Lower oxygen saturation targets in preterm infants are not associated with increased rates of pulmonary hypertension.

BACKGROUND: The optimal oxygen saturation target in preterm infants is not known. In this study, we aimed to assess the effect of lower oxygen saturation targets on the rate of bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), and pulmonary hypertension (PH) in preterm infants. METHODS: Retrospective cohort study comparing BPD, ROP, and PH incidence among two cohorts of infants born at≤32 weeks gestation with different oxygen saturation targets at≥34 weeks post-menstrual age (PMA): cohort 1, 94-98% (n = 126); cohort 2, 92-97% (n = 121). Groups compared by Chi-square test, t-test, and multivariable logistic regression. RESULTS: When comparing cohort 1 (average gestational age 29.8 weeks, average birth weight 1271g) with cohort 2 (average gestational age 29.6 weeks, average birth weight 1299g), there was no difference in rate of BPD (24% vs. 19%, p = 0.38), ROP (4% vs. 3%, p = 0.49), or PH (2% vs. 4%, p = 0.44). CONCLUSION: An oxygen saturation target of 92-97% at≥34 weeks PMA was not associated with a higher rate of PH or lower rate of BPD or ROP when compared with a higher target of 94-98%.

ß-2 adrenergic receptor gene methylation is associated with decreased asthma severity in inner-city schoolchildren: asthma and rhinitis.

BACKGROUND: Genetic variation in the ß-2 adrenergic receptor gene (ADRB2) has been implicated in asthma severity and control with conflicting results. Epigenetic variation in the ADRB2 may play an important role in asthma phenotype. OBJECTIVE: We aimed to evaluate whether DNA methylation of ADRB2 is associated with asthma phenotypes in inner-city school-aged children. METHODS: Multiple CpG sites in the promoter region of ADRB2 gene were analysed in 177 children enrolled in the School Inner-City Asthma Study. Blood- or saliva-derived DNA was measured by bisulphite-polymerase chain reaction pyrosequencing assay. Average percentage DNA methylation across the sites was evaluated for association with asthma severity (report of dyspnoea, night-time symptoms, rescue medication use, and baseline spirometry) and morbidity (school absences and unscheduled healthcare visits). Three clades composed of highly correlated methylation sites within the methylated segment of ADRB2 were further analysed. RESULTS: Methylation of individual sites generally ranged from 0% to 6% with average percentage methylation across sites of 2.4%. Univariate analyses strongly favoured the association of higher percentage methylation with lower asthma severity measured by report of dyspnoea. Furthermore, there was a non-significant trend towards less rescue medication use, night-time symptoms, school absences, activity limitation due to asthma, and improved lung function measurements with increased methylation. Multivariate analysis demonstrated methylation of ADRB2 gene significantly associated with less dyspnoea (odds ratio (OR) 0.2, 95% confidence interval (CI), 0.1-0.6, P = 0.002). Each of the three clades of methylation sites showed a strong, but not statistically significant, effect on decreased dyspnoea. CONCLUSIONS AND CLINICAL RELEVANCE: DNA methylation in the ADRB2 gene is associated with decreased asthma symptom severity, suggesting a role for methylation in asthma phenotypes.

Examining the nature of the comorbidity between pediatric attention deficit/hyperactivity disorder and post-traumatic stress disorder.

OBJECTIVE: This study sought to address the link between attention deficit/hyperactivity disorder (ADHD) and post-traumatic stress disorder (PTSD) in youth by providing a comprehensive comparison of clinical correlates of ADHD subjects with and without PTSD across multiple non-overlapping domains of functioning and familial patterns of transmission. METHOD: Participants were 271 youths with ADHD and 230 controls without ADHD of both sexes along with their siblings. Participants completed a large battery of measures designed to assess psychiatric comorbidity, psychosocial, educational, and cognitive parameters. RESULTS: Post-traumatic stress disorder was significantly higher in ADHD probands vs. controls (5.2% vs. 1.7%, χ(2) (1) = 4.36, P = 0.04). Irrespective of the comorbidity with PTSD, ADHD subjects had similar ages at onset of ADHD, similar type and mean number of ADHD symptoms, and similar ADHD-associated impairments. PTSD in ADHD probands was significantly associated with a higher risk of psychiatric hospitalization, school impairment, poorer social functioning and higher prevalences of mood, conduct disorder, and anxiety disorders. The mean onset of PTSD (12.6 years) was significantly later than that of ADHD and comorbid disorders (all P < 0.05). Siblings of ADHD and ADHD + PTSD probands had higher prevalences of ADHD vs. siblings of controls (35% vs. 18%, z = 4.00, P < 0.001 and 67% vs. 18%, z = 4.02, P < 0.001 respectively) and siblings of ADHD+PTSD probands had a significantly higher prevalence of PTSD compared with the siblings of ADHD and control probands (20% vs. 3% and 3%, z = 2.99, P = 0.003 and z = 2.07, P = 0.04 respectively). CONCLUSION: Findings indicate that the comorbidity with PTSD in ADHD leads to greater clinical severity as regards psychiatric comorbidity and psychosocial dysfunction. ADHD is equally familial in the presence of PTSD in the proband indicating that their co-occurrence is not owing to diagnostic error.

Deficient emotional self-regulation and pediatric attention deficit hyperactivity disorder: a family risk analysis.

BACKGROUND: Although deficient emotional self-regulation (DESR) is associated with attention deficit hyperactivity disorder (ADHD), little research investigates this association and little is known about its etiology. Family studies provide a method of clarifying the co-occurrence of clinical features, but no family studies have yet addressed ADHD and DESR in children. METHOD: Subjects were 242 children with ADHD and 224 children without ADHD. DESR was operationalized using an aggregate score ≥180 and <210 in the anxious/depressed, attention and aggression scales (AAA profile) of the Child Behavior Checklist (CBCL), termed the CBCL-DESR profile. The CBCL-bipolar (CBCL-BP) profile was defined as ≥210 on the CBCL-AAA scale. We examined the familial transmission of ADHD and the CBCL-AAA scale in families selected through probands with and without these conditions. RESULTS: We found a linear increase in the prevalence of CBCL-DESR in siblings as indexed by the Control, ADHD, ADHD+CBCL-DESR and ADHD+CBCL-BP proband groups. While the ADHD siblings were at elevated risk for both the CBCL-DESR and CBCL-BP compared with non-ADHD siblings, a significantly higher rate of CBCL-BP in the siblings of ADHD+CBCL-BP probands was found compared with siblings of the Control probands. CONCLUSIONS: ADHD shows the same degree of familial transmission in the presence or absence of DESR. CBCL-DESR and CBCL-BP are familial, but further work is needed to determine if these definitions are distinctly familial or represent a continuum of the same psychopathology.

Predictors of persistence in girls with attention deficit hyperactivity disorder: results from an 11-year controlled follow-up study.

OBJECTIVE: This study sought to examine the age-dependent persistence of attention deficit hyperactivity disorder (ADHD) and its predictors in a large sample of girls with and without ADHD followed prospectively for 11 years into young adulthood. METHOD: Participants were girls with (N=96) and without (N=91) ADHD and were 6-17 years old at the baseline assessment (mean age, 11 years) and 15-30 years old at the follow-up assessment (mean: 22 years). Participants were comprehensively and blindly assessed with structured diagnostic interviews and assessments of cognitive, social, school, and family functioning. RESULTS: At the 11-year follow-up, 33.3% met full criteria for ADHD, 29.2% showed partial persistence of the disorder, 10.4% had impaired functioning, and 4.2% were remitted but treated (77.1% of the sample). Predictors of persistence were psychiatric comorbidity, family history of psychopathology, and family and school functioning at baseline. CONCLUSION: These long-term, prospective, follow-up findings extend to girls findings that ADHD is persistent over the long term and can be predicted from psychosocial adversity and psychiatric comorbidity ascertained 11 years earlier.

The long-term longitudinal course of oppositional defiant disorder and conduct disorder in ADHD boys: findings from a controlled 10-year prospective longitudinal follow-up study.

BACKGROUND: A better understanding of the long-term scope and impact of the co-morbidity with oppositional defiant disorder (ODD) and conduct disorder (CD) in attention deficit hyperactivity disorder (ADHD) youth has important clinical and public health implications. METHOD: Subjects were assessed blindly at baseline (mean age=10.7 years), 1-year (mean age=11.9 years), 4-year (mean age=14.7 years) and 10-year follow-up (mean age=21.7 years). The subjects' lifetime diagnostic status of ADHD, ODD and CD by the 4-year follow-up were used to define four groups (Controls, ADHD, ADHD plus ODD, and ADHD plus ODD and CD). Diagnostic outcomes at the 10-year follow-up were considered positive if full criteria were met any time after the 4-year assessment (interval diagnosis). Outcomes were examined using a Kaplan-Meier survival function (persistence of ODD), logistic regression (for binary outcomes) and negative binomial regression (for count outcomes) controlling for age. RESULTS: ODD persisted in a substantial minority of subjects at the 10-year follow-up. Independent of co-morbid CD, ODD was associated with major depression in the interval between the 4-year and the 10-year follow-up. Although ODD significantly increased the risk for CD and antisocial personality disorder, CD conferred a much larger risk for these outcomes. Furthermore, only CD was associated with significantly increased risk for psychoactive substance use disorders, smoking, and bipolar disorder. CONCLUSIONS: These longitudinal findings support and extend previously reported findings from this sample at the 4-year follow-up indicating that ODD and CD follow a divergent course. They also support previous findings that ODD heralds a compromised outcome for ADHD youth grown up independently of the co-morbidity with CD.

Stability of executive function deficits into young adult years: a prospective longitudinal follow-up study of grown up males with ADHD.

OBJECTIVE: Although individuals with attention deficit-hyperactivity disorder (ADHD) commonly exhibit deficits in executive functions that greatly increase the morbidity of the disorder, all available information on the subject is cross sectional. METHOD: Males (n = 85) 9-22 years with ADHD followed over 7 years into young adulthood were assessed on measures of sustained attention/vigilance, planning and organization, response inhibition, set shifting and categorization, selective attention and visual scanning, verbal and visual learning, and memory. A binary definition of executive function deficits (EFDs) was defined based on a subject manifesting at least two abnormal tests 1.5 standard deviations from controls. RESULTS: The majority of subjects maintained EFDs over time (kappa: 0.41, P < 0.001; sensitivity: 55%, specificity: 85%, positive predictive value: 69%, and negative predictive value: 75%). CONCLUSION: Considering the morbidity of EFDs, these findings stress the importance of their early recognition for prevention and early intervention strategies. EFDs are stable over time.