[Contribution of ultrasound pulmonary ratio in pre-viable premature ruptures of membranes]. / Apport des ratio pulmonaires échographiques dans les ruptures prématurées précoces des membranes.

OBJECTIVE: To evaluate the ultrasound measurement of the observed-to-expected (o/e) lung-to-head ratio (LHR) and the Quantitative Lung Index (QLI) for the prediction of pulmonary hypoplasia in the pre-viable preterm premature ruptures of membranes (PPROM) before 24 weeks gestational age (GA). METHODS: Thirty-four patients with a PPROM before 24 weeks GA and who delivered a live birth between October 2008 and October 2015 at Croix-Rousse's hospital were included. The measurements of both the LHR (right, left and total) and the QLI (right, left) were retrospectively performed by ultrasounds during the latency period. The observed LHR was divided by the expected LHR, which was obtained from recent literature data. The primary outcome was the onset of a lethal pulmonary hypoplasia. Receiver operating characteristics (ROC) curves assessed the predictive value of these ultrasound measurements for pulmonary hypoplasia. RESULTS: The areas under the ROC curves (AUCs) for the right o/eLHR, the right QLI and the total o/e LHR measured by manually drawing the pulmonary area on the last ultrasound before the delivery, were respectively 0.87 [95% CI: 0.75-1], 0.83 [95% CI: 0.69-0.98] and 0.78 [95% CI: 0.51-1]. Only the total o/e LHR measurements remained associated with lethal pulmonary hypoplasia after adjusting for prematurity and persistent oligohydramnios. CONCLUSION: The right and total o/eLHR and the right QLI measurements might be helpful in predicting pulmonary hypoplasia in pre-viable PPROM.

Rapid quantitative procalcitonin measurement to diagnose nosocomial infections in newborn infants.

BACKGROUND AND OBJECTIVE: Serum procalcitonin (PCT) monitoring may help clinicians to manage nosocomial infections in neonates. This study investigated the diagnostic value of a new, rapid method to measure PCT and sought to determine the best cut-off value. METHODS: This monocentric, prospective study included all newborn infants with clinical suspicion of infection in a neonatal intensive care unit. Rapid, automated PCT measurements were performed on blood samples obtained for C-reactive protein (CRP) measurement. Negative and positive predictive values, sensitivity and specificity were calculated. Logistic regression analysis determined the best cut-off value to obtain a negative predictive value of PCT that was at least 15% above that of CRP. RESULTS: Between June 2005 and May 2006, 73 newborn infants with a median (Q25-Q75) gestational age of 28 (26-30) weeks and a birth weight of 995 (720-1350) g were included. Thirty (41%) were infected. The best PCT cut-off value was 0.6 ng/ml, which provided a negative predictive value of 100%. The sensitivity, specificity and positive predictive value were 100%, 65%, and 67%, respectively, for PCT at the 0.6 ng/ml cut-off value. CONCLUSION: Rapid measurement of PCT could help to rule out nosocomial infection in newborn infants hospitalised in intensive care units.

Is neonatal neurological damage in the delivery room avoidable? Experience of 33 levels I and II maternity units of a French perinatal network.

OBJECTIVE: To determine the frequency of avoidable neonatal neurological damage. STUDY DESIGN: We carried out a retrospective study from January 1st to December 31st 2003, including all children transferred from a level I or II maternity unit for suspected neurological damage (SND). Only cases confirmed by a persistent abnormality on clinical examination, EEG, transfontanelle ultrasound scan, CT scan or cerebral MRI were retained. Each case was studied in detail by an expert committee and classified as "avoidable", "unavoidable" or "of indeterminate avoidability." The management of "avoidable" cases was analysed to identify potentially avoidable factors (PAFs): not taking into account a major risk factor (PAF1), diagnostic errors (PAF2), suboptimal decision to delivery interval (PAF3) and mechanical complications (PAF4). RESULTS: In total, 77 children were transferred for SND; two cases were excluded (inaccessible medical files). Forty of the 75 cases of SND included were confirmed: 29 were "avoidable", 8 were "unavoidable" and 3 were "of indeterminate avoidability". Analysis of the 29 avoidable cases identified 39 PAFs: 18 PAF1, 5 PAF2, 10 PAF3 and 6 PAF4. Five had no classifiable PAF (0 death), 11 children had one type of PAF (one death), 11 children had two types of PAF (3 deaths), 2 had three types of PAF (2 deaths). CONCLUSION: Three quarters of the confirmed cases of neurological damage occurring in levels I and II maternity units of the Aurore network in 2003 were avoidable. Five out of six cases resulting in early death involved several potentially avoidable factors.

Population pharmacokinetics of amikacin at birth and interindividual variability in renal maturation.

OBJECTIVE: Pharmacokinetic (PK) interindividual variability in amikacin has been shown to be wide in neonates. This study evaluated the evolution of this variability with gestational age (GA) at birth in relation to renal maturation. METHODS: Population PK values of amikacin were studied in 131 newborns (postnatal age 1 day, GA 24-41 weeks) divided into 16 groups, defined by GA, from 24 to 41 weeks (with a mean of 8.2 infants per group). PK variables were Kel/Vol, Ks/Vs, Cl/Vol. Cls/ where: Kel = Kslope x GA + Kintercept, Cl = Clslope x GA + Clintercept, and Vol = Vs x body weight. Ki and Cli were held as constants. The nonparametric distribution of the probability density function (PDF) was obtained, as were mean, median, and SD values of each PK variable for each GA group. RESULTS: Amikacin elimination increased linearly with GA, showing that GA is a good covariate of renal elimination. Amikacin volume of distribution increased with body weight up to a GA of about 38 weeks and then decreased for highest GA values. However, the PDF for the individual GA groups showed a multimodal PK distribution. Kel, Vol, Vs, Cl, and Cl, standard deviations increased linearly with GA, showing differential renal maturation. The higher the GA, the more interindividual PK variability increased. CONCLUSIONS: These results show that amikacin elimination and the volume of distribution are dependent upon GA, and that differential renal maturation in neonates is responsible for the wider PK interindividual variability with high GA. Dosage regimens of amikacin and other aminoglycosides should be revised in newborns with high GA. Bayesian adaptive control of therapeutics might be particularly indicated to obtain efficacy for each neonate as early as the first dose.

Once-a-day individualized amikacin dosing for suspected infection at birth based on population pharmacokinetic models.

Amikacin is widely used in the treatment of suspected or confirmed neonatal infections. However, dosage regimens are not well defined in this group of patients because of a wide inter-individual pharmacokinetic variability. An individualized goal-oriented amikacin dosage design was applied using population pharmacokinetic data. A dosing chart was developed for neonates during the first 2 days of life, by using population pharmacokinetic parameter values and USCPACK software. This dosing chart based on gestational age (GA) and body weight gives a once-a-day amikacin dosage regimen involving an injection every 24 h. Validation was performed in 57 neonates less than 2 days old, divided into three GA groups and prospectively treated using the dosing chart. Target peak serum levels of amikacin were obtained in 62-80% of patients after the first dose and in 80-100% after the second dose, and trough concentrations were obtained in 100%. This study has confirmed the need for individualization of amikacin dosage regimens in neonates.

Procalcitonin and C-reactive protein levels in neonatal infections.

In order to assess the potential fo procalcitonin measurement in the management of neonatal sepsis, daily variations in serum procalcitonin (measured by an immunoluminometric assay) were evaluated in 94 control and infected newborn infants in comparison to C-reactive protein (measured by an immunonephelometric method). High levels of procalcitonin correlated with bacterial invasion and showed no discrepancies with C-reactive protein. procalcitonin increased (up to 400 micrograms l-1 and returned to the normal range (< 0.1 microgram l-1) more quickly than C-reactive protein, suggesting that procalcitonin may be an early marker of favourable outcome. Another finding is a significant procalcitonin peak on the first day of life in the control group, independent of any infectious stimulus. In conclusion, procalcitonin seems to be an interesting marker of neonatal sepsis but additional investigations are needed to understand better its mechanism of synthesis in order to determine its clinical usefulness.