An agenda for 21st century neurodevelopmental medicine: lessons from autism. / Una agenda para la medicina del neurodesarrollo en el siglo XXI: lecciones aportadas por el autismo.

The future of neurodevelopmental medicine has the potential of situating child neurology at the forefront of a broad-based public health effort to optimize neurodevelopmental outcomes of children born with high-prevalence and diverse genetic, pre- and peri-natal, and environmental burdens compromising early brain development and leading to lifetime disabilities. Building on advancements in developmental social neuroscience and in implementation science, this shift is already occurring in the case of emblematic neurodevelopmental disorders such as autism. Capitalizing on early neuroplasticity and on quantification of trajectories of social-communicative development, new technologies are emerging for high-throughput and cost-effective diagnosis and for community-viable delivery of powerful treatments, in seamless integration across previously fragmented systems of healthcare delivery. These solutions could be deployed in the case of other groups of children at greater risk for autism and communication delays, such as those born extremely premature or with congenital heart disease. The galvanizing concept in this aspirational future is a public health focus on promoting optimal conditions for early brain development, not unlike current campaigns promoting pre-natal care, nutrition or vaccination.

TITLE: Una agenda para la medicina del neurodesarrollo en el siglo XXI: lecciones aportadas por el autismo.El futuro de la medicina de los trastornos del neurodesarrollo posee el potencial de situar a la neurologia infantil en la vanguardia de un amplio esfuerzo de la sanidad publica con miras a optimizar los resultados del proceso de neurodesarrollo en los niños nacidos con diversas cargas geneticas, pre y perinatales y ambientales, de prevalencia elevada, que ponen en riesgo el desarrollo temprano de su cerebro y acaban provocando incapacidad durante toda la vida. Construida sobre los avances de la neurociencia del desarrollo social y de la ciencia traslacional, esa transformacion ya esta teniendo lugar en el ambito de un trastorno del neurodesarrollo emblematico como es el autismo. Aprovechando la neuroplasticidad temprana y la cuantificacion de las trayectorias del desarrollo comunicativo y social, estan viendo la luz nuevas tecnologias de diagnostico con alta capacidad, rentables y viables para administrar potentes tratamientos en el ambito comunitario, en perfecta integracion entre redes de atencion sanitaria que en el pasado estaban fragmentadas. Estas soluciones son susceptibles de utilizarse para atender a otros colectivos de recien nacidos y niños con un riesgo acusado de autismo y retraso de la comunicacion, como los prematuros extremos o los niños con cardiopatias congenitas. La idea motriz de este futuro ambicioso es que la sanidad publica se concentre en la promocion de las condiciones optimas para el desarrollo inicial del cerebro, de modo similar a las actuales campañas de fomento de la atencion prenatal, la nutricion o la vacunacion.

Comparison of inguinal hernia and asymptomatic patent processus vaginalis in term and preterm infants.

INTRODUCTION: The aim of this study was to evaluate the characteristics of inguinal hernia (IH) and patent processus vaginalis (PPV) in term and preterm infants less than the age of 6months. METHOD: Between January 2004 and December 2012, 246 term and 165 preterm infants underwent laparoscopic herniorrhaphy within the first 6months of life. Preoperative clinical presentation and intraoperative anatomical findings during the laparoscopic procedure were evaluated. Additionally, initial side of hernia, laterality of IH and PPV were analyzed in term and preterm infants. RESULTS: In the group of term infants, most infants presented with a primary right-sided IH (58.5%) versus 17.9% left-sided and 23.6% bilateral IH. Babies with primary unilateral IH were found to have a contralateral PPV in 41.0% of cases. A difference between left-sided PPV and right-sided PPV could not be identified. In the group of preterm infants, initial bilateral presentation was predominant (38.8%) versus right-sided (30.3%) and left-sided IH (30.9%). Infants with primary unilateral IH were found to have a contralateral PPV in 56.4%. We identified a slight difference between left-sided PPV (54.0%) and right-sided PPV (58.8%). CONCLUSION: IH is predominantly right sided in term infants, whereas preterm infants mostly present with bilateral IH. The incidence of PPV was found to be significantly higher in the preterm group. Regarding the incidence of a contralateral PPV in term and preterm infants, no difference between initial left-sided and right-sided IH could be identified between both groups.

[Infantile swallowing]. / Frühkindliches Schlucken.

BACKGROUND: Increasing numbers of preterm infants 1 and ever-improving potentials in neonatal medicine will lead to a rising incidence in infantile feeding problems. Profound knowledge regarding the development and anatomy of pre- and postnatal swallowing functions is essential for the assessment and therapy of infantile feeding and swallowing problems. METHOD: For this systematic review a selective literature research in PubMed has been carried out. RESULTS: Oropharyngeal structures and oral-motor skills for sucking and swallowing develop during embryonic and foetal stages and enable postnatal oral feeding. Knowledge of pre- and postnatal developmental stages of oral-motor development and swallowing serves as a base for the assessment of preterm infants' abilities and tolerance for feeding. A direct comparison of the swallowing process between infants, children and adults is not possible due to different anatomical characteristics. Developmental processes and neurologically triggered coordination procedures of early feeding skills are complex and very susceptible to faults. Disruption can cause severe disorders of swallowing coordination. Feeding problems are a common problem in preterm infants. Differentiated assessments on the basis of these results and early intervention facilitating oral-motor skills can accelerate the transition from tube to oral feeding and prevent further feeding issues.

Neuroblastoma in monozygotic twins with distinct presentation pathology and outcome: is it familial or in utero metastasis.

To date ten sets of monozygotic twins with neuroblastoma have been reported in the literature. Twin-to-twin in utero metastasis have been proposed as the mechanism of tumor development in the second twin; based on similar pathology, presence of metastatic disease, absence of a primary tumor, and/or later presentation in the second twin. Hereditary neuroblastoma has not been described in this context. We propose that primary neuroblastoma can occur in monozygotic twins without twin-twin transmission; due to the different ages of presentation, histology, ploidy, and tumor behavior.

Extrahepatic vitelline vein aneurysm: prenatal diagnosis and follow up.

Umbilical vein varix is a well-described prenatal anomaly in which the prognosis remains unclear. We describe a very rare venous malformation that mimicked an umbilical vein varix consisting of a persistent vitelline vein. From 2003 to 2010, three patients were referred starting at 20 weeks gestation to our prenatal centers for an umbilical vein varix diagnosis. Fetal follow up was unremarkable, with the exception of the dilated vein size (mean: 35 mm at 33 weeks gestation). After birth, the three children presented with thrombosis from the aneurysmal sac to the portal trunk. All the children underwent surgical thrombectomy and resection of the aneurysmal sac after birth. Operative findings showed no umbilical vein but an abnormal dilated and thrombosed vein coming from the umbilicus to the portal vein following the right vitelline vein trajectory. One child was treated with systemic heparin. Median follow up is 5.6 years. Currently, one patient has a normal portal flow. The other two have persistent portal vein thrombosis with portal cavernoma and portal hypertension. This malformation is rare and should be considered in cases of early diagnosed umbilical vein varix whose diameter is greater than 20mm. We advocate an early surgical thrombectomy with heparinization to prevent portal vein thrombosis.

Antenatal steroids and the IUGR fetus: are exposure and physiological effects on the lung and cardiovascular system the same as in normally grown fetuses?

Glucocorticoids are administered to pregnant women at risk of preterm labour to promote fetal lung surfactant maturation. Intrauterine growth restriction (IUGR) is associated with an increased risk of preterm labour. Hence, IUGR babies may be exposed to antenatal glucocorticoids. The ability of the placenta or blood brain barrier to remove glucocorticoids from the fetal compartment or the brain is compromised in the IUGR fetus, which may have implications for lung, brain, and heart development. There is conflicting evidence on the effect of exogenous glucocorticoids on surfactant protein expression in different animal models of IUGR. Furthermore, the IUGR fetus undergoes significant cardiovascular adaptations, including altered blood pressure regulation, which is in conflict with glucocorticoid-induced alterations in blood pressure and flow. Hence, antenatal glucocorticoid therapy in the IUGR fetus may compromise regulation of cardiovascular development. The role of cortisol in cardiomyocyte development is not clear with conflicting evidence in different species and models of IUGR. Further studies are required to study the effects of antenatal glucocorticoids on lung, brain, and heart development in the IUGR fetus. Of specific interest are the aetiology of IUGR and the resultant degree, duration, and severity of hypoxemia.

Ex utero intrapartum treatment in the management of giant cervical teratomas.

PURPOSE: The purpose of this study is to present the outcome and technical details of the Ex Utero Intrapartum Treatment (EXIT) procedure performed in the management of the fetus with a giant cervical teratoma. METHODS: A retrospective review of the medical records of patients undergoing the EXIT procedure between September 1995 and September 2010 was performed. RESULTS: Eighty-seven EXIT procedures were performed. In 20% of cases (17/87), the indication was giant cervical teratoma. There were 10 females and 7 males. Polyhydramnios was present in 82%. Median gestational age at EXIT was 35 weeks (range, 30-39 weeks). Median birth weight was 2.5 kg (range, 1.7-3.7 kg). Access to the airway under placental support was established in all cases via direct laryngoscopy/bronchoscopy in 8 patients (47%) and via surgical exploration (tracheostomy or retrograde intubation) in 9 patients (53%). The mortality rate under placental support was zero. Seven patients had the tumors resected immediately after the EXIT, 6 patients had the resection later, and 4 patients died before resection. The neonatal mortality rate was 23% (4/17 patients). Patients who died had severe pulmonary hypoplasia that resulted from the upward traction by the giant cervical mass on the airway and compression of the lungs against the thoracic apex. CONCLUSIONS: We conclude that the EXIT procedure continues to be the optimal delivery strategy for patients with prenatally diagnosed giant cervical teratomas and potential airway obstruction at birth. A thorough evaluation of the prenatal images and an experienced multidisciplinary team are key factors for an effective approach to the obstructed fetal airway.

[Intracerebral neurenteric cysts in newborn infants]. / Quistes neuroentericos intracerebrales en neonatos.

INTRODUCTION: Intracranial neurenteric cysts are very infrequent congenital lesions. Within the nervous system, they are most commonly located in the rachis. Another frequent site is the craniocervical junction. Few cases of supratentorial location have been reported. A differential diagnosis is required to distinguish them from other cysts. They are not often diagnosed in the paediatric age. The clinical features they give rise to are due to the mass effect or episodes of chemical meningitis. Magnetic resonance imaging is the best diagnostic method although on many occasions they cannot be distinguished from arachnoid cysts. Treatment consists in surgery with complete resection of the membranes in order to prevent recurrences. CASE REPORTS: We report two cases of infants who, in the last weeks of gestation, presented supratentorial intracerebral cystic lesions that resembled arachnoid cysts. A neonatal magnetic resonance scan confirmed the existence of such supratentorial cysts with septae inside them. After presenting an increase in the cranial perimeter, surgical treatment was undertaken with a neuronavigation-guided craniotomy and debridement of the cysts. The cysts contain mucus and have thick membranes. Pathological study results are consistent with a neurenteric cyst. One of the patients presented complete resolution after the intervention with good cerebral expansion. In the second case, there was persistence of an adjoining arachnoid cyst, in which placement of a cyst-peritoneal shunt was necessary with full resolution. CONCLUSIONS: Most intracranial cysts are arachnoid cysts, but there are other cystic lesions that must be treated by surgical means so that they can be completely excised and sent for pathological analyses.

Prenatal sonographic assessment and perinatal course of ichthyosis prematurity syndrome.

All cases of ichthyosis prematurity syndrome (IPS), registered at the National Center for Fetal Medicine in Trondheim, Norway between 1987 and 2010 were identified and the findings analyzed. Five fetuses with IPS were identified between 1988 and 2000. All five developed polyhydramnios between 28 and 31 weeks. The fetal stomach appeared to be empty in four cases, and was not described in one case. The fetal skin was described as 'uneven' at ultrasound examination in two cases. Separation of chorionic and amniotic membranes with a peculiar appearance of echo-free fluid in the chorionic cavity and echogenic sediment in the amniotic cavity were observed between 28 + 5 and 32 + 3 weeks in all cases. All fetuses were delivered prematurely between 30 and 34 weeks. All neonates had difficulties in breathing, two developed aspiration pneumonia, and one had bilateral pneumothorax after intubation and died at 6 months because of pulmonary and cardiac sequelae. Prenatal sonographic signs of IPS are separation of the membranes, echogenic amniotic fluid and echo-free chorionic fluid occurring between 28 and 32 weeks' gestation. Delivery occurs at 30-34 weeks and, as there is a high risk of asphyxia, an experienced neonatal intensive care unit team should be present at delivery.

Primary anastomosis for meconium peritonitis: first choice of treatment.

PURPOSE: Newborn surgery for meconium peritonitis (MP) is sometimes very difficult owing to severe adhesions and bleeding. The aim of this study was to reveal the benefit of primary anastomosis (PA) for MP by comparing PA with multistep operations (MO). PATIENTS AND METHODS: We retrospectively reviewed 38 patients with MP who underwent surgery in our institution from 1983 to 2009. From 1983 to 2000, we essentially used MO. After 2001, we used PA with the exception of 1 patient. We performed MO on 20 patients (group A) and PA on 18 patients (group B). RESULTS: Mortality was 4 in 20 in group A and 1 in 18 in group B. Three patients in group A and 2 in group B required reoperation because of complications. After 2001, 14 of 16 patients underwent PA. Of the 2 patients for whom PA could not be performed, one was postresuscitation from cardiopulmonary arrest and the other was an extremely low-birth-weight infant. The only mortality among the patients who underwent PA occurred in a very low-birth-weight infant who died from intraoperative hepatic hemorrhage. CONCLUSION: PA can be performed for almost all patients with MP except for extremely low-birth-weight infants.

Synchronous ipsilateral Bochdalek and Morgagni diaphragmatic hernias: a case report.

The etiology of congenital diaphragmatic hernia (CDH) is unknown. Phenotypic patterns of CDH defects provide clues about normal diaphragm development and the pathophysiology of CDH. We report a case of a patient who was diagnosed with CDH postnatally and was found on imaging to have simultaneous Bochdalek and Morgagni hernias on the right side. During the operative repair of these defects, an additional left-sided Morgagni-type defect was also found. To the best of our knowledge, this form of CDH has not been previously reported.

The IUGR newborn.

Intrauterine growth restriction (IUGR) is characterized by fetal growth less than normal for the population and growth potential of a given infant. IUGR can be symmetrical with low weight, length and head circumference indicative usually of a process with its origin early in pregnancy or asymmetrical with sparing of head circumference and length due to processes occurring later in gestation. The acute neonatal consequences of IUGR are perinatal asphyxia and neonatal adaptive problems. These adaptive problems that include respiratory distress due to meconium aspiration, persistent pulmonary hypertension or pulmonary hemorrhage, abnormalities of glucose regulation, temperature instability, and polycythemia are reviewed in this article. Issues specific to the IUGR preterm infant are reviewed as well including an increased incidence of chronic lung disease, necrotizing enterocolitis, retinopathy of prematurity and postnatal growth failure.

Placental anomalies in children with infantile hemangioma.

Evaluation of the placenta provides some important insights into pathophysiologic changes that take place during the prenatal and intrapartum process. We investigated the pathogenic significance of placental features and their relationship to the development of infantile hemangioma in order to obtain a better understanding of its cause. Placental specimens were reviewed from 26 singleton pregnancies of women whose offspring weighed less than 1500 g. A group of 13 neonates who developed infantile hemangioma in the immediate neonate period were compared with 13 healthy preterm infants of comparable postconception age who had no infantile hemangioma. Pathologic placental changes were analyzed in both groups. Gross lesions with disturbance of the utero-placental circulation were found in all placentas from children who developed infantile hemangioma, including massive retroplacental hematoma in two infants, extensive ischemic infarction in seven, and large dilatated vascular communications, severe vasculitis, chorioamnionitis and funiculitis in four. Placental features included percentages greater than 25% of avascular villi, platelet and fibrin aggregates, and multifocal disease involving more than one histologic section. Examination of 13 placentas of low-birth-weight infants without infantile hemangioma only showed abnormal placentation in one and isolated villous dismaturity in two. The higher ratio of placental pathologic findings in patients with infantile hemangioma suggests that reduced placental oxygen diffusive conductance contributes to fetal hypoxic stress and that hypoxic/ischemic changes in the placenta could be related to infantile hemangioma development via vascular endothelial growth factor and placental growth factor expression, among others, within the villious vessels and throphoblasts.

Antenatal infection/inflammation and fetal tissue injury.

There is a clear association between antenatal infection/inflammation and preterm labour, with intrauterine infection complicating up to one third of preterm deliveries. In addition to this, there is now accumulating evidence that intrauterine infection and inflammation can lead to the development of a systemic inflammatory response in the fetus and subsequent tissue injury. The fetal inflammatory response is characterized by funisitis, high levels of pro-inflammatory cytokines in the amniotic fluid and cord blood, and systemic immune activation. This review discusses the evidence for this process and focuses on the clinical and experimental data supporting the hypothesis that these inflammatory processes contribute to brain and lung injury in the newborn.

Are routine cranial ultrasounds necessary in premature infants greater than 30 weeks gestation?

The purpose of this study was to validate the recommendation of the American Academy of Neurology and the Child Neurology Society that screening cranial ultrasonography be performed routinely on all infants of less than 30 weeks gestation at 7 to 14 days of age and again between 36 and 40 weeks postmenstrual age, and, by using this practice parameter, to determine the number of babies with a clinically significant abnormal screening cranial ultrasound (US) who would otherwise have been missed. A retrospective study of 486 infants of 30 to 33 weeks gestation born January 1, 1999 to June 30, 2004 was done. All had screening cranial ultrasounds. Grade III and/or grade IV intraventricular hemorrhage (IVH) occurred in 4 (0.8%) infants of 30 to 31 weeks gestation. Infants with significant IVH had either risk factors for brain injury or symptoms that would eventually warrant US during their hospitalization. Seven (1.4%) infants had periventricular leukomalacia (PVL). All infants with a final diagnosis of PVL had pre- and/or perinatal risk factors associated with PVL. There was a significant trend toward fewer abnormal cranial ultrasounds from 30 to 33 weeks gestation (p=0.04). Our study supports the recommendation by the American Academy of Neurology and the Child Neurology Society that screening US can be limited but suggests that the gestational age cut off should be 30 weeks or less.

Magnetic resonance imaging assessment of brain maturation in preterm neonates with punctate white matter lesions.

INTRODUCTION: Early white matter (WM) injury affects brain maturation in preterm infants as revealed by diffusion tensor imaging and volumetric magnetic resonance (MR) imaging at term postmenstrual age (PMA). The aim of the study was to assess quantitatively brain maturation in preterm infants with and without milder forms of WM damage (punctate WM lesions, PWML) using conventional MRI. METHODS: Brain development was quantitatively assessed using a previously validated scoring system (total maturation score, TMS) which utilizes four parameters (progressive myelination and cortical infolding, progressive involution of glial cell migration bands and germinal matrix tissue). PWML were defined as foci of increased signal on T1-weighted images and decreased signal on T2-weighted images with no evidence of cystic degeneration. A group of 22 preterm infants with PWML at term PMA (PWML group) were compared with 22 matched controls with a normal MR appearance. RESULTS: The two groups were comparable concerning gestational age, birth weight and PMA. TMS was significantly lower in the PWML group than in the control group (mean TMS 12.44 +/- 2.31 vs 14.00 +/- 1.44; P = 0.011). Myelination (mean 2.76 +/- 0.42 PWML group vs 3.32 +/- 0.55 control group, P = 0.003) and cortical folding (3.64 +/- 0.79 vs 4.09 +/- 0.43, P = 0.027) appeared to be significantly delayed in babies with PWML. CONCLUSION: Conventional MRI appears able to quantify morphological changes in brain maturation of preterm babies with PWML; delayed myelination and reduced cortical infolding seem to be the most significant aspects.

Perinatal outcome and later implications of intrauterine growth restriction.

This chapter reviews outcomes for children who have intrauterine growth retardation (IUGR) or small-for-gestation-age (SGA) status at birth. Such infants are at risk for increased perinatal mortality, birth adaptation complications, including perinatal acidosis, hypoglycemia, hypothermia, coagulation abnormalities, and selected immunologic deficiencies. IUGR infants also appear to be at great risk for complications of prematurity, including chronic lung disease and necrotizing enterocolitis. Childhood implications for IUGR include an increased risk for short stature, cognitive delays with decreased academic achievement, and a small but significant increased risk of neurologic disorders, including cerebral palsy. Low socioeconomic status is correlated with the occurrence of IUGR and is significantly related to long-term disabilities. Morbidities associated with preterm delivery appear to be additive to those associated with fetal growth restriction so IUGR, preterm infants may be at great risk for poor neurodevelopmental outcome.