16q24.1 microdeletion in a premature newborn: Usefulness of array-based comparative genomic hybridization in persistent pulmonary hypertension of the newborn.

OBJECTIVE:: Report of a 16q24.1 deletion in a premature newborn, demonstrating the usefulness of array-based comparative genomic hybridization in persistent pulmonary hypertension of the newborn and multiple congenital malformations. DESIGN:: Descriptive case report. SETTING:: Genetic department and neonatal intensive care unit of a tertiary care children's hospital. INTERVENTIONS:: None. PATIENT:: We report the case of a preterm male infant, born at 26 wks of gestation. A cardiac malformation and bilateral hydronephrosis were diagnosed at 19 wks of gestation. Karyotype analysis was normal, and a 22q11.2 microdeletion was excluded by fluorescence in situ hybridization analysis. A cesarean section was performed due to fetal distress. The patient developed persistent pulmonary hypertension unresponsive to mechanical ventilation and nitric oxide treatment and expired at 16 hrs of life. MEASUREMENTS AND MAIN RESULTS:: An autopsy revealed partial atrioventricular canal malformation and showed bilateral dilation of the renal pelvocaliceal system with bilateral ureteral stenosis and annular pancreas. Array-based comparative genomic hybridization analysis (Agilent oligoNT 44K, Agilent Technologies, Santa Clara, CA) showed an interstitial microdeletion encompassing the forkhead box gene cluster in 16q24.1. Review of the pulmonary microscopic examination showed the characteristic features of alveolar capillary dysplasia with misalignment of pulmonary veins. Some features were less prominent due to the gestational age. CONCLUSIONS:: Our review of the literature shows that alveolar capillary dysplasia with misalignment of pulmonary veins is rare but probably underreported. Prematurity is not a usual presentation, and histologic features are difficult to interpret. In our case, array-based comparative genomic hybridization revealed a 16q24.1 deletion, leading to the final diagnosis of alveolar capillary dysplasia with misalignment of pulmonary veins. It emphasizes the usefulness of array-based comparative genomic hybridization analysis as a diagnostic tool with implications for both prognosis and management decisions in newborns with refractory persistent pulmonary hypertension and multiple congenital malformations.

Treatment of genital mycoplasma in colonized pregnant women in late pregnancy is associated with a lower rate of premature labour and neonatal complications.

Mycoplasma hominis and Ureaplasma spp. may colonize the human genital tract and have been associated with adverse pregnancy outcomes such as preterm labour and preterm premature rupture of membranes. However, as these bacteria can reside in the normal vaginal flora, there are controversies regarding their true role during pregnancy and so the need to treat these organisms. We therefore conducted a retrospective analysis to evaluate the treatment of genital mycoplasma in 5377 pregnant patients showing symptoms of potential obstetric complications at 25-37 weeks of gestation. Women presenting with symptoms were routinely screened by culture for the presence of these bacteria and treated with clindamycin when positive. Compared with uninfected untreated patients, women treated for genital mycoplasma demonstrated lower rates of premature labour. Indeed preterm birth rates were, respectively, 40.9% and 37.7% in women colonized with Ureaplasma spp. and M. hominis, compared with 44.1% in uncolonized women (Ureaplasma spp., p 0.024; M. hominis, p 0.001). Moreover, a reduction of neonatal complications rates was observed, with 10.9% of newborns developing respiratory diseases in case of Ureaplasma spp. colonization and 5.9% in the presence of M. hominis, compared with 12.8% in the absence of those bacteria (Ureaplasma spp., p 0.050; M. hominis, p <0.001). Microbiological screening of Ureaplasma spp. and/or M. hominis and pre-emptive antibiotic therapy of symptomatic pregnant women in late pregnancy might represent a beneficial strategy to reduce premature labour and neonatal complications.

Reduction in the use of diagnostic tests in infants with risk factors for early-onset neonatal sepsis does not delay antibiotic treatment.

Despite a low positive predictive value, diagnostic tests such as complete blood count (CBC) and C-reactive protein (CRP) are commonly used to evaluate whether infants with risk factors for early-onset neonatal sepsis (EOS) should be treated with antibiotics. We investigated the impact of implementing a protocol aiming at reducing the number of diagnostic tests in infants with risk factors for EOS in order to compare the diagnostic performance of repeated clinical examination with CBC and CRP measurement. The primary outcome was the time between birth and the first dose of antibiotics in infants treated for suspected EOS. Among the 11,503 infants born at ≥35 weeks during the study period, 222 were treated with antibiotics for suspected EOS. The proportion of infants receiving antibiotics for suspected EOS was 2.1% and 1.7% before and after the change of protocol (p = 0.09). Reduction of diagnostic tests was associated with earlier antibiotic treatment in infants treated for suspected EOS (hazard ratio 1.58; 95% confidence interval [CI] 1.20-2.07; p <0.001), and in infants with neonatal infection (hazard ratio 2.20; 95% CI 1.19-4.06; p = 0.01). There was no difference in the duration of hospital stay nor in the proportion of infants requiring respiratory or cardiovascular support before and after the change of protocol. Reduction of diagnostic tests such as CBC and CRP does not delay initiation of antibiotic treatment in infants with suspected EOS. The importance of clinical examination in infants with risk factors for EOS should be emphasised.

Population pharmacokinetic study to evaluate dosing strategies of imipenem in neonates and infants

Objective: Imipenem is a broad spectrum antibiotic used to treat severe infections in critically ill patients. Imipenem pharmacokinetics (PK) was evaluated in a cohort of neonates treated in the Neonatal Intensive Care Unit of the Lausanne University Hospital. The objective of our study was to identify key demographic and clinical factors influencing imipenem exposure in this population. Method: PK data from neonates and infants with at least one imipenem concentration measured between 2002 and 2013 were analyzed applying population PK modeling methods. Measurement of plasma concentrations were performed upon the decision of the physician within the frame of a therapeutic drug monitoring (TDM) programme. Effects of demographic (sex, body weight, gestational age, postnatal age) and clinical factors (serum creatinine as a measure of kidney function; co-administration of furosemide, spironolactone, hydrochlorothiazide, vancomycin, metronidazole and erythromycin) on imipenem PK were explored. Model-based simulations were performed (with a median creatinine value of 46 μmol/l) to compare various dosing regimens with respect to their ability to maintain drug levels above predefined minimum inhibitory concentrations (MIC) for at least 40 % of the dosing interval. Results: A total of 144 plasma samples was collected in 68 neonates and infants, predominantly preterm newborns, with median gestational age of 27 weeks (24 - 41 weeks) and postnatal age of 21 days (2 - 153 days). A two-compartment model best characterized imipenem disposition. Actual body weight exhibited the greatest impact on PK parameters, followed by age (gestational age and postnatal age) and serum creatinine on clearance. They explain 19%, 9%, 14% and 9% of the interindividual variability in clearance respectively. Model-based simulations suggested that 15 mg/kg every 12 hours maintain drug concentrations over a MIC of 2 mg/l for at least 40% of the dosing interval during the first days of life, whereas neonates older than 14 days of life required a dose of 20 mg/kg every 12 hours. Conclusion: Dosing strategies based on body weight and post-natal age are recommended for imipenem in all critically ill neonates and infants. Most current guidelines seem adequate for newborns and TDM should be restricted to some particular clinical situations.

Early detection and intervention for infants at risk of autism spectrum disorders

Autism is a developmental disorder that is characterized by abnonnal social interactions and communications as well as repetitive and restricted activities and interests. There is evidence of a genetic component, as 5% of younger siblings are diagnosed if their older sibling has been diagnosed. Autism is generally not diagnosed until age 3 at the earliest, yet it has been shown that early intervention for children with autism can greatly increase their functioning. Because of this, it is important that symptoms of autism are identified as early as possible so that diagnosis can occur as soon as possible to allow these children the earliest intervention. This thesis was divided into two parts. The first looked at the psychometrics of two proposed measures, the Parent Observation Checklist (POC), administered monthly, and the Infant Behavior Summary Evaluation (mSE), administered bimonthly, to see if they can be used with the infant population to identify autistic symptoms in infants who are at high risk for autism or related problems because they have an older sibling with autism. Study 1 reported acceptable psychometric properties of both the POC and IBSE in terms of test-retest reliability, internal consistency, construct validity and predictive validity. These results provide preliminary evidence that parent report measures can help to detect early symptoms of ASD in infants. The POC was shown to differentiate infants who were diagnosed from a matched group that was not diagnosed by 3 years of age. The second part of this thesis involved a telephone interview of parents who reported developmental and/or behavior problems in their high-risk infants that may be early signs of Autism Spectrum Disorder (ASD). During the interview, a service questionnaire was administered to see what interventions (including strategies recommended by the researchers) their at risk infants and affected older siblings were receiving, how satisfied the parents were with them and how effective they felt the interventions were. 3 Study 2 also yielded promising results. Parents utilized a variety of services for at risk infants and children with ASD. The interventions included empirically validated early intervention (e.g., ABA) to non-empirically validated treatments (e.g., diet therapy). The large number of nonempirically validated treatments parents used was surprising, yet parents reported being involved and satisfied, and thought that the services were effective. Parents' perceptions of their stress levels went down slightly and feelings of competence rose when they accessed services for their infants. Overall, the results of this thesis provide new evidence that parent-report methods hold promise as early detection instruments for ASD in at-risk infants. More research is needed to further validate these instruments as well as to understand the variables related to the parents' choice of early intervention for their at risk and affected children.

Using the Reliable Change Index Statistic to Analyze Developmental Changes in Infants at Risk for Autism Spectrum Disorder

Longitudinal studies of the development of autism spectrum disorders (ASD) provide an understanding of which variables may be important predictors of an ASD. The objective of the current study is to apply the reliable change index (RCI) statistic to examine whether the Parent Observation of Early Markers Scale (POEMS) is sensitive to developmental change, and whether these changes can be quantified along a child’s developmental trajectory. Ninety-six children with older siblings with autism were followed from 1-36 months of age. Group-based RCI analysis confirms that the POEMS is capable of detecting significant changes within pre-defined diagnostic groups. Within-subject analysis suggests that ongoing monitoring of a child at-risk for an ASD requires interpretation of both significant intervals identified by the RCI statistic, as well as the presence of repeated high (i.e., >70) scores. This study provides preliminary evidence for a reasonably sensitive and specific means by which individual change can be clinically monitored via parent report.

Comparison of the Behavioural Development of Infants at Low and High-Risk for Autism Spectrum Disorders

By identifying early signs of Autism Spectrum Disorder, early intervention or parent training could be implemented and assist in increasing the developmental trajectory for these infants. This cross sectional study used the Parent Observation of Early Markers Scale (POEMS) to identify early signs of ASD in 69 high-risk (older sibling diagnosed with ASD) and 69 matched low-risk infants' families (no family history of ASD) between 6 and 36 months of age. The preliminary results showed the high-risk children had significantly more elevated POEMS items than the low-risk children at 12, 18,24,30 and 36 months of age. The results suggest that at-risk infants may show signs of ASD as early as 12 months of age, and that the POEMS could be used to guide early intervention or parent training for children 12 months or older.

Parent Prediction of Autism Spectrum Disorder in Infants At Risk: A Follow-up Study

Later-born siblings of children with autism spectrum disorder (ASD) are considered at biological risk for ASD and the broader autism phenotype. Early screening may detect early signs of ASD and facilitate intervention as soon as possible. This follow-up study revisits and re-examines a second-degree autism screener for children at biological risk of autism, the Parent Observation Early Markers Scale (POEMS, Feldman et al., 2012). Using available follow-up information, 110 children (the original 108 infants plus 2 infants recruited after the completion of the original study) were divided into three groups: diagnosed group (n = 13), lost diagnosis group (n = 5), and undiagnosed group (n = 92). The POEMS continued to show acceptable predictive validity. The POEMS total scores and mean number of elevated items were significantly higher in the diagnosed group than the undiagnosed group. The lost diagnosis group did not differ from the undiagnosed group on POEMS total scores and elevated items at any age, but the lost diagnosis group had significantly lower total scores and number of elevated items than the diagnosed group starting at 18 months. Both ASD core and subsidiary behaviours differentiated the diagnosed and undiagnosed groups from 9−36 months of age. Using 70 as a cut-off score, sensitivity, specificity, and positive predictive value (PPV) were .69, .84, and .38, respectively. The study provides further evidence that the POEMS may serve as a low-cost early screener for ASD in at risk children and pinpoint specific developmental and behavioural problems that may be amenable to very early intervention.

Use of anti-infective drugs during pregnancy : prevalence, predictors of use and the risk of preterm birth and small-for-gestational-age newborns

Résumé: Les anti-infectieux sont parmi les médicaments les plus utilisés pendant la grossesse. Les indications pour l’utilisation de ces médicaments, telles que les infections bactériennes, figurent parmi les facteurs de risque les plus importants pour la prématurité et les enfants nés petits pour l'âge gestationnel («Small-for-gestational-age », SGA). Ces complications de la grossesse peuvent avoir des incidences sur la santé du nouveau né et sur son développement futur. Compte tenu des impacts sur la santé de la mère et de l’enfant, la prise en charge et le traitement efficace de ces infections sont impératifs. Cependant, l'utilisation des anti-infectieux, pour éviter des issues de grossesse défavorables, fait l’objet d’une controverse dans la littérature. Cette controverse est en partie liée à la qualité méthodologique discutable des études disponibles sur le sujet. Les quatre études présentées dans cette thèse ont donc pour objectif d’investiguer l’utilisation des anti-infectieux durant la grossesse ainsi que d’évaluer le risque de prématurité et de SGA après utilisation de ces médicaments en période gestationnelle. Une révision systématique de la littérature sur l’utilisation du métronidazole durant la grossesse est également présentée. Nous avons utilisé, comme source de données le Registre des Grossesses du Québec, une cohorte longitudinale conçue à partir du jumelage de trois bases de données administratives de la province du Québec (RAMQ, Med-Echo et ISQ). Le registre fournit des informations sur les prescriptions, les services pharmaceutiques et médicaux, ainsi que des donnés sur les soins d’hospitalisation de courte durée et démographiques. Les deux premières études présentées dans cette thèse ont eu pour objectif d’évaluer la prévalence, les tendances, les indications et les prédicteurs de l’utilisation des anti-infectieux dans une cohorte, extraite du registre, de 97 680 femmes enceintes. A l’aide d’un devis cas-témoins, les 2 dernières études ont mesuré l’association entre l’utilisation d’anti-infectieux durant les 2 derniers trimestres de grossesse et le risque de prématurité et de SGA, respectivement. Un cas de prématurité a été défini comme un accouchement survenu avant 37 semaines de gestation. Un cas de SGA a été défini comme l’accouchement d’un enfant dont le poids à la naissance se situe sous le 10ème percentile du poids normalisé à la naissance (compte tenu de l’âge gestationnel et du sexe du bébé). Les données ont été recueillies pour les agents systémiques oraux, ainsi que pour les classes et les agents individuels. Nos résultats ont montré que la prévalence de l’utilisation des anti-infectieux durant la grossesse était comparable à celle d’autres études déjà publiées (25%). Nous avons observé une augmentation de l’utilisation des agents plus anciens et ayant des profils d’innocuité connus. Les prédicteurs de l’usage en début de grossesse identifiés sont : avoir eu plus de deux différentes prescriptions (OR ajusté = 3,83, IC 95% : 3,3-4,3), avoir eu un diagnostic d’infection urinaire (OR= 1,50, IC 95% : 1,3-1,8) et un diagnostic d’infection respiratoire (OR= 1,40, IC 95% : 1,2-1,6). L’utilisation des macrolides a été associée à une diminution du risque de prématurité (OR =0,65, IC 95% : 0,50-0,85). En revanche, les femmes ayant été exposées au métronidazole ont vu leur risque augmenté de 80% (OR=1,81, IC 95% : 1,30-2,54). L’utilisation d’azithromycine a été associée à une diminution importante du risque chez les femmes ayant un diagnostic de rupture prématurée des membranes (OR=0,31, IC 95% : 0,10-0,93). Cependant, l'utilisation de sulfaméthoxazole-triméthoprime (SXT) a été significativement associée à une augmentation du risque de SGA (OR= 1,61, IC 95% : 1,16-2,23), tandis que celle des anti-infectieux urinaires a été associée à une diminution du risque (OR= 0,80, 95%CI : 0.65-0.97). Les conclusions de nos travaux suggèrent que l’utilisation des macrolides et des pénicillines diminuent le risque de prématurité et de SGA. Nous devons considérer l'utilisation de différents choix thérapeutiques tels que l’azithromycine, lors de la prise en charge des infections pouvant induire la prématurité et le SGA.

Intervention éducationnelle de massage auprès de parents de nouveau-nés prématurés dans le but de favoriser leur sensibilité parentale

Rapport de stage présenté à la Faculté des sciences infirmières en vue de l'obtention du grade de Maître ès sciences (M.Sc.) en sciences infirmières option expertise-conseil en soins infirmiers

Socio-affective development in infants with Down' s Syndrome. 'Desarrollo socio-afectivo en ni??os con s??ndrome de Down'

El libro es el resultado de la compilaci??n de las colaboraciones de expertos internacionales reunidos en un Simposio Internacional sobre Psicolog??a y Psicobiolog??a Educativa e Integraci??n Social de las personas con S??ndrome de Down, organizado por Juan Perera (Asociaci??n S??ndrome de Down de Baleares. Universidad de las Islas Baleares) y Jean A. Rondal (Laboratorio de Psicoling????stica de la Universidad de Lieja, B??lgica), bajo los auspicios del Gobierno Balear y otras instituciones y organismos. La colaboraci??n de los autores murcianos (Candel, Carranza y P??rez L??pez) versa sobre el desarrollo socio-afectivo de los ni??os afectados por el S??ndrome y presenta los resultados de una investigaci??n longitudinal sobre el temperamento de los ni??os con s??ndrome Down. Los objetivos de la investigaci??n son: el estudio de los componentes temperamentales en el desarrollo de los ni??os con S??ndrome Down. La evaluaci??n del grado de estabilidad/inestabilidad de las diferencias temperamentales en los ni??os con S??ndrome Down y an lisis del grado de homogeneidad de los componentes temperamentales de estos ni??os como grupo y las diferencias con un grupo de control de ni??os no retrasados. Los resultados confirman la existencia de diferencias individuales en el temperamento de los ni??os con S??ndrome Down.

Espai creatiu. Conte per a infants. El saquet de l'àvia

Conte per a infants guanyador del concurs literari organitzat a la Facultat per celebrar la Diada de St. Jordi 2005 amb el lema "Sentir paraules"

Psychometric properties of the d2 selective attention test in a sample of premature and born-at-term babies. 'Caracter??sticas psicom??tricas del test de atenci??n selectiva d2 en ni??os prematuros y nacidos a termino''

Resumen tomado de la publicaci??n. Resumen tambi??n en ingl??s

L'adaptació dels infants i les seves famílies a les escoletes de Menorca. 'La adaptación de los niños y sus familias en las guarderías de Menorca'.

Resumen tomado de la publicación