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PubMed1997

The effect of intracranial pressure on myelination and the relationship with neurodevelopment in infantile hydrocephalus.

The effect of raised intracranial pressure (ICP), due to infantile hydrocephalus, on the process of myelination has been suggested in the literature. In this study 19 hydrocephalic infants were followed-up with anterior fontanelle pressure (AFP) measurement (assessment of ICP), MRI (assessment of the myelination process and the CSF volume), and neurodevelopmental testing (NDT). There was a high correlation (r = 0.80) between the myelination and NDT scores. The size of the CSF volume showed a poor correlation with the mean AFP, the degree of myelination and the NDT scores. There was, however, a significant correlation between the mean AFP and the degree of myelination (r = 0.67) and also between the mean AFP and the NDT scores (r = 0.70). Longer-term follow-up (mean = 27 months) showed a significant correlation between the early progress of myelination and later developmental level (r = 0.78). Most of the children with a severely delayed myelination, preoperatively, showed a recovery of myelination following CSF drainage. It was concluded that: (1) raised ICP is related to developmental outcome, through the process of myelination; (2) the delay in myelination can be (partially) reversible; and (3) CSF volume is of minor importance regarding neurodevelopment.

Brain↗
PubMed2004

Low plasma taurine and later neurodevelopment.

Dietary taurine intake may explain the benefits of both breast milk and preterm formula to neurodevelopment. Low plasma neonatal taurine was associated with lower scores on the Bayley mental development index at 18 months and the WISC-R arithmetic subtest at 7 years. Currently it is not mandatory to add taurine to infant formulas.

Breast Feeding↗
PubMed2002

Long term health and neurodevelopment in children exposed to antiepileptic drugs before birth.

OBJECTIVE: To investigate the frequency of neonatal and later childhood morbidity in children exposed to antiepileptic drugs in utero. DESIGN: Retrospective population based study. SETTING: Population of the Grampian region of Scotland. PARTICIPANTS: Mothers taking antiepileptic drugs in pregnancy between 1976 and 2000 were ascertained from hospital obstetric records and 149 (58% of those eligible) took part. They had 293 children whose health and neurodevelopment were assessed. MAIN OUTCOME MEASURES: Frequencies of neonatal withdrawal, congenital malformations, childhood onset medical problems, developmental delay, and behaviour disorders. RESULTS: Neonatal withdrawal was seen in 20% of those exposed to antiepileptic drugs. Congenital malformations occurred in 14% of exposed pregnancies, compared with 5% of non-exposed sibs, and developmental delay in 24% of exposed children, compared with 11% of non-exposed sibs. After excluding cases with a family history of developmental delay, 19% of exposed children and 3% of non-exposed sibs had developmental delay, 31% of exposed children had either major malformations or developmental delay, 52% of exposed children had facial dysmorphism compared with 25% of those not exposed, 31% of exposed children had childhood medical problems (13% of non-exposed sibs), and 20% had behaviour disorders (5% of non-exposed). CONCLUSION: Prenatal antiepileptic drug exposure in the setting of maternal epilepsy is associated with developmental delay and later childhood morbidity in addition to congenital malformation.

Abnormalities, Drug-Induced↗
PubMed2003

Differential effect of fetal, neonatal and treatment variables on neurodevelopment in infants with congenital hypothyroidism.

OBJECTIVES: To identify the influence of fetal, neonatal and treatment variables on neurodevelopment in children with congenital hypothyroidism. METHODS: A multiple regression analysis was performed in the neurodevelopmental scores of 26 children with CH who were assessed at 3, 6, 12 and 18 months for postural control, fine eye-hand coordination and language. The independent variables were: duration of fetal hypothyroidism, initial biochemical severity, days at starting treatment, initial dose, and efficiency of treatment. RESULTS: Postural control was predicted by duration of fetal hypothyroidism and language by the biochemical severity of the disease at birth. Fine eye-hand coordination was not predicted by any variable. CONCLUSION: This pattern of influences suggests that fetal and neonatal hypothyroidism have different effects on brain maturation sites during the first 2 years of life and that some subtle neurocognitive deficits are probably unavoidable.

Child Development↗
PubMed2003

Canavan's leukodystrophy is associated with defects in cochlear neurodevelopment and deafness.

The authors present the temporal bone histopathology of two siblings (4 months old and 6 months old at autopsy) with Canavan's disease, an autosomal recessive leukodystrophy that is variably associated with sensorineural hearing loss. The histopathology demonstrated bilateral absence of the organ of Corti throughout the apical and basal cochlea and mild secondary atrophy of the spiral ganglia neurons. The vestibular end organs and ganglia were normal. These findings implicate a role of aminoacylase II in the neurodevelopment of the organ of Corti.

Atrophy↗
PubMed2002

[Impact of prenatal methylmercury exposure on child neurodevelopment in the Faroe Islands].

Recent interest concerning methylmercury that accumulates in the aquatic food chain appears to be directed not to the adverse effects of high-dose exposure in humans, but to the critical concentration at which methylmercury may affect the progeny of the exposed population. In epidemiological studies, however, uncertainties and limitations in estimating exposure make it difficult to quantify dose-response associations and can thereby lead to inaccuracies when deriving such concentrations. In this respect, benchmark dose calculation for quantitative outcomes may shed new light on the epidemiological procedure for estimating the critical concentration. After the epidemic outbreaks of methylmercury poisoning in Japan and Iraq, large-scale follow-up studies were carried out in the Faroe Islands, Seychelles and New Zealand, to clarify the effects of prenatal methylmercury exposure on child neurodevelopment in the latter half of the 1980s. This article presents an overview of the outcomes obtained from the Faroe Islands Prospective Study, as well as a brief interpretation of the benchmark dose calculation. Although the Faroe and Seychelles Islands studies did not seem to differ greatly in the study setting, such as the exposure level and sample size, the former study observed some significant dose-effect relationships between methylmercury concentrations at birth and neurobehavioral end-points, but the latter failed to find any significant associations except in one test. The discrepancy between the two conclusions is also discussed.

Adolescent↗
PubMed2006

Chlorpyrifos affects phenotypic outcomes in a model of mammalian neurodevelopment: critical stages targeting differentiation in PC12 cells.

The organophosphate insecticide chlorpyrifos (CPF) adversely affects mammalian brain development through multiple mechanisms. To determine if CPF directly affects neuronal cell replication and phenotypic fate, and to identify the vulnerable stages of differentiation, we exposed PC12 cells, a model for mammalian neurodevelopment, to CPF concentrations spanning the threshold for cholinesterase inhibition (5-50 microM) and conducted evaluations during mitosis and in early and mid-differentiation. In undifferentiated cells, exposure to 5 microM CPF for 1-3 days reduced DNA synthesis significantly without eliciting cytotoxicity. At the same time, CPF increased the expression of tyrosine hydroxylase (TH), the enzymatic marker for the catecholamine phenotype, without affecting choline acetyltransferase (ChAT), the corresponding marker for the cholinergic phenotype. Upon exposure to nerve growth factor (NGF), PC12 cells developed neuritic projections in association with vastly increased TH and ChAT expression accompanying differentiation into the two phenotypes. CPF exposure begun at the start of differentiation significantly reduced ChAT but not TH activity. In contrast, when CPF was added in mid-differentiation (4 days of NGF pretreatment), ChAT was unaffected and TH was increased slightly. Thus, CPF exerts stage-specific effects, reducing DNA synthesis in the undifferentiated state, impairing development of the cholinergic phenotype at the start of differentiation, and promoting expression of the catecholaminergic phenotype both in undifferentiated and differentiated cells. CPF administration in vivo produces deficits in the number of neurons and cholinergic function, and because we were able to reproduce these effects in vitro, our results suggest that CPF directly influences the phenotypic fate of neuronal precursors.

Animals↗
PubMed2004

Neurodevelopment in children born small for gestational age: a randomized trial of nutrient-enriched versus standard formula and comparison with a reference breastfed group.

OBJECTIVE: Many studies have shown that children born small for gestational age (SGA) are at a neurodevelopmental disadvantage. We have shown that nutrient enrichment of formula fed to term SGA infants improves their growth and hypothesized that it also would improve their neurodevelopmental outcome. DESIGN: A randomized, controlled trial of standard term-infant (n = 147) or nutrient-enriched (n = 152) formula for the first 9 months. A reference group of 175 breastfed SGA infants was also recruited. SETTING: Subjects were recruited in 5 maternity hospitals in Cambridge, Nottingham, and Leicester, all in the United Kingdom. PARTICIPANTS: Healthy, term infants (gestation: > or =37 weeks) with birth weight <10th centile. OUTCOME MEASURES: Bayley mental and psychomotor scores at 18 months (primary) and developmental scores from Knobloch, Pasamanick, and Sherrard's developmental screening inventory at 9 months (secondary). RESULTS: There was no significant intergroup difference in Bayley Mental Development Index (MDI) or Psychomotor Development Index (PDI) scores at 18 months. However, at 9 months, children fed the enriched formula had a significantly lower developmental quotient (99.5 vs 102.0; 95% confidence interval [CI] for difference: -4.6, -0.4). A significant disadvantage was seen in girls (-5.1; 95% CI: -7.8, -2.4) but not in boys (0.9; 95% CI: -2.4, 4.2). Breastfed infants had significantly higher MDI and PDI scores at 18 months than formula-fed infants. Confounding factors accounted for approximately 34% of the observed association between breastfeeding and MDI score and none of the association between breastfeeding and PDI score. CONCLUSIONS: The previously reported enhanced linear growth in SGA children fed enriched formula was not matched by a neurodevelopmental advantage. At 9 months, girls fed the enriched formula had a significant developmental disadvantage, although this was not seen at 18 months. Later follow-up will determine any long-term effects on health or development. Meanwhile, use of enriched formula for term SGA children should not be promoted. It seems that breastfeeding may be especially beneficial for neurodevelopment in children born SGA.

Breast Feeding↗
PubMed2006

Impact of prenatal chlorpyrifos exposure on neurodevelopment in the first 3 years of life among inner-city children.

OBJECTIVE: The purpose of this study was to investigate the impact of prenatal exposure to chlorpyrifos on 3-year neurodevelopment and behavior in a sample of inner-city minority children. METHODS: As part of an ongoing prospective cohort study in an inner-city minority population, neurotoxicant effects of prenatal exposure to chlorpyrifos were evaluated in 254 children through the first 3 years of life. This report examined cognitive and motor development at 12, 24, and 36 months (measured with the Bayley Scales of Infant Development II) and child behavior at 36 months (measured with the Child Behavior Checklist) as a function of chlorpyrifos levels in umbilical cord plasma. RESULTS: Highly exposed children (chlorpyrifos levels of >6.17 pg/g plasma) scored, on average, 6.5 points lower on the Bayley Psychomotor Development Index and 3.3 points lower on the Bayley Mental Development Index at 3 years of age compared with those with lower levels of exposure. Children exposed to higher, compared with lower, chlorpyrifos levels were also significantly more likely to experience Psychomotor Development Index and Mental Development Index delays, attention problems, attention-deficit/hyperactivity disorder problems, and pervasive developmental disorder problems at 3 years of age. CONCLUSIONS: The adjusted mean 36-month Psychomotor Development Index and Mental Development Index scores of the highly and lower exposed groups differed by only 7.1 and 3.0 points, respectively, but the proportion of delayed children in the high-exposure group, compared with the low-exposure group, was 5 times greater for the Psychomotor Development Index and 2.4 times greater for the Mental Development Index, increasing the number of children possibly needing early intervention services.

Adult↗
PubMed2005

[Neurodevelopment of full-term small-for-gestational age infants in the second month of life].

The objective of the present study was to assess and to compare the neurodevelopment of full-term adequate (AGA) or small-for-gestational age (SGA) infants in the second month of life. Sixty-seven infants were evaluated: 43 AGA and 24 SGA, making use of the Bayley Scales of Infant Development. The SGA group Index Score (IS) was significantly lower in Mental and Motor Scales. Considering the body proportionality (Asymmetric, Symmetric-SGA and Control group) there was difference in Motor Scale (p=0.003) with lower scores in the Symmetric-SGA group. Comparing to the Control group IS percentiles, in Mental Scale there was difference between Asymmetric X Symmetric-SGA; in Motor Scale, there was difference between the Asymmetric X Control (p=0.039) and Symmetric-SGA X Control (p=0.007) groups; there was no difference between Asymmetric and Symmetric-SGA although both exhibited lower scores than the Control group.

Anthropometry↗
PubMed2003

Neurodevelopment and mood stabilizers.

Mood disorders and schizophrenia share a number of common properties, including: genetic susceptibility; differences in brain structure and drug based therapy. Some genetic loci may even confer susceptibility for bipolar mood disorder and schizophrenia, and some atypical antipsychotic drugs are used as mood stabilizers. As schizophrenia is associated with aberrant neurodevelopment, could this also be true for mood disorders? Such changes could arise pre- or post-natal, however the recent interest in neurogenesis in the adult brain has suggested involvement of these later processes in the origins of mood disorders. Interestingly, the common mood stabilizing drugs, lithium, valproic acid (VPA) and carbamazepine, are teratogens, affecting a number of aspects of animal development. Recent work has shown that lithium and VPA interfere with normal cell development, and all three drugs affect neuronal morphology. The molecular basis for mood stabilizer action in the treatment of mood is unknown, however these studies have suggested both targets and potential mechanisms. Lithium directly inhibits two evolutionarily conserved signal transduction pathways: the protein kinase Glycogen Synthase Kinase-3 (GSK-3) and inositol signaling. VPA can up-regulate gene expression through inhibition of histone deacetylase (HDAC) and indirectly reduce GSK-3 activity. VPA effects are not conserved between cell types, and carbamazepine has no effect on the GSK-3 pathway. All three mood stabilizers suppress inositol signaling, results further supported by studies on the enzyme prolyl oligopeptidase (PO) and the sodium myo-inositol transporter (SMIT). Despite these intriguing observations, it remains unclear whether GSK-3, inositol signaling or both underlie the origins of bipolar disorder.

Glycogen Synthase Kinase 3↗
PubMedDate not supplied

Neurodevelopment until the adjusted age of 2 years in extremely low birth weight infants after early intervention--a case-control study.

A total of 104 infants with birth weights of less than 1000 grams were enrolled in this prospective case-control study in order to examine the effect of occupational therapy based on sensory integration (SI) and neurodevelopmental therapy (NDT) on neurological development. The children were grouped as matched pairs on the basis of a set of developmental risks assessed at the age of 3 months. The intervention children had a weekly session of 60 minutes of occupational therapy from the corrected age of 6 months up to 12 months. All the children were examined at the corrected age of 3, 6, 9, 12, 18 and 24 months. The neurodevelopment of the cases and the controls did not differ essentially and the only significant difference was found in the social development of the children at the age of 12 months to the advantage of the intervention group. It is concluded that this amount of occupational therapy in at-risk children does not have a relevant effect on neurological development.

Case-Control Studies↗
PubMed2000

Hypothyroxinemia of prematurity and infant neurodevelopment: a pilot study.

To assess whether hypothyroxinemia has specific effects on neurodevelopment in premature infants, thyroid hormone levels were determined at 2 weeks of life and 40 weeks postconceptional age (PCA), and infants were evaluated at 3 months corrected age using the Bayley Scales of Infant Development and Early Infancy Temperament Questionnaire. Additional attention scales were derived from the factor analysis of relevant Bayley items. Fifteen infants born between 30 and 35 weeks and 21 full-term infants were studied. Results indicated no group differences on the Bayley or derived attention scales, whereas the temperament questionnaire revealed lower sensory thresholds and greater reactivity in the preterm group. The preterm group had normal thyroxine (T4) levels at 2 weeks of age, which declined by 40 weeks PCA for both free T4 (p < .01 for reference value and p < .0001 for gestational age-adjusted value) and total T4 (p < .05 for age-adjusted value). Correlations revealed that higher 40-week PCA free T4 levels were associated with better attentiveness ratings (p < .01 for reference and p < .0001 for gestational-age values) and sustained attention (p < .05) and higher 40-week total T4 with better motor skills (p < .05 for gestational-age value). These findings signify that a mild degree of hypothyroxinemia is evident in preterm infants without neurological risk and predicts subsequently poorer cognitive and motor abilities.

Brain↗
PubMed2001

Neurodevelopment of adopted children exposed in utero to cocaine: the Toronto Adoption Study.

BACKGROUND: Published studies of children's neurodevelopment after in utero exposure to cocaine have not separated intrauterine from postnatal environmental effects as cocaine-using mothers cluster in low socioeconomic classes and have other risk factors. METHODS: To overcome this limitation, a study was done to assess physical and neurodevelopmental characteristics of 52 children: 26 were adopted by parents who sought counselling in the Motherisk Program at the University of Toronto for prenatal cocaine exposure, and 26 were controls matched for maternal intelligence quotient (IQ), socioeconomic status and gestational age. MAIN OUTCOME MEASURES: Head circumference, McCarthy General Cognitive Index (GCI) score, language performance and temperament tests. RESULTS: The children in the study group had smaller head circumferences (34th versus 54th percentiles p = 0.009), lower McCarthy GCI scores (102.8 versus 114.2, p = 0.02), poorer receptive and expressive language performance on the Reynell test, and higher activity levels, less persistence and increased distractibility on temperament tests. On multivariate analysis, cocaine exposure was significantly (p = 0.001) associated with lower IQ and poorer language development independent of intrauterine growth retardation and other potential confounders. INTERPRETATION: By controlling for postnatal environmental factors, this adoption study documents intrauterine developmental risks associated with cocaine exposure. Follow-up into school years is warranted to evaluate the extent of these effects.

Adoption↗
PubMed2003

[Schizophrenia, neurodevelopment and glycogen synthase kinase-3].

The Neurodevelopmental Hypothesis of the etiology of schizophrenia suggests that interaction between genetic and environmental events occurring during critical early periods in neuronal growth may negatively influence the way by which nerve cells are laid down, differentiated and selectively culled by apoptosis. Recent advances toward understanding the regulation of brain development offer insights into possible mechanisms of developmental brain changes. One such factor is the Wnt family of genes, which plays a central role in normal brain development. Activation of the Wnt cascade leads to inactivation of glycogen synthase kinase-3 beta (GSK-3 beta), accumulation and activation of beta-catenin and expression of genes involved in neuronal development. It has been proposed that alteration in the transduction cascade of the Wnt signaling pathway represents an aberrant neurodevelopment in schizophrenia. The role of GSK-3 in developmental brain changes in schizophrenia may not be restricted to the Wnt signaling cascade. GSK-3 alpha, reported to be 80% lower in lymphocytes of schizophrenic patients is a regulatory enzyme of some neuronal proteins implicated to be aberrant in schizophrenia. Programmed cell death is an essential component of normal brain development. Spatial or temporal errors in the stimuli that initiate this pathway or processes within it can result in pathological neuronal development. Increased density of neuronal population in the cortical subplate, found in postmortem brains of schizophrenic patients may imply reduced programmed cell death. The possible role of GSK-3 beta, a pro-apoptotic factor participating in signal transduction involved in cell survival, is discussed in relation to schizophrenia.

Brain↗
PubMed2005

The effect of supplementation of docosahexaenoic acid and arachidonic acid on visual acuity and neurodevelopment in larger preterm infants.

BACKGROUND: Preterm infants may be born with deficits of both docosahexaenoic acid (DHA) and arachidonic acid (AA), but studies on supplementation of DHA and AA for preterm infants are limited. METHODS: Preterm infants with a gestational age between 30 and 37 weeks who met all the inclusion criteria were enrolled in this double blind, randomized, comparative study. Infants over 2000 g body weight, over 32 weeks of gestation and in full feeding status would enter into the active intervention period of 6 months. Sixteen infants received Neoangelac Plus with AA and DHA supplementation. Eleven infants received Neoangelac without AA and DHA supplementation. The babies had scheduled physical examinations and their cognitive development, visual acuity, and vital signs to be checked. Adverse events were also recorded. RESULTS: The mean Mental Development Index (MDI) scores for the supplementation and non-supplementation groups were 96.1 +/- 8.6 and 91.7 +/- 10.4 respectively at 6 months and 98.7 +/- 8.0 and 90.5 +/- 6.9 respectively at 1 year. The mean Physical Development Index (PDI) scores of these two groups were 102.2 +/- 10.5 and 95.4 +/- 13.2 respectively at 6 months and 98.0 +/- 5.8 and 86.7 +/- 11.1 respectively at 1 year. By repeated measures ANOVA, significant differences existed between groups for MDI and PDI (p = 0.020 and 0.008). However, there were no differences in visual acuity, physical examination variables or vital signs between these two groups. No obvious adverse effects were observed during the study period. CONCLUSION: These results showed possible benefits in the neurodevelopment of larger preterm infants given formula supplemented with DHA and AA.

Arachidonic Acid↗
PubMed1990

A longitudinal follow up of neurodevelopment of high risk newborns--a comparison of Amiel-Tison's method with Bayley Scales of Infant Development.

The neurodevelopment of 42 high risk babies and 7 control babies was assessed longitudinally till the age of 12 months by using two different methods. The method of neurological evaluation described by Amiel-Tison was used, and the results compared with those of a standard developmental test, the Bayley Scales of Infant Development. The Amiel-Tison method was found to be a sensitive test for picking up abnormalities till the age of 9 months, but lost its advantage over the Bayley Scales at 12 months. Besides, the test was quick, simple to learn and did not need a special kit or a trained psychologist and was hence found to be a good screening method.

Child, Preschool↗
PubMed1994

Neurodevelopment of adopted children exposed in utero to cocaine.

OBJECTIVE: To assess the neurodevelopment of adopted children who had been exposed in utero to cocaine. DESIGN: A case-control observational study. PARTICIPANTS: Twenty-three children aged 14 months to 6.5 years exposed in utero to cocaine and their adoptive mothers, and 23 age-matched control children not exposed to cocaine and their mothers, matched with the adoptive mothers for IQ and socioeconomic status. SETTING: The Motherisk Programme at The Hospital for Sick Children, Toronto, a consultation service for chemical exposure during pregnancy. MAIN OUTCOME MEASURES: Height, weight and head circumference at birth and at follow-up, and achievement on standard tests of cognitive and language development. RESULTS: Compared with the control group, children exposed in utero to cocaine had an 8-fold increased risk for microcephaly (95% confidence interval 1.5 to 42.3); they also had a lower mean birth weight (p = 0.005) and a lower gestational age (p = 0.002). In follow-up the cocaine-exposed children caught up with the control subjects in weight and stature but not in head circumference (mean 31st percentile v. 63rd percentile) (p = 0.001). Although there were no significant differences between the two groups in global IQ, the cocaine-exposed children had significantly lower scores than the control subjects on the Reynell language test for both verbal comprehension (p = 0.003) and expressive language (p = 0.001). CONCLUSIONS: This is the first study to document that intrauterine exposure to cocaine is associated with measurable and clinically significant toxic neurologic effects, independent of postnatal home and environmental confounders. Because women who use cocaine during pregnancy almost invariably smoke cigarettes and often use alcohol, it is impossible to attribute the measured toxic effects to cocaine alone.

Adoption↗