Early insulin therapy offers little clinical benefit in very-low-birth-weight infants. It reduces hyperglycemia but may increase hypoglycemia (Current Controlled Trials number, ISRCTN78428828.)

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Background: A patent ductus arteriosus (PDA) is common among preterms, and prophylactic medical treatment has been advocated as the first-line approach. Conservative treatment may result in similar outcome, but without exposure to the harmful side effects of medication. A retrospective analysis revealed a ductal closure rate of 94% after conservative treatment with adjustment of ventilation (lowering the inspiratory time and increasing positive end expiratory pressure) and fluid restriction. Objective: To study prospectively over one year the rate of PDA closure, and morbidity and mortality following conservative treatment. Method: Prospective study (1 January 2005 -31 December 2005) including 30 newborns (30 weeks' gestation, all of whom were being ventilated and required surfactant. Echocardiography was performed 48-72 h after birth. Clinically important PDA was conservatively treated as described above. The percentage of children with PDA, ductal ligation and major complications was determined. Results: Ten neonates (33%) developed a clinical important PDA. Following conservative treatment the duct closed in all neonates (100%), and none required ductal ligation or medical treatment. The rates of major complications were no higher than those reported by the Vermont Oxford Network and in the literature. Conclusion: The managed care plan resulted in an overall ductal closure rate of 100%. These results suggest that conservative treatment of PDA is a worthy alternative to prophylactic medical treatment.

Aminoglycosides and glycopeptides are almost exclusively eliminated by renal excretion. Postmenstrual age (PMA) is the best predictor of their clearance, presumably because it predicts the time course of development of the glomerular filtration rate (GFR). Intrauterine growth restriction has an impact on the normalized weight of the kidney, on the number of nephrons, on GFR, and on tubular function in human perinatal life. We investigated whether prenatal growth also affects clearance of drugs such as aminoglycosides or glycopeptides that are eliminated through the kidney. Observations collected in two population pharmacokinetic studies involving preterm neonates and investigating amikacin and vancomycin in the first month of postnatal life were used to estimate the impact of prenatal growth (as judged by birth weight for gestational age) on the clearance of these drugs. Data from 1212 drug measurements (vancomycin, 648; amikacin, 564) in 531 subjects (vancomycin, 249; amikacin, 282) were available for study. Neonates born small for gestational age (SGA) were found to have a 16.2% (coefficient of variation, 12.2%) reduction in drug clearance. This effect was present from birth up to the postnatal age of 4 weeks. The covariate size (weight 0.75) explained 47.3% of drug clearance; PMA, 25.2%; coadministration of a nonselective cyclo-oxygenase inhibitor, 3.5%; renal function, 7.6%; and SGA, 1.7%. Renal drug clearance is significantly lower in preterm neonates born SGA than in appropriate-for-gestational-age (AGA) controls. This reduced clearance was observed not only at birth but also up to the postnatal age of 4 weeks.

SummaryObjectives: We suggested a loading dose (20 mgÁkg À1 ) followed by 10 mgÁkg À1 q6h of intravenous (IV) paracetamol to achieve an effect compartment concentration of 11 mgÁl À1 in neonates. Since there are no pharmacodynamic data to support such an effect compartment concentration, pain scores collected in neonates treated with an IV paracetamol loading dose (20 mgÁkg À1

ABSTRACT:In preterms, low serum levels of IGF (IGF-I) correlate with retinopathy of prematurity (ROP). In mice, IGF-I is a prerequisite for normal retinal development. We further explored the link between IGF-I and oxygen-induced retinopathy (OIR). To assess the role of endogenous IGF-I, pups were redistributed into smaller versus larger litters at birth; in one subgroup, we measured body weight and circulating IGF-I; in another, we applied hyperoxia and assessed retinal neovascularization (NV). To screen for the potential role of exogenous IGF-I, we administered a single bolus of rhIGF-I on postnatal day (P) 4 to pups in normal litters, and applied hyperoxia; body weight and IGF-I were measured; maturation and NV were assessed. Neonatal mice in larger litters had a lower body weight than mice in smaller litters; they had lower levels of circulating IGF-I, and developed more OIR (p ϭ 0.002). Mice who had received rhIGF-I, weighed more and had higher endogenous IGF-I levels; they matured faster and developed less OIR (p ϭ 0.00001). These findings in mice are the first to support the notion that higher availability of endogenous or exogenous IGF-I reduces OIR risk, and thus sharpen the perspective that ROP may be preventable by briefly up-regulating IGF-I after birth. (Pediatr Res 65: 307-310, 2009) R etinopathy of prematurity (ROP) is a blinding disease initiated by delayed retinal vessel growth and regression of existing vessels after premature birth (1,2). Major risk factors are low gestational age and oxygen; despite more controlled oxygen use, there is no decrease in the overall prevalence of ROP, possibly due to increased survival of very low birth weight infants (2,3).In humans, ROP risk has been linked to low circulating levels of IGF I (IGF-I) (4,5) and slow postnatal weight gain (6,7). In mice, IGF-I is a prerequisite for normal development of retinal vessels (8 -10). These findings have led to the concept that up-regulation of IGF-I shortly after birth may contribute to prevent ROP (11,12). In mice, we further explored the link between circulating IGF-I and oxygeninduced retinopathy (OIR). MATERIALS AND METHODSHyperoxia. The murine OIR model of Smith was applied (13). In brief, 7-d-old C57BL/6J WT mice with their dams were exposed to 75% oxygen for 5 d; on postnatal day (P), 12 the mice were returned to room air. Pups were nursed by their dams; food (standard mouse chow) and water were given ad libitum. Pups were killed on P17 after 5 d of room air recovery, when retinal neovascularization (NV) is known to peak.Endogenous IGF-I. Circulating IGF-I levels were measured in prenatal and neonatal mice from normal litters (median 7 pups per litter) from embryonic day (E) 17.5 till P14.Smaller versus larger litter. As depicted in Figure 1 (panel A), pups from concomitantly born litters were on P1 redistributed among dams, so that there were smaller litters (median, 6 pups; range 4 -9) and larger litters (median, 15 pups; range, 14 -16). On P7-12, the OIR model was applied. Body weight and circulating IGF-I wer...

Unintended PG administration (34 mg/kg/24 h) for a maximum of 48 h seems to be tolerated in (pre)term neonates and does not affect short-term postnatal adaptations. Further studies on PG disposition and the level of safe exposure to PG, including long-term safety data in neonates are needed.

Compared with phase I isoenzymes, data on isoenzyme-specific phenotypic activity of uridine diphosphate glucuronosyltransferase (UGT) and its covariates in neonates are limited. In vivo observations on morphine, paracetamol (acetaminophen), and propofol disposition throughout childhood confirm the overall low-glucuronidation activity in neonates observed in in vitro studies. In addition to the phenotypic low-glucuronidation activity, in vivo observations of bilirubin (UGT1A1), morphine (UGT2B7), paracetamol (UGT1A6), and propofol (UGT1A9) glucuronidation in neonates display extensive interindividual variability, only in part explained by postmenstrual and postnatal age. Covariates like disease state characteristics (decreased morphine metabolism during therapeutic head cooling), genetic polymorphisms (UGT1A1 genetic variants and differences in bilirubin metabolism), or environmental factors (increased urinary excretion of paracetamol-glucuronide by repeated administration of paracetamol) further contribute to this variability. A focused approach to unveil covariates of the interindividual range is needed to improve our knowledge on drug disposition in early life.