Universal screening is recommended to reduce the age of diagnosis for autism spectrum disorder (ASD). However, there are insufficient data on children who screen negative and no study of outcomes ...from truly universal screening. With this study, we filled these gaps by examining the accuracy of universal screening with systematic follow-up through 4 to 8 years.
Universal, primary care-based screening was conducted using the Modified Checklist for Autism in Toddlers with Follow-Up (M-CHAT/F) and supported by electronic administration and integration into electronic health records. All children with a well-child visit (1) between 16 and 26 months, (2) at a Children's Hospital of Philadelphia site after universal electronic screening was initiated, and (3) between January 2011 and July 2015 were included (
= 25 999).
Nearly universal screening was achieved (91%), and ASD prevalence was 2.2%. Overall, the M-CHAT/F's sensitivity was 38.8%, and its positive predictive value (PPV) was 14.6%. Sensitivity was higher in older toddlers and with repeated screenings, whereas PPV was lower in girls. Finally, the M-CHAT/F's specificity and PPV were lower in children of color and those from lower-income households.
Universal screening in primary care is possible when supported by electronic administration. In this "real-world" cohort that was systematically followed, the M-CHAT/F was less accurate in detecting ASD than in previous studies. Disparities in screening rates and accuracy were evident in traditionally underrepresented groups. Future research should focus on the development of new methods that detect a greater proportion of children with ASD and reduce disparities in the screening process.
Although the American Academy of Pediatrics recommends screening for autism spectrum disorder (ASD) for all young children, disparities in ASD diagnosis and intervention in minority children persist. ...One potential contributor to disparities could be whether physicians take different actions after an initial positive screen based on patient demographics. This study estimated factors associated with physicians completing the follow-up interview for the Modified Checklist for Autism in Toddlers with Follow-up (M-CHAT-F), and referring children to diagnostic services, audiology, and Early Intervention (EI) immediately after a positive screen.
Children seen in a large primary care network that has implemented universal ASD screening were included if they screened positive on the M-CHAT parent questionnaire during a 16-30 month well child visit (N = 2882). Demographics, screening results, and referrals were extracted from the electronic health record.
Children from lower-income families or on public insurance were more likely to have been administered the follow-up interview. Among children who screened positive, 26% were already in EI, 31% were newly referred to EI, 11% were referred each to audiology and for comprehensive ASD evaluation. 40.2% received at least one recommended referral; 3.7% received all recommended referrals. In adjusted multivariable models, male sex, white versus black race, living in an English-speaking household, and having public insurance were associated with new EI referral. Male sex, black versus white race, and lower household income were associated with referral to audiology. Being from an English-speaking family, white versus Asian race, and lower household income were associated with referral for ASD evaluation. A concurrent positive screen for general developmental concerns was associated with each referral.
We found low rates of follow-up interview completion and referral after positive ASD screen, with variations in referral by sex, language, socio-economic status, and race. Understanding pediatrician decision-making about ASD screening is critical to improving care and reducing disparities.
Objective Many studies of neurodevelopmental outcomes after neonatal and infant cardiac surgery have focused on potentially modifiable risk factors for adverse outcomes, primarily intraoperative ...management strategies and the use of deep hypothermic circulatory arrest. There is increasing evidence that patient-specific factors are more important determinants of outcome. Methods We investigated predictors of neurodevelopmental outcomes at 1 year of age after neonatal and infant cardiac surgery in a subgroup of infants enrolled in a prospective study of apolipoprotein E (APOE) genotype and neurodevelopmental outcome. Children with a variety of 2-ventricle cardiac defects repaired with only 1 operation with cardiopulmonary bypass and no more than 1 episode of deep hypothermic circulatory arrest were included. Neurodevelopmental outcomes at 1 year of age included the Bayley Scales of Infant Development-II, which yield 2 indices, the Mental Developmental Index and the Psychomotor Developmental Index. Results Two hundred forty-seven infants underwent surgical repair between October 1998 and April 2003 with 1 hospital death and 3 deaths before 1 year of age. Neurodevelopmental evaluation was performed in 188 (77%) of 243 survivors, including 56 patients with tetralogy of Fallot, 39 with transposition of the great arteries with intact ventricular septum, 34 with ventricular septal defects, and 59 with other defects. The median age at operation was 56 days (1–186 days), including 72 (38%) neonates. Confirmed or suspected genetic syndromes were present in 59 (31%) of 188 infants. Deep hypothermic circulatory arrest was used in 67 (35%) infants with a median duration of 34 minutes (1-80 minutes). For the entire cohort, the mean Mental Developmental Index was 90.6 ± 14.9 and the mean Psychomotor Developmental Index was 81.6 ± 17.2. For patients without genetic syndromes, the mean Mental Developmental Index was 93.7 ± 13.6 and the mean Psychomotor Developmental Index was 85.1 ± 14.6. For the entire cohort, predictors of lower scores for both the Mental Developmental Index and Psychomotor Developmental Index were presence of a confirmed or suspected genetic syndrome, lower birth weight, and presence of the APOE ϵ2 allele (all P < .04). Black race was associated with higher scores on the Psychomotor Developmental Index ( P = .018). Lower nasopharyngeal temperature during cardiopulmonary bypass was associated with a lower score on the Psychomotor Developmental Index ( P = .03) and was the only intraoperative factor that was a significant predictor of either the Mental or Psychomotor Developmental Index. Conclusions The strongest predictors of a worse neurodevelopmental outcome at 1 year of age were patient-specific factors including presence of a genetic syndrome, low birth weight, and presence of the APOE ϵ2 allele. Patient-specific factors eclipsed the use and duration of deep hypothermic circulatory arrest as predictors of worse neurodevelopmental outcomes.
Background Myelomeningocele (MMC) represents the first nonlethal anomaly to be treated by prenatal intervention. Case series and a prospective, randomized study show that fetal surgery for MMC before ...26 weeks’ gestation may preserve neurological function. Long-term follow-up is a fundamental component to evaluate the overall efficacy of any new medical or surgical procedure. To further delineate the long-term impact of fMMC surgery, we continued to follow children treated in our institution before the Management of Myelomeningocele Study trial by the means of parental questionnaires to assess changes in functional, developmental, and cognitive status as these unique patients grow older. Objective The objective of the study was to evaluate the long-term neurological outcome, executive functioning (EF), and behavioral adaptive skills (BAS) following fetal myelomeningocele (fMMC) surgery. Study Design Prior to the Management of Myelomeningocele Study trial, 54 patients underwent fMMC surgery at our institution. Parents of 42 children (78%) participated in structured questionnaires focusing on neurofunctional outcome. EF and BAS were measured by the Behavior Rating Inventory of Executive Function (BRIEF) and the Adaptive Behavioral Assessment System II. The BRIEF is organized into 3 primary indices including the following: Global Executive Composite, Metacognition Index, and Behavioral Regulation Index. The Adaptive Behavioral Assessment System II results in a general adaptive composite score. Based on SD intervals, EF and BAS were categorized as being average, borderline, or impaired. Results At a median follow-up age of 10 years (range, 8-14 years), 33 (79%) are community ambulators, 3 (9%) are household ambulators, and 6 (14%) are wheelchair dependent. Preschool ambulation was predictive of long-term ambulation ( P < .01), whereas the need for tethered cord surgery was associated with persistent deterioration of ambulatory status ( P = .007). Normal bladder function was found in 26%. Although the majority scored within the average range for the Behavioral Regulation Index, Metacognition Index, and Global Executive Composite indices, significantly more children who had fMMC surgery had deficits in EF in all 3 BRIEF indices compared with the population norms. The general adaptive composite scores were also more likely to fall below average following fMMC surgery. Normal early neurodevelopmental outcomes were predictive of normal EF and BAS ( P < .01). Need for shunting was associated with a significant impairment of BAS ( P = .02). Conclusion The present study suggests that fMMC surgery improves long-term functional outcome. The majority of fMMC children can successfully complete everyday tasks at home and at school. Abnormalities of BAS appear to be more common than impairments in EF and therefore offer an area for early screening and interventional therapy for these at-risk children. Non-shunted fMMC children with normal early neurodevelopmental outcome are less likely to experience problems with EF and BAS. fMMC surgery improves long-term ambulatory status. Symptomatic spinal cord tethering with or without intradural inclusion cyst is associated with functional loss. More than expected fMMC children are continent, but bowel and bladder control continue to be an ongoing challenge for the fMMC children.
Objectives To evaluate the neurodevelopmental outcomes of very preterm (<30 weeks) infants who underwent tracheostomy. Study design Retrospective cohort study from 16 centers of the Eunice Kennedy ...Shriver National Institute of Child Health and Human Development Neonatal Research Network over 10 years (2001-2011). Infants who survived to at least 36 weeks (N = 8683), including 304 infants with tracheostomies, were studied. Primary outcome was death or neurodevelopmental impairment (NDI; a composite of ≥1 of developmental delay, neurologic impairment, profound hearing loss, severe visual impairment) at a corrected age of 18-22 months. Outcomes were compared using multiple logistic regression. We assessed the impact of timing by comparing outcomes of infants who underwent tracheostomy before and after 120 days of life. Results Tracheostomies were associated with all neonatal morbidities examined and with most adverse neurodevelopmental outcomes. Death or NDI occurred in 83% of infants with tracheostomies and 40% of those without (OR adjusted for center 7.0, 95% CI 5.2-9.5). After adjustment for potential confounders, odds of death or NDI remained higher (OR 3.3, 95% CI 2.4-4.6), but odds of death alone were lower (OR 0.4, 95% CI 0.3-0.7) among infants with tracheostomies. Death or NDI was lower in infants who received their tracheostomies before, rather than after, 120 days of life (aOR 0.5, 95% CI 0.3-0.9). Conclusions Tracheostomy in preterm infants is associated with adverse developmental outcomes and cannot mitigate the significant risk associated with many complications of prematurity. These data may inform counseling about tracheostomy in this vulnerable population.
Children with congenital heart defects have an increased risk of neurodevelopmental disability. The impact of environmental chemical exposures during daily life on neurodevelopmental outcomes in ...toddlers with congenital heart defects is unknown.
This prospective study investigated the impacts of early childhood exposure to mixtures of environmental chemicals on neurodevelopmental outcomes after cardiac surgery. Outcomes were assessed at 18 months of age using The Bayley Scales of Infant and Toddler Development-III. Urinary concentrations of exposure biomarkers of pesticides, phenols, parabens, and phthalates, and blood levels of lead, mercury, and nicotine were measured at the same time point. Bayesian profile regression and weighted quantile sum regression were utilized to assess associations between mixtures of biomarkers and neurodevelopmental scores.
One-hundred and forty infants were enrolled, and 110 (79%) returned at 18 months of age. Six biomarker exposure clusters were identified from the Bayesian profile regression analysis; and the pattern was driven by 15 of the 30 biomarkers, most notably 13 phthalate biomarkers. Children in the highest exposure cluster had significantly lower adjusted language scores by -9.41 points (95%CI: -17.2, -1.7) and adjusted motor scores by -4.9 points (-9.5, -0.4) compared to the lowest exposure. Weighted quantile sum regression modeling for the overall exposure-response relationship showed a significantly lower adjusted motor score (β = -2.8 points 2.5th and 97.5th percentile: -6.0, -0.6). The weighted quantile sum regression index weights for several phthalates, one paraben, and one phenol suggest their relevance for poorer neurodevelopmental outcomes.
Like other children, infants with congenital heart defects are exposed to complex mixtures of environmental chemicals in daily life. Higher exposure biomarker concentrations were associated with significantly worse performance for language and motor skills in this population.
Objectives The study objectives were to compare the neurodevelopmental outcomes of preschool survivors of the Fontan procedure with those of children with congenital heart disease undergoing ...biventricular repair and to investigate predictors of neurodevelopmental outcome for those with single ventricle congenital heart disease, including hypoplastic left heart syndrome. Methods Neurodevelopmental outcomes were assessed at 4 years of age, including cognition, visual–motor integration, behavior, social skills, and academic achievement. Unadjusted outcomes were compared between patients with biventricular circulation and patients with single ventricles. Predictors of neurodevelopmental outcome were assessed in the patients with single ventricles. Multiple covariate models were evaluated using patient-related, operative, and postoperative covariates. Results Neurodevelopmental evaluation was performed in 365 children, 112 after the Fontan procedure (hypoplastic left heart syndrome, n = 91; other single ventricle, n = 21) and 253 after biventricular repair. Compared with patients with biventricular circulation, patients with single ventricles performed worse in terms of processing speed, inattention, and impulsivity. Otherwise, there were no significant differences between the groups for any domain. There was a trend toward lower performance for patients with single ventricles on visual motor integration. Outcomes for patients with hypoplastic left heart syndrome were not worse than for other forms of functional single ventricle. Patient factors were more important predictors of neurodevelopmental outcomes than were operative management variables. Conclusions In this cohort, unadjusted neurodevelopmental outcomes for preschool survivors of the Fontan procedure are similar to those for children with congenital heart disease undergoing biventricular repair for most domains. Among the patients undergoing the Fontan procedure, hypoplastic left heart syndrome was not associated with worse outcomes compared with other forms of single ventricle.
Objective To investigate differences in risk factors for depression and anxiety, such as central nervous system involvement in systemic lupus erythematosus (SLE)/mixed connective tissue disease ...(MCTD), by comparing youth with SLE/MCTD to peers with type 1 diabetes mellitus (T1D). Study design We conducted a cross-sectional study of 50 outpatient pairs, ages 8 years and above, matching subjects with SLE/MCTD and T1D by sex and age group. We screened for depression, suicidal ideation, and anxiety using the Patient Health Questionnaire-9 and the Screen for Childhood Anxiety Related Emotional Disorders, respectively. We collected parent-reported mental health treatment data. We compared prevalence and treatment rates between subjects with SLE/MCTD and T1D, and identified disease-specific risk factors using logistic regression. Results Depression symptoms were present in 23%, suicidal ideation in 15%, and anxiety in 27% of participants. Compared with subjects with T1D, subjects with SLE/MCTD had lower adjusted rates of depression and suicidal ideation, yet poorer rates of mental health treatment (24% vs 53%). Non-White race/ethnicity and longer disease duration were independent risk factors for depression and suicidal ideation. Depression was associated with poor disease control in both groups, and anxiety with insulin pump use in subjects with T1D. Conclusion Depression and anxiety are high and undertreated in youth with SLE/MCTD and T1D. Focusing on risk factors such as race/ethnicity and disease duration may improve their mental health care. Further study of central nervous system and other disease-related factors may identify targets for intervention.
Abstract Objectives Despite improved survival in children with hypoplastic left heart syndrome (HLHS), significant concern persists regarding their neurodevelopmental (ND) outcomes. Previous studies ...have identified patient factors, such as prematurity and genetic syndromes, to be associated with worse ND outcomes. However, no consistent relationships have been identified among modifiable management factors, including cardiopulmonary bypass strategies, and ND outcomes after cardiac surgery in infancy. Studies in immature animals, including primates, have demonstrated neurodegeneration and apoptosis in the brain after certain levels and extended durations of anesthetic exposure. Retrospective human studies have also suggested relationships between adverse ND effects and anesthetic exposure. Methods Cumulative minimum alveolar concentration hours (MAC-hrs) of exposure to volatile anesthetic agents (VAA) (desflurane, halothane, isoflurane, and sevoflurane) were collected from an anesthetic database and medical record review for 96 patients with HLHS or variants. ND testing was performed between ages 4 and 5 years, including full-scale IQ, verbal IQ, performance IQ, and processing speed. Four generalized linear modes were hypothesized a priori and tested using a Gaussian (normal) distribution with an identity link. Results Cumulative VAA exposure ranged from 0 to 35.3 MAC-hrs (median 7.5 hours). Using specified covariates identified previously as significant predictors of ND outcomes, statistically significant relationships were identified between total MAC-hrs exposure and worse full-scale IQ and verbal IQ scores ( P 's < .05) alone and after adjusting for relevant covariates. Conclusions Increased cumulative MAC-hrs exposure to VAA is associated with worse ND outcomes in certain domains in children with HLHS and variants.
The goal was to determine the relative effects of underlying genetic factors and current management strategies on neurodevelopmental disabilities among one-year old survivors of palliation for ...hypoplastic left heart syndrome.
Children who underwent staged reconstruction for hypoplastic left heart syndrome and variants were assessed at 1 year of age by using a neuromuscular examination and the Bayley Scales of Infant Development II, which provide the Mental Development Index and the Psychomotor Development Index. The effects of perioperative, operative, and genetic variables on developmental scores were evaluated.
The median birth weight was 3.3 kg (range: 2.1-4.5 kg). Eight-three patients (94%) underwent multiple operations with cardiopulmonary bypass during the first year of life (median: 2 operations). Seven patients (8%) required extracorporeal membrane oxygenation. Twenty-five patients (28%) had a confirmed or suspected genetic syndrome. At 1 year of age, the neuromuscular examination results were abnormal or suspect for 57 patients (65%). The median Mental Development Index score was 90, and 10 patients (11%) had scores of <70 (2 SDs below the general population mean). The median Psychomotor Development Index score was 73, and 42 patients (48%) had scores of <70. In multivariate analyses, younger gestational age, the presence of a genetic syndrome, and the need for preoperative intubation had significant negative effects on neurodevelopmental outcomes. No association was found with operative factors, including duration of deep hypothermic circulatory arrest.
At 1 year of age, there was a significant incidence of neurodevelopmental disabilities in children with hypoplastic left heart syndrome and variants; motor scores were particularly concerning. Many children had suspected or confirmed genetic syndromes, which negatively affected neurodevelopmental outcomes. Surgical variables did not affect neurologic outcomes.
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