Long-term Neurodevelopmental Outcome In Children Research Articles

Long-term neurodevelopmental outcomes in children born with gastroschisis: the tiebreaker

Purpose We evaluated 2-year neurodevelopmental outcomes in children with gastroschisis. Methods We reviewed the records of children with gastroschisis treated between August 2001 and July 2008. Children discharged from the neonatal intensive care unit were referred to the state-sponsored Developmental Tracking Infant Progress Statewide (TIPS) program. We reviewed TIPS assessments performed before age 2 years. School districts evaluated children referred by TIPS and determined their eligibility for early intervention services. Poor outcomes were defined as scores of “failure” or “moderate/high risk” on the screening assessment or enrollment in early intervention services by 2 years. Children with gastroschisis were compared with case-matched nonsurgical, nonsyndromic children of similar gestational age and birth weight. Results One hundred five children were born with gastroschisis, and 46 were followed up with TIPS. There was no statistically significant difference in performance on screening assessments or in the rate of enrollment in early intervention services between the gastroschisis children and controls. Conclusions Children born with gastroschisis have similar 2-year neurodevelopmental outcomes as nonsurgical, nonsyndromic neonatal intensive care unit children of similar gestational age and birth weight. Both groups of children have a higher rate of enrollment in early intervention than their healthy peers. These data suggest that neurodevelopmental outcomes in gastroschisis children are delayed secondary to prematurity rather than the presence of the surgical disease.

Long-Term follow up after intra-Uterine transfusionS; the LOTUS study

BackgroundThe Leiden University Medical Center (LUMC) is the Dutch national referral centre for pregnancies complicated by haemolytic disease of the fetus and newborn (HDFN) caused by maternal alloimmunization. Yearly, 20-25 affected fetuses with severe anaemia are transfused with intra-uterine blood transfusions (IUT). Mothers of whom their fetus has undergone IUT for HDFN are considered high responders with regard to red blood cell (RBC) antibody formation. Most study groups report high perinatal survival, resulting in a shift in attention towards short- and long-term outcome in surviving children.Methods/DesignWe set up a large long-term observational follow-up study (LOTUS study), in cooperation with the Sanquin Blood Supply Foundation and the LUMC departments of Obstetrics, Neonatology and ImmunoHematology & Bloodtransfusion.The first part of this study addresses several putative mechanisms associated with blood group alloimmunization in these mothers. The second part of this study determines the incidence of long-term neurodevelopment impairment (NDI) and associated risk factors in children treated with IUT. All women and their life offspring who have been treated with IUT for HDFN in the LUMC from 1987-2008 are invited to participate and after consent, blood or saliva samples are taken. RBC and HLA antigen profile and antibodies are determined by serologic or molecular techniques. Microchimerism populations are tested by real time polymerase chain reaction (RT PCR).All children are tested for their neurological, cognitive and psychosocial development using standardised tests and questionnaires. The primary outcome is neurodevelopmental impairment (NDI), a composite outcome defined as any of the following: cerebral palsy, cognitive or psychomotor development < 2 standard deviation, bilateral blindness and/or bilateral deafness.DiscussionThe LOTUS study includes the largest cohort of IUT patients ever studied and is the first to investigate post-IUT long-term effects in both mother and child. The results may lead to a change in transfusion policy, in particular future avoidance of certain incompatibilities. Additionally the LOTUS study will provide clinicians and parents better insights in the long-term neurodevelopmental outcome in children with HDFN treated with IUTs, and may improve the quality of antenatal counselling and long-term guidance.

Long-Term Neurodevelopment of Children Exposed In Utero to Ciclosporin After Maternal Renal Transplant

Immunosuppressant therapy is essential in the prevention of organ transplant rejection. To evaluate the long-term neurodevelopmental outcomes of children following in utero ciclosporin (cyclosporine) exposure after maternal renal transplantation. A cohort study with matched controls using a prospectively collected database was conducted to assess neurocognitive and behavioral outcomes using standardized measures. Thirty-nine children exposed in utero to ciclosporin therapy following maternal renal transplantation were assessed (15 single pregnancies, 24 multiple pregnancies) and compared with 38 matched unexposed children. Intelligence, visuomotor abilities, and psychologic adjustment were measured using the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R), the Beery Developmental Test of Visual-Motor Integration (VMI-4) and the Wide Range Assessment of Visual Motor Abilities (WRAVMA), and the Child Behavior Checklist (CBCL), respectively. Statistical analysis, including regression, was performed to determine the significant predictors for the main outcome, full-scale IQ (FIQ). There were no significant differences in FIQ, verbal IQ (VIQ), performance IQ (PIQ) or behavioral outcomes between exposed and unexposed children or between single and multiple delivery groups. Thirty-three percent of exposed children were premature versus 0.5% in unexposed controls (p < 0.01). Prematurity was associated with low birthweight, high rates of perinatal complications, and instrumental deliveries. Relative to full-term children, premature, low birthweight children in the ciclosporin-exposed group had significantly lower FIQ and VIQ scores (101.04 vs 111.31 [p = 0.008] and 102.31 vs 113.08 [p = 0.021], respectively). Maternal IQ and socioeconomic status were positive and significant predictors for children's IQ (p < 0.001 and p = 0.03, respectively). There were no statistically significant differences in exposed children's IQ who were and were not breastfed. In this cohort, there was no association between in utero exposure to ciclosporin and long-term neurocognitive and behavioral development in children after maternal renal transplantation. Maternal IQ and socioeconomic status are positive predictors for children's intelligence. However, maternal renal transplantation and associated co-morbidity is associated with higher rates of premature delivery and consequent poorer neurocognitive and behavioral outcomes. Proper management of maternal morbidity and improved obstetric care may improve the child's profile.

Neurodevelopmental outcome in prenatally diagnosed isolated agenesis of the corpus callosum

To evaluate long-term neurodevelopmental outcomes in children with prenatally diagnosed, isolated agenesis of the corpus callosum (ACC). We retrospectively reviewed data for 20 children born between January 1991 and November 2003 in the Haute-Normandie region of France with a prenatal diagnosis of isolated ACC. We collected data on pre-and postnatal neuroimaging findings, clinical features at birth and neurodevelopmental outcomes. Follow-up ranged from 3 to 16 years. ACC was complete in 11 patients (55%), partial in 2 (10%), hypoplastic in 3 (15%) and associated with an interhemispheric cyst in 4 (20%). Neurodevelopmental outcome was normal in 11 (55%) patients, including 8 with complete ACC; moderate disability was present in 5 (25%) patients and severe disability in 4 (20%) patients. In 3 of the 4 patients with severe disability, postnatal cerebral magnetic resonance imaging (MRI) showed additional major cerebral abnormalities. Neurodevelopmental outcome was good in most of our patients with isolated ACC, with 80% of patients having normal outcomes or moderate disabilities. A prenatal diagnosis of isolated ACC may not warrant termination of pregnancy. A carefully interpreted prenatal cerebral MRI is crucial to detect associated cerebral abnormalities; a longer follow-up is necessary to look for moderate disabilities.

Perioperative Neuroprotective Strategies

Long-term neurodevelopmental impairment is common in newborns and infants undergoing corrective or palliative congenital heart surgery. The etiologies of neurodevelopmental morbidity in these children are multifactorial and include prenatal, preoperative, intraoperative, and postoperative factors. Perioperative neurologic monitoring is thought to be integral to prevention or rescue from adverse neurologic events. Recent advances in perfusion techniques for congenital heart surgery now ensure adequate cerebral O(2) delivery during all phases of cardiopulmonary bypass. Periventricular leukomalacia and other serious neurologic injury can be minimized by an optimized perfusion strategy of continuous high-flow, high hematocrit cardiopulmonary bypass, minimal use of deep hypothermic circulatory arrest, antegrade cerebral perfusion during aortic arch reconstruction, pH-stat blood gas strategy, and cerebral monitoring with NIRS and trans-cranial Doppler. Because there is evidence that brain injury can also occur in the prenatal, preoperative, and postoperative periods, improved strategies to prevent injury in these arenas are much needed. Extensive further clinical investigation is warranted to identify neuroprotective management strategies for the operating room and intensive care unit to preserve neurologic function and optimize long-term neurodevelopmental outcomes in children with congenital heart disease.

Long-term neurodevelopmental outcome in twin-to-twin transfusion syndrome in the eurofoetus trial

SYNDROME IN THE EUROFOETUS TRIAL LISA ORTQVIST, SYLVIE CHEVRET, LAURENCE BUSSIERES, STEPHANIE STARACI, FABIENNE HUARD, YVES VILLE, Paris-Ouest University VSQ, Department of Gynecology and Obstetrics, Paris, France, Universite Paris 7, INSERM 444, Statistics, Paris, France, Delegation Regionale a la Recherche Clinique, Hopital Saint-Louis, Clinical Research, Paris, France OBJECTIVE: To investigate long-term neuro-developmental outcome of children born in the Eurofoetus RCT comparing endoscopic laser surgery and serial amnioreduction in twin-to-twin transfusion syndrome (TTTS). STUDY DESIGN: Survivors beyond 6 months were followed-up and evaluated by standardized examination (Amiel-Tison and Gosselin) and by the Ages and Stages questionnaires (ASQ). Primary outcome was the incidence of severe neurological abnormalities leading to permanent disability. In addition children were subjected to cognitive evaluation using Wechsler Intelligence Scale for Children (WISC-IV) at the age of 6. RESULTS: 120 children (73 treated with laser (L) and 47 with amnioreduction (A)) survived beyond 6 months. Six were lost to follow-up. 114 children (69 L and 45 A) were examined at a median (25-75 percentile) of 5.3 (4.4-6.1) years. Incidence of major neurological problems was 15/114 (13.1%). Univariate analysis is summarized in Table 1. Multivariate analysis showed that only gestational age at delivery, 1-minute Apgar score and Quintero staging were predictive factors. Neurological evaluation changed over time with improvement or worsening in 4/114 and 5/114 cases but remained stable from the age of 2. Normal ASQ scores were found in 72% and 89% and in 72% and 80% of cases at 2 and 4 years in the L and A groups respectively (NS). IQ was below 85 in 0/10 and 2/9 children in L and A groups at the age of 6. CONCLUSION: Among TTTS survivors, the risk of developing long-term major neurological impairment depends upon perinatal factors but not of fetal treatment.

Long-Term Neurodevelopmental Outcome of 167 Children After Intrauterine Laser Treatment for Severe Twin???Twin Transfusion Syndrome

Between 10% and 15% of monochorionic diamniotic twin pregnancies are complicated by severe twin–twin transfusion syndrome (TTTS), a cause of perinatal morbidity and death. The syndrome results from an unbalanced transfusion of blood across placental vascular anastomoses from one twin, the donor, to the other, the recipient. This prospective study was done to ascertain long-term neurodevelopmental outcomes in children born after intrauterine laser coagulation. The subjects were 167 infants from 127 pregnancies who survived severe TTTS in the years 1997 through 1999. At a mean age of 38 months, the children were assessed by a detailed physical and neurologic examination, Griffiths Developmental Test Scales and Snijders-Oomen NonVerbal-Intelligence Test (SON). Normal neurological findings were recorded in 87% of the children, and another 7% had minor abnormalities. Only 10 children, 6% of the total, had major neurologic abnormalities. Outcomes were comparable in former donors and recipients, and in infants born as twins and those born as singletons. The Griffiths test identified developmental delay in 25% of the 40 children tested. Seven of these 10 infants had severe neurologic abnormalities and the other 3 had minor abnormalities. Only 2 of 112 infants tested by the SON had subnormal results. All children who were neurologically normal had normal test results. Significantly more children with major or minor neurologic abnormalities were born before 32 weeks gestation compared with those who were neurologically normal. However, neither birth weight nor gestational age at the time of treatment was related to the outcome. These results, in children with severe TTTS who underwent fetoscopic laser coagulation, are more favorable than those reported from other studies. At present, this would appear to be the best available treatment for severe TTTS.

Long-term neurodevelopmental outcome of 167 children after intrauterine laser treatment for severe twin-twin transfusion syndrome

This study was undertaken to investigate long-term neurodevelopmental outcome of children born after intrauterine laser coagulation for severe twin-twin transfusion syndrome. One hundred sixty-seven surviving infants treated between June 1997 and September 1999 were investigated at a median age of 3 years and 2 months. All children underwent a detailed standardized physical and neurologic examination and a standardized developmental test (Griffiths' Developmental Test Scales and Snijders-Oomen Non-Verbal-Intelligence Test). One hundred forty-five infants (86.8%) showed normal development, 12 infants (7.2%) showed minor neurologic abnormalities, and 10 infants (6.0%) major neurologic abnormalities. There was no difference in outcome for the former donors/recipients (P = .349) and between infants who were born as twins or singletons (P = .088). With a high rate (86.8%) of normal neurodevelopmental outcome and an incidence of only 6.0% of major neurologic deficiencies, intrauterine laser coagulation seems to be the best treatment option for severe twin-twin transfusion syndrome.

Long-term neurodevelopmental outcome in twin-to-twin transfusion syndrome

Objective The purpose of this study was to determine the long-term neurodevelopmental outcome in children after twin-to-twin transfusion syndrome. Study design Maternal and neonatal medical records of all twin-to-twin transfusion syndrome patients who were admitted to our center between 1990 and 1998 were reviewed. Neurologic and mental development at school age was assessed during a home visit in all twin-to-twin transfusion syndrome survivors. Results A total of 33 pregnancies with twin-to-twin transfusion syndrome were identified. Four couples opted for termination of pregnancy. All other pregnancies were treated conservatively, 18 pregnancies (62%) with serial amnioreductions and 11 pregnancies (38%) without intrauterine interventions. Mean gestational age at delivery was 28.6 weeks (range, 20-37 weeks). The perinatal mortality rate was 50% (29/58 infants). The birth weight of the donor twins was less than the recipient twins ( P<.001). Systolic blood pressure at birth was lower in donors than in recipients ( P = .023), and donors required inotropic support postnatally more frequently than did recipients ( P = .008). The incidence of hypertension at birth was higher in recipients than in donors ( P = .038). Abnormal cranial ultrasonographic findings were reported in 41% of the neonates (12/29 neonates). All long-term survivors (n = 29 neonates) were assessed during a home visit. Mean gestational age at birth of the surviving twin was 31.6 weeks (range, 25-37 weeks). The mean age at follow-up was 6.2 years (range, 4-11 years). The incidence of cerebral palsy was 21% (6/29 infants). Five of 6 children with cerebral palsy had an abnormal mental development. The incidence of cerebral palsy in the group of survivors who were treated with serial amnioreduction was 26% (5/19 infants). Four children were born after the intrauterine fetal demise of their co-twin, 2 of which had cerebral palsy. Conclusion The incidence of adverse neurodevelopmental outcome in twin-to-twin transfusion syndrome survivors is high, especially after the intrauterine fetal demise of a co-twin.

Early predictors of neurodevelopmental outcome in symptomatic congenital cytomegalovirus infection

Objective: To determine the ability of neonatal clinical, audiologic, and computed tomography (CT) findings to predict long-term neurodevelopmental outcome in children with symptomatic congenital cytomegalovirus (CMV) infection. Methods: Longitudinal cohort study of children (n = 41) with symptomatic congenital CMV infection evaluated at birth and followed up with serial age-appropriate neurodevelopmental testing. The performance of birth characteristics as predictors of long-term outcome were determined, and clinical and CT scoring systems were developed and correlated with intellectual outcome. Results: Microcephaly was the most specific predictor of mental retardation (100%; 95% CI 84.5-100) and major motor disability (92.3%; 95% CI 74.8-99). An abnormality detected by CT was the most sensitive predictor for mental retardation (100%; 95% CI 82.3-100) and motor disability (100%; 95% CI 78.2-100). A highly significant (P <.001) positive correlation was found between head size at birth and the intelligence/developmental quotient (IQ/DQ). Approximately 29% of children had an IQ/DQ >90. There was no association between sensorineural hearing loss at birth and cognitive outcome. However, children with sensorineural hearing loss on follow-up (congenital and late-onset) had a lower IQ/DQ (P =.006) than those with normal hearing. Conclusions: The presence of microcephaly at birth was the most specific predictor of poor cognitive outcome in children with symptomatic congenital CMV infection, whereas children with normal findings on head CT and head circumference proportional to weight exhibited a good cognitive outcome. (J Pediatr 2001;138:325-31)

Acute and long-term neurodevelopmental outcomes in children following bone marrow transplantation.

Bone marrow transplantation offers a potential cure for a number of childhood cancers, sickle cell anemia, and stabilization of a deteriorating and debilitating process in a number of metabolic disorders and leukodystrophies. Depending upon the disease, treatment prior to BMT, and natural history of the disease, BMT may increase the risk of neuropsychological toxicity for children undergoing BMT, or may actually improve their long-term neurodevelopmental outlook. The role of factors such as pre-BMT therapy, age at time of treatment, presence or absence of total body irradiation, and toxicities associated with GVHD are presented for consideration. A developmental model for understanding the emergence of neurocognitive effects of BMT is reviewed, and strategies for intervention are considered.

Acute and long-term neurodevelopmental outcomes in children following bone marrow transplantation

Acute and long-term neurodevelopmental outcomes in children following bone marrow transplantation