Marsha Gerdes

Neurodevelopmental Outcomes in Children With Congenital Heart Disease: Evaluation and Management A Scientific Statement From the American Heart Association

Background— The goal of this statement was to review the available literature on surveillance, screening, evaluation, and management strategies and put forward a scientific statement that would comprehensively review the literature and create recommendations to optimize neurodevelopmental outcome in the pediatric congenital heart disease (CHD) population. Methods and Results— A writing group appointed by the American Heart Association and American Academy of Pediatrics reviewed the available literature addressing developmental disorder and disability and developmental delay in the CHD population, with specific attention given to surveillance, screening, evaluation, and management strategies. MEDLINE and Google Scholar database searches from 1966 to 2011 were performed for English-language articles cross-referencing CHD with pertinent search terms. The reference lists of identified articles were also searched. The American College of Cardiology/American Heart Association classification of recommendations and levels of evidence for practice guidelines were used. A management algorithm was devised that stratified children with CHD on the basis of established risk factors. For those deemed to be at high risk for developmental disorder or disabilities or for developmental delay, formal, periodic developmental and medical evaluations are recommended. A CHD algorithm for surveillance, screening, evaluation, reevaluation, and management of developmental disorder or disability has been constructed to serve as a supplement to the 2006 American Academy of Pediatrics statement on developmental surveillance and screening. The proposed algorithm is designed to be carried out within the context of the medical home. This scientific statement is meant for medical providers within the medical home who care for patients with CHD. Conclusions— Children with CHD are at increased risk of developmental disorder or disabilities or developmental delay. Periodic developmental surveillance, screening, evaluation, and reevaluation throughout childhood may enhance identification of significant deficits, allowing for appropriate therapies and education to enhance later academic, behavioral, psychosocial, and adaptive functioning.

Cognitive and behavior profile of preschool children with chromosome 22q11.2 deletion

A microscopic deletion of chromosome 22q11.2 has been identified in most patients with the DiGeorge, velocardiofacial syndrome, conotruncal anomaly face syndrome, and in some patients with isolated conotruncal cardiac anomalies. This study presents the neurodevelopmental outcome, including cognitive development, language development, speech, neuromuscular development, and behavioral characteristics of 40 preschool children (ages 13 to 63 months) who have been diagnosed with the 22q11.2 deletion. The impact of cardiac disease, cardiac surgery, and the palatal anomalies on this population was also studied. In the preschool years, children with a 22q11.2 deletion are most commonly found to be developmentally delayed, have mild hypotonia, and language and speech delays. The more significantly delayed children are at high risk to be subsequently diagnosed with mild or moderate mental retardation. The global delays and the variations in intelligence found are directly associated with the 22q11.2 deletion and are not explained by physical anomalies such as palatal defects or cardiac defects, or therapeutic interventions such as cardiac surgery. Our findings demonstrate that there is a pattern of significant speech disorders within this population. All of the children had late onset of verbal speech. Behavioral outcomes included both inhibition and attention disorders. Early intervention services are strongly recommended beginning in infancy to address the delays in gross motor skills, speech and language, and global developmental delays.

Apolipoprotein E genotype and neurodevelopmental sequelae of infant cardiac surgery

BACKGROUND There has been increasing recognition of adverse neurodevelopmental sequelae in some children after repair of congenital heart defects. Even among children with the same cardiac defect, significant interindividual variation exists in developmental outcome. Polymorphisms of apolipoprotein E have been identified as a risk factor for worse neurologic recovery after central nervous system injury. METHODS A single-institution prospective study of patients <or=6 months of age undergoing cardiopulmonary bypass for repair of congenital heart defects was undertaken to evaluate the association between apolipoprotein E genotype and postoperative neurodevelopmental dysfunction. Developmental outcomes were evaluated at 1 year of age by using the Bayley Scales of Infant Development. RESULTS One-year evaluation was performed in 244 patients. After adjustment for preoperative and postoperative covariates-including gestational age, age at operation, sex, race, socioeconomic status, cardiac defect, and use of deep hypothermic circulatory arrest-the apolipoprotein E epsilon2 allele was associated with a worse neurologic outcome as assessed by the Psychomotor Developmental Index of the Bayley Scales of Infant Development (P =.036). Patients with the apolipoprotein E epsilon2 allele had approximately a 7-point decrease in the Psychomotor Developmental Index. CONCLUSIONS Apolipoprotein E epsilon2 allele carriers had significantly lower Psychomotor Development Index scores at 1 year of age after infant cardiac surgery. The effect was independent of ethnicity, socioeconomic status, cardiac defect, and use of deep hypothermic circulatory arrest. An effect of the apolipoprotein E epsilon4 allele was not detected. Genetic polymorphisms that decrease neuroresiliency and impair neuronal repair after central nervous system injury are important risk factors for neurodevelopmental dysfunction after infant cardiac surgery.

Effectiveness of Developmental Screening in an Urban Setting

OBJECTIVE: To determine the effectiveness of developmental screening on the identification of developmental delays, early intervention (EI) referrals, and EI eligibility. METHODS: This randomized controlled, parallel-group trial was conducted from December 2008 to June 2010 in 4 urban pediatric practices. Children were eligible if they were <30 months old, term, without congenital malformations or genetic syndromes, not in foster care, and not enrolled in EI. Children were randomized to receive 1 of the following: (1) developmental screening using Ages and Stages Questionnaire-II (ASQ-II and Modified Checklist for Autism in Toddlers (M-CHAT) with office staff assistance, (2) developmental screening using ASQ-II and M-CHAT without office staff assistance, or (3) developmental surveillance using age-appropriate milestones at well visits. Outcomes were assessed using an intention-to-treat analysis. RESULTS: A total of 2103 children were enrolled. Most were African-American with family incomes less than

Predictors of impaired neurodevelopmental outcomes at one year of age after infant cardiac surgery

30 000. Children in either screening arm were more likely to be identified with delays (23.0% and 26.8% vs 13.0%; P < .001), referred to EI (19.9% and 17.5% vs 10.2%; P < .001), and eligible for EI services (7.0% and 5.3% vs 3.0%; P < .001) than children in the surveillance arm. Children in the screening arms incurred a shorter time to identification, EI referral, and EI evaluation than children in the surveillance arm. CONCLUSIONS: Children who participated in a developmental screening program were more likely to be identified with developmental delays, referred to EI, and eligible for EI services in a timelier fashion than children who received surveillance alone. These results support policies endorsing developmental screening.

Apolipoprotein E Genotype Modifies the Risk of Behavior Problems After Infant Cardiac Surgery

OBJECTIVE For most newborns, congenital heart defects (CHD) appear to be isolated anomalies and the brain is presumed to have normal developmental potential. Most studies of neurodevelopmental outcomes have focused on operative management strategies. METHODS Infants with complex CHD and no identified syndromes other than 22q11 microdeletions enrolled in a study of apolipoprotein E (APOE) polymorphisms and developmental outcome were evaluated at one year of age; including genetic evaluation and the Bayley Scales of Infant Development-II [mental (MDI) and psychomotor developmental indices (PDI)]. RESULTS Five hundred and fifty infants enrolled and 359 (20 with 22q11) of 501 survivors (72%) returned. Mean MDI was 90+/-15 and PDI was 78+/-18. Genetic syndromes not identified at birth were confirmed in 28 (8.1%) and suspected in 51 (15.0%). By multivariable analysis, suspected/confirmed genetic syndromes and APOE varepsilon2 allele predicted lower MDI and PDI, all p<0.04. Lower birth weight (p<0.001) and preoperative intubation (p=0.012) predicted lower MDI. Higher hematocrit during the initial operation was associated with higher MDI (p=0.007). Longer postoperative length of stay was predictive of lower PDI (p=0.002). Additional operations with cardiopulmonary bypass were associated with lower MDI and PDI (both p<0.002), but use of deep hypothermic circulatory arrest was not. CONCLUSIONS Patient factors (birth weight and preoperative status) are significant determinants of neurodevelopmental outcomes as opposed to operative management strategies. In this cohort, genetic syndromes unsuspected at birth were surprisingly common and correlate with poor neurodevelopmental outcomes. Without multiple congenital anomalies, syndromes may be missed in infancy. Genetic evaluation should be considered in all infants with CHD.

Taking advantage of early diagnosis: Preschool children with the 22q11.2 deletion

OBJECTIVE: The goal was to evaluate polymorphisms of the APOE gene as modifiers of neurobehavioral outcomes for preschool-aged children with congenital heart defects, after cardiac surgery. METHODS: A prospective observational study with neurodevelopmental evaluation between the fourth and fifth birthdays was performed. Attention and behavioral skills were assessed through parental report. RESULTS: Parents of 380 children completed the neurobehavioral measures. Child Behavior Checklist scores for the pervasive developmental problem scale were in the at-risk or clinically significant range for 15% of the cohort, compared with 9% for the normative data (P < .00001). Attention problem scores were in the at-risk or clinically significant range for 12% of the cohort, compared with 7% for the normative data (P = .0002). The Attention-Deficit/Hyperactivity Disorder Rating Scale-IV, Preschool Version, was completed for 378 children; 30% scored in the clinically significant range for inattention and 22% for impulsivity. After adjustment for covariates, the APOE ε2 allele was significantly associated with higher scores (worse problems) for multiple Child Behavior Checklist indices, including somatic complaints (P = .009), pervasive developmental problems (P = .032), and internalizing problems (P = .009). In each case, the ε4 allele was associated with a better outcome. APOE ε2 carriers had impaired social skills, compared with ε4 carriers (P = .009). CONCLUSIONS: For preschool-aged children with congenital heart defects requiring surgery, parental rating scales showed an increased prevalence of restricted behavior patterns, inattention, and impaired social interactions. The APOE ε2 allele was associated with increased behavior problems, impaired social interactions, and restricted behavior patterns.

Neurodevelopmental outcome of infants with congenital diaphragmatic hernia prospectively enrolled in an interdisciplinary follow-up program.

Purpose: The purpose of this study is to review the neurodevelopmental outcome of infants and preschoolers with a 22q11.2 microdeletion and to discuss the our clinical observations of clinical implications for educational and therapeutic interventions.Methods: One hundred twelve children (4 to 70 mos) with the 22q11.2 deletion were assessed using standardized tests (Bayley Scales of Infant Development-II, Preschool Language Scales, Wechsler Preschool and Primary Scales of Intelligence–Revised).Results: Fifty-four percent of the children were significantly delayed, 24% had mild delay, 22% had average cognitive development, and 80% were below average in language development. Delays are not explained by cardiac defects or palatal defects.Conclusion: Developmental delays, mild hypotonia, language and speech delays, and feeding disorders are common, and this finding indicates the need for early intervention services beginning in infancy for children with the 22q11.2 deletion.

Lower Extremity Neuromotor Function and Short-Term Ambulatory Potential following in utero Myelomeningocele Surgery

PURPOSE The purpose of the study was to evaluate the neurodevelopmental outcome in infants with congenital diaphragmatic hernia (CDH). METHODS Between June 2004 and September 2007, 41 CDH survivors were prospectively enrolled in an interdisciplinary follow-up program. Neurodevelopmental status was evaluated using the Bayley Scales of Infant Development II (prior 2006, n = 9), the Bayley Scales of Infant Development III (after 2006, n = 27), or the Wechsler Preschool and Primary Scale of Intelligence III (children older than 4 years, n = 5). Scores were grouped as average, mildly delayed, and severely delayed by standard deviation intervals (115-85, 71-84, <70), and mixed if average and mildly delayed in either cognitive or language. RESULTS Median age at last assessment was 24 months (range, 6-62). Average, mixed, mildly delayed, and severely delayed scores for neurocognitive and language skills were found in 49%, 19%, 17%, and 15%, respectively. Psychomotor scores were normal, mildly delayed, and severely delayed in 46%, 23%, and 31%, respectively. Autism was present in 7%. Abnormal muscle tonicity was found in 51% (49% hypotonic, 2% hypertonic). Multivariate risk factors for borderline or delayed neurodevelopmental, neurocognitive, and/or psychomotor outcome were intrathoracic liver position (P = .02), presence of a right-sided CDH (P = .02), extracorporeal membrane oxygenation need (P < .001), Gore-Tex patch repair (P = .02), O(2) requirement at 30 days of life (P < .01), and hypotonicity (P < .01). CONCLUSIONS The prospective evaluation in an interdisciplinary follow-up program uncovered striking morbidities in neurodevelopmental status in approximately half of the CDH infants. The most common neurologic sequelae are neuromuscular hypotonicity and psychomotor dysfunction. Patient-specific factors are important determinants of adverse neurologic outcome.

Communication issues in 22q11.2 deletion syndrome: children at risk.

Objective: To evaluate lower extremity neuromotor function (LENF) and short-term ambulatory potential following fetal myelomeningocele (fMMC) closure. Methods: Retrospective chart review of 54 children that underwent fMMC closure at our institution prior to the NIHCD-MOMS trial. Neonatal LENF was compared to predicted function based on spinal lesion level assigned by prenatal ultrasound. Ambulatory status was classified as independent walkers (walks without assistive appliances), assisted walker (requires walking aid), and non-ambulatory (wheelchair bound). Results: Thoracic, lumbar, and sacral level lesions were present in 4, 44 and 6 fMMC infants, respectively. 31/54 of fMMC children (57.4%; median: 2 levels, range: 1–5) had better than predicted, 13/54 (24.1%) same as predicted and 10/54 (18.5%; median: 1 level, range: 1–2) worse than predicted LENF at birth. At a median follow-up age of 66 months (36–113), 37/54 (69%) walk independently, 13/54 (24%) are assisted walkers, and 4/54 (7%) are wheelchair dependent. The strongest factors predicting a lower likelihood to walk independently were higher-level lesion (>L4, p = 0.001) and the development of clubfoot deformity after fetal intervention (p = 0.026). Despite the observed improved ambulatory status, structured evaluation of coordinative skills revealed that the majority of independent ambulators and all children that require assistive devices to walk experience significant deficits in lower extremity coordination. Conclusions: We observed that fMMC surgery in this highly selective population results in better than predicted LENF at birth and short-term ambulatory status. However, fMMC toddlers continue to demonstrate deficits in movement coordination that are characteristic for children with spina bifida.