Cumulative Antenatal Risk and Kindergarten Readiness in Preterm-Born Preschoolers.

A suboptimal intrauterine environment is thought to increase the probability of deviation from the typical neurodevelopmental trajectory, potentially contributing to the etiology of learning disorders. Yet the cumulative influence of individual antenatal risk factors on emergent learning skills has not been sufficiently examined. We sought to determine whether antenatal complications, in aggregate, are a source of variability in preschoolers' kindergarten readiness, and whether specific classes of antenatal risk play a prominent role. We recruited 160 preschoolers (85 girls; ages 3-4 years), born ≤336/7 weeks' gestation, and reviewed their hospitalization records. Kindergarten readiness skills were assessed with standardized intellectual, oral-language, prewriting, and prenumeracy tasks. Cumulative antenatal risk was operationalized as the sum of complications identified out of nine common risks. These were also grouped into four classes in follow-up analyses: complications associated with intra-amniotic infection, placental insufficiency, endocrine dysfunction, and uteroplacental bleeding. Linear mixed model analyses, adjusting for sociodemographic and medical background characteristics (socioeconomic status, sex, gestational age, and sum of perinatal complications) revealed an inverse relationship between the sum of antenatal complications and performance in three domains: intelligence, language, and prenumeracy (p = 0.003, 0.002, 0.005, respectively). Each of the four classes of antenatal risk accounted for little variance, yet together they explained 10.5%, 9.8%, and 8.4% of the variance in the cognitive, literacy, and numeracy readiness domains, respectively. We conclude that an increase in the co-occurrence of antenatal complications is moderately linked to poorer kindergarten readiness skills even after statistical adjustment for perinatal risk.

Biological Evidence in Adult and Adolescent Sexual Assault Cases: Timing and Relationship to Arrest.

This study examined the timing of the crime laboratory report relative to arrests in sexual assault cases and explored the relationship between biological evidence and arrest in those cases in which the crime laboratory report came first and thus could have influenced the arrest decision. A random sample (N = 528) of cases that occurred between 2008 and 2010 and included a report to police was drawn from a Massachusetts statewide database of medical reports on sexual assault cases. Data from medical providers were merged with data abstracted from crime laboratory reports and with data requested from police departments. The vast majority (91.5%) of arrests took place before crime laboratory analysis could be conducted. The crime laboratory report was available before or near in time to the arrest in 11 cases. These cases were significantly more likely than other cases to have DNA profiles of the assailant, DNA matches to the suspect, and a match to another investigation in the FBI's CODIS DNA database. Given that the probable cause needed to make an arrest in these cases was presumably established only after crime laboratory analysis was available, DNA may have helped lead to the arrest in these cases. However, these results should be interpreted very cautiously, because statistically significant results in early, small studies can have inflated effect sizes and often do not replicate in future studies. Because most arrests occur well before biological evidence is available, improvements in recovering biological evidence may have modest effects on arrest rates, though they may impact arrest rates by identifying more serial offenders. Future research on the relationship of biological evidence to arrest should use methods to increase sample size of relevant cases, such as oversampling cases with later arrests and using case control study designs. Future studies should also use case abstraction and interview methods to explore how police use biological evidence to make arrests.

Intrainsular connectivity and somatosensory responsiveness in young children with ASD.

BACKGROUND: The human somatosensory system comprises dissociable paths for discriminative and affective touch, reflected in separate peripheral afferent populations and distinct cortical targets. Differences in behavioral and neural responses to affective touch may have an important developmental role in early social experiences, which are relevant for autism spectrum disorder (ASD). METHODS: Using probabilistic tractography, we compared the structural integrity of white matter pathways for discriminative and affective touch in young children with ASD and their typically developing (TD) peers. We examined two tracts: (1) a tract linking the thalamus with the primary somatosensory cortex, which carries discriminative tactile information, and (2) a tract linking the posterior insula-the cortical projection target of unmyelinated tactile afferents mediating affective touch-with the anterior insula, which integrates sensory and visceral inputs to interpret emotional salience of sensory stimuli. We investigated associations between tract integrity and performance on a standardized observational assessment measuring tactile discrimination and affective responses to touch. RESULTS: Both the thalamocortical and intrainsular tracts showed reduced integrity (higher mean diffusivity) in the ASD group compared to those in the TD group. Consistent with the previous findings, the ASD group exhibited impaired tactile discriminative ability, more tactile defensiveness, and more sensory seeking (e.g., enthusiastic play or repetitive engagement with a specific tactile stimulus). There was a significant relation between intrainsular tract integrity and tactile seeking. The direction of this relation differed between groups: higher intrainsular mean diffusivity (MD) (reflecting decreased tract integrity) was associated with increased tactile seeking in the TD group but with decreased tactile seeking in the ASD group. In the TD group, decreased tactile defensiveness was also associated with higher intrainsular MD, but there was no relation in the ASD group. Discriminative touch was not significantly associated with integrity of either tract in either group. CONCLUSIONS: These results support previous findings suggesting a central role for the insula in affective response to touch. While both discriminative and affective touch and both somatosensory tracts are affected in ASD, the restriction of brain-behavior associations to the intrainsular tract and tactile seeking suggests more complex and perhaps higher-order influence on differences in tactile defensiveness and discrimination.

Association of Rigid-Compulsive Behavior with Functional Constipation in Autism Spectrum Disorder.

Based upon checklist data from the Autism Speaks Autism Treatment Network, we hypothesized that functional constipation (FC) would be associated with rigid-compulsive behavior in children with autism spectrum disorder (ASD). We used the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III to assess FC symptoms in 108 children with ASD. As hypothesized, FC was associated with parent ratings on the Repetitive Behavior Scales-Revised (RBS-R) Compulsive, Ritualistic, and Sameness subscales in the overall population. Of note, FC was less common in children who were not taking medications that target behavior or treat FC. In the medication-free children, rigid-compulsive behavior was not significantly associated with FC. More research is needed to understand the mechanisms underlying these associations.

Neuropsychological Functioning in Preterm-Born Twins and Singletons at Preschool Age.

OBJECTIVES: A limited body of research is available on the relationships between multiplicity of birth and neuropsychological functioning in preterm children who were conceived in the age of assisted reproductive technology and served by the modern neonatal intensive care unit. Our chief objective was to evaluate whether, after adjustment for sociodemographic factors and perinatal complications, twin birth accounted for a unique portion of developmental outcome variance in children born at-risk in the surfactant era. METHODS: We compared the neuropsychological functioning of 77 twins and 144 singletons born preterm (<34 gestational weeks) and served by William Beaumont Hospital, Royal Oak, MI. Children were evaluated at preschool age, using standardized tests of memory, language, perceptual, and motor abilities. RESULTS: Multiple regression analyses, adjusting for sociodemographic and perinatal variables, revealed no differences on memory or motor indices between preterm twins and their singleton counterparts. In contrast, performance of language and visual processing tasks was significantly lower in twins despite reduced perinatal risk in comparison to singletons. Effect sizes ranged from .33 to .38 standard deviations for global language and visual processing ability indices, respectively. No significant group by sex interactions were observed, and comparison of first-, or second-born twins with singletons yielded medium effect sizes (Cohen's d=.56 and .40, respectively). CONCLUSIONS: The modest twin disadvantage on language and visual processing tasks at preschool-age could not be readily attributable to socioeconomic or perinatal variables. The possibility of biological or social twinning-related phenomena as mechanisms underlying the observed performance gaps are discussed. (JINS, 2016, 22, 865-877).

Juvenile Firesetting.

Juvenile firesetting is a significant cause of morbidity and mortality in the United States. Male gender, substance use, history of maltreatment, interest in fire, and psychiatric illness are commonly reported risk factors. Interventions that have been shown to be effective in juveniles who set fires include cognitive behavior therapy and educational interventions, whereas satiation has not been shown to be an effective intervention. Forensic assessments can assist the legal community in adjudicating youth with effective interventions. Future studies should focus on consistent assessment and outcome measures to create more evidence for directing evaluation and treatment of juvenile firesetters.

Brief Report: Whole Blood Serotonin Levels and Gastrointestinal Symptoms in Autism Spectrum Disorder.

Elevated whole blood serotonin levels are observed in more than 25% of children with autism spectrum disorder (ASD). Co-occurring gastrointestinal (GI) symptoms are also common in ASD but have not previously been examined in relationship with hyperserotonemia, despite the synthesis of serotonin in the gut. In 82 children and adolescents with ASD, we observed a correlation between a quantitative measure of lower GI symptoms and whole blood serotonin levels. No significant association was seen between functional constipation diagnosis and serotonin levels in the hyperserotonemia range, suggesting that this correlation is not driven by a single subgroup. More specific assessment of gut function, including the microbiome, will be necessary to evaluate the contribution of gut physiology to serotonin levels in ASD.

Physical growth in the neonatal intensive-care unit and neuropsychological performance at preschool age in very preterm-born singletons.

We studied the associations between early postnatal growth gains and neuropsychological outcome in very preterm-born children. Specifically, we wished to establish whether relationships exist between gains in head circumference (relative to gains in body-weight or length), from birth to hospital discharge, and intellectual, language, or motor, performance at preschool age. We used data from 127 preschoolers, born <33 weeks, all graduates of the William Beaumont Hospital Neonatal Intensive-Care Unit (NICU) in Royal Oak, MI. Cognitive, motor, and language outcomes were evaluated using the Wechsler Preschool and Primary Scales of Intelligence-Revised, Peabody Developmental Scales - 2(nd) Edition, and the Preschool Language Scale - 3(rd) Edition, respectively. Differences between Z-scores at birth and hospital discharge, calculated for three anthropometric measures (head circumference, weight, length), were variables of interest in separate simultaneous multiple regression procedures. We statistically adjusted for sex, socioeconomic status, birth weight, length of hospitalization, perinatal complications, and intrauterine growth. Examination of the relationships between anthropometric indices and outcome measures revealed a significant association between NICU head growth and global intelligence, with the Z-difference score for head circumference accounting for a unique portion of the variance in global intelligence (ηp(2) =.04). Early postnatal head growth is significantly associated with neuropsychological outcome in very preterm-born preschoolers. To conclude, despite its relative brevity, NICU stay, often overlapping with the end of 2(nd) and with the 3(rd) trimester of pregnancy, appears to be a sensitive developmental period for brain substrates underlying neuropsychological functions.

Postnatal growth and neuropsychological performance in preterm-birth preschoolers.

OBJECTIVE: Compromised postnatal growth is an important risk factor accounting for poorer neuropsychological performance of preterm children during the preschool years, yet its unique contribution to explaining outcome variance within this high risk group has yet to be determined. Therefore, we examined within a large preterm sample (1) the relationships between head growth, measured either at birth or preschool age, and outcome; (2) the relationships of binary versus dimensional head growth measures and performance; and (3) the unique contribution of preschool-age head growth, after adjustment for general physical development (indexed by stature), to variance in neuropsychological functioning. METHOD: We evaluated 264 preterm (<36 weeks) preschoolers, without severe handicaps, using cognitive, language, and motor skill measures. Multiple regression analyses, adjusting for sociodemographic factors and pre-, peri-, and postnatal confounds, were used to study associations between growth indices and performance. RESULTS: While suboptimal head growth classification at birth was significantly associated only with motor performance, suboptimal head growth at preschool age explained a significant portion of variance in intellectual and language measures (g = .46 to .60). Treating preschool head size as a continuous dimension yielded null results, however, with body-height explaining a significant portion of the variance across several domains. CONCLUSION: Among postnatal anthropometric indices, preschool stature, rather than head circumference, remains a consistent correlate of preschool outcome in preterm children, highlighting the contribution of general physical development to neuropsychological performance. Further investigation of the underlying mechanisms likely involves exploration of complex relationships between postnatal nutrition, growth hormone levels, body and brain development, and neuropsychological functioning.

Rigid-compulsive behaviors are associated with mixed bowel symptoms in autism spectrum disorder.

Based on clinical experience, we hypothesized that rigid-compulsive behaviors are associated with severe constipation and co-occurring diarrhea or underwear staining in children with autism spectrum disorder. Using data from the Autism Treatment Network, we evaluated the association between these gastrointestinal symptoms and measures of rigid compulsive behavior in children ages 2-17. Following statistical correction, four of five primary measures were significantly associated with constipation and diarrhea or underwear staining, including parental report of repetitive behavior, parental report of compulsive behavior, clinician diagnosis of obsessive-compulsive disorder, and report of rituals observed on the autism diagnostic observation schedule. This association could point to a causal connection between these symptoms or to a common biological pathway that impacts both gut and brain.

Diagnostic yield of chromosomal microarray analysis in an autism primary care practice: which guidelines to implement?

Genetic testing is recommended for patients with ASD; however specific recommendations vary by specialty. American Academy of Pediatrics and American Academy of Neurology guidelines recommend G-banded karyotype and Fragile X DNA. The American College of Medical Genetics recommends Chromosomal Microarray Analysis (CMA). We determined the yield of CMA (N = 85), karyotype (N = 119), and fragile X (N = 174) testing in a primary pediatrics autism practice. We found twenty (24%) patients with abnormal CMA results (eight were clinically significant), three abnormal karyotypes and one Fragile X syndrome. There was no relationship between CMA result and cognitive level, seizures, dysmorphology, congenital malformations or behavior. We conclude that CMA should be the clinical standard in all specialties for first tier genetic testing in ASD.

Safety and efficacy of high dose intravenous desferrioxamine for reduction of iron overload in sickle cell disease.

BACKGROUND: Patients with sickle cell disease (SCD) receiving chronic blood transfusions are at risk of developing iron overload and organ toxicity. Chelation therapy with either subcutaneous (SQ) desferrioxamine (DFO) or oral deferasirox is effective in preventing and reducing iron overload but poses significant challenges with patient compliance. Intravenous (IV) infusions of high dose DFO have been utilized in non-compliant patients with heavy iron overload in small case series. PROCEDURE: We review our experience of high dose IV DFO in 27 patients with SCD who had significant iron overload and were noncompliant with subcutaneous (SQ) DFO. All patients were treated in-hospital with DFO 15 mg/kg/hr IV for 48 hr every 2-4 weeks with a mean duration of 19.6 months. RESULTS: We observed a significant decrease in liver iron burden with high dose intermittent IV DFO. Histological examination of liver biopsies revealed a decrease in the grade of liver iron storage. Also there was significant improvement in liver enzymes (ALT, AST) after high dose IV DFO. No audiologic or ophthalmologic toxicity or acute or chronic pulmonary complications were observed. CONCLUSIONS: In our cohort of patients with SCD we observed a significant decrease in liver iron burden with high dose IV DFO. Our patients tolerated the therapy well without any major toxicity. This regimen is safe and may be an option for poorly compliant patients with significant iron overload.