Antenatal steroids and neonatal outcome after chorioamnionitis: a meta-analysis.

BACKGROUND: There is debate concerning the safety and efficacy of antenatal steroids in preterm labour with suspected intrauterine infection (chorioamnionitis). OBJECTIVES: We performed a systematic literature review and meta-analysis aimed at evaluating the efficacy and safety of antenatal steroids in clinical and histological chorioamnionitis. SEARCH STRATEGY: MEDLINE, EMBASE, BioMed Central and the Cochrane databases were searched using the terms 'chorioamnionitis OR intrauterine infection' and '*steroids OR *corticoids'. SELECTION CRITERIA: Studies that reported selected neonatal outcome measures in preterm infants with clinical or histological chorio-amnionitis, according to antenatal steroid exposure, were eligible. DATA COLLECTION AND ANALYSIS: Study selection, data extraction and data analysis were performed by two independent investigators. The meta-analysis techniques used included: Mantel-Haenszel analysis; an assessment of study heterogeneity using the Q statistic; and Egger's regression test and funnel plots, to assess publication bias. MAIN RESULTS: Seven observational studies were included. In histological chorioamnionitis (five studies), antenatal steroids were associated with reduced mortality (OR = 0.45; 95% CI = 0.30-0.68; P = 0.0001), respiratory distress syndrome (OR = 0.53; 95% CI = 0.40-0.71; P < 0.0001), patent ductus arteriosus (OR = 0.56; 95% CI = 0.37-0.85; P = 0.007), intraventricular haemorrhage (IVH; OR = 0.35; 95% CI = 0.18-0.66; P = 0.001) and severe IVH (OR = 0.39; 95% CI = 0.19-0.82; P = 0.01). In clinical chorioamnionitis (four studies), antenatal steroids were associated with reduced severe IVH (OR = 0.29; 95% CI = 0.10-0.89; P = 0.03) and periventricular leucomalacia (OR = 0.35; 95% CI = 0.14-0.85; P = 0.02). CONCLUSIONS: Antenatal steroids may be safe and reduce adverse neonatal outcome after preterm birth associated with chorioamnionitis. There is a need for randomised clinical trials to address this issue.

Effect of perfluorochemical liquid ventilation on cardiac output and blood pressure variability in neonatal piglets with respiratory insufficiency.

Respiration and mechanical ventilation induce cyclic variation in cardiac output and blood pressure. We examined these phasic hemodynamic influences of mechanical ventilation during gas ventilation and partial and tidal liquid ventilation in 7 anesthetized and paralyzed young piglets (body weight, 3.0-4.9 kg) made respiratory-insufficient by repeated saline lung lavage. Nonlinear regression analysis of cardiovascular parameters vs. time was done to quantify respiratory-induced fluctuations in hemodynamic variables. The amplitude of oscillations was expressed as a percentage of the mean hemodynamic variable during the study period, and was called the relative oscillation amplitude. The relative oscillation amplitude of left ventricular stroke volume, left ventricular output, systemic arterial pressure, and systemic perfusion pressure was significantly larger (at least twofold) during tidal liquid ventilation compared to partial liquid ventilation. No such differences were observed between gas and partial liquid ventilation at comparable gas ventilator settings. We conclude that in this animal model, within-breath modulation of left ventricular output, systemic blood pressure, and perfusion pressure was significantly increased during tidal liquid ventilation as compared to partial liquid ventilation.

Perfluorochemical liquid ventilation: from the animal laboratory to the intensive care unit.

Perfluorochemical or perfluorocarbon liquids have an enormous gas-carrying capacity. During tidal liquid ventilation the respiratory medium of both functional residual capacity and tidal volume is replaced by neat perfluorocarbon liquid. Tidal liquid ventilation is characterized by convective and diffusive limitations, but offers the advantage of preserved functional residual capacity, high compliance and improved ventilation-perfusion matching. During partial liquid ventilation only the functional residual capacity is replaced by perfluorocarbon liquid. Both tidal and partial liquid ventilation improve gas exchange and lung mechanics in hyaline membrane disease, adult respiratory distress models and meconium aspiration. Compared to gas ventilation, there is less histologic evidence of barotrauma after liquid ventilation. Cardio-pulmonary interaction, inherent to the high density of liquid, and long term safety need further study. However, extrapolating from animal data, and taking into account promising human pilot studies, liquid ventilation has the desired properties to occupy an important place in the therapy of restrictive lung disease in man.

A feedback controller for the maintenance of FRC during tidal liquid ventilation: theory, implementation, and testing.

The necessity of controlling functional residual capacity (FRC) during tidal liquid ventilation has been recognized since the first description of this respiratory support technique by Kylstra et al in 1962. We developed a microcomputer feedback system that adjusts the inspired tidal volume (VT,I) of a liquid ventilator based on the end-expiratory quasi-static alveolar pressure (PA,EE), in order to maintain a stable FRC. The system consists of three subunits: (1) a tracheal pressure catheter to estimate breath by breath FRC changes, derived from PA,EE changes, and (2) a roller pump interfaced with (3) a personal computer in which a closed-loop control is implemented. The regulator sets the actual PA,EE against the corresponding desired value. Any discrepancy is offset by changes in VT,I and the required change in pump velocity is communicated to the roller pump. The size of any change in pump velocity is determined to both the observed and target or desired PA,EE (i.e., the error) and the (calibration) pressure-volume curve. To evaluate the efficacy of the controller, a set of laboratory bench tests were conducted under steady state and transient conditions. Closed-loop control was effective in keeping FRC and PA,EE near the desired level, with an acceptable oscillatory behaviour. The feedback controller successfully compensated for transient disturbances of PFC liquid balance. The steady state stability was confirmed during a five hour period of liquid ventilation in five preterm lambs.

Conventional gas ventilation, liquid-assisted high-frequency oscillatory ventilation, and tidal liquid ventilation in surfactant-treated preterm lambs.

This study was designed to compare the efficacy and potential protective or injurious effects of tidal liquid ventilation (TLV), liquid-assisted high-frequency oscillatory ventilation (LA-HFOV), and high PEEP conventional mechanical ventilation (CMV) in neonatal respiratory distress syndrome. Preterm lambs (124-126 days gestation), prophylactically treated with natural surfactant, were allocated to one of the treatment modalities or to an untreated fetal control group (F), euthanised after tracheal ligation. LA-HFOV animals received an intratracheal loading dose of 5 mL x kg(-1) followed by a continuous intrapulmonary instillation of 12 mL x kg(-1);h(-1) FC-75 perfluorocarbon liquid. The ventilation strategies aimed at keeping clinically appropriate arterial blood gases for a study period of 5 hours. A histological lung injury score was calculated and semiquantitative morphometry was performed on lung tissue fixed by vascular perfusion. The alveolar-arterial pressure difference for O2 was significantly lower throughout the study in TLV compared to CMV lambs; at 1, 2, and 5 hours, oxygenation was better in TLV when compared to LA-HFOV. Total lung injury scores in TLV lambs were significantly lower than in either CMV or LA-HFOV animals, but higher when compared to F. CMV and LA-HFOV induced an excess of collapsed and overdistended alveoli, whereas in TLV alveolar expansion was normally distributed around predominantly normal alveoli. CMV and LA-HFOV, but not TLV, were associated with an excess of dilated airways. Thus, in the ovine neonatal RDS model, TLV compared favourably to either gas ventilation strategy by its more uniform ventilation, reduced lung injury, and improved gas exchange.

Amoxicillin pharmacokinetics in (preterm) infants aged 10 to 52 days: effect of postnatal age.

The pharmacokinetic parameters of amoxicillin were determined in 32 newborn infants aged 10 to 52 days (mean postnatal age, 24.7 +/- 12.4 days) to improve amoxicillin dosing in this age group. Amoxicillin plasma concentrations were determined using reversed-phase high-performance liquid chromatography in surplus plasma samples from routine gentamicin assays. Amoxicillin pharmacokinetic parameters (mean +/- SD) were as follows: first-order elimination constant (K(el)) = 0.27 +/- 0.10 h(-1), volume of distribution corrected for body weight (V/W) = 0.66 +/- 0.27 L/kg, total body clearance corrected for body weight (CL/W) = 0.18 +/- 0.10 Lkg(-1)h(-1), and elimination half-life (t(1/2)) = 3.0 +/- 1.3 hours. Amoxicillin body clearance was approximately twofold greater in our patients compared with published values in younger neonates (mean postnatal age, 0.76 +/- 1.57 days). Simulation studies using the observed amoxicillin pharmacokinetic data suggest an amoxicillin dose of 40 mg/kg administered every 8 hours in infants older than 9 days postnatal age, independent of gestational age and postconceptional age, to achieve satisfactory target plasma amoxicillin concentrations less than 140 mg/L and time above minimum inhibitory concentration of at least 40%. Prospective evaluation of this suggested new dosage regimen is necessary before implementation in the care of ill neonates.

Neuroradiological findings in Jadassohn nevus phakomatosis: a report of four cases.

Four patients with Jadassohn nevus phakomatosis (linear nevus sebaceus syndrome, Schimmelpenning-Feuerstein syndrome) are described. Neuroradiological findings consisted of skull asymmetry shown by X-rays and hemimegalencephaly with ventricular system asymmetry on CT. Three of the patients showed, in addition, a widened insula. In two patients areas of increased density suggesting calcium deposits were seen. Skull asymmetry was progressive during infancy in two of the patients. It is presumed that these findings are secondary to the progression of the underlying central nervous system disorder.

The effects of a somatostatin analogue on the metabolism of an infant with Beckwith-Wiedemann syndrome and hyperinsulinaemic hypoglycaemia.

Hypoglycaemia is a frequent finding during the neonatal period and may be due to insulin overproduction. Patients with Beckwith-Wiedemann syndrome have reduced numbers of somatostatin-producing cells and decreased extractable somatostatin. In this study the effect of long-acting somatostatin (SMS201-995) on the glucose and insulin levels in an infant with Beckwith-Wiedemann syndrome and hyperinsulinaemic non-ketotic hypoglycaemia is described. SMS201-995 lowered basal insulin levels while maintaining normal glucose and insulin homeostasis. During fasting however, both glucose levels declined rapidly whereas insulin levels did not. The absence of both ketosis and elevated levels of free fatty acids and lactate during hypoglycaemia, as observed in our patient, are important diagnostic clues since the insulin levels themselves may sometimes be only slightly elevated.

Fasting gastric fluid and fecal polyamine concentrations in premature infants.

BACKGROUND: The role of milk polyamines in the development of the gastrointestinal tract of human infants is presently unknown. Polyamine concentrations are higher in human milk than in infant formulas. The aim of the present study was to gather data on luminal polyamines by measuring gastric fluid and fecal polyamine concentrations in premature infants during the postnatal period. We further compared gastric fluid polyamine concentrations with those reported for milk and looked for possible relationships between luminal polyamine concentrations, age, and growth rate. METHODS: High-performance liquid chromatography was used for the measurement of polyamine concentrations in both fecal and gastric fluid samples. RESULTS: Ninetieth centiles for gastric polyamines during the first week were 62, 28, 82, and 14 microM for putrescine, spermidine, spermine, and cadaverine, respectively. These values are higher than those reported for human milk and infant formulas. Polyamine concentrations were unrelated to either age or growth rate. Ninetieth centiles for fecal polyamines during the first week were 7668, 5176, 53, and 75 microM for cadaverine, putrescine, spermidine, and spermine, respectively. CONCLUSIONS: Fasting gastric fluid polyamine concentrations in premature infants are higher than those reported for either human milk or infant formulas. The high fecal cadaverine and putrescine concentrations are probably of bacterial origin.

High-frequency oscillatory ventilation, partial liquid ventilation, or conventional mechanical ventilation in newborn piglets with saline lavage-induced acute lung injury. A comparison of gas-exchange efficacy and lung histomorphology.

It has been reported that, in diseased lungs, either partial liquid ventilation (PLV) or high-frequency oscillatory ventilation (HFOV) can improve oxygenation better and with less lung injury than conventional mechanical ventilation (CMV). This study was intended as a preclinical comparison between the effects of HFOV, PLV and CMV on gas exchange, lung mechanics and histology. Fifteen anesthetized newborn piglets, with respiratory insufficiency due to repeated saline lung lavage, were allocated to either a PLV, HFOV or CMV (n = 5 each) strategy, and treated for 4 h. Within 30 min of commencing therapy, PLV, HFOV, and CMV improved arterial PO2 (Pa,O2), alveoloarterial oxygen gradient (P(A-a),O2), oxygenation index (OI), venous admixture (va), and arterial PCO2 (Pa,CO2). After 4 h, oxygenation parameters (Pa,O2, P(A-a),O2, OI and venous admixture) were significantly better in the HFOV group than in the PLV group; the CMV group showed a higher Pa,O2 and lower OI than the PLV group. Gas exchange at the end of the experiment was not different from baseline in the HFOV and CMV groups. Lung histology and morphometry were performed after perfusion-fixation at endotracheal deflation pressure corresponding to mean airway pressure at the end of the experiment. Lung injury score and mean linear intercept were not different between the three treatment groups. We conclude that in this model, gas exchange improved significantly in all three ventilation strategies. Indices of oxygenation improved less during PLV. The saline lavage-induced acute lung injury model used as in this study, is less stable than previously thought. The final lung injury is not influenced by the ventilation strategy. We speculate that the impaired gas exchange during PLV is an expression of diffusion limitation and ventilation-perfusion mismatch in a recovering lung.

Use of teicoplanin in preterm neonates with staphylococcal late-onset neonatal sepsis.

OBJECTIVE: To study the clinical pharmacology of teicoplanin in babies admitted to a newborn intensive care unit, by monitoring serum levels, efficacy and potential side effects. METHODS: An open, nonrandomized descriptive study was performed in the neonatal intensive and high care unit of the University Hospital Maastricht, The Netherlands. Twenty-three preterm neonates, gestational age ranging from 26 to 32 weeks (median 28.4 weeks), postnatal age from 5 to 47 days, and birth weight from 570 to 1,740 g, presenting with (suspected) late onset septicemia, were studied. Of 21 culture-proven septicemias, 20 were caused by staphylococci. The teicoplanin loading dose was 15 mg/kg i.v., followed by a maintenance dose of 8 mg/kg every 24 h. Intravenous gentamicin was also administered pending blood culture. Serum teicoplanin concentrations were measured by fluorescence polarization immunoassay. Clinical and microbiological cure/failure rates were determined and possible side effects were monitored. RESULTS: The study of individual pharmacokinetics during multiple-dose intravenous infusions was rendered impossible by apparently inaccurate dosing. Peak (30 min after end of the infusion) and trough teicoplanin levels were stable throughout the study and averaged 27.8 (interquartile range 23.7-32.9) and 12.3 (interquartile range 9.1-16.8) mg/l, respectively. The microbiological and clinical cure rates were 90% in gram-positive septicemia. There was no apparent toxicity. CONCLUSIONS: Inaccurate drug administration was a problem in this study, making a multidose pharmacokinetic study impossible. It is possible that inaccurate drug administration and not current dosage guidelines yielded trough levels below 10 mg/l in 57 (32%) of 176 instances. This pharmaceutical aspect clearly warrants further study. However, microbiological and clinical cure rates were high in gram-positive septicemias. No side effects attributable to teicoplanin therapy were encountered.

Population pharmacokinetics and relationship between demographic and clinical variables and pharmacokinetics of gentamicin in neonates.

Population pharmacokinetic parameter estimates were calculated from 725 routine plasma gentamicin concentrations obtained in 177 neonates of 24 to 42 weeks' gestational age in their first week of life. Kel increases and V/W decreases with increasing gestational age. Almost identical results were obtained with iterative two-stage Bayesian fitting (MW\PHARM 3.30) as with a non-parametric maximization algorithm (NPEM2). The effect of various covariates on drug disposition was investigated retrospectively using multiple regression analysis. Predictive power for Kel increases with rising gestational age. For neonates 28.5 weeks and 30.9 weeks (r2 = 0.482), with gestational age, postnatal age, and Apgar score at 5 minutes being predictors. A very strong correlation existed between volume of distribution and weight (r2 = 0.83). Volume as a function of weight could be described with low predictivity by gestational age and to a lesser degree by Apgar score at 5 minutes (r2 = 0.298). The developed models need appropriate prospective clinical validation.