ZDHHC15 as a candidate gene for autism spectrum disorder.

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: Further delineation of disease phenotype and discussion of pathophysiological mechanisms.

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.

Necessary resources and barriers perceived by professionals in the implementation of the NIDCAP.

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.

Staff perceptions on Newborn Individualized Developmental Care and Assessment Program (NIDCAP) during its implementation in two Spanish neonatal units.

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.

Twelve-month neurodevelopmental outcome in preterm infants with and without intrauterine growth restriction.

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.

Orientacions per a l'alimentació dels nadonsnascuts prematurament durant els primers mesosdesprés de l'alta / No disponible

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Prevalence of neonatal ultrasound brain lesions in premature infants with and without intrauterine growth restriction.

AIM: To compare the prevalence of transient periventricular echodensities (TPE), periventricular leukomalacia (PVL) and haemorrhagic brain lesions (HBL) in singleton intrauterine growth-restricted (IUGR) infants and in those appropriate for gestational age (AGA). METHODS: Thirty-five IUGR and 35 AGA singleton infants born between 24- and 34-week gestational age were studied. The presence of TPE, PVL and HBL was assessed with ultrasound (US) at day 3 (US-I), 2 weeks (US-II) after delivery and at term-equivalent age (US-III). RESULTS: IUGR neonates had an increased prevalence of TPE at US-I (18/35 vs. 8/35, p= 0.02) and an increased prevalence of PVL at US-II (8/32 vs. 1/31, p = 0.03) and US-III (8/29 vs. 1/29, p = 0.02). No significant differences in the prevalence of HBL were found between the two groups. CONCLUSIONS: IUGR is associated with an increased prevalence of white matter damage on US brain scans in preterm neonates.

Resultats del programa de seguiment dels nadons prematurs extrems nascuts en els límits de la viabilitat de 24 i 25 setmanes d’edat gestacional / Results of the follow-up program of extremely preterm infants born at limits of viability (24 and 25 weeks of gestational age)

Fonament. Els avenços perinatològics han suposat unincrement de la supervivència dels prematurs extrems,amb una progressiva disminució dels límits de la viabilitat.Objectiu. Conèixer els resultats del seguiment dels nadons«fetals».Mètode. Han estat avaluats tots els supervivents de 24i 25 setmanes (s) d’edat gestacional que van ser donatsd’alta des de l’1 de juny de 1998 i que tenen al menys 12mesos d’edat corregida: 45 nens (14 de 24 s i 31 de 25 s).Resultats. Desenvolupament motor: normal en el 50%de 24 s i en el 78.6% de 25 s; retard motor simple en el 33%i en el 14.2%, respectivament; paràlisi cerebral en el 16%de 24 s (2 nens, 1 diplegia, 1 tetraplegia espàstica, tots dosgreus) i en el 7.1% de 25 s (2 nens, 1 moderada, 1 greu).Desenvolupament cognitiu: normal en el 25% de 24 s ien el 64.2% de 25 s; retard lleu en el 50% i en el 28.5%; retardmoderat-greu en el 25% i en el 7.1%, respectivament.Desenvolupament sensorial: visió normal en el 41.6%de 24 s i en el 64,2% de 25 s; alteracions lleus: 41.6% i32.1%; afectació greu: 16.6% i 3.6% respectivament.Seqüeles globals: en els nascuts a les 24 s: 0% lliures deseqüeles, 58.3% lleus, 16.6% moderades, 25% seqüelesgreus; en els nascuts a les 25 s: 32,1% sense seqüeles,53.6% lleus, 7.1% moderades, 7.1% seqüeles greus.Pèrdua de seguiment: 5 nens (11%).Conclusions. En la nostra població de supervivents enels límits de la viabilitat hi ha un risc de seqüeles elevat, toti que la majoria són lleus. És imprescindible continuar ambel seguiment per avaluar les conseqüències de la prematuritatextrema a llarg termini

Background. Modern obstetric and neonatal care haveincreased the survival of the extremely preterm neonates.As the limits of viability decrease, it is of paramount importanceto have reliable data on long-term morbidity.Objectives. To study the outcome of fetal infantsMethods. All surviving children of 24 and 25 weeks ofgestational age (GA) discharged from a single hospitalsince June 1st 1998, and who were at least 12 months of corrected age, were evaluated in this retrospective study.A total of 45 infants (GA 24 weeks, 14; GA 25 weeks, 31)were included.Results. Five children were lost to follow-up. Motor Development:Normal in 50% and 78.6 of GA 24 and 25 weeksinfants, respectively; mild motor delay in 33% and14.2% of GA 24 and 25 weeks, respectively; cerebral palsyin 16% of GA 24 weeks (2 children: 1 diplegia, and 1 spastictetraplegia, both severe), and 7.1% of GA 25 weeks (2children: 1 moderate and 1 severe).Cognitive development: Normal in 25% and 64.2% ofGA 24 and 25 weeks, respectively; mild delay in 50% and28.5% of GA 24 and 25 weeks, respectively; moderate tosevere delay in 25% and 7.1% of GA 24 and 25 weeks,respectively.Visual development: Normal vision in 41.6% and64.2% of GA 24 and 25 weeks, respectively; mild deficits in41.6% and 32.1% of GA 24 and 25 weeks, respectively;severe deficits in 16.6% and 3.6% of GA 24 and 25 weeks,respectively.Global impairment: In the GA 24 weeks infants, nonewere free of disabilities, 58.3% were considered to havemild sequelae, 16.6% had moderate sequelae, and 25%had severe sequelae. In the GA 25 weeks infants, 32.1% hadno disabilities, and 53.6%, 7.1%, and 7.1% were consideredto have mild, moderate, and severe sequelae, respectively.Conclusions. Newborns at the threshold of viabilityhave a high risk of developing disabilities, although inmost cases the impairments are mild. Continued follow-upinto late childhood is needed to evaluate long-term effects of extreme prematurity

Gemelos monocoriales afectos de transfusión feto-fetal: consecuencias a corto y largo plazo / Monochorionic twins with twin-to-twin transfusion syndrome: acute and long-term effects

No disponibleFundamentos y fisiopatología básica. La transfusiónfeto-fetal es una complicación presente aproximadamenteen un 10% de las gestaciones monocoriales. Su origen fisiopatológicose sitúa en la presencia de determinadas conexionesvasculares intraplacentarias que dan lugar a undesequilibrio en el pase de sange de un gemelo al otro.Ello condiciona que uno de los dos gemelos resulte hipovolémico(donante) y el otro hipervolémico (receptor). Loscriterios diagnósticos clásicos (diferencia en el peso y en lahemoglobinemia al nacimiento) ya no son válidos, dadoque en la actualidad el diagnóstico de la transfusión fetofetales exclusivamente ecográfico prenatal.Objetivo. Actualizar la problemática neonatal y pediátrica.Las consecuencias sobre los niños se clasifican en lassiguientes categorías: hidropesía fetal, lesiones cerebrales,problemas propios del gemelo donante, problemas propiosdel feto receptor, presencia de infartos, problemas delgemelo superviviente, trastornos hormonales, prematuridad,mortalidad y neurodesarrollo a largo plazo.Método. Cada categoría es revisada exhaustivamente,mediante un repaso fisiopatológico, una descripción de laincidencia, las implicaciones sobre el manejo en las unidadesde neonatología y un análisis de las principales referenciasbibliográficas.Conclusiones. La población de gemelos afectos detranfusión feto-fetal puede presentar una patología muyvariada, a menudo de conocimiento impreciso, que condicionauna elevada mobimortalidad. La aplicación de lasdiferentes medidas terapéuticas –en especial la ablacióncon láser de las anastomosis placentarias– ha conseguidomejorar su pronóstico, aunque sigue considerándose unapoblación de alto riesgo que requiere un estricto controlobstétrico, una detallada valoración neonatal y un cuidadososeguimiento a largo plazo

Background. Twin-to-twin transfusion syndrome (TTTS)occurs in 10% of monochorionic twin pregnancies, and itresults from the presence of placental vascular anastomosesthat lead to an umbalance of the normal inter-twinblood flow. One fetus becomes hypovolemic (donor twin)whereas the other becomes hypervolemic (recipient twin).The classical diagnostic criteria of TTTS (discordance inbirthweight and hemoglobin concentrations at birth) havenow been replaced by the prenatal ultrasonographicfindings. Objectives. To provide an update on TTTS. The effectsof TTTS on both twins are classified as follows: hydropsfaetalis, brain damage, individual problems for donor andrecipient twins and for the survivor twin, infarctions, hormonaldisturbances, prematurity, early mortality, andeffects on neurodevelopment.Method. A review of the literature is performed, andthe pathophysiology, incidence, and management of TTTSare reviewed.Conclusions. Monochorionic twins with TTTS are at riskof developing multiple problems, which result in highmorbidity and mortality rates. Although better outcomesare currently obtained with prenatal techniques (such asplacental laser surgery) and better postnatal management,this is a high-risk population whose managementinvolves obstetric control and treatment, careful neonatalevaluation and treatment, and a long-term follow-up

Pregnancy and infant outcome of 80 consecutive cord coagulations in complicated monochorionic multiple pregnancies.

OBJECTIVE: This study was undertaken to document pregnancy and infant outcome after cord coagulation with laser and/or bipolar as a technique for selective feticide in complicated monochorionic multiple pregnancies. STUDY DESIGN: Prospective follow-up study in 2 tertiary fetal medicine centers. RESULTS: Eighty cases were included in the study (73 twins, 7 triplets). The survival rate was 83% (72/87). There were 9 intrauterine fetal deaths (10%), 5 within 24 hours and 4 between 4 and 10 weeks after the procedure. There was 1 termination of pregnancy because of chorioamnionitis. Median gestational age at delivery was 35.4 weeks, with 79% of patients delivering after 32 weeks. Preterm prelabor rupture of the membranes before 25 weeks accounted for all perinatal deaths (n = 5). Of the children older than 1 year of age (n = 67), 62 (92%) have a normal development. CONCLUSION: Cord coagulation is an effective method for selective feticide in monochorionic multiple pregnancies.