Jean-François Tolsa

Early neurological impairment and severe anemia in a newborn with Pearson syndrome

BackgroundPearson marrow-pancreas syndrome (PS) is usually a fatal mitochondrial disease, mostly diagnosed during infancy or postmortem. PS is caused by the deletions or duplications of mitochondrial DNA (mtDNA). The tissue distribution and relative proportions of expressed abnormal mtDNA determine the phenotype and the clinical course.Materials and methodsWe describe the case of a term baby boy who was diagnosed with PS early in the neonatal period due to severe aregenerative anemia and persistent lactic acidosis.ResultsHis neurological examination was abnormal since birth. Brain magnetic resonance imaging (MRI) at term was abnormal, indicating that mitochondrial encephalopathy in PS can be already manifested in the neonatal period. To our knowledge, neonatal encephalopathy in PS has not been previously described.ConclusionPS is a rare condition diagnosed in the newborn. It should be suspected in the presence of severe anemia and persistent lactic acidosis, and may manifest with early encephalopathy.

Gentamicin Exposure and Sensorineural Hearing Loss in Preterm Infants

Objective To evaluate the impact of gentamicin exposure on sensorineural hearing loss (SNHL) in very low birth weight (VLBW) infants. Methods Exposure to gentamicin was determined in infants born between 1993 and 2010 at a gestational age < 32 weeks and/or with a birthweight < 1500 g, who presented with SNHL during the first 5 years of life. For each case, we selected two controls matched for gender, gestational age, birthweight, and year of birth. Results We identified 25 infants affected by SNHL, leading to an incidence of SNHL of 1.58% in our population of VLBW infants. The proportion of infants treated with gentamicin was 76% in the study group and 70% in controls (p = 0.78). The total cumulated dose of gentamicin administered did not differ between the study group (median 10.2 mg/kg, Q1-Q3 1.6–13.2) and the control group (median 7.9 mg/kg, Q1-Q3 0–12.8, p = 0.47). The median duration of gentamicin treatment was 3 days both in the study group and the control group (p = 0.58). Maximum predicted trough serum levels of gentamicin, cumulative area under the curve and gentamicin clearance were not different between cases and controls. Conclusion The impact of gentamicin on SNHL can be minimized with treatments of short duration, monitoring of blood levels and dose adjustment.

Being Small for Gestational Age: Does it Matter for the Neurodevelopment of Premature Infants? A Cohort Study

Background Whether being small for gestational age (SGA) increases the risk of adverse neurodevelopmental outcome in premature infants remains controversial. Objective to study the impact of SGA (birthweight < percentile 10) on cognition, behavior, neurodevelopmental impairment and use of therapy at 5 years old. Methods This population-based prospective cohort included infants born before 32 weeks of gestation. Cognition was evaluated with the K-ABC, and behavior with the Strengths and Difficulties Questionnaire (SDQ). Primary outcomes were cognitive and behavioral scores, as well as neurodevelopmental impairment (cognitive score < 2SD, hearing loss, blindness, or cerebral palsy). The need of therapy, an indirect indicator of neurodevelopmental impairment, was a secondary outcome. Linear and logistic regression models were used to analyze the association of SGA with neurodevelopment. Results 342/515 (76%) premature infants were assessed. SGA was significantly associated with hyperactivity scores of the SDQ (coefficient 0.81, p < 0.04), but not with cognitive scores, neurodevelopmental impairment or the need of therapy. Gestational age, socio-economic status, and major brain lesions were associated with cognitive outcome in the univariate and multivariate model, whereas asphyxia, sepsis and bronchopulmonary dysplasia were associated in the univariate model only. Severe impairment was associated with fetal tobacco exposition, asphyxia, gestational age and major brain lesions. Different neonatal factors were associated with the use of single or multiple therapies: children with one therapy were more likely to have suffered birth asphyxia or necrotizing enterocolitis, whereas the need for several therapies was predicted by major brain lesions. Discussion In this large cohort of premature infants, assessed at 5 years old with a complete panel of tests, SGA was associated with hyperactive behavior, but not with cognition, neurodevelopmental impairment or use of therapy. Birthweight <10th percentile alone does not appear to be an independent risk factor of neurodevelopmental adverse outcome in preterm children.

Adverse obstetrical and neonatal outcomes in elective and medically indicated inductions of labor at term

Abstract Objective: To compare the adverse neonatal and maternal outcomes after medically indicated and elective labor induction. Both induction groups were also compared to women with spontaneous onset of labor. Method: Retrospective cohort study of 13 971 women with live, cephalic singleton pregnancies who delivered at term (from 1997 to 2007). Adverse maternal and neonatal outcomes were compared between women who underwent an induction of labor in the presence and absence of standard medical indications. Results: Among 5090 patients with induced labor, 2059 (40.5%) underwent elective labor inductions, defined as inductions without any medical or obstetrical indication. Risks of cesarean or instrumental delivery, postpartum hemorrhage >500 ml, prolonged maternal hospitalization >6 days, Apgar<7 at 5 min of life, arterial umbilical cord pH<7.1, admission in neonatal intensive care unit (NICU) and prolonged NICU hospitalization >7 days were similar between nulliparous who underwent elective and medical labor induction. Similar results were obtained for multiparous. All the above mentioned risks, but the Apgar<7 at 5 min of life, were significantly increased after induction in comparison to spontaneous labor. Conclusion: Elective induction of labor carries similar obstetrical and neonatal risks as a medically indicated labor induction. Thus, elective induction of labor should be strongly discouraged.

Comparison of Griffiths-II and Bayley-II tests for the developmental assessment of high-risk infants.

INTRODUCTION Two important risk factors for abnormal neurodevelopment are preterm birth and neonatal hypoxic ischemic encephalopathy. The new revisions of Griffiths Mental Development Scale (Griffiths-II, [1996]) and the Bayley Scales of Infant Development (BSID-II, [1993]) are two of the most frequently used developmental diagnostics tests. The Griffiths-II is divided into five subscales and a global development quotient (QD), and the BSID-II is divided into two scales, the Mental scale (MDI) and the Psychomotor scale (PDI). The main objective of this research was to establish the extent to which developmental diagnoses obtained using the new revisions of these two tests are comparable for a given child. MATERIAL AND METHODS Retrospective study of 18-months-old high-risk children examined with both tests in the follow-up Unit of the Clinic of Neonatology of our tertiary care university Hospital between 2011 and 2012. To determine the concurrent validity of the two tests paired t-tests and Pearson product-moment correlation coefficients were computed. Using the BSID-II as a gold standard, the performance of the Griffiths-II was analyzed with receiver operating curves. RESULTS 61 patients (80.3% preterm, 14.7% neonatal asphyxia) were examined. For the BSID-II the MDI mean was 96.21 (range 67-133) and the PDI mean was 87.72 (range 49-114). For the Griffiths-II, the QD mean was 96.95 (range 60-124), the locomotors subscale mean was 92.57 (range 49-119). The score of the Griffiths locomotors subscale was significantly higher than the PDI (p<0.001). Between the Griffiths-II QD and the BSID-II MDI no significant difference was found, and the area under the curve was 0.93, showing good validity. All correlations were high and significant with a Pearson product-moment correlation coefficient >0.8. CONCLUSIONS The meaning of the results for a given child was the same for the two tests. Two scores were interchangeable, the Griffiths-II QD and the BSID-II MDI.

Impact of Early Nutritional Intake on Preterm Brain: A Magnetic Resonance Imaging Study

Objectives To investigate the association between early nutritional intake and brain development assessed by magnetic resonance imaging (MRI). Study design A cohort of neonates born at ≤30 weeks gestational age underwent MRI at term equivalent age. Brain maturation and injury were assessed using the Kidokoro score. Two groups were defined by severity of the scores. The associations between macronutrients intake during the first 2 weeks of life, clinical factors, and imaging scores were analyzed using logistic regression. Results MRI scores from group 1 patients (n = 27) were normal to mildly abnormal (0‐5). Group 2 (n = 15) had more abnormal scores (6‐12). The median gestational ages (IQR) were 27.4 (1.9) weeks in group 1 and 27.0 (2.9) weeks in group 2, with birth weights of 900 (318) g (group 1) and 844 (293) g (group 2). In group 2, energy, lipid, and carbohydrate intake were significantly lower than in group 1. Group 2 also showed higher rates of sepsis and clinical risk scores than group 1. After adjustments in bivariate models, higher energy and lipid intake remained significantly associated with improved scores on MRI. This association was stronger for the gray matter component of the score. Conclusions Higher energy and lipid intake during the first 2 weeks after birth was associated with a lower incidence of brain lesions and dysmaturation at term equivalent age in preterm neonates.

Stability of prostaglandin E1 solutions stored in polypropylene syringes for continuous intravenous administration to newborns

Objective We aimed to monitor the physicochemical stability of prostaglandin E1 (PGE1) 1.5 and 15 µg/mL in 10% dextrose stored in polypropylene syringes. Methods We developed a liquid chromatography-high resolution mass spectrometry (LC-HRMS) method to detect and quantify levels of PGE1. Method selectivity was performed with a mixture of PGE1 and its degradation products. Forced degradation tests were performed to determine which degradation products were most likely to form. PGE1 injection solutions in 10% dextrose were stored in unprotected and shielded-from-light polypropylene syringes in a climatic chamber. Samples were taken immediately after preparation (T0) and after 24, 48, 72 and 168 hours for analysis. PGE1 solutions were considered stable if ≥90.0% of the initial concentration was retained. Results The LC-HRMS method was validated in the range of 0.086-0.200µg/mL PGE1 with trueness values between 98.2% and 100.3%, and repeatability and intermediate precision values of <2.2%and <4.7%, respectively. The quantification and detection limits of the method were 0.086 and 0.026µg/mL, respectively. PGE1 and its degradation products were resolved chromatographically. PGE1 injection solutions were≥90.0%stable after 48hours in unprotected from light (UPL) syringes. The solutions remained clear without precipitation, colour or pH modification and subvisible particles within the permitted levels. Prostaglandin A1 was the sole degradation product observed. Conclusions A LC-HRMS method to evaluate PGE1 stability in a 10% dextrose was developed and validated. PGE1 1.5 and 15µg/mL in 10% dextrose solution are stable for 48hours when stored at 30ºC in UPL polypropylene syringes.

PS-069 Introducing a preformatted medical order sheet and a taught course to decrease prescription errors in newborns

Background Prescription errors are common in neonatal intensive care units (NICU). Computerised physician order entry (CPOE) is one of the most effective interventions to decrease these errors but its implementation is expensive and time consuming. Completion of CPOE in our NICU is planned for 2015. Meanwhile, alternative options are necessary in order to improve the quality of prescriptions and to decrease medicines errors. Purpose To assess whether a preformatted medical order sheet and a taught course had an effect on the quality of prescriptions and the frequency of errors during the prescription stage. Materials and methods A two-phase observational study, pre- (Phase 0) and post-intervention (Phase I), over 4 consecutive months, was conducted in an 11-bed NICU. Interventions included: introduction of a new preformatted medical order sheet (enhancement in completeness of prescriptions); a taught course on appropriate prescription and medicines errors. Errors were identified every morning during the prescription process (medical round), using National Coordinating Council for Medication Error Reporting and Prevention taxonomy. Error rates between pre- and post-intervention phases were compared with a χ2 test. Results 83 patients were included in Phase 0 and 81 in Phase I. 505 prescriptions were analysed in Phase 0 and 523 in Phase I. The rate of prescription errors decreased from 26.9% (Phase 0) to 15.3% (Phase I) (p < 0.05). Dose errors decreased from 11.7% to 4.6%, unit errors from 1.6 % to 0.4%, frequency errors from 3.4% to 1.3% and ambiguous prescriptions from 8.1% to 3.8%. Complete prescriptions increased from 0.2% to 33.3%. Conclusions We demonstrated that a cheap and simple method to implement interventions can also improve completeness and intelligibility of prescriptions and decrease medicines errors. No conflict of interest.