Search

The aim of this study was to determine the population pharmacokinetics of darbepoetin alfa in hypothermic neonates with hypoxic-ischemic encephalopathy treated with hypothermia. Neonates ≥36 weeks gestation and

To assess the effect of massage on weight gain and body fat deposition in preterm infants.Preterm infants (29-32 weeks) were randomized to the massage group (n = 22, 12 girls, 10 boys) or the control group (n = 22, 12 girls, 10 boys). Treatment was masked with massage or control care administered twice-daily by licensed massage therapists (6 d/wk for 4 weeks). Body weight, length, Ponderal Index (PI), body circumferences, and skinfold thickness (triceps, mid-thigh, and subscapular [SSF]) were measured. Circulating insulin-like growth factor I, leptin, and adiponectin levels were determined by enzyme-linked immunosorbent assay. Daily dietary intake was collected.Energy and protein intake as well as increase in weight, length, and body circumferences were similar. Male infants in the massage group had smaller PI, triceps skinfold thickness, mid-thigh skinfold thickness, and SSF and increases over time compared with control male infants (P .05). Female infants in the massage group had larger SSF increases than control female infants (P .05). Circulating adiponectin increased over time in control group male infants (group × time × sex interaction, P .01) and was correlated to PI (r = 0.39, P .01).Twice-daily massage did not promote greater weight gain in preterm infants. Massage did, however, limit body fat deposition in male preterm infants. Massage decreased circulating adiponectin over time in male infants with higher adiponectin concentrations associated with increased body fat. These findings suggest that massage may improve body fat deposition and, in turn, growth quality of preterm infants in a sex-specific manner.

Preterm delivery (

Despite therapeutic hypothermia, neonates with encephalopathy (NE) have high rates of death or disability. Darbepoetin alfa (Darbe) has comparable biological activity to erythropoietin, but has extended circulating half-life (t(1/2)). Our aim was to determine Darbe safety and pharmacokinetics as adjunctive therapy to hypothermia.Thirty infants (n = 10/arm) ≥36 wk gestation undergoing therapeutic hypothermia for NE were randomized to receive placebo, Darbe low dose (2 μg/kg), or high dose (10 μg/kg) given intravenously within 12 h of birth (first dose/hypothermia condition) and at 7 d (second dose/normothermia condition). Adverse events were documented for 1 mo. Serum samples were obtained to characterize Darbe pharmacokinetics.Adverse events (hypotension, altered liver and renal function, seizures, and death) were similar to placebo and historical controls. Following the first Darbe dose at 2 and 10 μg/kg, t(1/2) was 24 and 32 h, and the area under the curve (AUC(inf)) was 26,555 and 180,886 h*mU/ml*, respectively. In addition, clearance was not significantly different between the doses (0.05 and 0.04 l/h). At 7 d, t(1/2) was 26 and 35 h, and AUC(inf) was 10,790 and 56,233 h*mU/ml*, respectively (*P0.01).Darbe combined with hypothermia has similar safety profile to placebo with pharmacokinetics sufficient for weekly administration.

Premature birth is associated with increased adipose deposition after birth. Standard anthropometry (body weight, length, and head circumference) may not adequately assess fat deposition. Validated methods to assess adiposity are needed to optimize growth quality in preterm infants. The purpose of this study was to identify covariates of infant body fat. Air displacement plethysmography (ADP), standard anthropometry, and body circumferences were measured at hospital discharge in preterm (n = 28; 31–35 wk postmenstrual age (PMA)) and term (n = 28; 38–41 wks PMA) infants. Body weight, length, and head circumference were lower for preterm infants (P < 0.05) at hospital discharge compared with that of term infants. Despite smaller body size and younger PMA, preterm infant percent body fat (%BF) by ADP was 12.33 ± 4.15% vs. 9.64 ± 4.01% in term infants (P = 0.01). Mid-arm circumference (MAC) is a covariate of %BF in both preterm and term infants (adjusted R2 = 0.49; P < 0.001). In preterm infants alone, MAC accounted for 60.4% of the variability of percent body fat (%BF) by ADP (P < 0.01). Preterm infants have increased body fat deposition as they approach term-corrected age, and MAC is a reliable, low-cost measure for monitoring infant body fat deposition in preterm and term infants.

OBJECTIVES Previous studies in adults suggest that various types of physiologic stress appear to decrease phagocytic cell function. Adherence and chemotaxis of, and phagocytosis and bacterial killing by, neonatal neutrophils are altered compared with adult neutrophil function. Stresses encountered by the fetus and neonate, such as asphyxia, were hypothesized to further alter neonatal neutrophil function. To investigate the impact of asphyxia on systemic immunity, we developed a rat model of acute asphyxia and evaluated the effect of asphyxia on neutrophil number and function. DESIGN Prospective, laboratory study. SETTING Research laboratory. SUBJECTS Adult female Wistar rats. INTERVENTIONS Exposure to CO2 and cold stress. MEASUREMENTS AND MAIN RESULTS Arterial blood gas, blood glucose, neutrophil number, neutrophil-mediated, complement-dependent bacterial phagocytosis and killing were determined. After a 20-sec exposure to CO2 and cold stress (dry ice vapors), adult rats developed acute respiratory acidosis (pH 6.89 +/- 0.26, PaCO2 220 +/- 183 torr [29.3 +/- 24.3 kPa]), and mild hypoxia (60 +/- 20 torr [8.0 +/- 2.7 kPa]) followed by significant metabolic acidosis (base deficit = -12.0 +/- 1.5). Neutrophil number slowly increased and reached statistical significance by 72 hrs (5.0 +/- 1.5 x 10(3)/mm3) compared to controls (2.9 +/- 1.6 x 10(3)/mm3) (p = .03). Phagocytosis and killing of group B streptococci by neutrophils isolated immediately after asphyxia were significantly impaired (p = .03), and this decrease in function lasted for 24 hrs after asphyxia (p = .04), as measured by two different in vitro complement and antibody-mediated functional assays. CONCLUSIONS After brief exposure to CO2 and cold stress, rats developed an acute respiratory acidosis and subsequent metabolic acidosis similar to acute asphyxia. Neutrophil number did not increase until 72 hrs after asphyxia. However, neutrophil-mediated phagocytosis and killing of bacteria were immediately impaired. We speculate that asphyxia may increase the risk for sepsis secondary to altered neutrophil function.

SJL mice were injected intraperitoneally with adipocyte plasma membranes or with intrinsic membrane proteins obtained by extraction of plasma membranes with dimethylmaleic anhydride. Three days after the boost injection, the spleens were removed and fused with NS-1, a thioguanine-resistant myeloma cell line derived from P3X63 Ag8 (Balb/c). Following selection for hybrids with hypoxanthine, aminopterin, and thymidine, medium of the hybrid cells was tested for its ability to bind to the plasma membrane of the adipocyte and to stimulate the oxidation of D-(1-14C) glucose to 14CO2. Approximately 40% of the wells containing hybridomas derived from splenocytes of SJL mice immunized with plasma membranes produced immunoglobulin that bound to adipocyte plasma membranes. About 30% of these mimicked the ability of insulin to stimulate the oxidation of D-(1-14C) glucose to 14CO2 in adipocytes. Media from 51% of the wells containing hybridomas derived from splenocytes of SJL mice immunized with intrinsic membrane proteins produced immunoglobulin that bound to the plasma membrane and 48% of those stimulated glucose oxidation. The bioactivity of the hybrid cell media could be blocked by adsorption with intrinsic membrane proteins or by the removal of immunoglobulins using formalin-fixed Staphylococcus aureus. The hybrids generated in this study can be divided into three categories: (1) hybrids that secrete antibodies that can bind to plasma membranes and mimic insulin action of glucose transport; (2) hybrids that secrete antibodies that bind to plasma membranes but do not stimulate the oxidation of D-(1-14C) glucose to 14CO2; and (3) hybrids that produce no antimembrane antibodies. The data suggest that interaction of immunoglobulins with specific membrane proteins is essential in mimicking the action of insulin on glucose transport and oxidation in the rat adipocyte.