Effects of intravenous secretin on language and behavior of children with autism and gastrointestinal symptoms: a single-blinded, open-label pilot study.

BACKGROUND: Autism is a severe developmental disorder with poorly understood etiology. A recently published case series describes 3 autistic children with gastrointestinal symptoms who underwent endoscopy and intravenous administration of secretin and were subsequently noted by their parents to demonstrate improved language skills over a 5-week period. This report sparked tremendous public interest, and investigators at several sites moved quickly to design controlled trials to test the efficacy of secretin as a therapy for autistic children. However, this is the first effort specifically designed to replicate the initial reported findings in terms of patient age, presenting symptoms, and drug administration. OBJECTIVE: To rigorously apply the scientific method by assessing the reproducibility of the reported effects of intravenous secretin on the language of young children with autism and gastrointestinal symptoms. METHODS: We performed a single-blinded, prospective, open-label trial by conducting formal language testing and blinded behavioral rating both before and repeatedly after a standardized infusion of secretin. We selected autistic children who were similar in age and profile to those described in the published retrospective case review. Inclusion criteria for study participation included age (3-6 years), confirmed diagnosis of autism, and reported gastrointestinal symptoms (16 had chronic diarrhea, 2 had gastroesophageal reflux, and 2 had chronic constipation). Twenty children (18 male) were admitted to the Pediatric Clinical Research Center at the University of California, San Francisco after administration of the Preschool Language Scale-3 (PLS-3). A 3 CU/kg dose of secretin (Secretin-Ferring) was administered intravenously (upper endoscopy was not performed). Behavioral ratings were derived using the Autism Observation Scale applied to a 30-minute time sample of the child's behavior consisting of a videotape of the PLS-3 (structured setting) and a second free play session with a standard set of developmentally appropriate toys. Participants then returned for follow-up evaluations, with readministrations of the PLS-3 at 1, 2, 3, and 5 weeks' postinfusion, and videotaping of each session for later blinded review by 2 independent observers using the Autism Observation Scale, uninformed about week of posttreatment. We also surveyed parents of our study children about their impressions of the effects of secretin using a 5-point Likert scale for parents to rate changes seen in their child. RESULTS: With a total study completion rate across all participants of 96%, repeated measures analyses of variance revealed no significant increases in children's language skills from baseline across all 5 study time periods after a single infusion of secretin. Similarly, neither significant decreases in atypical behaviors nor increases in prosocial behaviors and developmentally appropriate play skills emerged. Furthermore, no relationship was found between parental reports of change and observable improvement in the sample. Despite the objective lack of drug effect, 70% of parents in our study reported moderate to high change in their child's language and behavior. Furthermore, 85% of parents reported that they felt that their child would obtain at least some additional benefits from another infusion of secretin. CONCLUSIONS: The results of our pilot study indicate that intravenous secretin had no effects in a 5-week period on the language and behavior of 20 children with autism and gastrointestinal symptoms. The open-label, prospective design of our study with blinded reviews of patients both before and after secretin administration follows the scientific method by seeking to reproduce an observed phenomenon using validating and reliable outcome measures. Pilot studies remain a mandatory step for the design of future randomized, clinical trials investigating potential treatments for children with autism.

Updates in pediatric nutrition.

Ongoing research in several areas of pediatric nutrition has new practical applications for community-based pediatricians. For example, a fresh understanding of risk factors for rickets persuades pediatricians to recognize and treat this disease, which was thought to be nearly extinct in the modern industrialized world. Similarly, an expanded awareness of the antibacterial components of breast milk encourages a more complete dialogue between pediatricians and new mothers about the potential benefits of breast-feeding. For those infants with feeding intolerance, new data help to refine the indications for hypoallergenic formulas, which are increasingly recommended for children with a variety of symptoms. The past year also has seen breakthroughs in our understanding of supplemental nutrition for children. Vitamin A may provide direct benefits for the most vulnerable of children, namely premature infants at high risk for lung disease. At the other end of the pediatric spectrum, adolescent athletes seeking to enhance their performance are consuming poorly studied sports supplements that may not be beneficial and may even be toxic. Finally, a greater appreciation for the epidemic of obesity that is sweeping the United States and other countries suggests that children at high risk may represent a far more diverse population than had been recognized previously.

Updates in pediatric nutrition.

There have been many remarkable advances in pediatric nutrition. Solid scientific evidence now supports certain fundamental assumptions long held in the pediatric community. For example, obesity in children has for some time been believed to have adverse health effects; recent large scale studies now confirm relationships between childhood obesity and specific morbidities. Likewise, the beneficial effects of human breast milk on growth and development have been the focus of recent prospective studies of full term and preterm infants. There has been active research in the area of formula intolerance and allergy, allowing practicing physicians to better counsel parents about dietary choices. Although many health problems are caused by the abundance of high fat and high calorie foods in the average US child's diet, a large number of children remain at risk for hunger in the United States. Other research provides important breakthroughs in our understanding of the impact of pediatric nutrition on lifelong health. Retrospective epidemiological studies have uncovered relationships between prenatal factors and health later in life. These studies have lead to ongoing prospective observational trials that should provide further information about the extent to which certain health factors are determined before birth. In addition, basic science research has revealed previously unknown mechanisms by which essential minerals, such as iron, are transported into the body. In sum, this section reviews exciting new information in the areas of childhood diet quality, obesity, breast milk, formula intolerance, and iron metabolism.

The role of pediatricians in the care of children with liver transplants.

OBJECTIVE: To examine the role of pediatricians in posttransplantation care of pediatric liver transplant recipients. DESIGN: Written survey of parents and pediatricians of children enrolled in a pediatric liver transplant program. SETTING: Questionnaires were mailed from a liver transplant center (LTC), set in a university-affiliated, tertiary-care medical center, to the homes of families and the offices of pediatricians in a variety of urban, suburban, and rural locales worldwide. STUDY POPULATION: Eighty-four percent of families and 81% of pediatricians who met study criteria participated. RESULTS: Only 8.9% of all pediatricians reported feeling comfortable providing all care for their liver transplant patients, while 82.2% were most comfortable sharing responsibility for care with the LTC. The remaining 8.9% of pediatricians were most comfortable with the LTC providing care. The more comfort pediatricians reported in providing care, the more likely parents were to report contacting pediatricians for medical problems. The more comfort pediatricians reported, the more parents perceived that (1) pediatricians and the LTC work well together (P<.03); (2) the LTC is informed about their child (P<.001); and (3) pediatricians are similarly up-to-date (P<.001). Furthermore, the more comfort pediatricians felt, the more parents believed that the liver transplant improved their child's health (P<.03) and that their child enjoys school (P=.08). Of the pediatricians, 15.6% who reported attending a continuing medical education course were significantly more comfortable (P=.05). The 18.9% of participating pediatricians who reported receiving some training in pediatric gastroenterology were also significantly more comfortable caring for children with liver transplants (P<.05). CONCLUSION: Increasing pediatrician comfort levels in providing posttransplantation care for children with liver transplants is critical to the continuing success of pediatric liver transplantation.

Psychosocial barriers to health promotion in an American Indian population.

Northern Plains Indians (N = 200) completed the Indian Specific Health Risk Appraisal and measures assessing beliefs about risk factors and personal risk. Participants rated personal risk optimistically, judged their risk factor standing as superior to that of their peers, and neglected to consider risk factor standing when appraising personal risk. Moreover, participants were often not improving their standing on risk factors they considered relevant to their health. Such biases in health beliefs may prevent health interventions from being successful.

Along for the ride: the prevalence of motor vehicle passengers riding with drivers who have been drinking in an American Indian population.

American Indians, especially those residing in the Northern Plains, experience considerable preventable morbidity and mortality from alcohol-related motor vehicle events. Research focusing on unintentional injuries associated with drinking drivers has disregarded the epidemiology of their passengers, who are equally at risk. The purpose of this investigation was to define the prevalence of motor vehicle passengers riding with drivers who have been drinking on a Northern Plains Reservation. We surveyed a sample of 151 Northern Plains Indians about their experiences riding with drinking drivers. Associated behavioral and demographic risk factors were also examined to identify possible predictor variables. The majority (54%) of respondents reported riding with a driver who had been drinking at least once during the previous three months. Most often, passengers ride with a friend who has been drinking, on a weekend night. Injury risk may be compounded because few respondents reported regular seat-belt use. The results off our study suggest the need for immediate comprehensive prevention efforts focusing on motor vehicle passengers.