The phenotypic repercussion of ZDHHC15 haploinsufficiency is not well-known. This gene was initially suggested as a candidate for X-linked mental retardation, but such an association was later questioned. We studied a multiplex family with three members with autism spectrum disorder (ASD) by array CGH, karyotype, exome sequencing and X-chromosome inactivation patterns. Medical history interviews, cognitive and physical examinations, and sensory profiling were also assessed. The three family members with ASD (with normal cognitive abilities and an abnormal sensory profile) were the only carriers of a 1.7 Mb deletion in the long arm of chromosome X, involving: ZDHHC15, MAGEE2, PBDC1, MAGEE1, MIR384 and MIR325. The normal chromosome X was preferentially inactivated in female carriers, and the whole exome sequencing of an affected family member did not reveal any additional genetic variant that could explain the phenotype. Thus, in the present family, ASD segregates with a deletion on chromosome X that includes ZDHHC15. Considering our results together with gene data (regarding function, expression, conservation and animal/cellular models), ZDHHC15 is a candidate gene for ASD. Emerging evidence also suggests that this gene could be associated with other neurodevelopmental disorders, with incomplete penetrance and variable expressivity.

GLYT1 encephalopathy is a form of glycine encephalopathy caused by disturbance of glycine transport. The phenotypic spectrum of the disease has not yet been completely described, as only four unrelated families with the disorder have been reported to date. Common features of affected patients include neonatal hypotonia, respiratory failure, encephalopathy, myoclonic jerks, dysmorphic features, and musculoeskeletal anomalies. All reported affected patients harbor biallelic genetic variants in SLC6A9. SNP array together with Sanger sequencing were performed in a newborn with arthrogryposis and severe neurological impairment. The novel genetic variant c.997delC in SLC6A9 was detected in homozygous state in the patient. At protein level, the predicted change is p.(Arg333Alafs*3), which most probably results in a loss of protein function. The variant cosegregated with the disease in the family. A subsequent pregnancy with ultrasound anomalies was also affected. The proband presented the core phenotypic features of GLYT1 encephalopathy, but also a burst suppression pattern on the electroencephalogram, a clinical feature not previously associated with the disorder. Our results suggest that the appearance of this pattern correlates with higher cerebrospinal fluid glycine levels and cerebrospinal fluid/plasma glycine ratios. A detailed discussion on the possible pathophysiological mechanisms of the disorder is also provided.

Objective: To evaluate the association between prematurity (by the gestational week [gw]) and ADHD during childhood. Method: Observational, matched cohort study using data from children born in a tertiary-level hospital (Hospital Universitari Vall d’Hebron, Catalonia, Spain) during 1995-2007 and data from the Information System for the Development of Research in Primary Health Care (SIDIAP database, Catalonia, Spain). Results: Prevalence of ADHD increases as gestational age decreases, 12.7% for those born ≤28 gw, compared to 3.2% for those born after the 37 gw. The risk of developing ADHD in the non-premature children tends to increase as the gw decreases (35-36 gw, hazard ratio [HR] = 1.70, 95% confidence interval [CI] [1.19, 2.44]; 33-34 gw, HR = 3.38, 95% CI [2.08, 5.50]; 29-32 gw, HR = 2.37, 95% CI [1.54, 3.63]; and ≤28 gw, HR = 5.57, 95% CI [2.49, 12.46]) Conclusion: Being born preterm is associated with a risk of developing ADHD, also in late preterm children (35-36 gw). Attention when taking care of these infants regarding their mental health must be made.

Recopilar la información publicada sobre estabilidad de los fármacos usados en el paciente crítico, evaluar la calidad de los datos publicados y generar una tabla de compatibilidad con información actualizada.1) Se realizó una búsqueda sistemática en las bases de datos Medline, Stabilis, Handbook on Injectable Drugs y Micromedex, para completar y actualizar la información disponible. Se incluyeron los estudios publicados entre 1990 y 2017 redactados en inglés, español y francés; 2) se analizó la calidad de los artículos según los criterios indicados en las guías de práctica para estudios de estabilidad; 3) se construyó una tabla de compatibilidades con los datos hallados para las combinaciones binarias de 44 fármacos de uso frecuente en unidades de cuidados intensivos (UCI).UCI de hospitales españoles e internacionales.La revisión sistemática incluyó 29 artículos (27 originales y 2 revisiones). Ningún estudio cumplió todos los criterios de calidad establecidos, aunque el 93% garantizaba una correcta reproducibilidad. La tabla final aporta datos de compatibilidad fisicoquímica de 475 de las 945 combinaciones posibles (50,3%), de las cuales 366 (77,1%) son compatibles y 80 (16,8%) son incompatibles.Se proporciona una actualización de las compatibilidades entre los fármacos habitualmente empleados en las UCI, con la intención de contribuir a la administración segura de medicamentos en pacientes críticos.To gather all published information about the stability of drugs commonly used in Intensive Care Units (ICU); evaluate the methodology of published data; and generate a compatibility table.i) A systematic review was conducted searching the following databases: Medline, Stabilis, Handbook of Injectable Drugs and Micromedex. Articles published from 1990 to 2017 in English, Spanish and French were included. ii) Article quality was analyzed according to the stability studies practice guidelines. iii) A compatibility table was produced with data for 44 binary combinations of drugs frequently used in the ICU.Spanish and international hospital ICU.The systematic review included 29 studies (27 originals, 2 reviews). None of the included studies followed all the methodological requirements. However, 93% guaranteed correct reproducibility. Accordingly, drug stability knowledge was available for 50.3% of the studied admixtures, in which 77.1% of the binary combinations proved compatible and 16.8% proved incompatible.This review provides new reliable evidence about the physicochemical stability of drugs commonly used in the critical care setting. The study contributes to the safe administration of intravenous drugs in critical patients with a view to avoiding adverse events in this frail population.

Intrauterine growth restriction (IUGR) and prematurity have been associated with increased perinatal morbidity and mortality and also with cardiovascular foetal programming. However, there are few studies on the impact of placenta-related IUGR on perinatal outcomes and cardiovascular biomarkers in pre-term infants.To determine differences in neonatal morbidity, mortality and cord blood biomarkers of cardiovascular dysfunction between pre-term placenta-related IUGR and non-IUGR new-borns, and to analyse their relationship with the severity of IUGR according to foetal Doppler evaluation.Prospective cohort study: pre-term infants with placenta-related IUGR and matched pre-term infants without IUGR. A Doppler scan was performed, and placenta-IUGR was classified according to severity. Comparative analysis of perinatal outcomes, neonatal morbidity and mortality, and cord blood levels of biomarkers of cardiovascular dysfunction was performed.IUGR new-borns present lower weight, length, head circumference, and Apgar score at birth, as well as increased neonatal and cardiovascular dysfunction biomarker levels, compared with pre-term new-borns without IUGR. These differences increase with the severity of IUGR determined by prenatal umbilical artery Doppler scan.Placenta-related-IUGR pre-term infants, irrespective of gestational age, present increased neonatal morbidity and mortality that is significantly proportional to the severity of IUGR. Placental impairment and severity also determine levels of cardiovascular dysfunction biomarkers at birth.

Introduction: Intrauterine growth restriction (IUGR) and prematurity have been associated with increased perinatal morbidity and mortality and also with cardiovascular foetal programming. However, there are few studies on the impact of placenta-related IUGR on perinatal outcomes and cardiovascular biomarkers in pre-term infants.Objectives: To determine differences in neonatal morbidity, mortality and cord blood biomarkers of cardiovascular dysfunction between pre-term placenta-related IUGR and non-IUGR new-borns, and to analyse their relationship with the severity of IUGR according to foetal Doppler evaluation.Material and methods: Prospective cohort study: pre-term infants with placenta-related IUGR and matched pre-term infants without IUGR. A Doppler scan was performed, and placenta-IUGR was classified according to severity. Comparative analysis of perinatal outcomes, neonatal morbidity and mortality, and cord blood levels of biomarkers of cardiovascular dysfunction was performed.Results: IUGR new-borns present lower weight, length, head circumference, and Apgar score at birth, as well as increased neonatal and cardiovascular dysfunction biomarker levels, compared with pre-term new-borns without IUGR. These differences increase with the severity of IUGR determined by prenatal umbilical artery Doppler scan.Conclusions: Placenta-related-IUGR pre-term infants, irrespective of gestational age, present increased neonatal morbidity and mortality that is significantly proportional to the severity of IUGR. Placental impairment and severity also determine levels of cardiovascular dysfunction biomarkers at birth. (C) 2015 Asociacion Espanola de Pediatria. Published by Elsevier Espana, S.L.U. All rights reserved.

La UNED en TVE-2 (Redifusion programa emitido 06/02/2016) Llamamos bebes prematuros a los ninos y ninas que nacen antes de las 37 semanas de gestacion. Se considera que son muy prematuros los menores de 32 semanas y prematuros extremos los nacidos antes de las 28 semanas de embarazo. En las ultimas decadas el enfoque de los cuidados a los bebes prematuros ha evolucionado y se ha visto transformado por nuevos puntos de vista que se centran en el desarrollo emocional y neurologico de los ninos, incorporando y revalorizando el papel de las familias. Uno de los enfoques mas revolucionarios ha sido el de la Psicologa Heidelise Als, la creadora del metodo NIDCAP, tambien llamado “Programa de Cuidados Individualizados y de Evaluacion del Desarrollo del Recien Nacido”. Una propuesta de Purificacion Sierra

A method for analyzing the influence of noise on newborns is proposed. The method consists of defining three different types of time interval (quiet, noisy and nursing) and, for each period, environmental noise levels, heart rate, mean arterial pressure and oxygen saturation is continuously measured. The statistical analysis of the influence of the equivalent noise level, rather than instantaneous noise level, on the behavior of the physiological variables is carried out. Great influence of noise is found by using this method, which is also easily translatable to other intensive care units as actual noise conditions are used in the investigation. Moreover, episodes of Bradycardia, Hypoxia and Hypertension are easily related to simultaneous direct nursing activity or a short but high enough noise event, suggesting that both sustained noisy environment and isolated peak noises lead to the alteration of the physiological variables.

Objectives: To evaluate the perinatal results of infants born between 23 and 25.6 weeks of gestation.Methods: Medical charts of all women giving birth prematurely (23-25.6 w) from January 2005 to December 2011 were retrospectively reviewed. Cases of malformed infants or deliveries elsewhere were excluded.Results: 198 infants were included. Chorioamnionitis occurred in 86 (43.4%) of the whole group: 26 (86.7%) in the 23-week; 35 (53.8%) in the 24-week and 25 (24.3%) in the 25-week groups. Foetal maturation with antenatal corticosteroids was complete in 119 cases (60.1%): 4 (13.3%) in the 23-week; 35 (53.8%) in the 24-week and 80 (77.7%) in the 25-week groups. Foetal death at birth occurred in 22 cases (11%) and 61 newborns (30.8%) died in the neonatal period. Of the 106 survivors with 2 years complete follow-up, 45 infants (42.4%) did not present sequelae; 16 infants (15.1%) had severe sequelae. A 66.6% (4) of infants born at 23 weeks of gestation did not present sequelae compared with a 32.3% (11) at 24 weeks and 45.4% (30) at 25 weeks.Conclusions: The chorioamnionitis rate was higher when gestational age was lower. The foetal maturation rate was higher when gestational age was higher. A low severe sequelae rate was observed in the whole series, particularly in the 23-week group where the rate was lower than expected; however, these results could have been influenced by the small size of the 23-week group.

To compare growth, fat mass (FM), and fat-free mass in surgical infants vs matched controls at similar postconceptional age (PCA).Anthropometric and body composition measurements by air-displacement plethysmography (PeaPod-Infant Body Composition System; LMI, Concord, California) were performed at the same PCA in 21 infants who received gastrointestinal surgery and in 21 controls matched for gestational age, birth weight, and sex.Despite similar anthropometry at birth, postsurgical infants were shorter (50.4 [4.7] cm vs 53.2 [4.1] cm, P = .001), lighter (3516 [743] g vs 3946 [874] g, P < .001), and had lower FM content (%FM 14.8 [4.7]% vs 20.2 [5.8]%, P < .0001) than their peers at similar PCA (43 [4] weeks). All surgical infants but 1 (20/21) received parenteral nutrition (PN). Mean PN duration was 40 (30) days. Five infants in the control group received PN because of prematurity for 15 (9-30) days. Nine infants in the surgical group and 1 in the control group had PN-associated cholestasis.Neonates having surgery for gastrointestinal diseases were shorter, had lower weight, and lower FM content than their peers, despite receiving more PN. Body composition evaluation and monitoring may help optimize growth in these newborns.

Objective: Intrauterine-growth restriction is associated with impaired neurodevelopment. However, studies on early childhood neurodevelopment of premature infants with placenta-related intrauterine-growth restriction (IUGR) are scarce and heterogeneous. We aimed to analyze the impact of placenta-related IUGR on preschool age neurodevelopment in preterm infants, and to ascertain which prenatal and postnatal factors influence neurodevelopment in these infants.Methods: Prospective cohorts study: 48 placenta-related IUGR premature infants and 25 matched non-IUGR premature infants (mean gestational age: 31.4 and 31.6 weeks, respectively). Preschool neurodevelopment assessment with cognitive Bayley Scales III and with ASQ-III surveys (age interval: 34.07-42.50 months). Inter-cohort result comparison. Analysis of perinatal and environmental factors associated with impaired neurodevelopment in both cohorts.Results: No statistically significant neurodevelopment differences were observed at preschool age between both preterm cohorts. Multivariate analysis of perinatal and environmental factors showed daycare, breastfeeding, higher parental educational level, and absence of severe neonatal morbidity to be associated with a lower risk of altered neurodevelopment at preschool age.Conclusions: Placenta-related IUGR does not have a significant impact on preschool neurodevelopment in our preterm patients. Instead, post-natal positive environmental factors such as parental educational level, breastfeeding, and daycare attendance make a difference towards an improvement in neurodevelopment in these infants.

Background: The implementation of the Newborn Individualized Developmental Care and Assessment Program (NIDCAP) requires a significant effort from all professionals involved.Aim: To determine the necessary requirements and barriers perceived by health professionals in the implementation of the NIDCAP.Study design: A questionnaire covering requirements and obstacles perceived in the implementation of the NIDCAP was developed and validated in two Spanish level III neonatal intensive care units. The questionnaire was answered by 305 health professionals (response rate of 85%).Results: The requirements identified in the questionnaire were considered by most respondents as necessary to implementing the NIDCAP, especially more time, education, and staff. Nurses, compared to doctors, thought that more staff was necessary (93% vs. 74%; p < .01). The main obstacle identified in the survey was lack of coordination among different professionals (77%), followed by noise level in the unit (35%). Doctors, in comparison to nurses, considered noise level (61% vs. 23%; p < .01) and nursing staff (56% vs. 29%; p = .05) the most relevant obstacles to NIDCAP implementation. The more experienced professionals perceived their own colleagues as an obstacle, particularly among nursing staff.Conclusions: The implementation of the NIDCAP requires a series of conditions that confirm it is not a trivial process but rather a somewhat laborious one. The lack of coordination among different professionals is often considered the main obstacle. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

Background: The implementation of the Newborn Individualized Developmental Care and-Assessment Program (NIDCAP) requires great effort. Few studies evaluating staff perception of NIDCAP exist, especially in Southern Europe, and these few studies usually have a low representation of the medical staff.Aims: Exploration of staff perception (neonatologists, nurses and nursing assistants) of NIDCAP during its implementation and their attitude towards it and intention to put it into practice.Study design: This study is a descriptive survey measuring staff perceptions of NIDCAP and its effects on their work in two Spanish neonatal level III intensive care units (NICUs). Validated questionnaires were distributed to neonatologists, nurses and nursing assistants of which 305 were completed (response rate: 85%).Result: Virtually all the items which assess the infant's well being and the parents' role received a positive evaluation. However, three items got slightly negative evaluations: NIDCAP was more time consuming and nurses' working conditions and lighting in the unit were less optimal than in earlier practices. The professionals also had a positive attitude and a willingness to use the NIDCAP. Neonatologists perceived NIDCAP more positively than the nursing staff with statistically significant differences.Conclusion: The neonatal unit staff in two Spanish NICUs perceived NIDCAP positively. This assessment is more positive for neonatologists than for nurses. (c) 2012 Elsevier Ireland Ltd. All rights reserved.

Aim:To evaluate the neurodevelopmental outcome at 12 months' corrected age in preterm infants with and without severe intrauterine growth restriction.Methods:This prospective follow-up study included 37 infants with severe intrauterine growth restriction and 36 appropriate-for-gestational-age infants born between 26 and 34 weeks. Neonatal and infant data were prospectively recorded. Infants were assessed at 12 +/- 2 months' corrected age with the Hammersmith Infant Neurological Examination and the Bayley Scale for Infant Development version-II.Results:Both groups were similar in demographic characteristics and perinatal status. No significant differences in neurodevelopmental performance were found. The mental development index was 98.8 (SD 9.0) vs 98.4 (SD 13.1) (p = 0.9) and the psychomotor development index was 91.7 (SD 9.9) vs 95.5 (SD 13.4) (p = 0.2) for the study and reference groups respectively. Neurological assessment showed no significant differences between the two groups.Conclusion:Although the study group showed a non-significant trend towards a lower score in the psychomotor development index than the reference group, significant differences at 12 months could not be demonstrated. IUGR infants continued to have significantly lower weight, length and head circumference at 1 year.

Aim: To evaluate the neurodevelopmental outcome at 12 months’ corrected age in preterm infants with and without severe intrauterine growth restriction. Methods: This prospective follow-up study included 37 infants with severe intrauterine growth restriction and 36 appropriate-for-gestational-age infants born between 26 and 34 weeks. Neonatal and infant data were prospectively recorded. Infants were assessed at 12 ± 2 months’ corrected age with the Hammersmith Infant Neurological Examination and the Bayley Scale for Infant Development version-II. Results: Both groups were similar in demographic characteristics and perinatal status. No significant differences in neurodevelopmental performance were found. The mental development index was 98.8 (SD 9.0) vs 98.4 (SD 13.1) (p = 0.9) and the psychomotor development index was 91.7 (SD 9.9) vs 95.5 (SD 13.4) (p = 0.2) for the study and reference groups respectively. Neurological assessment showed no significant differences between the two groups. Conclusion: Although the study group showed a non-significant trend towards a lower score in the psychomotor development index than the reference group, significant differences at 12 months could not be demonstrated. IUGR infants continued to have significantly lower weight, length and head circumference at 1 year.