Antagonism of NMDA receptors as a potential treatment for Down syndrome: a pilot randomized controlled trial.

Down syndrome (DS) is the most common genetic cause of intellectual disability. The N-methyl-D-aspartate (NMDA) receptor uncompetitive antagonist, memantine hydrochloride (memantine), has been shown to improve learning/memory and rescue one form of hippocampus synaptic plasticity dysfunction in the best-studied mouse model of DS available, the Ts65Dn mouse. Given the status of memantine as a treatment for Alzheimer's disease (AD) approved by the Food and Drug Administration, the preclinical evidence of potential efficacy in Ts65Dn mice, and the favorable safety profile of memantine, we designed a study to investigate whether the findings in the mouse model could be translated to individuals with DS. In this pilot, proof-of-principle study we hypothesized that memantine therapy would improve test scores of young adults with DS on measures of episodic and spatial memory, which are generally considered to be hippocampus dependent. Accordingly, in this randomized, double-blind, placebo-controlled trial, we compared the effect of 16-week treatment with either memantine or placebo on cognitive and adaptive functions of 40 young adults with DS using a carefully selected set of neuropsychological outcome measures. Safety and tolerability were also monitored. Although no significant differences were observed between the memantine and placebo groups on the two primary outcome measures, we found a significant improvement in the memantine group in one of the secondary measures associated with the primary hypothesis. Only infrequent and mild adverse events were noted.

Integración sensorial y síndrome X frágil / Sensory integration and fragile X syndrome

El síndrome X frágil es la forma más común de retraso mental hereditario ligado al cromosoma X. Ocurre en aproximadamente 1 de cada 1.000 nacimientos y afecta tanto a varones como a mujeres. Es de gran interés que un número significativo de estos niños y niñas, además de la variedad de dificultades físicas, cognitivas y conductuales, tienen trastornos en la función de integración sensorial, que les afecta gravemente su conducta y su capacidad de aprender y funcionar en el seno de sus familias y comunidad. (AU)

Sensory modulation dysfunction in children with attention-deficit-hyperactivity disorder.

This study investigates the presence of sensory modulation dysfunction (SMD) among children with attention-deficit-hyperactivity disorder (ADHD). Twenty-six children with ADHD (mean age 8.3 years, 18 males, 8 females), and 30 typically developing children (mean age 8.2 years, 21 males, 9 females) were tested using a laboratory procedure that gauges responses to repeated sensory stimulation by measuring electrodermal reactivity (EDR). Parental report measures of limitations in sensory, emotional, and attentional dimensions were administered using the Short Sensory Profile, the Leiter International Performance Scale-Revised, Parent Rating subscales, and the Child Behavior Checklist (CBCL). Compared to the typical sample, the children with ADHD displayed greater abnormalities in sensory modulation on both physiological and parent-report measures. The children with ADHD also displayed more variability in responses. Within the group with ADHD, levels of SMD were highly correlated with measures of psychopathology on the CBCL. Implications of findings relate to the importance of considering sensory processing abilities in a subgroup of children with ADHD.

The prenatal visit.

In their role as advocates for children and families, pediatricians are in an excellent position to support and guide parents during the prenatal period. Prenatal visits allow the pediatrician to gather basic information from parents, provide information and advice to them, and identify high-risk situations in which parents may need to be referred to appropriate resources for help. In addition, prenatal visits are the first step in establishing a relationship between the pediatrician and parents and help parents develop parenting skills. The prenatal visit may take several possible forms depending on the experience and preferences of the parents, competence and availability of the pediatrician, and provisions of the health care plan.

[Sensory integration and fragile X syndrome]. / Integración sensorial y síndrome X frágil.

The fragile X syndrome is the most common inherited sex-linked form of mental retardation. It occurs in approximately 1/1,000 live births and affects both males and females. What is of considerable interest is that a significant number of these children, in addition to a variety of physical, cognitive and behavioral difficulties, also have disturbances of sensory integration function which can, and do, severely effect their behavior and capacity to learn and function in their families and communities.

Impact of infants born at the threshold of viability on the neonatal mortality rate in Colorado.

OBJECTIVE: To determine the contribution of infants born at the threshold of viability (< 750 gm) on neonatal mortality in Colorado. STUDY DESIGN: For the period of January 1991 to December 1996, all Colorado live births who expired were evaluated for gestational age, birth weight, gender, hospital level of care, age at time of death, delivery room resuscitation, mechanical ventilation, medical and surgical complications, and serious malformations. RESULTS: Although infants weighing < 750 gm represent only 0.31% of all live births, they account for 46.3% of deaths. While those infants weighing < 500 gm and with a gestation of < 24 weeks almost always died (94.7%), the majority born in the 500- to 745-gm category (55.8%) survived. The vast majority (88.5%) of deaths occurred on the first day of life. A total of 38.4% of births in which the infant weighed < 750 gm occurred outside bona fide regional perinatal centers. CONCLUSION: Future attempts to reduce the Colorado neonatal mortality rate would best focus on the 500- to 750-gm weight group through the re-regionalization of high-risk perinatal care.

The effect of war on children.

The objective of this paper is to provide an overview of the effects of war on children during the 20th century. It is argued that wars have both direct and indirect effects on the population. It also is noted that wars have changed from being "conventional" to being of "low intensity". Under these latter circumstances civilians, including children, as well as the infrastructure of the society become targets whereas in the past, the targets were usually only military ones. The effects of the strategy used in "low intensity" conflicts is the disruption of the medical, social, educational, and public services of a country and the terrorization of the population. Under these circumstances children suffer inordinately. Their homes are destroyed, their families disrupted, and their chances of becoming mature productive members of society are compromised.

Change in the hospital setting: adopting a team approach for nonorganic failure-to-thrive.

The change process is described for the adoption of a multidisciplinary team approach to nonorganic failure-to-thrive (NOFTT) management at a pediatric care facility. A member of the nursing staff acted as a change agent. The need for change was documented with medical record audits. A team was developed and a management protocol derived from an external evaluation of successful programs described in the literature. Preliminary outcomes of the project are reported. Box 1 at the end of this article contains criteria for NOFTT diagnosis and an outline of the team's protocol.

The fragile X syndrome.

We have begun to appreciate that the extent of this disorder is much wider than merely mental retardation. It is also a common cause of learning and emotional problems in mildly affected female carriers with normal IQs. These children present an enormous challenge to all child-care providers, be they in medicine, education, or in various therapy disciplines. Early identification is essential, and the key to effective management is an innovative and multidisciplinary approach. As disciplines become more familiar with and knowledgeable about this frequently occurring form of mental retardation or cause of learning disabilities, they should become more adept at early identification and early referral for support and intervention.

Eight-year school performance, neurodevelopmental, and growth outcome of neonates with bronchopulmonary dysplasia: a comparative study.

Eight-year outcome is reported for three groups of preterm infants with bronchopulmonary dysplasia--group 1 with a birth gestation of less than or equal to 31 weeks receiving supplemental oxygen until the equivalent of 36 weeks' gestation, group 2 of the same gestation receiving supplemental oxygen to 28 days postnatal age but not to 36 weeks gestational age, and group 3 with a gestation of greater than or equal to 32 weeks requiring supplemental oxygen for greater than 28 days--and for an individually matched preterm neonatal comparison group and a term peer comparison group for each bronchopulmonary dysplasia group. The subjects all had parents whose mother tongue was English and were matched for gender, mother's education, and father's socioeconomic status, and in the case of the neonatal comparison groups they also were matched for birth gestation and birth weight. Physical growth and psychoeducational and school performance test scores were similar for the three bronchopulmonary dysplasia study groups with the exception of lower intelligence quotient for those receiving supplemental oxygen for the longest time. Children in groups 1 and 2 had outcome scores similar to those of the neonatal comparison group and significantly below those of their peer comparison groups. On multivariate analysis for group 1 children, 61% of the variance of academic achievement was related to lowest recorded pH, father's socioeconomic status, and lowest recorded PaO2. Compared with the peer groups, the study groups continued to show academic delay when the disabled children were excluded from analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

The affective and cognitive sequelae of child maltreatment.

This article discusses the affective and cognitive sequelae of child maltreatment. It provides a brief historical overview and various definitional issues in the field. The tasks of childhood are identified, and developmental processes are discussed. A review of the literature of the sequelae of maltreatment is presented, followed by a discussion of the impact of these sequelae and the implications for the child's development.

Outcome of very-low-birth-weight infants: does antepartum versus neonatal referral have a better impact on mortality, morbidity, or long-term outcome?

To evaluate the effect of aggressive intrapartum and early neonatal resuscitation on perinatal mortality, neonatal morbidity, and long-term outcome, we evaluated two groups of low-birth-weight infants who received different intrapartum and early neonatal care. One group of infants was delivered at a university-based regional perinatal center offering both high-risk obstetric and tertiary neonatal care. The second population consisted of infants from five community hospitals with level I nurseries. These two groups were selected because they differed in the ability to provide intrapartum and early neonatal care and because a total base population could be evaluated. During the 4-year study period, 174 infants with birth weights of 500 to 1499 gm were delivered at the university center and 297 infants were delivered at the community hospitals. At the university center, there was a significant reduction in fetal deaths, a delay in the time of neonatal deaths, and a reduction in hyaline membrane disease. Neonatal mortality rates at the university center were not reduced, and the incidence of sequelae was not affected. These data suggest that for the smallest infant, intrapartum and immediate neonatal care at a tertiary center may decrease fetal mortality and neonatal morbidity rates. Neonatal mortality and long-term outcome, however, may be less affected.

Outcome of very-low-birth-weight infants: are populations of neonates inherently different after antenatal versus neonatal referral?

Postnatal transfer of high-risk infants to a neonatal intensive care unit has been an accepted medical practice for more than two decades. More recently, antepartum maternal referral for the smallest infants has been recommended to reduce infant mortality, morbidity, and long-term handicaps. The limited data available to compare in utero and postnatal transfer suggest that maternal risk factors may also influence antenatal referral. We evaluated antepartum maternal and postnatal infant referrals from five metropolitan Denver hospitals with level I facilities. Mothers who were referred to the tertiary perinatal center before delivery were more likely to have one or more high-risk conditions. The presence of a maternal risk factor (preeclampsia, antepartum bleeding, prolonged rupture of the membranes, or chorioamnionitis) was significantly more common in the maternal transfer group (p less than 0.002). Neonatal weight was higher for the maternal referrals compared with neonatal referrals. Neonatal survival was independently improved by transport of mother or infant, increasing birth weight, and higher Apgar scores. We suggest that maternal risk factors were an important determinant in the choice of antenatal referral to our perinatal center for both the community and regional hospitals during this study period. Studies that compare outcome of infants after maternal and infant transfer must control for potentially inherent differences between the antenatally and postnatally transferred infants.

A unique teletransmission system for extended four-channel esophageal pH monitoring in infants and children.

A new computerized telemetry system for extended esophageal pH monitoring is prospectively evaluated and compared with other diagnostic modalities in 38 pediatric patients suspected of having gastroesophageal reflux (GER). Unique circuitry allows connection of 1.5 mm diameter antimony electrodes to a patient-worn digital recorder that continuously samples pH at four levels from pharynx to distal esophagus. Ambulatory studies in a "physiologic" environment are possible and data is teletransmitted by the satellite computer to the central laboratory for analysis. Of 41 studies completed, four were lost to interpretation because of battery, electrode, or computer failure. Thirty-seven studies could be analyzed in five clinical groups: emesis and failure to thrive; status post esophageal atresia repair; apnea/bradycardia; central nervous system damage; and status post antireflux procedure. Pathologic GER was noted 14 times and an antireflux procedure was clinically required in 13 instances. In five cases the upper GI series failed to detect the GER. Twenty-three studies showed no GER, and the clinical symptoms resolved with appropriate medical therapy in 21 cases. The upper GI series demonstrated GER five times in this group. In the nine instances that esophagoscopy/biopsy was employed, the pH study findings were uniformly confirmed. This computerized system provided a technically complete and interpretable study 90% of the time. Based on patient outcome, the extended pH monitoring was 92% accurate in detecting clinically important GER with a sensitivity of 87% and specificity of 93%. The upper GI series demonstrated a 69% accuracy with a 60% sensitivity and 64% specificity (P = .01).(ABSTRACT TRUNCATED AT 250 WORDS)