Sleep in Infants and Children with Prenatal Alcohol Exposure

Prenatal exposure to alcohol can result in a range of neurobehavioral impairments and physical abnormalities. The term “fetal alcohol spectrum disorders (FASD)” encompasses the outcomes of prenatal alcohol exposure (PAE), the most severe of which is fetal alcohol syndrome. These effects have lifelong consequences, placing a significant burden on affected individuals, caregivers, and communities. Caregivers of affected children often report that their child has sleep problems, and many symptoms of sleep deprivation overlap with the cognitive and behavioral deficits characteristic of FASD. Alcohol‐exposed infants and children demonstrate poor sleep quality based on measures of electroencephalography, actigraphy, and questionnaires. These sleep studies indicate a common theme of disrupted sleep pattern, more frequent awakenings, and reduced total sleep time. However, relatively little is known about circadian rhythm disruption and the neurobehavioral correlates of sleep disturbance in individuals with PAE. Furthermore, there is limited information available to healthcare providers about identification and treatment of sleep disorders in patients with FASD. This review consolidates the findings from studies of infant and pediatric sleep in this population, providing an overview of typical sleep characteristics, neurobehavioral correlates of sleep disruption, and potential avenues for intervention in the context of PAE.     

Relationship Between Low-Level Lead Exposure and Neurobehaviors of Preschool Children

目的　探讨低水平铅暴露对儿童神经行为的影响。方法　整群随机抽取某市幼儿园 4～ 6岁 2 11名儿童为研究对象 ,采指端末梢血 2 0 μl,原子吸收石墨炉法测定血铅 ,以血铅水平 10 0 μg/L为界 ,分为高血铅组(≥ 10 0 μg/L)和低血铅组 (<10 0 μg/L) ,采用Achenbach儿童行为量表 (CBCL)及自拟调查表进行问卷调查 ,其结果运用t ,χ2 检验 ,简相关及多元逐步回归等方法进行统计分析。结果　高血铅组外向行为得分及行为异常率(13.2 8± 6 .2 6 ,18.2 6 % )显著高于低血铅组 (9.98± 5 .4 6 ,7.2 9% ) (t =4 .0 6 77,χ2 =5 .4 70 ,均P <0 .0 5 ) ,血铅值与外向行为中多动、攻击、违纪因子分显著正相关 (r =0 .316 4 ,0 .2 82 8,0 .1886 ,P <0 .0 5 ) ,血铅值≥ 15 0 μg/L时 ,行为异常率显著增加 (χ2 =13.6 95 ,P <0 .0 5 )。结论　低水平铅暴露对儿童外向行为具有负性影响。     

Critical windows of susceptibility in the association between manganese and neurocognition in Italian adolescents living near ferro-manganese industry

IntroductionUnderstanding the neurodevelopmental effects of manganese (Mn) is complicated due to its essentiality for growth and development. While evidence exists for the harmful effects of excess Mn, pediatric epidemiologic studies have observed inconsistent associations between Mn and child cognition.ObjectiveWe sought to estimate prospective associations between Mn measured in three different early-life time windows with adolescent cognition using deciduous teeth biomarkers.MethodsDeciduous teeth were collected from 195 participants (ages 10–14 years) of the Public Health Impact of Manganese Exposure (PHIME) study in Brescia, Italy. Measurements of tooth Mn represented prenatal (∼14 weeks gestation – birth), early postnatal (birth – 1.5 years) and childhood (∼1.5 – 6 years) time windows. Neuropsychologists administered the Wechsler Intelligence Scale for Children, 3rd edition (WISC-III), to obtain composite IQ and subtest scores. Associations between tooth Mn at each time window and adolescent WISC-III scores were estimated using multivariable linear regression. We tested differences in associations between Mn and outcomes across time windows using multiple informant models. Sex-specific associations were explored in stratified models.ResultsAdjusted associations between tooth Mn and composite IQ scores were positive in the prenatal period and negative in the childhood period. Associations were strongest for subtest scores that reflect working memory, problem solving, visuospatial ability and attention: prenatal Mn was positively associated with Digits backward [SD change in score per interquartile range increase in Mn: β = 0.20 (95 % CI: 0.02, 0.38)] and Block design [β = 0.21 (0.01, 0.41)] and early postnatal Mn was positively associated with Digits forward [β = 0.24 (0.09, 0.40)], while childhood Mn was negatively associated with Coding [β = -0.14 (-0.28, -0.001)]. Sex-stratified analyses suggested different Mn-cognition associations for boys and girls and was also dependent on the time window of exposure.ConclusionOur results suggest that exposure timing is critical when evaluating Mn associations between Mn and cognition. Higher prenatal Mn was beneficial for adolescent cognition; however, these beneficial associations shifted towards harmful effects in later time windows. Cognitive domains most sensitive to Mn across time windows included visuospatial ability, working memory, attention and problem-solving.     

Interaction of Toxoplasma gondii infection and elevated blood lead levels on children’s neurobehavior

A chronic infection caused by Toxoplasma gondii was considered asymptomatic in immunologically healthy humans, but results from animal and epidemiological studies led to a reconsideration of this assumption. The objective of this study was to evaluate the seroprevalence of T. gondii infection and its possible effects on the behavior of school-aged children in Bahia, Brazil. Serum anti-body determinations were performed by Enzyme-linked Immunosorbent Assay (ELISA). Blood lead levels (BLL) were measured by graphite furnace atomic absorption spectrometry (GFAAS). The evaluation of a child’s behavior was assessed using the Child Behavior Check List (CBCL). Multivariate models applying logistic regression were used to test the association of chronic T. gondii infection and BLL with behavioral outcomes in children. Seroprevalence for anti-T. gondii IgG antibody was 43.7 % (95 %-CI: 35.8–51.9). Significant associations between chronic T. gondii infection and total behavioral problems (OR = 2.50; 95 %-CI: 1.06–5.88), internalizing spectrum problems (OR = 4.35; 95 %-CI: 1.11–17.14) and rule breaking (OR = 2.61; 95 %-CI: 1.12–6.05) were observed. A possible interaction between toxoplasmosis prevalence and lead exposure was detected. Children with above the median BLL and positive for IgG anti-T. gondii showed a 5.51-fold increase (95 %-CI: 1.75–17.38) in the chance of displaying disobedient behavior. The results suggest that T. gondii infection may be contributing to the high indices of behavioral changes. Moreover, these findings are the first evidence for a possible interaction between chronic T. gondii infection and elevated blood lead levels on children’s neurobehavior.     

Transplacental and early life exposure to inorganic arsenic affected development and behavior in offspring rats

To evaluate the developmental neurotoxicity of arsenic in offspring rats by transplacental and early life exposure to sodium arsenite in drinking water, the pregnant rats or lactating dams, and weaned pups were given free access to drinking water, which contained arsenic at concentrations of 0, 10, 50, 100 mg/L from GD 6 until PND 42. A battery of physical and behavioral tests was applied to evaluate the functional outcome of pups. Pups in arsenic exposed groups weighed less than controls throughout lactation and weaning. Body weight of 10, 50 and 100 mg/L arsenic exposed groups decreased significantly on PND 42, 16 and 12, respectively. Physical development (pinna unfolding, fur appearance, incisor eruption, or eye opening) in pups displayed no significant differences between control and arsenic treated groups. The number of incidences within the 100 mg/L arsenic treated group, in tail hung, auditory startle and visual placing showed significant decrease compared to the control group (p < 0.05). In square water maze test, the trained numbers to finish the trials successfully in 50 and 100 mg/L arsenic exposed groups increased remarkably compared to control group, and there was a dose-related increase (p < 0.01) observed. Taken together, these data show that exposure of inorganic arsenite to pregnant dams and offspring pups at levels up to 100 mg/L in drinking water may affect their learning and memory functions and neuromotor reflex.     

Neurobehavioral effects of exposure to organophosphates and pyrethroid pesticides among Thai children

The use of pesticides for crop production has grown rapidly in Thailand during the last decade, resulting in significantly greater potential for exposure among children living on farms. Although some previous studies assessed exposures to pesticides in this population, no studies have been conducted to evaluate corresponding health effects. Twenty-four children from a rice farming community (exposed) and 29 from an aquaculture (shrimp) community (control) completed the study. Participants completed a neurobehavioral test battery three times at 6 month intervals: Session I: preliminary orientation; Session II: high pesticide use season; Session III: low pesticide-use season. Only sessions II and III were used in the analyses. High and low pesticide use seasons were determined by pesticide use on rice farms. Urinary metabolites of organophosphates (OPs) and pyrethroids (PYR) were analyzed from first morning void samples collected the day of neurobehavioral testing. Rice farm participants had significantly higher concentrations of dialkylphosphates (DAPs) (common metabolites of OPs) and TCPy (a specific metabolite of chlorpyrifos) than aquaculture farm children during both seasons. But, TCPy was significantly higher during the low rather than the high pesticide use season for both participant groups. Rice farm children had significantly higher DCCA, a metabolite of PYR, than aquaculture participants only during the high exposure season. Otherwise, no significant differences in PYR metabolites were noted between the participant groups or seasons. No significant adverse neurobehavioral effects were observed between participant groups during either the high or low pesticide use season. After controlling for differences in age and the Home Observation for Measurement of the Environment (HOME) scores, DAPs, TCPy, and PYR were not significant predictors of adverse neurobehavioral performance during either season. Increasing DAP and PYR metabolites predicted some relatively small improvement in latency of response. However, due to the small sample size and inability to characterize chronic exposure, any significant differences observed should be regarded with caution. Moreover although not statistically significant, confidence intervals suggest that small to moderate adverse effects of pesticide exposure cannot be ruled out for some indicators of neurobehavioral performance.     

Focal brain injury and its effects on cerebral mantle, neurons, and fiber tracks

Following a mild cortical impact injury delivered by a piston to the right sensorimotor cortex of the anesthetized rat, we evaluated mantle loss, neuronal changes, and fiber track degeneration by deOlmos silver stains up to 8 weeks after injury. Darkened neurons indicating damage (chromatolysis) occurred widely throughout both hemispheres and were seen from 1 h to 8 weeks after injury. This effect might have occurred from pressure wave damage from piston impact, brain displacement or deafferentation. Cerebral mantle loss was variable but fiber track degeneration related to projection and corticofugal descending tracks associated with the right sensorimotor system was rather constant. Unexpectedly, considerable fiber track degeneration occurred within the cerebellum, especially the inferior vermis. Cells directly under the piston face were surprisingly well-preserved but axon degeneration studies showed that these apparently intact neuronal cell bodies were surrounded by a dense network of degenerating fiber tracks. The intact cells, therefore, may have been functionally cut off from the rest of the brain owing to interruption of their efferents and afferents. The increased susceptibility of axons compared to cell bodies seen with this focal injury is similar to that observed with diffuse brain injury. The early appearing, severe and widespread axon damage we observed suggests that amelioration of focal traumatic brain injury will have to be directed promptly to the preservation of axons as well as cell bodies.     

康复训练对脑损伤患儿视觉反应时的影响

目的了解康复训练对脑损伤患儿视觉反应时的影响及其在残疾儿童脑功能评价和康复疗效分析中的作用。方法观察组为51例脑损伤患儿，对照组为29例正常儿童，均进行光刺激的复杂视觉反应时测试，并比较观察组康复训练前、后的反应时成绩。结果观察组训练前各项反应时成绩明显较对照组延长（P〈0．01）。训练后观察组的反应时成绩则明显改善（除左侧第二反应时），第一反应时与对照组差异无统计学意义（P〉0．05）；中度障碍的观察组患儿训练后反应时的改善程度最明显。结论脑损伤患儿注意力和反应速度均有异常，但经过训练后可有明显改善。反应时作为一种简单、易测、灵敏、客观的神经心理活动指标，在残疾儿童高级脑功能评价和康复疗效分析中具有重要意义。     

Influence of prenatal cocaine exposure on full-term infant neurobehavioral functioning

This study investigated infant neurobehavioral functioning during the newborn period in 334 full-term, African American neonates (187 cocaine exposed, 147 non-cocaine exposed) enrolled prospectively at birth, with documentation of drug exposure status through maternal interview and urine and meconium toxicology assays. Infants were assessed using the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) during the newborn period (0–6 postnatal days). Findings from multivariate profile analyses support a consistent, modest effect of prenatal cocaine exposure on neurobehavioral functioning in full-term neonates. All of the BNBAS cluster scores, with the exception of abnormal reflexes, were similarly affected, sharing a common slope (D=−0.14; 95% CI=−0.27, −0.003; P=.046) representing a −0.14 point difference between cocaine-exposed and non-cocaine-exposed infants after controlling for prenatal exposure to alcohol, tobacco, and marijuana (ATM); maternal age, education, employment, primigravida status, and prenatal care visits; and infant sex and postnatal age in days. Fetal growth was also related to neurobehavioral functioning and, in part, mediated the relationship between cocaine exposure and the BNBAS cluster scores. Cocaine exposure during each trimester similarly influenced infant neurobehavioral profiles, with cocaine-associated deficits most pronounced in infants with exposure in all three trimesters. Results from qualitative and quantitative urine and meconium bioassay indicators further substantiated these results. Findings, while significant, represent modest effect sizes in full-term infants.     

影响新生儿神经行为发育的多因素分析

目的：探讨影响新生儿神经行为发育的多种因素及敏感性。方法：随机选取中国第一冶金建筑公司职工医院妇产科1999年1-10月出生的足月新生儿103例，用鲍秀兰的20项新生儿神经行为检查法测定新生儿神经行为能力，用武汉科技大学医学院附属医院儿科设计的问卷收集有关影响因素，同时测定新生儿脐血铅和胎粪铅含量。以新生儿神经行为总评分作为因变量，以问卷中的影响因素及脐血铅、胎粪铅等24项指标作为自变量，采用多项有序分类反应型变量的logistic逐步回归的分析方法，在P=0.10水平筛选出相应的影响因素。结果：孕周、孕期服药月份、血红蛋白、孕期情绪、胎粪铅、孕期服药6项选入模型。结论：新生儿神经行为发育受多项因素的影响。孕期营养状况好、孕周长、孕期情绪好有利于新生儿神经行为的发育。孕期服药不利于新生儿神经行为的发育，尤其是妊娠早期用药。胎粪铅含量增高将不利于新生儿神经行为的发育。