C lobe of CaBP1 that are exposed after Ca(2+) binding interact with a complementary cluster of hydrophobic residues (L302, I364, and L393) in the ß-domain of the InsP3-binding core. These residues are essential for CaBP1 binding to the NT and for inhibition of InsP3R activity by CaBP1. Docking analyses and paramagnetic relaxation enhancement structural restraints suggest that CaBP1 forms an extended tetrameric turret attached by the tetrameric NT to the cytosolic vestibule of the InsP3R pore. InsP3 activates InsP3Rs by initiating conformational changes that lead to disruption of an intersubunit interaction between a "hot-spot" loop in the suppressor domain (residues 1-223) and the InsP3-binding core ß-domain. Targeted cross-linking of residues that contribute to this interface show that InsP3 attenuates cross-linking, whereas CaBP1 promotes it. We conclude that CaBP1 inhibits InsP3R activity by restricting the intersubunit movements that initiate gating.

Sex-dependent changes in the pulmonary vasoconstriction potential of newborn rats following short-term oxygen exposure.

BACKGROUND: Chronic exposure to supplemental oxygen (O(2)) induces lung damage and mortality in a sex-dependent manner. The effect of short-term hyperoxia on the newborn pulmonary vasculature is unknown but is, however, of clinical significance in the neonatal resuscitation context. We hypothesize that short-term hyperoxia has a sex-dependent effect on the pulmonary vasculature. METHODS: Following 1-h 100% O(2) exposure, the pulmonary arteries and lung tissues of newborn rats were evaluated. RESULTS: Superoxide dismutase 3 (SOD3) expression in female pups' lungs was increased as compared with that in the lungs of male pups. As compared with air-treated pups, the response of male pups to thromboxane was increased by O(2), whereas the opposite effect was documented in the vessels of female pups. The enhanced force of hyperoxia-exposed arteries of the male pups was suppressed with superoxide or peroxynitrite scavengers, and increased lung SOD activity and hydrogen peroxide content were seen in female, but not in male, rats. Hyperoxia induced an increase in lung tissue oxidative products and Rho-kinase (ROCK) activity in male, but not in female, pups. CONCLUSION: A lower lung SOD content and failure to upregulate SOD activity facilitates peroxynitrite generation and ROCK activation in hyperoxia-exposed males, predisposing them to pulmonary vasoconstriction. These observations, if relevant to humans, may explain the increased mortality and higher incidence of pulmonary hypertension in male neonates.

High-dose calcium reduces early-onset hyperkalemia in extremely preterm neonates.

BACKGROUND: Early-onset hyperkalemia often occurs in extremely preterm infants during a few days after birth. While there are several treatments for hyperkalemia, calcium infusion to reduce plasma potassium concentrations remains controversial. The purpose of this study is to investigate whether a high dosage of calcium reduces early-onset hyperkalemia. METHODS: Extremely low-birthweight neonates born at 22-25 weeks' gestation were enrolled. We analyzed data using multivariate regression analysis and performed a retrospective cohort study with patients divided into two groups according to the dosage of calcium in their initial infusion. RESULTS: A total of 103 patients were eligible. Early-onset hyperkalemia was observed in 27 patients. The dosage of calcium gluconate during 24 h after birth was the only independent factor affecting early-onset hyperkalemia. The maximum plasma potassium concentration during 72 h after birth was negatively correlated with the dosage of calcium. High-dose calcium reduced occurrences of hyperkalemia and hypoglycemia caused by insulin infusion given for treatment of hyperkalemia, without increasing the risk of any other complications. CONCLUSIONS: Infusion of calcium gluconate may reduce early-onset hyperkalemia in a dose-dependent manner.