Objective We sought to investigate the preschool neurodevelopmental outcomes of children following fetal myelomeningocele (fMMC) surgery. Study Design Prior to the Management of Myelomeningocele ...Study trial, 54 children underwent fMMC closure at our institution. Thirty (56%) returned at 5 years of age for standardized neurocognitive examination. Scores were grouped as high-average, average, mildly delayed, and severely delayed by SD intervals. Results Mean verbal intelligence quotient (VIQ), performance intelligence quotient (PIQ), and full intelligence quotient (FIQ) scores were within normal population range. High-average or average scores for VIQ, PIQ, FIQ, and processing speed were found in 93%, 90%, 90%, and 60%, respectively. Mean FIQ and processing speed of nonshunted children were significantly higher than for those who required shunt placement ( P = .02 and P = .01, respectively). Mean VIQ and PIQ tended to be higher in nonshunted fMMC children ( P = .05). Conclusion The majority of fMMC children in this highly selective population had average preschool neurodevelopmental scores. fMMC children who did not require shunt placement were more likely to have better scores.
Objectives We sought to estimate the prevalence and identify the predictors of impaired growth after infant cardiac surgery. Methods We performed a secondary analysis of a prospective study of the ...role of apolipoprotein E gene polymorphisms on neurodevelopment in young children after infant cardiac surgery. Prevalence estimates for growth velocity were derived by using anthropometric measures (weight and head circumference) obtained at birth and at 4 years of age. Genetic evaluation was also performed. Growth measure z scores were calculated by using World Health Organization Child Growth Standards. Growth velocity was evaluated by using 2 different techniques: first by clustering the children into one of 3 growth velocity subgroups based on z scores (impaired growth, difference < −0.5 standard deviation; stable growth, difference of −0.5 to 0.5 standard deviation; and improving growth, difference > 0.5 SD) and second by using continuous difference scores. Statistical analyses were conducted with a combination of proportional odds models for the ordered categories and simple linear regression for the continuous outcomes. Results Three hundred nineteen full-term subjects had complete anthropometric measures for weight and head circumference at birth and 4 years. The cohort was 56% male. Genetic examinations were available for 97% (309/319) of the cohort (normal, 74%; definite or suspected genetic abnormality, 26%). Frequency counts for weight categories were as follows: impaired growth, 37%; stable growth, 31%; and improving growth, 32%. Frequency counts for head circumference categories were as follows: impaired growth, 39%; stable growth, 28%; and improving growth, 33%. The presence of a definite or suspected genetic syndrome ( P = .04) was found to be a predictor of impaired growth for weight but not for head circumference. When growth z scores were used as continuous outcomes, the apolipoprotein E ϵ2 allele was found to be predictive of lower z scores for both weight ( P = .02) and head circumference ( P = .03). Conclusions Impaired growth for both weight and head circumference is common (both >30%) in this cohort of children after infant cardiac surgery. Both the apolipoprotein E ϵ2 allele and the presence of a definite or suspected genetic syndrome were associated with impaired weight growth velocity. The apolipoprotein E ϵ2 allele was also associated with impaired growth velocity for head circumference. Persistent poor growth might have long-term implications for the health and development of children with congenital heart defects.
Objective Adverse neurodevelopmental sequelae are common in children with congenital heart defects. Tetralogy of Fallot is part of the clinical phenotype of many genetic syndromes. We evaluated the ...determinants of neurodevelopmental outcome in patients with tetralogy of Fallot. Methods We performed a subgroup analysis of children with tetralogy of Fallot undergoing complete repair before 6 months of age who were enrolled in a trial assessing apolipoprotein E genotype as a predictor of neurodevelopmental outcome. Assessment included genetic evaluation, neurologic examination, and the Bayley Scales of Infant Development-II, yielding the Mental Developmental Index and Psychomotor Developmental Index. Results Sixty children were tested at 1 year of age. A confirmed or suspected genetic syndrome was identified in 18.3%. The mean Mental Developmental Index was 89 ± 13, and the mean Psychomotor Developmental Index was 81 ± 17. Scores for the Mental Developmental Index (76 ± 13 vs 92 ± 11) and Psychomotor Developmental Index (63 ± 13 vs 85 ± 15) were significantly lower for patients with genetic syndromes. The presence of a genetic syndrome was a predictor of lower Mental Developmental Index and Psychomotor Developmental Index ( P = .002 and P = .001). The presence of tetralogy of Fallot with pulmonary atresia and the apolipoprotein E ε2 allele were predictive of a lower Mental Developmental Index ( P = .001 and P = .035). No other preoperative or operative variables were predictive of worse neurodevelopmental outcome. Conclusions At 1 year of age after repair of tetralogy of Fallot, most patients had neurodevelopmental scores within the normal range. Genetic syndromes and the apolipoprotein E ε2 allele were important risk factors for neurodevelopmental dysfunction and accounted for some interindividual differences in outcome.
To evaluate lower extremity neuromotor function (LENF) and short-term ambulatory potential following fetal myelomeningocele (fMMC) closure.
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).
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.
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.
Adverse neurodevelopmental sequelae are reported among children who undergo early cardiac surgery to repair congenital heart defects (CHD). APOE genotype has previously been determined to contribute ...to the prediction of these outcomes. Understanding further genetic causes for the development of poor neurobehavioral outcomes should enhance patient risk stratification and improve both prevention and treatment strategies.
We performed a prospective observational study of children who underwent cardiac surgery before six months of age; this included a neurodevelopmental evaluation between their fourth and fifth birthdays. Attention and behavioral skills were assessed through parental report utilizing the Attention Deficit-Hyperactivity Disorder-IV scale preschool edition (ADHD-IV), and Child Behavior Checklist (CBCL/1.5-5), respectively. Of the seven investigated, three neurodevelopmental phenotypes met genomic quality control criteria. Linear regression was performed to determine the effect of genome-wide genetic variation on these three neurodevelopmental measures in 316 subjects.
This genome-wide association study identified single nucleotide polymorphisms (SNPs) associated with three neurobehavioral phenotypes in the postoperative children ADHD-IV Impulsivity/Hyperactivity, CBCL/1.5-5 PDPs, and CBCL/1.5-5 Total Problems. The most predictive SNPs for each phenotype were: a LGALS8 intronic SNP, rs4659682, associated with ADHD-IV Impulsivity (P=1.03 × 10(-6)); a PCSK5 intronic SNP, rs2261722, associated with CBCL/1.5-5 PDPs (P=1.11 × 10(-6)); and an intergenic SNP, rs11617488, 50 kb from FGF9, associated with CBCL/1.5-5 Total Problems (P=3.47 × 10(-7)). 10 SNPs (3 for ADHD-IV Impulsivity, 5 for CBCL/1.5-5 PDPs, and 2 for CBCL/1.5-5 Total Problems) had p<10(-5).
No SNPs met genome-wide significance for our three neurobehavioral phenotypes; however, 10 SNPs reached a threshold for suggestive significance (p<10(-5)). Given the unique nature of this cohort, larger studies and/or replication are not possible. Studies to further investigate the mechanisms through which these newly identified genes may influence neurodevelopment dysfunction are warranted.
Objectives: To examine the psychoeducational profile associated with the chromosome 22q11.2 microdeletion (DiGeorge/velocardiofacial syndrome).
Study design: Thirty-three patients (aged 6 to 27 ...years) with a 22q11.2 microdeletion underwent psychoeducational testing as part of a comprehensive evaluation. Nonparametric statistics were used to compare verbal and performance IQ, academic achievement scores, and receptive versus expressive language scores. Post hoc comparisons were made of IQ subtest scores and of language versus verbal IQ.
Results: Full-scale IQ ranged from the normal to the moderately retarded range. Mean verbal IQ was significantly higher than mean performance IQ. In a similar manner, mean reading and spelling scores were superior to the mean mathematics score, although achievement scores typically were in the range of verbal IQ. In addition, many children showed clinically significant language impairments, with mean language scores lower than mean verbal IQ.
Conclusions: The IQ and academic profiles are reminiscent of a “nonverbal learning disability,” although achievement was not discrepant from IQ. The coincidence of language impairment with a relative strength in reading belies a unique neuropsychologic profile. Educational programming for these children must address both verbal and nonverbal deficits. (J Pediatr 1999;134:193-8)
Hyperglycemia has been associated with worse outcome after traumatic brain injury and cardiac surgery in adults. It is not known whether postoperative hyperglycemia results in worse ...neurodevelopmental outcome after infant cardiac surgery.
Secondary analysis of postoperative glucose levels was performed in infants younger than 6 months of age enrolled in a prospective study of genetic polymorphisms and neurodevelopmental outcomes who were undergoing repair of two-ventricle cardiac defects. Neurodevelopmental outcomes at 1 year of age were assessed with the Bayley Scales of Infant Development-II, yielding two indices: Mental Developmental Index and Psychomotor Developmental Index.
Surgical repair was performed in 247 infants with 1 in-hospital and 3 late deaths. Neurodevelopmental evaluation was performed in 188 of 243 (77%) survivors. Glucose levels at cardiac intensive care unit admission and during the first 48 postoperative hours were available for 180 of 188 patients. Mean admission glucose was 328 +/- 106 mg/dL; maximum glucose was 340 +/- 109 mg/dL. At least one glucose was greater than 200 mg/dL in 160 of 180 patients, and 49 of 180 patients (27%) had a glucose greater than 400 mg/dL. Only 1 patient had a glucose less than 50 mg/dL. Female sex (p = 0.02), but no other patient or operative variable, was associated with higher glucose levels. Mean Mental Developmental Index and Psychomotor Developmental Index were 90.6 +/- 14.9 and 81.6 +/- 17.2, respectively. Hyperglycemia was not associated with lower Mental Developmental Index and Psychomotor Developmental Index scores for the entire cohort or for neonates alone.
Hyperglycemia is common early after infant cardiac surgery, but is not associated with worse neurodevelopmental outcome at 1 year of age.
Abstract Introduction Correcting age for prematurity is recommended by the American Academy of Pediatrics and the Centers for Disease Control and Prevention. The use of chronological age instead of ...corrected age for infants born prematurely may result in incorrect interpretations regarding the adequacy of a child’s growth or developmental progress and has the potential to negatively affect care. This study examined the frequency and impact of the use of corrected age by primary care providers. Method A retrospective cross-sectional electronic health record review was performed for all infants < 32 weeks’ gestation who were seen for a health supervision visit in a 31-site pediatric network during a 1-year period. Primary care providers used an electronic health record that defaulted to chronological age information. Results Primary care providers used corrected age for developmental surveillance for 24% of visits, they used chronological age for 71% of visits, and the age used was unclear in 5% of visits. The lower a child’s gestational age and the more that chronological age was used, the more concerns were identified by primary care providers. Dietary changes that included the introduction of solid foods, the start of fluoride, and the introduction of milk typically were recommended on the basis of chronological age. Discussion Primary care providers used chronological age more than corrected age, which influenced assessment and recommendations for care. This study illustrates the impact of not using corrected age, the importance of ensuring that care aligns with guidelines, and the possible influence of the design of the electronic health record on patient care. Because families of premature infants rely on primary care providers to accurately identify sequelae associated with prematurity, and to provide reassurance when it is warranted, these findings have implications for all health care providers who treat premature infants.
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