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PubMed1995

Effect of preterm premature rupture of membranes on neurodevelopmental outcome: follow up at two years of age.

OBJECTIVE: To evaluate the impact of preterm premature rupture of membranes on the neurodevelopmental outcome of infants, assessed at two years of age. DESIGN: A prospective observational study of surviving preterm infants born after premature rupture of membranes and of infants born after spontaneous preterm labour with intact membranes. The study was carried out in the period 1986 to 1991. SETTING: Pavia, Italy. SUBJECTS: One hundred and forty singleton infants born prematurely after premature rupture of membranes between 24 and 34 weeks of gestation and 120 controls of similar gestational age born after spontaneous preterm labour with intact membranes. MAIN OUTCOME MEASURES: Infant neurodevelopmental outcome at two-year follow up. RESULTS: After adjustment, by logistic analysis for the effect of gestational age and birthweight, infants born after premature rupture of membranes were more likely to have severe neurodevelopmental impairment (spastic tetraplegia and/or Bayley mental developmental index < 71) than controls (adjusted OR 5.75, 95% CI 1.22-27.18). Multivariate analysis of linear trend showed a statistically significant relation of duration of membrane rupture to occurrence of severe intraventricular haemorrhage, cystic periventricular leucomalacia and moderate to severe infant neurodevelopmental impairment. CONCLUSION: Infants born after prolonged premature rupture of membranes are at higher risk of subsequent moderate to severe neurodevelopmental impairment than those born after spontaneous labour with intact membranes.

Birth Weight↗
PubMed2005

Two-year neurodevelopmental outcome in children conceived by intracytoplasmic sperm injection: prospective cohort study.

OBJECTIVE: Primary outcome was to compare neurodevelopmental outcome at two years in intracytoplasmic sperm injection (ICSI) conceived children versus matched controls. Secondary outcome was to determine incidence of major congenital malformations and study perinatal outcome. DESIGN: Prospective cohort study. SETTING: Tertiary care perinatal centre over a period of 13 months. POPULATION: Seventy-six ICSI conceived children and 261 matched controls selected by matching for maternal age, sex, date of delivery, race, plurality and parity. METHODS: Mental Development Index (MDI) and Psychometric Development Index (PDI) of the Bayley's Scale of Development (BSID-II) and Vineland Adaptive Behaviour Scale (VABS) were used to assess the neurodevelopmental and functional outcome. The congenital malformations were classified according to ICD-9 code. MAIN OUTCOME MEASURES: Primary outcome measure--neurodevelopmental and functional outcomes. Secondary outcome measure--congenital malformations and perinatal outcomes. RESULTS: Neurodevelopmental and functional outcome were comparable in both groups. The mean MDI score was 92 [16] versus 90 [14] in the study and control groups respectively. Fourteen (18.4%) in the ICSI group had MDI <85 compared with 87 (33%) controls (P= 0.002). On linear regression the MDI was independently affected by plurality (P= 0.001), maternal education and socio-economic status (P= 0.01). The study group had a lower gestation (36 [3] vs 37.1 [2] weeks; P= 0.005) and a higher incidence of prematurity <34 weeks [19 (25%)] vs [31 (12%)] P= 0.012]. Six (7.9%) of the ICSI babies and seven (2.7%) of the controls had a major congenital malformation (P= 0.05). CONCLUSIONS: Children born by ICSI pregnancies did not have an adverse neurodevelopmental outcome. The incidence of major congenital malformations in ICSI needs further evaluation.

Child, Preschool↗
PubMed1995

Neurodevelopmental outcome of preterm infants with bronchopulmonary dysplasia.

The neurodevelopmental outcome of 78 infants with bronchopulmonary dysplasia (BPD) was compared with that of 78 control infants matched for birthweight. To determine the effect of the severity of BPD, 62 infants requiring oxygen at 36 weeks' postmenstrual age (sBPD) were compared with their matched controls. Infants were followed up to 2 years of age, corrected for prematurity, and were classified for neurological impairment, developmental delay, and neurodevelopmental disability. Seventy six (98%) BPD infants and 71 (91%) controls had follow up data available to two years. Neurological impairment, developmental delay, and neurodevelopmental disability occurred more frequently in infants with BPD than in controls but this was not significant. For infants with sBPD, the increased incidence of neurological impairment and definite developmental delay was not significant when compared with the controls, though neurodevelopmental disability occurred more frequently (odds ratio (OR) 3.6: 95% confidence intervals (CI) 1.1-11.8). Predictors of disability in infants with sBPD included periventricular haemorrhage (OR 19.4: 95% CI 4.3-86.6), ventricular dilatation (OR 12.8: 95% CI 2.9-57.3), and sepsis (OR 5.0: 95% CI 1.3-19.4). Adjusting for the presence of these factors, the association between BPD and disability was no longer apparent (OR 0.9: 95% CI 0.2-3.6). The findings suggest that BPD is not independently associated with adverse neurodevelopmental outcome.

Bronchopulmonary Dysplasia↗
PubMed2006

Neurodevelopmental outcome of severe neonatal hemolytic hyperbilirubinemia.

We recruited 128 neonates with hyperbilirubinemia over a 5-year period (1995-2000) to study the short- and long-term effects of hemolytic hyperbilirubinemia on the auditory brainstem pathway and neurodevelopmental status. These children were divided into two groups: (1) a hemolytic group (n = 29; ABO incompatibility [n = 19], Rh incompatibility [n = 1], glucose-6-phosphate dehydrogenase deficiency [n = 8] and both ABO incompatibility and glucose-6-phosphate dehydrogenase deficiency [n = 1]) and (2) a nonhemolytic group (n = 99). All received phototherapy. Exchange transfusions were performed for four (13.8%) in the hemolytic group and three (3%) in the nonhemolytic group. The brainstem auditory evoked potential was recorded at a mean age of 3.2 months in the hemolytic group and 3.1 months in the nonhemolytic group. Serial brainstem auditory evoked potential assessments were performed until 2 years of age (3 in the hemolytic group and 18 in the nonhemolytic group). All had regular physical, neurologic, visual, and auditory evaluation until 3 years of age. The rate of exchange transfusion was significantly higher in the hemolytic group than in the nonhemolytic group (P < .05). Brainstem auditory evoked potential abnormalities at the initial assessment occurred in three (10.4%) in the hemolytic group (all related to ABO incompatibility) and nine (9.1%) in the nonhemolytic group. At 2 years, the brainstem auditory evoked potential returned to normal except in three cases with a slightly increased hearing threshold (one [3.5%] in the hemolytic group at 60 dB nHL and two [2%] in the nonhemolytic group at 50 dB nHL]). There were no significant differences in the rate of brainstem auditory evoked potential abnormalities at the initial or subsequent assessments between both groups. All except five cases had a normal neurodevelopmental outcome at 3 years (three [two with ABO incompatibility and one with glucose-6-phosphate dehydrogenase deficiency] in the hemolytic group [10.4%] and two [2%] in the nonhemolytic group). All had mild motor delay and hypotonia, which returned to normal at 3 years. The rate of abnormal neurodevelopmental outcome was higher in the hemolytic group than in the nonhemolytic group, although with no significant difference between both groups (P = .08). All five cases in both groups with abnormal neurodevelopment had a normal brainstem auditory evoked potential at the initial assessment. There was no relationship between the abnormal initial brainstem auditory evoked potential and the final neurodevelopmental outcome. The toxic effect of hyperbilirubinemia on the auditory brainstem pathway and neurodevelopmental status in our cohort was transient. The prognosis of neonatal hemolytic hyperbilirubinemia in our Chinese cohort is excellent, possibly owing to an aggressive early-intervention approach.

Asian People↗
PubMed2003

Association between peak serum bilirubin and neurodevelopmental outcomes in extremely low birth weight infants.

OBJECTIVE: To assess the association between peak total serum bilirubin (PSB) levels during the first 2 weeks of life and neurodevelopmental outcomes of extremely low birth weight (ELBW) infants at 18 to 22 months' postmenstrual age. METHODS: A retrospective analysis was conducted of a cohort of ELBW infants (401-1000 g) who survived to 14 days of age in the 12 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network between January 1, 1994, and December 31, 1997. Demographic and clinical risk factors and PSB levels during the first 14 days were analyzed with reference to death or adverse neurodevelopmental outcomes at 18 to 22 months' postmenstrual age. The neurodevelopmental variables considered were Psychomotor Developmental Index (PDI) <70, Mental Developmental Index (MDI) <70, moderate or severe cerebral palsy (CP), hearing impairment (needs hearing aids), and a composite category designated as neurodevelopmental impairment (NDI). The NDI is defined as infants with any 1 or more of the following: PDI <70, MDI <70, moderate to severe CP, bilateral blindness, or bilateral hearing impairment requiring amplification. RESULTS: The subjects of this cohort analysis are infants who were admitted to the Network centers during calendar years 1994-1997 and survived beyond 14 days and had PSB recorded during the 14-day period. From this cohort, 3246 infants survived at discharge, 79 died after discharge, and 592 were lost to follow-up. Thus, 2575 of 3167 infants were seen in the follow-up clinics with a compliance rate of 81%. Logistic regression analysis showed that various demographic and clinical variables are associated with poor neurodevelopmental outcomes. After adjustment for these risk factor, significant association were found between PSB (mg/dL) and death or NDI (odds ratio: 1.068; 95% confidence interval [CI]: 1.03-1.11); PDI <70 (R = 1.057; 95% CI: 1.00-1.12), and hearing impairment requiring hearing aids (odds ratio: 1138; 95% CI: 1.00-1.30). There was no significant association between PSB (mg/dL) and CP, MDI <70, and NDI. CONCLUSIONS: PSB concentrations during the first 2 weeks of life are directly correlated with death or NDI, hearing impairment, and PDI <70 in ELBW infants. The statistical association based on retrospective analysis of observational data and relatively small effect size should be interpreted with caution. Furthermore, because of the possibility of compounding effects of variables on outcome, the potential benefits of moderate hyperbilirubinemia and the potential adverse effects of phototherapy, a randomized, controlled trial of aggressive and conservative phototherapy is needed to address this controversial issue.

Bilirubin↗
PubMed2005

Changes in neurodevelopmental outcomes at 18 to 22 months' corrected age among infants of less than 25 weeks' gestational age born in 1993-1999.

BACKGROUND: Increased survival rates for extremely preterm, extremely low birth weight infants during the postsurfactant era have been reported, but data on changes in neurosensory and developmental impairments are sparse. OBJECTIVE: To compare neuromotor and neurodevelopmental outcomes at 18 to 22 months' corrected age for infants of <25 weeks' estimated gestational age (EGA) who were born in the 1990s. METHODS: This was a multicenter, retrospective, comparative analysis of infants of <25 weeks' EGA, with birth weights of 501 to 1000 g, born between January 1993 and June 1996 (epoch I) or between July 1996 and December 1999 (epoch II), in the National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental assessments were performed at 18 to 22 months' corrected age. Logistic-regression models were constructed to evaluate the independent risk of cerebral palsy, Mental Development Index of <70, Psychomotor Development Index of <70, and neurodevelopmental impairment. RESULTS: A total of 366 patients in epoch I and 473 patients in epoch II were evaluated. Prenatal steroid use, cesarean section, surfactant treatment, bronchopulmonary dysplasia, and severe retinopathy of prematurity were more likely in epoch II, whereas Apgar scores of <5 at 5 minutes, patent ductus arteriosus, and severe intraventricular hemorrhage were more likely in epoch I. The prevalences of cerebral palsy, Psychomotor Development Index of <70, and neurodevelopmental impairment were similar between epochs. The prevalences of Mental Development Index of <70 were 40% for epoch I and 47% for epoch II. Regression analysis revealed that epoch II was an independent risk factor for Mental Developmental Index of <70 (epoch I versus II: odds ratio: 0.63; 95% confidence interval: 0.45-0.87) but not for other outcomes. CONCLUSIONS: Early childhood neurodevelopmental outcomes among infants of <25 weeks' EGA are not improving in the postsurfactant era, despite more aggressive perinatal and neonatal treatment. Later childhood follow-up assessment is needed to delineate trends in severe cognitive impairment in this extremely high-risk group.

Blindness↗
PubMed2006

Erythropoietin concentrations and neurodevelopmental outcome in preterm infants.

OBJECTIVE: Erythropoietin therapy is effective in decreasing transfusions to varying degrees in preterm infants. Recent animal studies using erythropoietin doses to achieve serum concentrations > 1000 mU/mL report neuroprotective effects. We evaluated the relationship between erythropoietin concentrations and neurodevelopmental outcome in extremely low birth weight infants. METHODS: Preterm infants who weighed < or = 1000 g at birth were randomly assigned to erythropoietin (400 U/kg 3 times per week) or placebo/control. Therapy was initiated by 4 days after birth and continued through the 35th postmenstrual week. All infants received supplemental parenteral and enteral iron. Peak serum erythropoietin concentrations were obtained every 2 weeks. Follow-up evaluation included anthropometric measurements, Bayley scales of mental and psychomotor development, neurologic examination, and determination of overall neurodevelopmental impairment. Data were collected at 18 to 22 months' corrected age by certified examiners who were masked to the treatment group. Analyses were performed to identify correlations between erythropoietin concentrations and outcomes. RESULTS: Sixteen extremely low birth weight infants were enrolled; 1 infant died at 2 weeks (placebo/control), and 15 had erythropoietin concentrations measured (7 erythropoietin, 8 placebo/control). Peak erythropoietin concentrations were significantly different between groups during the study (erythropoietin: 2027 +/- 1464 mU/mL; placebo/control: 26 +/- 11 mU/mL). Before follow-up, 3 infants died (1 erythropoietin, 2 placebo/control), and 12 were available for follow-up (6 erythropoietin, 6 placebo/control). At 18 to 22 months' follow-up, none of the erythropoietin recipients and 2 of the placebo/control infants had Mental Development Index scores < 70. Erythropoietin recipients had Mental Development Index scores of 96 +/- 11, and placebo/control infants had Mental Development Index scores of 78 +/- 7. Psychomotor Development Index scores were similar between groups (87 +/- 13 vs 80 +/- 7). There were no differences between groups with respect to anthropometric measurements. Two of 6 infants in the erythropoietin group and 4 of 6 infants in the placebo/control group had some form of neurodevelopmental impairment. Posthoc analysis showed that infants with erythropoietin concentrations > or = 500 mU/mL had higher Mental Development Index scores than infants with erythropoietin concentrations < 500 mU/mL. CONCLUSIONS: Erythropoietin concentrations did not correlate with Psychomotor Development Index or overall incidence of neurodevelopmental impairment; however, infants with elevated erythropoietin concentrations had higher Mental Development Index scores than those with lower erythropoietin concentrations. Close follow-up of infants who are enrolled in large, multicenter, high-dose erythropoietin studies is required to determine whether a correlation exists between elevated erythropoietin concentrations and improved neurodevelopmental outcome.

Blood Transfusion↗
PubMed1994

Two-year infant neurodevelopmental outcome after expectant management and indicated preterm delivery in hypertensive pregnancies.

BACKGROUND: To evaluate the impact of the expectant management of hypertensive disorders of pregnancy on infant neurodevelopmental outcome. METHODS: The two-year neurodevelopmental outcome of infants delivered prematurely because of complications of maternal hypertension after expectant management was compared with that of infants of uncomplicated age-matched pregnancies delivered after spontaneous preterm labor or premature rupture of membranes. RESULTS: The rate of cerebral palsy was similar between the two groups. Conditional logistic regression analysis of the matched sets showed an increased risk of minor neurodevelopmental impairment among infants delivered after severe hypertension (odds ratio (OR) = 4.0, 95% confidence interval (CI) 1.34-12.1) or preeclampsia (OR = 4.0, 95% CI = 1.61-10.2). Fetal growth retardation was not associated with increasing infant neurodevelopmental morbidity. CONCLUSIONS: Infants delivered prematurely because of preeclampsia or severe hypertension are at increased risk of later minor neurodevelopmental problems.

Cerebral Palsy↗
PubMed2023

H4C5 missense variant leads to a neurodevelopmental phenotype overlapping with Angelman syndrome.

Recurrent de novo missense variants in H4 histone genes have recently been associated with a novel neurodevelopmental syndrome that is characterized by intellectual disability and developmental delay as well as more variable findings that include short stature, microcephaly, and facial dysmorphisms. A 4-year-old male with autism, developmental delay, microcephaly, and a happy demeanor underwent evaluation through the Undiagnosed Disease Network. He was clinically suspected to have Angelman syndrome; however, molecular testing was negative. Genome sequencing identified the H4 histone gene variant H4C5 NM_003545.4: c.295T>C, p.Tyr99His, which parental testing confirmed to be de novo. The variant met criteria for a likely pathogenic classification and is one of the seven known disease-causing missense variants in H4C5. A comparison of our proband's findings to the initial description of the H4-associated neurodevelopmental syndrome demonstrates that his phenotype closely matches the spectrum of those reported among the 29 affected individuals. As such, this report corroborates the delineation of neurodevelopmental syndrome caused by de novo missense H4 gene variants. Moreover, it suggests that cases of clinically suspected Angelman syndrome without molecular confirmation should undergo exome or genome sequencing, as novel neurodevelopmental syndromes with phenotypes overlapping with Angelman continue to be discovered.

Male↗
PubMed2025

RNA sequencing offers new diagnostic opportunities in neurodevelopmental disorders: A systematic review.

PURPOSE: Transcriptomics by way of RNA sequencing (RNAseq) has emerged as a means to increase the diagnostic yield in genetic conditions. In this systematic review, we focus on the contribution of transcriptomics to improve the diagnostic yield in neurodevelopmental disorders. METHODS: We performed a systematic literature search in PubMed until January 2024, including articles describing diagnostic RNAseq on at least 1 individual with a primary neurodevelopmental phenotype. We extracted data on cohort size, phenotype, sample tissue, previously used diagnostic methods, added diagnostic yield of RNAseq, the use of control samples, and technical aspects of the RNA sequencing methodology. RESULTS: A total of 17 articles were eligible for inclusion in the systematic review. We found an average added diagnostic yield of 15.5% through RNA sequencing for individuals with neurodevelopmental disorders. There is heterogeneity in the tissue type, reported quality measures, and the computational pipeline. CONCLUSION: The significantly increased diagnostic yield demonstrates the value of this novel tool in the diagnostic setting of neurodevelopmental disorders. Our results offer an overview of common methodologies for RNAseq and allow us to formulate recommendations for genetic labs and clinicians when implementing RNAseq as a diagnostic tool. Lastly, we provide recommendations for future publications to increase transparency and reproducibility.

Humans↗
PubMed2026

Hemizygous loss-of-function variants of EIF1AX are associated with a syndromic neurodevelopmental disorder.

Pathogenic variants of genes encoding initiation factors can cause neurological diseases, including neurodevelopmental disorders and brain abnormalities. The eukaryotic translation initiation factor 1&#x2009;A, X-linked (EIF1AX) is a gene located at Xp22.12 that plays an important role in the regulation of translation initiation. Here, we identified de novo hemizygous EIF1AX variants in male individuals with neurodevelopmental disorders and explored their possible involvement in these neurological disorders. We performed trio-based exome or whole genome sequencing in four families. The pathogenicity of EIF1AX variants was evaluated using a molecular dynamic simulation and transgenic Drosophila models. We identified four de novo hemizygous EIF1AX variants in four male individuals with variable neurodevelopmental delay, dysmorphic features, behavioral problems, ophthalmological abnormalities, and structural abnormalities in the brain. One variant was predicted to cause a splicing alteration, and minigene analysis confirmed exon skipping leading to the generation of a premature termination codon. In transgenic Drosophila harboring wild-type (WT) EIF1AX or the three other EIF1AX missense variants, overexpression of WT and the p.(Asn17Asp) variant caused structural abnormalities in the compound eye, whereas the p.(Lys64Glu) and p.(Asp90Gly) variants significantly reduced these eye abnormalities. In addition, WT overexpression resulted in significant axonal toxicity in the Drosophila optic nerve, causing a significant reduction in the number of axons, whereas all mutants showed only a mild reduction in axonal number. Our findings indicated that all variants resulted in different degrees of EIF1AX loss-of-function. Overall, EIF1AX is a novel gene for which loss-of-function variants appear to produce syndromic neurodevelopmental disorders in males.

Humans↗
PubMed2026

Biallelic ABCA13 Loss-of-Function Variants in a Child With Neurodevelopmental Delay: A Case Report.

ABCA13 encodes ATP-binding cassette subfamily A member 13, one of the largest members of the ABC transporter family. Rare ABCA13 variants have been reported in neuropsychiatric and neurodevelopmental phenotypes, including schizophrenia, bipolar disorder, autism spectrum disorder, intellectual disability, and developmental delay; however, the mode of inheritance remains uncertain, and most published cases have focused on heterozygous variants in the context of a possible dominant or susceptibility model. We report a 5-year-old boy with neurodevelopmental delay, skeletal foot deformities, nonspecific dysmorphic features, convergent strabismus, and behavioral abnormalities. Initial genome sequencing analysis was nondiagnostic. Reanalysis after 6 months identified two rare predicted loss-of-function variants in ABCA13 in trans: c.2510del, p.(Leu837TyrfsTer21), a frameshift variant, and c.12064C>T, p.(Arg4022Ter), a nonsense variant previously reported in a patient with unexplained intellectual disability. The identification of compound heterozygous predicted loss-of-function variants supports the possibility that biallelic disruption of ABCA13 may contribute to neurodevelopmental disease, whereas previously reported heterozygous variants may represent incompletely penetrant risk alleles, susceptibility factors, or candidate findings rather than fully penetrant dominant causes. This case expands the emerging clinical and genetic spectrum associated with ABCA13 and supports further evaluation of a recessive model in patients with intellectual disability and neurodevelopmental delay.

ABCA13↗
PubMedDate not supplied

Neurodevelopmental evaluation of 9-month-old infants exposed to low levels of lead in utero: involvement of monoamine neurotransmitters.

The objective of this work is to investigate the neurotoxicty of low-level lead exposure in utero on infants and the possible involvement of dopaminergic and serotonergic neurotransmitters. The correlation analysis for cord blood lead level, the concentrations of dopamine metabolite homovanillic acid (HVA) and serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cord plasma and the neurodevelopmental scales of infants were conducted on 244 9-month-old children. Both score of sociability subscale and 5-HIAA concentration were correlated with cord blood lead level. The sociability score was negatively correlated with the concentration of HVA, whereas both the coordination score and the global score were negatively correlated with the concentration of 5-HIAA. With partial correlation analysis, after taking HVA into account, the significant negative correlation between the sociability score and the cord blood lead level that existed in the linear correlation analysis disappeared, and the score of global scale correlated negatively with lead level in cord blood. When taking 5-HIAA into account, the scores of all the neurodevelopmental subscales except the language subscale were significantly negatively correlated with lead level in cord blood. The results indicated that low-level lead exposure in utero could produce a neurotoxic effect on the developing serotonergic system in infants. The neurotoxicity of low-level lead exposure in utero may affect the sociability of infants. Serotonergic activity was shown to have a potential effect on neurodevelopmental assessment. It may interfere with the association between low-level lead exposure in utero and other neurodevelopmental performances of 9-month-old children.

Biogenic Monoamines↗
PubMed2002

Neurodevelopmental care in the NICU.

Neurodevelopmental care, which is any NICU intervention undertaken to improve neurodevelopmental outcome, includes NICU design, nursing routines, nursing care plans, management of pain, feeding methods and, most importantly, encouraging parental involvement with their NICU infant. Recognition that sensory stimulation can overwhelm preterm infants and increase physiologic signs of stress led to attempts to reduce sensory input. More recent approaches judiciously add back soothing sensory input (e.g., therapeutic touch, soft music). Circadian light/dark cycles and physical activity improve preterm growth. Attention to infant positioning and handling affects physiologic variables and joint mobility, if not functional motor abilities. A highly organized system of care for NICU infants is Als' NIDCAP (i.e., Neonatal Individualized Developmental Care and Assessment Program). Although NIDCAP may reduce need for respiratory support and hospital length of stay, it does not significantly influence neurodevelopmental outcome at 2-3 years. Pain management includes benign interventions (e.g., nonnutritive sucking, oral glucose), but the prolonged use of narcotics must be balanced against the consequences of sedation and dependency. The foremost challenge for NICUs remains parent disenfranchisement. Kangaroo care, which involves parent/infant skin-to-skin contact, improves preterm growth, decreases nosocomial infections and may shorten hospital length of stay. A great deal of work needs to be done to identify and demonstrate efficacy of specific interventions and changes that humanize the NICU, encourage parental involvement, support infant development and optimize preterm neurodevelopmental outcomes.

Breast Feeding↗
PubMed2001

Infectious and immune factors in the pathogenesis of neurodevelopmental disorders: epidemiology, hypotheses, and animal models.

Both genetic and environmental factors contribute to the pathogenesis of a wide variety of neurodevelopmental disorders, including autism, mental retardation, and schizophrenia. Some heritable disorders approach 100% penetrance; nonetheless, even in these disorders, subtle aspects of clinical disease expression may be influenced by the environment. In other disorders with genetic influences, exogenous factors, and the timepoint(s) during nervous system development at which they are introduced, modulate expression of disease. Elucidation of the mechanisms guiding this intricate interplay between host response genes, environmental agents, and the neurodevelopmental context within which these interactions occur, is necessary to understand the continuum of clinical outcomes. This chapter will review the evidence that infectious and immune factors may contribute to the pathogenesis of neurodevelopmental disorders, describe an animal model of neurodevelopmental disorders based upon viral infection, identify processes by which neural circuitry may be compromised, and outline areas for future research.

Animals↗
PubMedDate not supplied

Neurodevelopmental outcome of 'at risk' nursery graduates.

A cohort study at a tertiary care neonatal service was undertaken to determine the neurodevelopmental outcome of neonates who required intensive care. One hundred and nineteen nursery graduates were enrolled for follow up if they fulfilled any of the following risk factors: birth weight less than 1500 g, Apgar score less than 4 at 5 minutes, seizure(s), and required assisted ventilation for more than 24 hours. They were subjected to periodic clinical evaluation and administered the Bayley Scales of Infant Development in early childhood. Of the total infants enrolled, 101 completed the required follow up. They included 55 infants with birth weight < 1500 g, 45 with low Apgar scores, 12 with seizure(s) and 28 who received assisted ventilation. An overwhelming majority of subjects (85%) had normal neurodevelopmental outcome. The adverse outcome in the remaining 15 included mental retardation in all, subnormal motor development in 14, microcephaly in 1, hearing loss in 2 and visual impairment in 4. Among the neonatal risk factors, seizures, sepsis and hypoxic ischemic encephalopathy had a significant association with adverse outcome. Despite serious neonatal morbidity, the early neurodevelopmental outcome of nursery graduates was reasonably good. The association of neonatal sepsis with neurodevelopmental sequelae merits a prospective evaluation.

Brain Damage, Chronic↗
PubMed1999

Growth and neurodevelopmental outcome in extremely-low-birth-weight infants after laparotomy.

Twenty-one extremely-low-birth-weight (ELBW) and premature infants (<29 weeks' gestation and/or <1,000 g) underwent emergency laparotomy for acute intra-abdominal pathology (necrotising enterocolitis [NEC] 16, other bowel pathology 5) during the 4-year period from 1990 to 1993; 11 died. The neurodevelopmental outcome of the 10 survivors was assessed and compared with 20 living, otherwise normal controls matched for gestational age, birth weight, and year of birth to asses the effect of the abdominal event on quality of survival. Those who survived after laparotomy had a worse neurodevelopmental outcome than controls (P < 0.05). During this period, we also compared 24 infants in the ELBW category who developed NEC but did not require a laparotomy with the 16 ELBW infants with NEC who required a laparotomy. Those who required a laparotomy had worse disease and had significantly worse neurodevelopmental outcomes (P < 0.01). ELBW and premature infants who have acute intra-abdominal pathology requiring a laparotomy are thus at increased risk of neurodevelopmental problems and poor growth. Close long-term follow-up is important, and the families of such infants should be made aware before surgery of the increased risk the abdominal event has on their babies' developmental outcome if they survive.

Developmental Disabilities↗
PubMed2002

Colloid infusion in the perinatal period and abnormal neurodevelopmental outcome in very low birth weight infants.

UNLABELLED: In very low birth weight (VLBW) infants, colloid infusion is associated with impaired perinatal lung function and increased oxygen dependency duration. The aim of this study was to determine whether perinatal colloid infusion was associated with abnormal neurodevelopmental outcome. All perinatal fluid input (crystalloid and colloid) given to VLBW infants entered into a randomised trial was recorded. At 1 and/or 2 years, the neurodevelopmental status of VLBW infants was routinely assessed. Of 131 survivors, median gestational age 27 weeks (range 23-33 weeks), 95 were seen at follow-up. Nineteen had abnormal neurodevelopmental outcome and differed significantly from the rest of the cohort with regard to their birth weight, magnitude of colloid infusion received and the proportions who had received postnatal steroids, suffered prolonged oxygen dependency or having had intracerebral haemorrhage/periventricular leucomalacia development. Regression analysis demonstrated that only colloid infusion related significantly to abnormal neurodevelopmental outcome independent of other variables. CONCLUSION: These data suggest that colloid infusion should be used with caution in the perinatal period.

Brain↗