Case-control study of prenatal ultrasonography exposure in children with delayed speech

OBJECTIVE: To determine whether there is an association between prenatal ultrasound exposure and delayed speech in children. DESIGN: Case-control study. SETTING: Network of community physicians affiliated with the Primary Care Research Unit, University of Calgary. SUBJECTS: Thirty-four practitioners identified 72 children aged 24 to 100 months who had undergone a formal speech-language evaluation and were found to have delayed speech of unknown cause by a speech-language pathologist. For each case subject the practitioners found two control subjects matched for sex, date of birth, sibling birth order and associated health problems. MAIN OUTCOME MEASURES: Rates of prenatal ultrasound exposure and delayed speech. RESULTS: The children with delayed speech had a higher rate of ultrasound exposure than the control subjects. The findings suggest that a child with delayed speech is about twice as likely as a child without delayed speech to have been exposed to prenatal ultrasound waves (odds ratio 2.8, 95% confidence limit 1.5 to 5.3; p = 0.001). CONCLUSION: An association between prenatal ultrasonography exposure and delayed speech was found. If there is no obvious clinical indication for diagnostic in-utero ultrasonography, physicians might be wise to caution their patients about the vulnerability of the fetus to noxious agents.     

Effects of early prenatal dexamethasone on the cognitive and behavioral development of young children: results of a pilot study

The effect of early prenatal dexamethasone (DEX) exposure on cognitive and behavioral development, behavior problems, and temperament were examined in 26 consecutively identified children aged 6 mo to 5 1/2 years, whose mothers had been DEX-treated during pregnancy because their offspring was at risk for congenital adrenal hyperplasia (CAH), and compared with 14 children from untreated CAH-risk pregnancies. Three children in each group were CAH-affected. Assessments were performed by way of mother-completed standard questionnaires. No significant differences in cognitive abilities or behavior problems were identified. On temperament questionnaires, DEX-exposed children showed more Shyness (p < .004), greater Emotionality (p < .03), less Sociability (p < .04), and a trend for greater Avoiddance (p < .07) than unexposed children. DEX-exposed children also had significantly higher Internalizing (p < .002) and Total Problem scores (p < .05) on the behavior problem measure for 2-3 year olds. The results should be considered preliminary until they have been replicated by the study of a larger sample and direct examination of the children.     

Performance of children with ADHD on the Rey-Osterrieth complex figure: a pilot neuropsychological study

This study evaluates the performance of boys with Attention Deficit Hyperactivity Disorder (ADHD) on the Rey-Osterrieth Complex Figure (ROCF) taking into consideration familiality and comorbid psychiatric and learning disorders (LD). Sixty-five children with ADHD performed at developmentally lower levels of Copy Organization and Recall Style than did 45 controls. ADHD children with LD scored significantly lower on Copy Organization than did ADHD children without LD, whereas psychiatric comorbidity and familiality had no effect. These results suggest that a developmental analysis of the ROCF identifies organizational difficulties associated with ADHD and that these impairments cannot simply be attributed to comorbidities associated with ADHD.     

Effects of prenatal exposure to N-methylpyrrolidone on postnatal development and behavior in rats

Pregnant rats (Mol:WIST) were exposed to 150 ppm N-methylpyrrolidone for 6 hours per day on gestation days 7-20. The dose level was selected so as not to induce maternal toxicity or decrease viability of offspring. In the preweaning period, the exposed offspring had a lower body weight and their physical development was delayed. Neurobehavioral evaluation of the male pups revealed no effects on basal functions of the central nervous system. The animals appeared normal and motor function (rotarod), activity level (open field), and performance in learning tasks with a low grade of complexity were similar in the two groups. However, in more difficult tasks such as the reversal procedure in Morris water maze and operant delayed spatial alternation (Skinner boxes), performance was impaired in exposed offspring.     

Effects of prenatal exposure to low concentrations of carbon monoxide on sexual behaviour and mesolimbic dopaminergic function in rat offspring

1. Inhalation of low concentrations of carbon monoxide (CO) by pregnant rats (75 and 150 p.p.m. from day 0 to day 20 of gestation) leads to changes in mesolimbic dopaminergic transmission associated with an impairment of sexual behaviour in male offspring. 2. Eighty day old males exposed in utero to CO (150 p.p.m.) exhibited a significant increase in mount/ intromission latency as well as a significant decrease in mount/intromission frequency. A significant decrease in ejaculation frequency was also found in CO (150 p.p.m.)-exposed animals. 3. The acute administration of amphetamine, at a dose (0.5 mg kg(-1) s.c.) stimulating copulatory activity in control rats, failed to reduce mount/intromission latency and did not increase mount frequency in 80-day offspring exposed to CO (150 p.p.m.) during gestation. 4. These behavioural alterations were paralleled by neurochemical changes (in vivo microdialysis) showing that prenatal CO exposure, at concentrations (150 p.p.m.) that did not affect basal extracellular levels of dopamine in the nucleus accumbens, blunted the amphetamine (0.5 mg kg(-1) s.c.)-induced increase in dopamine release in 80-day old male rats. 5. No significant changes in either behavioural or neurochemical parameters were observed in 10-month old rats exposed prenatally to CO. 6. Since the alterations in sexual behaviour and dopaminergic transmission have been produced by prenatal exposure to CO levels resulting in maternal blood carboxyhaemoglobin concentrations equivalent to those maintained by human cigarette smokers, the present data further point out the large risk that the smoking mother poses for her offspring.     

Hypertension and neuropsychological function: a lifespan perspective

This article explores the relationship of hypertension to neuropsychological performance from a lifespan perspective. First, I examine cross-sectional and longitudinal studies of neuropsychological performance in cohorts of young to middle-aged hypertensive patients (ages 20-60); older hypertensive patients (ages 60-80+); and the young, normotensive offspring of hypertensive parents (ages 18-25). The pattern of performance deficits associated with hypertension is generally found to differ from that related to hypertension risk. Next, I discuss potential mechanisms underlying hypertension-performance relationships in the aforementioned cohorts. I suggest that lowered levels of performance in the offspring of hypertensives reflect genetic risk for hypertension. Compromised neuropsychological function in young and middle-aged hypertensives may occur secondary to alterations in neurophysiological function that result from elevated blood pressure. Such neurophysiological changes may predispose to neuroanatomical changes in older hypertensive patients.     

Neuromuscular responses to disturbance of balance in children with prenatal exposure to alcohol

Alcohol-exposed children display delayed motor development and impaired fine- and gross-motor skills, including deficits in the maintenance of balance. In a recent study, we assessed the contribution of visual, somatosensory, and vestibular information to the ability to maintain balance. Our findings suggested that alcohol-exposed children were overly reliant on somatosensory information and were unable to compensate by using the visual and/or vestibular systems. To understand the nature of these observed balance deficits, corrective postural reactions were examined by exposing standing subjects to rapid toe-up movements of the support surface. Subjects for this study were alcohol-exposed (ALC) and normal control (NC) children matched for age and sex. Postural reactions were quantified by measuring electromyographic activity of the triceps surae and anterior tibialis muscles. Analyses revealed no differences between the ALC and NC groups on short- and medium-latency electromyographic responses, which are thought to be involuntary mono- and polysynaptic spinal reflexes, respectively. However, when compared with the NC group, the ALC group displayed increased long-latency responses, which are thought to involve a transcortical pathway. Although we are not able to rule out the possibility of additional peripheral (e.g., vestibular) disturbance as a contributing factor to postural instability, our findings suggest that the balance deficits seen in alcohol-exposed children are, at least in part, central in nature.     

Effects of prenatal exposure to 5-fluoro-2'-deoxyuridine on developing central nervous system and reproductive function in male offspring of mice

The effect of 5-fluoro-2'-deoxyuridine (FrdU) on the developing brain and postpubertal reproductive function of male mouse offspring treated prenatally was investigated. FrdU was administered intraperitoneally to pregnant ICR mice at 1.5, 3, 6, 12.5, 25, and 50 mg/kg/day on days 8 through 13 of gestation or 12.5, 25, and 50 mg/kg/day on days 14 through 18 of gestation. Dams were allowed to deliver spontaneously. Dams treated with FrdU at 12.5, 25, and 50 mg/kg/day on days 8 through 13 of gestation did not deliver because of entire intrauterine death of embryos. Male offspring were aged for 10 or 15 weeks and then cohabited with untreated female mice for assessment of reproductive performance. Histological examination of the testis, epididymis, prostate, and seminal vesicle of offspring at 12 weeks of age, and sperm analysis of offspring at 12 or 17 weeks of age were performed. Dose-dependent decreases in body weight gain were noticed throughout the life of offspring. A marked decrease in the copulation rate was noted in the group treated with FrdU at 6 mg/kg/day on days 8 through 13 of gestation. However, neither histological examination of testes and sex-accessory glands nor sperm analysis revealed adverse effects of FrdU on the reproductive function in the male offspring of dams treated with FrdU at 6 mg/kg/day on days 8 through 13 of gestation. There were no significant differences in the relative weight of testes and epididymides between the group treated with FrdU at 6 mg/kg/day on days 8 through 13 of gestation and the control group. Absolute brain weight in the groups treated with FrdU on days 8 through 13 of gestation significantly decreased, while relative brain weight increased in the group treated at 6 mg/kg/day on days 8 through 13, and at 25 and 50 mg/kg/day on days 14 through 18 of gestation. Dilatation of the lateral and third ventricles was observed in all of the male offspring of dams treated with FrdU at 6 mg/kg/day on days 8 through 13 of gestation, when inspected at 12 and 17 weeks of age. In the subsequent study, ICR mice were treated intraperitoneally with FrdU at 6.25-100 mg/kg on day 12 of gestation, and the fetuses obtained 24 h after treatment. Histological observation was performed in the ventricular zone of telencephalon, and in the ependymal and mantle layers of diencephalon in the fetal brain. The incidence of pyknotic cells in these areas was increased linearly with increasing FrdU dose. From these results and our previous findings, we suggest that damage to the central nervous system, a substantial neuronal deficit, resulting from excessive cell death in the developing brain may lead to reproductive dysfunction after puberty.     

Chronic obstructive pulmonary disease: effects of hypoxia on neurological and neuropsychological measures

Eighteen patients with chronic obstructive pulmonary disease (COPD) were administered a series of pulmonary, neurological, and neuropsychological measures to test if there was an effect of COPD on neurological and cognitive functioning. Overall, there was no evidence of general dementia in this sample. Measures of immediate and delayed memory, complex attention, and speed of information processing correlated highly with arterial carbon dioxide partial pressure and, to a lesser extent, with oxygen partial pressure. Measures of language abilities, perceptual-motor functioning, and simple attention generally were not related to arterial gas pressures. A similar pattern of findings was obtained when group differences were examined between participants classified as severely hypoxic or mildly hypoxic, although group differences were mitigated by premorbid IQ differences. Hypoxia in COPD results in a relatively focused pattern of impairment in measures of memory function and tasks requiring attention allocation. The memory dysfunction may be related to involvement of limbic memory regions necessary for explicit memory. The attentional deficits were attributed to diffuse brain involvement resulting in reduced resource allocation. Early diagnosis and treatment of the hypoxia is essential.     

Effects of prenatal exposure to cocaine on conditional discrimination learning in adult rats.

Adult male rats that were gestationally exposed to cocaine and control offspring were trained on an instrumental conditioning task for assessment of the acquisition and reversal of an appetitive conditional discrimination based on olfactory cues. Offspring were derived from Sprague-Dawley dams that had received subcutaneous/ly (sc) injections of 40 mg/kg/3 cc cocaine hydrochloride (C40) daily on Gestational Days 8–20, pair-fed (PF) dams that were injected with saline, nutritional control dams (NC) that received saline injections, and nontreated control dams (LC). There were no differences among the prenatal treatment groups in acquisition of the barpress response or response rate throughout all phases of training. All prenatal treatment groups required approximately the same number of sessions to criterion on the initial odor discrimination. In contrast, adult C40 offspring required more sessions to acquire the reversal of the conditional discrimination than did animals from the other treatment groups (PF, NC, and LC). In addition, even at criterion performance for acquisition of the reversal discrimination, C40 animals exhibited lower accuracy on the 1st 10 responses and made significantly more errors before the 1st reward. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of prenatal cocaine exposure on embryonic expression of sonic hedgehog

PURPOSE: To estimate the impact of visual impairment in older Australians on the use of community support services. METHODS: In the Blue Mountains Eye Study, 3654 people aged 49 or older were examined- 82.4% of eligible residents in an area west of Sydney, Australia. Presenting and best-corrected visual acuities were measured using a LogMAR chart. Subjects were categorized as having visual impairment if their better eye read 40 or fewer letters (20/40 or worse). Interview data included marital and other socioeconomic status measures, living status (alone or with spouse or other person), use of community support services, reliance on regular help from nonspouse family members or friends, and perceived ability to go out alone. RESULTS: After adjusting for age, gender, education, living status, walking disability, and health-related factors, for each one-line (five-letter) decrease in best-corrected visual acuity, there was a corresponding increase in reliance on community support services (odds ratio [OR], 1.17; 95% confidence interval, [CI] 1.07-1.28) or combined community and family support (OR 1.22; 95% CI, 1.12-1.32). Visually impaired persons were three times as likely to use regular support services provided by the municipality (OR 3.1; 95% CI, 1.8-5.1). A similar increased reliance on regular help from community, nonspouse family members, or friends was found. Visually impaired persons were also much more likely to state that they thought they were unable to go out alone (OR 6.2; 95% CI, 2.6-14.3). The findings were similar when presenting visual acuity was used to define visual impairment or after subjects with walking disabilities were excluded. Visual impairment seemed to have a greater effect on use of community support services in women than in men. CONCLUSIONS: After adjustment was made for confounding factors, visual impairment was found to affect significantly and negatively the independence of elderly people, particularly older women. Presenting visual acuity closely approximated best-corrected visual acuity in its impact on the use of community support services.     

Research on chronic, low-level exposure to formaldehyde: implications for neuropsychological assessment

Findings from empirical research serve as the foundation for neuropsychological assessment of individuals suspected of exposure to formaldehyde. Insofar as conclusions regarding causal relationships between exposure and neuropsychological deficits are based on research methodologies that are reliable, findings can be informative. Unfortunately, existing research is not rooted in sound methodology and findings may mislead rather than enlighten clinicians. Two prominent shortcomings in formaldehyde research are discussed: selection bias in recruitment of research participants and unreliability of participant recall for obtaining data on important background variables and exposure levels. Selected examples illustrate the influence of these shortcomings on research showing a causal relationship between long-term, low-level exposure to formaldehyde and chronic neurobehavioral deficiencies. The implications of these weaknesses for assessment of individual patients are discussed.     

Rules for neuropsychological diagnosis: Classification of brain function in older children.

A system of rules based on neuropsychological test data and the 2nd author's 4 methods of inference (level of performance, right–left differences, patterns of performance, and pathognomonic signs) was developed for classifying 3 samples (19 Ss each) of 9–14 yr old children as normal, learning disabled, or brain damaged. The 37 rules used a 4-point scaled scoring system with 0 representing adequate performance, 3 indicating distinctly abnormal performance, and 1 and 2 indicating intermediate performance. The rules system classified children into the 3 groups (normal, learning disabled, and brain damaged) with 73.3% accuracy. Although in need of replication, results indicate that the rules system is sensitive to neuropsychological differences between these groups and represents a set of initial guidelines for differentiating among normal, brain-damaged, and learning disabled children. Results also support the contention that learning disability often represents a degree of cerebral dysfunction that is frequently undetected by neurological examination but that can be reliably measured by neuropsychological tests. (9 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of prenatal alcohol exposure on the postnatal morphology of the rat oculomotor nucleus

Morphological development of the rat oculomotor nucleus was investigated on postnatal day 15 following a prenatal ethanol exposure. Analysis of toluidine blue stained plastic sections showed that the prenatal alcohol exposure caused a decrease in the density of neurons and an increase in the density of astrocytes in the center of the nucleus. There was an alcohol-induced reduction in the overall size of the cross-sectional region of the oculomotor nucleus, but no effect on the number of neurons per unit area of that total oculomotor region, indicating a delay or alteration of the migration of neurons to their normal clustered position in the center of the nucleus. The areas of the neuronal cell nucleus and nucleolus were not affected by the alcohol exposure. Analysis of Golgi-Cox-impregnated multipolar neurons showed that the alcohol exposure caused a reduction in area of the cell soma; a reduction in the number of dendritic branches; and a reduction in the complexity of the dendritic arbor relative to distance from the soma, based on concentric ring analysis. The results of this study demonstrate that gestational alcohol exposure can retard the maturation of the oculomotor nucleus.     

Effects of prenatal exposure to cocaine on Morris water maze performance in adult rats.

The spatial memory of adult rats prenatally exposed to cocaine and that of control offspring was assessed using the Morris water maze. Offspring were derived from Sprague Dawley dams that received subcutaneous injection of 40 mg/kg/3 cc cocaine hydrochloride (C40) daily on gestational Days 8-20, pair-fed dams injected with saline, or nontreated control dams. After acquisition, the platform was moved to a new location (reversal phase). Probe trials were conducted at the end of acquisition and reversal training. On the 1st acquisition day, adult male and female offspring prenatally exposed to cocaine required significantly more time and traversed a greater distance to find the hidden platform than did control offspring. Despite these initial differences observed in C40 offspring performance, all of the rats were performing at equivalent levels at the time probe trials were conducted. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Gender study of neuropsychological and neuromotor function in children with Tourette syndrome with and without attention-deficit hyperactivity disorder

Neuropsychological and neuromotor functions were compared between boys and girls with Tourette syndrome (TS only), attention-deficit hyperactivity disorder (ADHD only), Tourette syndrome with ADHD (TS+ADHD), and a comparison group, in an age (mean = 10 years) and IQ (Wechsler Full-Scale mean = 111) matched sample (n = 116). There were no timed-task neuromotor differences among the groups. Analyses of variance revealed a group x gender interaction for Letter Word Fluency and the Rapid Automatized Naming test. Girls with ADHD only were faster than boys on both tasks. When data for girls only were analyzed, girls with Tourette syndrome with ADHD had the greatest variability of reaction time on the Test of Variables of Attention, and were slowest on Letter Word Fluency. Girls with TS only were slower than girls in the other three groups on Letter Word Fluency. Poor Letter Word Fluency is explained as a linguistic executive dysfunction involving speed and efficiency of memory search in this bright group of girls with Tourette syndrome, not otherwise at risk for linguistic difficulties.     

Effects of prenatal PCB exposure on cognitive processing efficiency and sustained attention.

Assesses 4-yr-old children exposed prenatally to polychlorinated biphenyls (PCBs; an environmental toxin) on 3 tasks: 2 designed to evaluate cognitive processing efficiency and 1 to evaluate sustained attention. When compared with standardized IQ tests, these tasks provided greater specificity in identifying cognitive deficits. Adapted for 4-yr-old children in the present study, these paradigms demonstrated moderate levels of test–retest reliability. Prenatal exposure to PCBs was associated with less efficient visual discrimination processing and more errors in short-term memory scanning but not with sustained attention. Although much larger quantities of these contaminants are transferred postnatally via breastfeeding than prenatally across the placenta, postnatal exposure was unrelated to cognitive performance. The data link intrauterine PCB exposure to 2 dimensions of cognitive functioning fundamental to learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The developmental implications of prenatal and/or postnatal crack cocaine exposure in preschool children: a preliminary report

Previous studies examining the development of prenatally cocaine-exposed children through 3 years of age have found no significant differences between exposed and control groups. This study explored the developmental correlates of prenatal and/or postnatal crack cocaine exposure in children between 4 and 6 years of age. Three groups were studied: Group 1, 18 prenatally-exposed children whose mothers continue to use crack; Group II, 28 children without prenatal exposure whose mothers presently use crack; and Group III, 28 children whose mothers never used crack. Mothers were street-recruited and were comparable in race and socioeconomic status. The three groups of children did not differ on neurological gross motor and expressive language measures. However, prenatally exposed children performed significantly worse than others on receptive language and visual motor drawing tests. Prenatal crack exposure predicted poor visual motor performance even after control for intrauterine alcohol and marijuana exposure, age, birth weight, and duration of maternal crack use.     

A review of the neurobehavioral deficits in children with fetal alcohol syndrome or prenatal exposure to alcohol

HeLa cells and HeLa cells expressing the HIV-1 regulatory protein Rev were immunostained for Rev and pre-mRNA processing factors and examined histographically by confocal laser scanning microscopy. Following short pulse-labelling with bromouridine tri-phosphate nascent RNA gave a granular nucleoplasmic staining increasing somewhat towards the periphery as did also the heterogeneous ribonucleoproteins (hnRNPs) A1 and particularly C1/C2, a distribution pattern which has not been described. The sm-antigen of the small ribonucleoprotein particle (snRNP) proteins U1, U2, U4/U6 and U5 stained the nucleoplasm diffusely in addition to speckles which co-localised with speckles of the non-snRNP splicing factor SC-35. Brominated RNA and the hnRNPs A1 and C1/C2 were to varying degrees excluded from the speckles. Rev concentrated in the nucleolus and often as a perinucleolar ring/zone. Rev also stained the nucleoplasm and cytoplasm without co-localising with the above-mentioned proteins or brominated RNA and was not enriched or excluded in SC-35 speckles. The nucleolar proteins B23 and C23, like Rev, gave primarily a perinucleolar ring and stained the nucleoplasm but did not otherwise co-localise with Rev or with nuclear proteins. Histographic recording of immunofluorescence images proved to be a valuable tool in the study of localisation of HIV-1 Rev and cellular components and of possible co-localisations. A parallel comparison of the subcellular patterns of pre-mRNA processing factors versus major nucleolar antigens is new and suggests that the factors are not strictly separated in the nucleoplasm.