BACKGROUND & AIMS: INTRODUCTION:Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder of early onset, characterized by impaired sociability, cognitive function and stereotypies. The etiology of ASD involves a multidimensional link between genetic, neurobiological and environmental factors. Since existing, comprehensive animal models for ASD are time consuming and laborious, the need for simple, quick approaches to study subsets of ASD-associated characteristics has always been in demand for better understanding of disease. The aim of the present study was to develop a cost and time effective zebrafish model with quantifiable parameters to facilitate mechanistic studies as well as high-throughput screening of new molecules for autism. METHODS:Zebrafish embryos were treated with valproic acid (75 μM) beginning at 4-h post fertilization to 5-days post fertilization. A series of behavioral tests (anxiety, inattentive behavior and circling behavior) and molecular studies were performed as surrogate parameters of ASD-like characteristic on the larvae at 7-dayspost fertilization for a quick screen. The study was followed by validation of model by screening positive control and negative control drugs. The social interaction test was performed on 21-days post fertilization to confirm that the surrogate phenotypes were indicative of social deficit (a core symptom of ASD). RESULTS:The model showed a significant behavioral impairment (2-4fold difference) in valproic acid treated larvae compared to control larvae, which was further supported by alterations in select high-risk genes and proteins, implicated in human ASD. Reversal of behavioral impairments using standard drugs marketed for symptomatic treatment in ASD and no effect on behaviors when treated with paracetamol (negative control) signifies the role of model in preliminary drug screening. CONCLUSION:The model shows robust parameters to study behavior, molecular mechanism and drug screening approach in a single frame. Thus, we postulate that our 7-day larval model could be a useful preliminary screening tool to identify novel targets as well as potential drugs for autism and also can be applied to develop a high-throughput screening approach.

背景与目标： 简介：自闭症谱系障碍（ASD）是一种较早发作的复杂神经发育障碍，其特征是社交能力，认知功能和定型观念受损。 ASD的病因学涉及遗传，神经生物学和环境因素之间的多维联系。由于现有的全面的ASD动物模型既费时又费力，因此一直需要简单，快速的方法来研究与ASD相关的特征的子集，以便更好地了解疾病。本研究的目的是开发一种具有可量化参数的成本和时间有效的斑马鱼模型，以促进机理研究以及针对自闭症的新分子的高通量筛选。
方法：从受精后4小时至受精后5天，用丙戊酸（75μM）处理斑马鱼的胚胎。受精后7天，对幼虫进行一系列行为测试（焦虑，注意力不集中和盘旋行为）和分子研究，作为ASD样特征的替代参数，以便进行快速筛查。在研究之后，通过筛选阳性对照和阴性对照药物来验证模型。受精后21天进行社交互动测试，以确认替代表型指示社交缺陷（ASD的核心症状）。
结果：该模型显示丙戊酸处理的幼虫与对照组幼虫相比，行为上有明显的损伤（差异是2倍），这进一步得到与人类ASD有关的精选高风险基因和蛋白质的改变的支持。使用市售用于对症治疗的对症治疗标准药物来逆转行为障碍，用扑热息痛（阴性对照）治疗对行为无影响，表明该模型在初步药物筛选中的作用。
结论：该模型显示了可靠的参数，可在单一框架内研究行为，分子机理和药物筛选方法。因此，我们假设我们的7天幼虫模型可能是有用的初步筛选工具，用于识别新的靶标以及自闭症的潜在药物，也可以用于开发高通量筛选方法。

BACKGROUND & AIMS: :The vast majority of women (60-90%) hold infants on their left side. Such a population-level lateral bias has been shown to improve the processing of socio-emotional stimuli in both the woman and the baby. Recently, some studies related cradling lateralization and Autism Spectrum Disorders (which entail socio-communicative deficits and a reduction of the typical lateralization of brain functions), raising the possibility that the asymmetrical cradling behavior experienced during infanthood might be related to the infant's neurodevelopment. Any progress made towards earlier diagnoses could significantly increase the chance of successful intervention for these patients. We here suggest that a wide retrospective investigation on family photo albums and home movies of children diagnosed with Autism might provide useful data about early behavioral signs of this condition. We hypothesize that an atypical trajectory in maternal cradling might be one of the early signs of interference in dyadic socio-emotional communication, and thus of potential neurodevelopmental dysfunctions.

背景与目标： ：绝大多数女性（60-90％）的左侧抱着婴儿。这种人口水平的横向偏见已被证明可以改善妇女和婴儿的社会情感刺激的处理。最近，一些研究将婴儿的偏侧和自闭症谱系障碍（这会导致社交交流障碍和典型的脑功能偏侧化），这增加了婴儿期经历的不对称的婴儿举止行为可能与婴儿的神经发育有关的可能性。在早期诊断方面取得的任何进展都可能显着增加对这些患者进行成功干预的机会。我们在此建议，对诊断为自闭症儿童的家庭相册和家庭电影进行广泛的回顾性调查，可能会提供有关这种情况的早期行为征兆的有用数据。我们假设孕产妇的非典型轨迹可能是二元社会情感交流受干扰的早期迹象之一，因此可能是潜在的神经发育功能障碍。

BACKGROUND & AIMS: PURPOSE:A growing body of evidence links poor maternal mental health with negative outcomes on early child development. We examined the effect of antenatal and postnatal maternal mental health on infant neurodevelopment at age 18 months in a population-based mother-child cohort (Rhea Study) in Crete, Greece. METHODS:Self-reported measures of maternal depression (EPDS), trait anxiety (STAI-Trait) and personality traits (EPQ-R) were assessed in a sample of women during pregnancy and at 8 weeks postpartum (n = 223). An additional sample of 247 mothers also completed the EPDS scale at 8 weeks postpartum (n = 470). Neurodevelopment at 18 months was assessed with the use of Bayley Scales of Infant and Toddler Development (3rd edition). RESULTS:Multivariable linear regression models adjusted for confounders revealed that antenatal depressive symptoms (EPDS ≥ 13) were associated with decrease in cognitive development independently of postnatal depression. High trait anxiety and extraversion were associated with decrease and increase, respectively, in social-emotional development. Also, high trait anxiety and neuroticism had a positive effect on infants' expressive communication. Finally, postpartum depressive symptoms (EPDS ≥ 13) were associated with decrease in cognitive and fine motor development independently of antenatal depression. CONCLUSIONS:These findings suggest that antenatal and postnatal maternal psychological well-being has important consequences on early child neurodevelopment.

背景与目标： 目的：越来越多的证据表明，母亲心理健康状况不佳与早期儿童发育的负面结果有关。我们在希腊克里特岛的一个以人口为基础的母婴队列中研究了18月龄时产前和产后母亲的心理健康对婴儿神经发育的影响（Rhea研究）。
方法：在怀孕期间和产后8周（n = 223）的妇女样本中评估了自我报告的孕产妇抑郁（EPDS），性格焦虑（STAI-Trait）和人格特质（EPQ-R）的量度。另有247名母亲的样本在产后8周也完成了EPDS量表（n = 470）。使用贝利婴儿和幼儿发育量表（第3版）评估18个月时的神经发育。
结果：针对混杂因素进行调整的多变量线性回归模型显示，产前抑郁症状（EPDS≥13）与认知发育下降相关，而与产后抑郁无关。高特质焦虑和外向性分别与社会情感发展中的减少和增加有关。同样，高特质焦虑和神经质也对婴儿的表达交流有积极作用。最后，产后抑郁症状（EPDS≥13）与认知和精细运动发展的下降相关，而与产前抑郁无关。
结论：这些发现表明，产前和产后母亲的心理健康状况对儿童早期神经发育有重要影响。

BACKGROUND & AIMS: :General anesthesia has been unequivocally linked to abnormal development of the central nervous system, leading to neurocognitive impairments in laboratory models. In vitro and in vivo studies have consistently shown that exposure to GABA agonists (eg, volatile anesthetics, midazolam, and propofol) or NMDA antagonists (eg, ketamine, isoflurane, and nitrous oxide) produces dose dependent and developmental age dependent effects on various neuronal transmission systems. Exposure to these drugs increases neuronal cell death in juvenile animals including rats, mice, and non-human primates. The possibility of anesthetic induced neurotoxicity occurring in children has led to concerns about the safety of pediatric anesthesia. A spectrum of behavioral changes has been documented after general anesthetic exposure in young children, including emergence delirium, which may be evidence of toxicity. Most clinical studies are retrospective; specifics about medications or monitoring are unavailable and many of the outcomes may not be sensitive to detect small neurocognitive deficits. Some of these retrospective studies have shown an association between anesthesia exposure at a young age and neurocognitive deficits, but others have not. Practitioners and families should be reassured that although general anesthetics have the potential to induce neurotoxicity, very little clinical evidence exists to support this.

背景与目标： ：全身麻醉已明确地与中枢神经系统的异常发育相关，从而导致实验室模型中的神经认知损害​​。体外和体内研究一致表明，暴露于GABA激动剂（如挥发性麻醉剂，咪达唑仑和丙泊酚）或NMDA拮抗剂（如氯胺酮，异氟烷和一氧化二氮）对各种神经元产生剂量依赖性和发育年龄依赖性。传输系统。接触这些药物会增加幼年动物（包括大鼠，小鼠和非人类灵长类动物）的神经元细胞死亡。麻醉剂引起儿童神经毒性的可能性引起了对小儿麻醉安全性的担忧。已记录了幼儿全身麻醉后的一系列行为变化，包括出现emerge妄，这可能是毒性的证据。大多数临床研究都是回顾性的。无法获得有关药物或监测的详细信息，并且许多结果可能对检测小的神经认知功能障碍并不敏感。这些回顾性研究中的一些研究表明，年轻时的麻醉暴露与神经认知功能障碍之间存在关联，而其他研究则没有。从业者和家庭应该放心，尽管全身麻醉药具有诱发神经毒性的潜力，但很少有临床证据支持这一点。

BACKGROUND & AIMS: :The first description of the Reeler mutation in mouse dates to more than fifty years ago, and later, its causative gene (reln) was discovered in mouse, and its human orthologue (RELN) was demonstrated to be causative of lissencephaly 2 (LIS2) and about 20% of the cases of autosomal-dominant lateral temporal epilepsy (ADLTE). In both human and mice, the gene encodes for a glycoprotein referred to as reelin (Reln) that plays a primary function in neuronal migration during development and synaptic stabilization in adulthood. Besides LIS2 and ADLTE, RELN and/or other genes coding for the proteins of the Reln intracellular cascade have been associated substantially to other conditions such as spinocerebellar ataxia type 7 and 37, VLDLR-associated cerebellar hypoplasia, PAFAH1B1-associated lissencephaly, autism, and schizophrenia. According to their modalities of inheritances and with significant differences among each other, these neuropsychiatric disorders can be modeled in the homozygous (reln-/-) or heterozygous (reln+/-) Reeler mouse. The worth of these mice as translational models is discussed, with focus on their construct and face validity. Description of face validity, i.e., the resemblance of phenotypes between the two species, centers onto the histological, neurochemical, and functional observations in the cerebral cortex, hippocampus, and cerebellum of Reeler mice and their human counterparts.

背景与目标： ：对Reeler突变的最早描述可追溯到50多年前，后来在小鼠中发现了其致病基因（reln），并证明其人类直系同源基因（RELN）是lissencephaly 2（LIS2）的致病原因。约有20％的常染色体显性外侧颞叶癫痫（ADLTE）。在人类和小鼠中，该基因编码一种称为reelin（Reln）的糖蛋白，该蛋白在发育过程中的神经元迁移和成年期的突触稳定中起主要作用。除了LIS2和ADLTE外，RELN和/或其他编码Reln细胞内级联蛋白的基因已与其他疾病（例如7型和37型小脑共济失调，与VLDLR相关的小脑发育不全，PAFAH1B1相关的小脑，自闭症和精神分裂症。根据它们的遗传方式以及彼此之间的显着差异，可以在纯合子（reln-/-）或杂合子（reln /-）Reeler小鼠中模拟这些神经精神疾病。讨论了这些小鼠作为转化模型的价值，重点是它们的结构和面部有效性。面部有效性的描述，即两个物种之间的表型相似，集中于Reeler小鼠及其人类对应物的大脑皮层，海马和小脑的组织学，神经化学和功能观察。

BACKGROUND & AIMS: :Proper nutrition is crucial for normal brain and neurocognitive development. Failure to optimize neurodevelopment early in life can have profound long-term implications for both mental health and quality of life. Although the first 1000 days of life represent the most critical period of neurodevelopment, the central and peripheral nervous systems continue to develop and change throughout life. All this time, development and functioning depend on many factors, including adequate nutrition. In this review, we outline the role of nutrients in cognitive, emotional, and neural development in infants and young children with special attention to the emerging roles of polar lipids and high quality (available) protein. Furthermore, we discuss the dynamic nature of the gut-brain axis and the importance of microbial diversity in relation to a variety of outcomes, including brain maturation/function and behavior are discussed. Finally, the promising therapeutic potential of psychobiotics to modify gut microbial ecology in order to improve mental well-being is presented. Here, we show that the individual contribution of nutrients, their interaction with other micro- and macronutrients and the way in which they are organized in the food matrix are of crucial importance for normal neurocognitive development.

背景与目标： ：适当的营养对于正常的大脑和神经认知发育至关重要。无法在生命早期优化神经发育可能对心理健康和生活质量产生深远的长期影响。尽管生命的前1000天是神经发育的最关键时期，但中枢神经系统和周围神经系统在整个生命过程中仍在继续发展和变化。一直以来，发展和功能取决于许多因素，包括充足的营养。在这篇综述中，我们概述了营养素在婴幼儿认知，情感和神经发育中的作用，并特别关注极性脂质和高质量（可用）蛋白质的新兴作用。此外，我们讨论了肠脑轴的动态性质以及与多种结局有关的微生物多样性的重要性，包括脑成熟/功能和行为。最后，提出了有前景的精神药物治疗潜力，以改善肠道微生物生态，以改善心理健康。在这里，我们表明营养素的个体贡献，它们与其他微量和大量营养素的相互作用以及它们在食物基质中的组织方式对于正常的神经认知发展至关重要。

BACKGROUND & AIMS: :The polygenic nature and the contribution of common genetic variation to autism spectrum disorder (ASD) allude to a high degree of pleiotropy between ASD and other psychiatric and behavioral traits. In a pleiotropic system, a single genetic variant contributes small effects to several phenotypes or disorders. While analyzed broadly, there is a paucity of research studies investigating the shared genetic information between specific neurodevelopmental domains and ASD. We performed a phenome-wide association study of ASD polygenetic risk score (PRS) against 491 neurodevelopmental subdomains ascertained in 4,309 probands from the Philadelphia Neurodevelopmental Cohort (PNC) who lack an ASD diagnosis. Our main analysis calculated ASD PRS in 4,309 PNC probands using the per-SNP effects reported in a recent genome-wide association study of ASD in a case-control design. In a high-resolution manner, our main analysis regressed ASD PRS against 491 neurodevelopmental phenotypes with age, sex, and ten principal components of ancestry as covariates. Follow-up analyses included in the regression model PRS derived from brain-related traits genetically correlated with ASD. Our main finding demonstrated that 11-17-year old probands with the highest ASD genetic risk were able to identify angry faces (R2 = 1.06%, p = 1.38 × 10-7, pBonferroni-corrected = 1.9 × 10-3). This ability replicated in older probands (>18 years; R2 = 0.55%, p = 0.036) and persisted after covarying with other psychiatric disorders, brain imaging traits, and educational attainment (R2 = 0.2%, p = 0.019). We also detected several suggestive associations between ASD PRS and emotionality and connectedness with others. These data (i) indicate how genetic liability to ASD may influence neurodevelopment in the general population, (ii) reinforce epidemiological findings of heightened ability of ASD cases to predict certain social psychological events based on increased systemizing skills, and (iii) recapitulate theories of imbalance between empathizing and systemizing in ASD etiology.

背景与目标： ：自闭症谱系障碍（ASD）的多基因性质和常见遗传变异的贡献暗示了ASD与其他精神病和行为特征之间的高度多效性。在多效性系统中，单个遗传变异对几种表型或疾病的影响很小。虽然进行了广泛的分析，但很少有研究调查特定神经发育域和ASD之间共享的遗传信息。我们针对来自ASF诊断的费城神经发育队列（PNC）的4,309名先证者确定的491个神经发育亚域，对491个神经发育亚域进行了ASD多基因风险评分（PRS）的全基因组关联研究。我们的主要分析使用病例对照设计中最近对ASD进行的全基因组关联研究中报道的per-SNP效应，计算了4,309个PNC先证者的ASD PRS。以高分辨率的方式，我们的主要分析针对年龄，性别和祖先的十个主要成分作为协变量的491种神经发育表型回归了ASD PRS。回归模型PRS中的后续分析来自与ASD遗传相关的脑相关性状。我们的主要发现表明，具有最高ASD遗传风险的11-17岁先证者能够识别出愤怒的面孔（R2 = 1.06％，p = 1.38×10-7，pBonferroni校正= 1.9×10-3）。这种能力在较年长的先证者（> 18岁； R2 = 0.55％，p = 0.036）中复制，并在与其他精神病，脑影像学特征和受教育程度共同变化后继续存在（R2 = 0.2％，p = 0.019）。我们还发现了ASD PRS与他人的情绪和联系之间的一些暗示性关联。这些数据（i）表明对ASD的遗传易感性如何影响普通人群的神经发育，（ii）加强基于提高的系统化技能来提高ASD病例预测某些社会心理事件的能力的流行病学发现，以及（iii）概括了ASD的理论。在ASD病因中，移情和系统化之间的不平衡。

BACKGROUND & AIMS: BACKGROUND:The implications of congenital Zika Virus (ZIKV) infections for pediatric neurodevelopment and behavior remain inadequately studied. The aim of this study is to investigate patterns of neurodevelopment and behavior in groups of children with differening severities of ZIKV-related microcephaly and children with prenatal ZIKV exposure in the absence of microcephaly. METHODS:We conducted a cross-sectional study, nested in a cohort, of 274 children (aged 10-45 months) who were born during the peak and decline of the microcephaly epidemic in Northeast Brazil. Participants were evaluated between February 2017 and August 2019 at two tertiary care hospitals in Recife, Pernambuco, Brazil. We analyzed the children in four groups assigned based on clinical and laboratory criteria: Group 1 had severe microcephaly; Group 2 had moderate microcephaly; Group 3 had prenatal ZIKVexposure confirmed by maternal RT-PCR testing but no microcephaly; and Group 4 was a neurotypical control group. Groups were evaluated clinically for neurological abnormalities and compared using the Survey of Wellbeing of Young Children (SWYC), a neurodevelopment and behavior screening instrument validated for use in Brazil. Children with severe delays underwent further evaluation with an adapted version of the SWYC. RESULTS:Based on the SWYC screening, we observed differences between the groups for developmental milestones but not behavior. Among the 114 children with severe microcephaly of whom 98.2% presented with neurological abnormalities, 99.1% were 'at risk of development delay' according to the SWYC instrument. Among the 20 children with moderate microcephaly of whom 60% presented with neurological abnormalities, 65% were 'at risk of development delay'. For children without microcephaly, the percentages found to be 'at risk of developmental delay' were markedly lower and did not differ by prenatal ZIKV exposure status: Group 3 (N = 94), 13.8%; Group 4 (N = 46), 21.7%. CONCLUSIONS:Among children with prenatal ZIKV exposure, we found a gradient of risk of development delay according to head circumference. Children with severe microcephaly were at highest risk for delays, while normocephalic ZIKV-exposed children had similar risks to unexposed control children. We propose that ZIKV-exposed children should undergo first-line screening for neurodevelopment and behavior using the SWYC instrument. Early assessment and follow-up will enable at-risk children to be referred to a more comprehensive developmental evaluation and to multidisciplinary care management.

背景与目标： 背景：先天性寨卡病毒（ZIKV）感染对小儿神经发育和行为的影响仍未得到充分研究。这项研究的目的是调查严重程度不同的ZIKV相关小头畸形的儿童和没有小头畸形的产前ZIKV暴露儿童的神经发育和行为模式。
方法：我们在一个队列中进行了一项横断面研究，对274名儿童（年龄在10-45个月内）在巴西东北部小头症流行高峰和衰退期间出生进行了研究。参与者于2017年2月至2019年8月在巴西伯南布哥州累西腓的两家三级护理医院接受了评估。我们根据临床和实验室标准对四组儿童进行了分析：第一组患有严重的小头畸形；第2组为中度小头畸形；第3组经产妇RT-PCR检测证实有产前ZIKV暴露，但无小头畸形。第4组是神经型对照组。临床上对各组进行了神经系统异常评估，并使用经验证可在巴西使用的神经发育和行为筛查工具“幼儿健康调查”（SWYC）进行比较。严重延迟的儿童将接受改版的SWYC进行进一步评估。
结果：基于SWYC筛查，我们观察到两组之间在发展里程碑上的差异，但在行为上没有差异。根据SWYC仪器，在114名严重小头畸形儿童中，其中98.2％表现出神经系统异常，其中99.1％处于“发育迟缓风险中”。在20名中度小头畸形儿童中，其中60％表现出神经系统异常，其中65％处于“有发育迟缓的危险中”。对于没有小头畸形的儿童，发现“处于发育迟缓风险中”的百分比显着降低，并且与产前ZIKV暴露状态无差异：第3组（N = 94），13.8％；第4组（N = 46），占21.7％。
结论：在有产前ZIKV暴露的儿童中，我们发现根据头围的不同，发育延迟的风险呈梯度变化。患有严重小头畸形的儿童发生延迟的风险最高，而暴露于常头ZIKV的儿童与未暴露的对照儿童具有相似的风险。我们建议接触ZIKV的儿童应使用SWYC仪器进行一线筛查神经发育和行为。早期评估和随访将使处于危险中的儿童能够接受更全面的发育评估和多学科护理管理。

BACKGROUND & AIMS: OBJECTIVE:To examine the relationship between markers of vascular dysfunction and neurodevelopmental outcomes in perinatally HIV-infected (PHIV+) and perinatally HIV-exposed but uninfected (PHEU) youth. DESIGN:Cross-sectional design within a prospective, 15-site US-based cohort study. METHODS:Neurodevelopmental outcomes were evaluated in relation to nine selected vascular biomarkers in 342 youth (212 PHIV+, 130 PHEU). Serum levels were assessed for adiponectin, C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), soluble vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), monocyte chemoattractant protein (sMCP-1), intercellular adhesion molecule-1 (sICAM-1), and P-selectin (sP-selectin). The Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) was administered at entry, yielding a Full-Scale IQ score, and four index scores. Factor analysis was conducted to reduce the biomarkers to fewer factors with related biological roles. Structural equation models (SEMs) were used to measure associations between resulting factors and WISC-IV scores. RESULTS:Mean participant age was 11.4 years, 54% were female, 70% black. The nine biomarkers were clustered into three factor groups: F1 (fibrinogen, CRP, and IL-6); F2 (sICAM-1 and sVCAM-1); and F3 (MCP-1, sP-selectin, and sE-selectin). Adiponectin showed little correlation with any factor. SEMs revealed significant negative association of F1 with WISC-IV processing speed score in the total cohort. This effect remained significant after adjusting for HIV status and other potential confounders. A similar association was observed when restricted to PHIV+ participants in both unadjusted and adjusted SEMs. CONCLUSION:Aggregate measures of fibrinogen, CRP, and IL-6 may serve as a latent biomarker associated with relatively decreased processing speed in both PHIV+ and PHEU youth.

背景与目标： 目的：探讨围产期感染HIV（PHIV）和未患围产期HIV但未感染（PHEU）的年轻人中血管功能障碍标志物与神经发育结果之间的关系。
设计：一项前瞻性，位于美国的15个研究对象的队列研究中的横断面设计。
方法：评估了342名青年（212名PHIV，130名PHEU）中9种选择的血管生物标志物的神经发育结局。评估血清中的脂联素，C反应蛋白（CRP），纤维蛋白原，白介素6（IL-6），可溶性血管细胞粘附分子1（sVCAM-1），E选择素（sE-selectin），单核细胞趋化因子蛋白（sMCP-1），细胞间粘附分子1（sICAM-1）和P-选择素（sP-选择素）。韦氏儿童智力量表（第四版）（WISC-IV）在入学时进行管理，产生了智商全面得分和四个指数得分。进行因子分析以将生物标志物减少到具有相关生物学作用的较少因子。使用结构方程模型（SEM）来衡量结果因素与WISC-IV得分之间的关​​联。
结果：平均参与者年龄为11.4岁，女性为54％，黑人为70％。九种生物标志物被分为三个因子组：F1（纤维蛋白原，CRP和IL-6）； F1（纤维蛋白原，CRP和IL-6）； F1（纤维蛋白原，CRP和IL-6）。 F2（sICAM-1和sVCAM-1）；和F3（MCP-1，sP-选择素和sE-选择素）。脂联素与任何因素均无相关性。扫描电镜显示在整个队列中F1与WISC-IV处理速度得分显着负相关。调整HIV状况和其他潜在的混杂因素后，这种效果仍然很明显。在未经调整和调整后的扫描电子显微镜中，仅限于PHIV参与者时，观察到类似的关联。
结论：总的纤维蛋白原，CRP和IL-6的测定指标可能是潜在的生物标志物，与HIV和PHEU青年的加工速度相对降低有关。

BACKGROUND & AIMS: The relation of HIV-1 infection to infant growth and neurodevelopment was studied prospectively in a cohort of 65 infants born to women at risk for HIV infection. No differences were observed at birth between infected infants (INF) and uninfected infants (SR) of HIV-infected women, and infants of uninfected women (SN) with similar socioeconomic background and exposure to drugs. However, postnatal linear growth and cognitive-motor development of INF infants were impaired when compared to SR and SN infants. Declines in linear growth were observed within the first 6 months of life, whereas delays in neurodevelopment were first appreciated at 12 months. In INF infants, decreased linear growth was positively correlated with developmental delay. Moreover, growth and development were both correlated with HIV viral load. INF infants with high plasma HIV RNA copies (> 5 x 10(5)/ ml) at 6 months of life were more likely to exhibit severe growth and developmental delay than infants with a lower viral burden. The implications of these findings with respect to the mechanism of action of HIV-related growth and neurodevelopmental impairments are discussed.

背景与目标： 前瞻性研究了65名有感染HIV风险的妇女所生婴儿的队列，研究了HIV-1感染与婴儿生长和神经发育的关系。 HIV感染妇女的感染婴儿（INF）和未感染婴儿（SR）以及具有相似社会经济背景和接触药物的未感染女性（SN）婴儿在出生时未观察到差异。但是，与SR和SN婴儿相比，INF婴儿的产后线性生长和认知运动发育受到损害。在生命的头6个月内观察到线性增长的下降，而在12个月内首次发现了神经发育的延迟。在INF婴儿中，线性增长下降与发育延迟呈正相关。此外，生长和发育都与HIV病毒载量有关。与病毒载量较低的婴儿相比，在六个月的生命中具有较高血浆HIV RNA拷贝（> 5 x 10（5）/ ml）的INF婴儿更可能出现严重的生长和发育延迟。讨论了这些发现对与HIV相关的生长和神经发育受损的作用机制的意义。

BACKGROUND & AIMS: :Severe vitamin B(12) deficiency produces a cluster of neurological symptoms in infants, including irritability, failure to thrive, apathy, anorexia, and developmental regression, which respond remarkably rapidly to supplementation. The underlying mechanisms may involve delayed myelination or demyelination of nerves; alteration in the S-adenosylmethionine:S-adenosylhomocysteine ratio; imbalance of neurotrophic and neurotoxic cytokines; and/or accumulation of lactate in brain cells. This review summarizes the current knowledge concerning infantile vitamin B(12) deficiency, including a pooled analysis of case studies of infants born to mothers with untreated pernicious anemia or a strict vegetarian lifestyle and a discussion of the mechanisms that may underlie the manifestations of deficiency.

背景与目标： ：严重的维生素B（12）缺乏会在婴儿中产生一系列神经系统症状，包括易怒，壮成长，冷漠，厌食和发育退化，这些对补充食品的反应非常迅速。潜在的机制可能涉及神经的延迟髓鞘形成或脱髓鞘形成。 S-腺苷甲硫氨酸∶S-腺苷同型半胱氨酸比率的改变；神经营养和神经毒性细胞因子的失衡；和/或乳酸在脑细胞中的积累。这篇综述总结了有关婴儿维生素B（12）缺乏症的当前知识，包括对患有未经治疗的恶性贫血或严格的素食生活方式的母亲所生婴儿的案例研究的汇总分析，并讨论了可能导致缺乏症的机制。

BACKGROUND & AIMS: :Maternal prenatal stress influences offspring neurodevelopment and birth outcomes including the ratio of males to females born; however, there is limited understanding of what types of stress matter, and for whom. Using a data-driven approach with 27 variables from questionnaires, ambulatory diaries, and physical assessments collected early in the singleton pregnancies of 187 women, 3 latent profiles of maternal prenatal stress emerged that were differentially associated with sex at birth, birth outcomes, and fetal neurodevelopment. Most women (66.8%) were in the healthy group (HG); 17.1% were in the psychologically stressed group (PSYG), evidencing clinically meaningful elevations in perceived stress, depression, and anxiety; and 16% were in the physically stressed group (PHSG) with relatively higher ambulatory blood pressure and increased caloric intake. The population normative male:female secondary sex ratio (105:100) was lower in the PSYG (2:3) and PHSG (4:9), and higher in the HG (23:18), consistent with research showing diminished male births in maternal stress contexts. PHSG versus HG infants were born 1.5 wk earlier (P < 0.05) with 22% compared to 5% born preterm. PHSG versus HG fetuses had decreased fetal heart rate-movement coupling (P < 0.05), which may indicate slower central nervous system development, and PSYG versus PHSG fetuses had more birth complications, consistent with previous findings among offspring of women with psychiatric illness. Social support most strongly differentiated the HG, PSYG, and PHSG groups, and higher social support was associated with increased odds of male versus female births. Stress phenotypes in pregnant women are associated with male vulnerability and poor fetal outcomes.

背景与目标： ：产前产前压力会影响后代神经发育和出生结局，包括出生时男女比例；然而，对于什么类型的压力以及谁的压力却知之甚少。使用数据驱动的方法，从187名妇女的单胎妊娠早期收集的问卷，动态日记和身体评估中收集到27个变量，得出了3种潜在的产前产前压力特征，这些特征与出生时的性别，分娩结局和胎儿有不同的相关性。神经发育。大多数妇女（66.8％）属于健康组（HG）；心理压力组（PSYG）占17.1％，表明在感知压力，抑郁和焦虑方面具有临床意义的升高；身体压力组（PHSG）中有16％的患者具有较高的动态血压和较高的热量摄入。 PSYG（2：3）和PHSG（4：9）的人口规范男性与女性次要性别比（105：100）较低，而HG（23:18）较高，这与研究表明男性出生人数减少有关在孕产妇压力环境中。 PHSG和HG婴儿的出生时间早了1.5周（P <0.05），分别为22％和5％。 PHSG与HG胎儿的胎儿心率-运动耦合降低（P <0.05），这可能表明中枢神经系统发育较慢，而PSYG与PHSG胎儿的出生并发症更多，与先前患有精神病的妇女后代的发现一致。社会支持最能区分HG，PSYG和PHSG组，而更高的社会支持与男性和女性出生几率增加有关。孕妇的压力表型与男性脆弱性和不良的胎儿结局有关。

BACKGROUND & AIMS: :A number of chemicals have been shown to demonstrate neurotoxic effects either in human or laboratory animal studies. This article aims at evaluating the impact of exposure to several chemicals including: organophosphate, organochlorine pesticides, polychlorinated biphenyls (PCBs), mercury and lead on the neurodevelopment of children by reviewing the most recent published literature, and answer the question whether any progress has been made in the epidemiology of the neurodevelopment of children induced by exposure to those chemicals. The result of the presented studies show that exposure to the above-mentioned chemicals may impair the neurodevelopment of children. Neonates exposed to organophosphate pesticides demonstrated a higher proportion of abnormal reflexes, and young children had more attention problems. Exposure to organochlorine pesticides in children was associated with alertness, quality of alert responsiveness, cost of attention and other potential attention associated measures. The majority of studies indicate the negative impact of lead exposure at the level <10 µg/dl or even <5 µg/dl on the neurodevelopment of children. The results of studies on exposure to PCBs, mercury, and their effect on neurodevelopment are inconsistent. Some suggest that prenatal exposure to PCBs and mercury is related to performance impairments, attention and concentration problems, while other do not present any statistically significant association. The studies were mostly well designed, using prospective cohorts with the exposure assessment based on the biomarker of exposure. Concerning the covariates and confounders affecting the endpoints in most of the presented studies, confounders were included in data analysis. In order to recognize the early cognitive, motor and language outcomes of chemical exposures, well standardized tools were used for evaluating the neurodevelopmental effects and offer an early and fairly comprehensive measure of child development. Because the neurotoxicants may cross the placenta and the fetal brain, exposure consideration regarding the reduction of exposure to those chemicals should be implemented.

背景与目标： ：在人或实验动物研究中，许多化学物质均显示出神经毒性作用。本文旨在通过回顾最新发表的文献来评估接触多种化学物质的影响，这些化学物质包括：有机磷酸盐，有机氯杀虫剂，多氯联苯（PCB），汞和铅对儿童神经发育的影响，并回答是否取得了任何进展的问题暴露于这些化学物质引起的儿童神经发育的流行病学研究中。提出的研究结果表明，接触上述化学物质可能会损害儿童的神经发育。暴露于有机磷酸酯农药的新生儿表现出较高的异常反射比例，而幼儿有更多的注意力问题。儿童接触有机氯农药与机敏性，机敏响应质量，注意力成本和其他潜在的注意力相关措施有关。大多数研究表明，铅暴露水平低于10 µg / dl或什至<5 µg / dl会对儿童的神经发育产生负面影响。关于多氯联苯，汞及其对神经发育的影响的研究结果不一致。一些人认为，产前接触多氯联苯和汞与性能受损，注意力和集中度问题有关，而其他人则没有任何统计学上的显着关联。这些研究大多设计合理，采用前瞻性队列研究，并根据暴露的生物标志物进行暴露评估。关于影响大多数提出的研究的终点的协变量和混杂因素，混杂因素包括在数据分析中。为了识别化学暴露的早期认知，运动和语言结果，使用了标准化的工具来评估神经发育作用，并提供了对儿童发育的早期且相当全面的测量。由于神经毒性物质可能会穿过胎盘和胎儿大脑，因此应考虑减少接触这些化学物质的接触因素。

BACKGROUND & AIMS: :Neurodevelopment as Gesell development scores (GDSs) in relation to mercury exposure in infants (<6 months of age) of one urban center and two rural villages, respectively, of fisherman and cassiterite miners. Mean total hair-Hg (HHg) concentrations of infants from Itapuã (3.95 ± 1.8 ppm) were statistically (P = 0.0001) different from those of infants from Porto Velho (3.84 ± 5.5 ppm) and Bom Futuro (1.85 ± 0.9 ppm). Differences in vaccine coverage among these populations resulted in significantly higher (P = 0.0001) mean ethylmercury (EtHg) exposure in urban infants (150 μg) than in infants from either village (41.67 μg, Itapuã; 42.39 μg, Bom Futuro). There was an inverse significant (Spearman r = -0.2300; P = 0.0376) correlation between HHg and GDS for infants from Porto Velho, but not for the rural infants from Bom Futuro (Spearman r = 0.1336; P = 0.0862) and Itapuã (Spearman r = 0.1666; P = 0.5182). Logistic regression applied to variables above or below the median GDS showed that EtHg exposure (estimated probability = -0.0157; P = 0.0070) and breastfeeding score (estimated probability = -0.0066; P = 0.0536) score were significantly associated with GDS. Conclusion. In nurslings whose mothers are exposed to different levels of fish-MeHg (HHg), a higher score of neurological development at six months was negatively associated with exposure to additional TCV-EtHg. Results should be interpreted with caution because of unaccounted variables.

背景与目标： ：在一个城市中心和两个乡村，分别是渔民和锡石矿工的婴儿（<6个月大）的汞暴露情况下，神经发育作为Gesell发展分数（GDSs）。从统计学上来说，伊塔普阿（3.95±1.8 ppm）婴儿的平均头发总Hg（HHg）浓度（P = 0.0001）与Porto Velho（3.84±5.5 ppm）和Bom Futuro（1.85±0.9 ppm）的婴儿的平均总Hg（P = 0.0001）不同。这些人群中疫苗覆盖率的差异导致城市婴儿（150μg）的平均乙基汞（EtHg）暴露显着高于任一村庄的婴儿（41.67μg，Itapuã；42.39μg，Bom Futuro）。 Porto Velho婴儿的HHg和GDS之间呈负相关（Spearman r = -0.2300; P = 0.0376），而Bom Futuro的农村婴儿（Spearman r = 0.1336; P = 0.0862）和Itapuã（Spearman）之间没有显着相关性（Spearman r = -0.2300; P = 0.0376）。 r = 0.1666； P = 0.5182）。对高于或低于中位GDS的变量进行Logistic回归分析显示，EtHg暴露（估计概率= -0.0157； P = 0.0070）和母乳喂养评分（估计概率= -0.0066； P = 0.0536）与GDS显着相关。结论。在其母亲暴露于不同水平的鱼类MeHg（HHg）的护士中，六个月时较高的神经系统发育评分与暴露于其他TCV-EtHg呈负相关。由于不确定的变量，应谨慎解释结果。

BACKGROUND & AIMS: :A dietary supply of docosahexaenoic acid (DHA, 22:6n-3) during the perinatal period is postulated to be important for the neurodevelopmental outcome of children. This paper reviews the results of two large scale intervention trials in which equivalent dietary doses of DHA were assessed. One trial assessed the ex utero effect of DHA supplementation for preterm infants born <33 weeks' gestation while the other trial assessed the in utero effect of DHA supplementation during the second half of pregnancy. Ex utero DHA supplementation, which aimed to achieve the level of DHA accumulation that would occur in the womb, appeared more effective in improving the neurodevelopmental outcome of preterm children rather than in utero DHA supplementation of unborn infants. Significant treatment by sex and treatment by birth weight interactions were noted indicating that boys and girls respond differently to DHA supplementation and that birth weight may also be important in predicating the DHA responsiveness.

背景与目标： ：围产期饮食中二十二碳六烯酸的饮食供应（DHA，22：6n-3）被认为对儿童的神经发育结局很重要。本文回顾了两项大型干预试验的结果，其中评估了等效饮食剂量的DHA。一项试验评估了补充DHA对妊娠小于33周出生的早产儿的宫内作用，而另一项试验评估了补充DHA在怀孕后半期的宫内作用。旨在达到子宫中DHA积累水平的Exutero DHA补充剂在改善早产儿神经发育结局方面比在未出生婴儿的子宫DHA补充剂中更有效。注意到通过性别和出生体重相互作用进行的重要治疗，表明男孩和女孩对补充DHA的反应不同，出生体重在预测DHA反应性方面也可能很重要。