BACKGROUND & AIMS: BACKGROUND:Systematic reviews of prenatal alcohol exposure effects generally only include conventional observational studies. However, estimates from such studies are prone to confounding and other biases. OBJECTIVES:To systematically review the evidence on the effects of prenatal alcohol exposure from randomized controlled trials (RCTs) and observational designs using alternative analytical approaches to improve causal inference. SEARCH STRATEGY:Medline, Embase, Web of Science, PsychINFO from inception to 21 June 2018. Manual searches of reference lists of retrieved papers. SELECTION CRITERIA:RCTs of interventions to stop/reduce drinking in pregnancy and observational studies using alternative analytical methods (quasi-experimental studies e.g. Mendelian randomization and natural experiments, negative control comparisons) to determine the causal effects of prenatal alcohol exposure on pregnancy and longer-term offspring outcomes in human studies. DATA COLLECTION AND ANALYSIS:One reviewer extracted data and another checked extracted data. Risk of bias was assessed using customized risk of bias tools. A narrative synthesis of findings was carried out and a meta-analysis for one outcome. MAIN RESULTS:Twenty-three studies were included, representing five types of study design, including 1 RCT, 9 Mendelian randomization and 7 natural experiment studies, and reporting on over 30 outcomes. One study design-outcome combination included enough independent results to meta-analyse. Based on evidence from several studies, we found a likely causal detrimental role of prenatal alcohol exposure on cognitive outcomes, and weaker evidence for a role in low birthweight. CONCLUSION:None of the included studies was judged to be at low risk of bias in all domains, results should therefore be interpreted with caution. SYSTEMATIC REVIEW REGISTRATION:This study is registered with PROSPERO, registration number CRD42015015941.

背景与目标： 背景：对产前酒精暴露影响的系统评价通常仅包括常规观察性研究。但是，此类研究的估计值容易造成混淆和其他偏见。
目的：使用替代分析方法改善因果推理，系统地回顾随机对照试验（RCT）和观察性设计对产前酒精暴露影响的证据。
搜索策略：从成立到2018年6月21日，包括Medline，Embase，Web of Science，PsychINFO。手动检索已检索论文的参考文献清单。
选择标准：使用替代分析方法（准实验研究，例如孟德尔随机试验和自然实验，阴性对照比较）来确定妊娠期饮酒停止/减少干预措施的RCT，以确定产前饮酒对怀孕和更长寿的因果关系人类研究中的足月后代结局。
数据收集和分析：一位审阅者提取了数据，另一名检查了提取的数据。使用定制的偏见风险工具评估了偏见风险。对结果进行叙述性综合，并对一项结果进行荟萃分析。
主要结果：包括23项研究，代表五种研究设计类型，包括1项RCT，9项孟德尔随机和7项自然实验研究，并报告了30多种结果。一种研究设计-结果组合包括足够的独立结果以进行荟萃分析。基于多项研究的证据，我们发现产前饮酒对认知结局可能具有因果关系，而低出生体重的作用证据却较弱。
结论：所有纳入研究均未被判定在所有领域的偏倚风险均较低，因此应谨慎解释结果。
系统评价注册：本研究已在PROSPERO注册，注册号CRD42015015941。

BACKGROUND & AIMS: :The gut microbiome regulates a relationship with the brain known as the gut-microbiota-brain (GMB) axis. This interaction is influenced by immune cells, microbial metabolites and neurotransmitters. Recent findings show gut dysbiosis is prevalent in autism spectrum disorder (ASD) as well as attention deficit hyperactivity disorder (ADHD). There are previously established negative correlations among vitamin D, vitamin D receptor (VDR) levels and severity of ASD as well as ADHD. Both vitamin D and VDR are known to regulate homeostasis in the brain and the intestinal microbiome. This review summarizes the growing relationship between vitamin D/VDR signalling and the GMB axis in ASD and ADHD. We focus on current publications and summarize the progress of GMB in neurodevelopmental disorders, describe effects and mechanisms of vitamin D/VDR in regulating the microbiome and synoptically highlight the potential applications of targeting vitamin D/VDR signalling in neurodevelopment disorders.

背景与目标： 肠道微生物组调节与大脑的关系，称为肠道微生物群脑（GMB）轴。这种相互作用受到免疫细胞，微生物代谢产物和神经递质的影响。最近的发现表明，肠道自闭症在自闭症谱系障碍（ASD）和注意力缺陷多动障碍（ADHD）中普遍存在。维生素D，维生素D受体（VDR）的水平与ASD以及ADHD的严重程度之间先前建立了负相关。众所周知，维生素D和VDR均可调节大脑和肠道微生物组的体内稳态。这篇综述总结了维生素D / VDR信号与ASD和ADHD中GMB轴之间日益增长的关系。我们专注于当前出版物并总结了GMB在神经发育障碍中的进展，描述了维生素D / VDR在调节微生物组中的作用和机制，并突显了针对维生素D / VDR信号在神经发育障碍中的潜在应用。

BACKGROUND & AIMS: :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.

背景与目标： ：采用两种不同的方法纵向评估了42名高危婴儿和7名对照婴儿的神经发育，直至12个月大。使用了由Amiel-Tison描述的神经学评估方法，并将结果与​​标准发育测试Bayley婴儿发育量表进行了比较。人们发现，Amiel-Tison方法是一种用于检测异常直至9个月大的敏感测试，但在12个月时失去了其与Bayley量表相比的优势。此外，该测试快速，简单易学，不需要特殊的试剂盒或训练有素的心理学家，因此被认为是一种很好的筛查方法。

BACKGROUND & AIMS: BACKGROUND:Children with congenital heart disease are at risk for impaired neurodevelopment (ND). We investigated the association of fetal cerebrovascular resistance with ND in patients with single ventricle lesions. METHODS:In the Single Ventricle Reconstruction (SVR) and Infant Single Ventricle trials, 14-month ND was assessed using the Bayley Scales of Infant Development II. We investigated associations between ND scores and fetal middle cerebral artery pulsatility index (MCA-PI) z-scores, a Doppler-derived estimate of cerebrovascular resistance in a subset of those infants. RESULTS:Neurodevelopment assessments were performed at age 14.3 ± 1 months in 170 (74%) of 230 Infant Single Ventricle and 321 (58%) of 555 SVR subjects. Fetal echocardiographic data were available in 119 subjects, 72 (61%) of which had ND testing. Mean Psychomotor Development Index (PDI) (76 ± 20) and Mental Development Index (MDI) (89 ± 17) scores were lower than normative means (100 ± 15, P < .001). Mean MCA-PI z-score was -0.95 ± 1.52. Middle cerebral artery pulsatility index z-score correlated negatively with PDI (r = -0.27, P = .02) but was not associated with MDI. When MCA-PI z-score was added to a multivariable model controlling for factors identified in the SVR trial to predict PDI, the percentage of explained variation increased from 23% to 30%, and MCA-PI z-score remained an independent predictor (r = -3.864, P = .03). Middle cerebral artery pulsatility index z-score was not an independent predictor in a model adjusting for site. CONCLUSIONS:Among fetuses with single ventricle anomalies, lower cerebrovascular resistance was associated with higher ND scores. This relationship is opposite to that observed with advanced intrauterine growth retardation and may represent a unique ability of these congenital heart disease fetuses to compensate for diminished cerebral oxygen delivery.

背景与目标： 背景：患有先天性心脏病的儿童有神经发育受损（ND）的风险。我们调查了单脑室病变患者的胎儿脑血管阻力与ND的关系。
方法：在单室重构（SVR）和婴儿单室试验中，使用贝利婴儿发育量表II评估14个月的ND。我们调查了ND评分与胎儿中脑动脉搏动指数（MCA-PI）z评分之间的关​​联，该评分是多普勒推论得出的这些婴儿子集中的脑血管抵抗力的估计值。
结果：在230名婴儿单心室中的170名（74％）和555名SVR受试者中的321名（58％）进行了14.3±1个月的神经发育评估。 119位受试者可获得胎儿超声心动图数据，其中72位（61％）接受了ND测试。平均精神运动发育指数（PDI）（76±20）和精神发育指数（MDI）（89±17）得分低于标准均值（100±15，P <.001）。平均MCA-PI z评分为-0.95±1.52。大脑中动脉搏动指数z评分与PDI呈负相关（r = -0.27，P = .02），但与MDI不相关。当将MCA-PI z分数添加到控制SVR试验中确定的预测PDI的因素的多变量模型中时，解释的差异百分比从23％增加到30％，而MCA-PI z分数仍是独立的预测因子（ r = -3.864，P = .03）。在调整部位的模型中，大脑中动脉搏动指数z评分不是独立的预测因子。
结论：在具有单心室异常的胎儿中，较低的脑血管阻力与较高的ND评分有关。这种关系与子宫内晚期发育迟缓所观察到的相反，并且可能代表了这些先天性心脏病胎儿弥补脑氧输送减少的独特能力。

BACKGROUND & AIMS: BACKGROUND:Lifelong HIV and antiretroviral therapy may confer neurodevelopmental risk on the children of women with perinatally acquired HIV infection (PHIV). SETTING:We analyzed data from HIV-exposed uninfected (HEU) infants born to women with PHIV vs. non-perinatally acquired HIV (NPHIV) enrolled in the Surveillance Monitoring for Antiretroviral Therapy Toxicities (SMARTT) study. METHODS:Using the Bayley Scales of Infant and Toddler Development, third Ed. (Bayley-III), we compared neurodevelopmental outcomes at the age of 1 year in HEU infants born to women with PHIV vs. NPHIV. Those with valid Bayley-III data at the age of 1 year and a mother born after 1982 were included. Cognitive, language, and motor domains were assessed as continuous composite scores. Linear mixed effects models were fit to estimate the mean difference in Bayley-III scores between groups, adjusting for confounders. RESULTS:Five hundred fifty women with HIV gave birth to 678 HEU children (125 and 553 born to women with PHIV and NPHIV, respectively). Mean scores for each of the Bayley-III domains were not significantly different between infants born to women with PHIV vs. NPHIV in unadjusted models. After adjustment, infants of women with PHIV had lower language (91.9 vs. 94.8, P = 0.05) and motor (93.7 vs. 96.8, P = 0.03) composite scores, but no differences in cognitive composite scores. CONCLUSIONS:Cognitive domain outcomes of infants born to women with PHIV vs. NPHIV are reassuring. Differences in early language and motor functioning, while of modest clinical significance, highlight the importance of long-term monitoring of neurodevelopment in children of women with PHIV.

背景与目标： 背景：终身艾滋病毒和抗逆转录病毒疗法可能会给围生期获得性HIV感染（PHIV）的妇女的孩子带来神经发育风险。
地点：我们分析了参加抗逆转录病毒疗法毒性监测监测（SMARTT）研究的PHIV妇女与非感染性HIV（NPHIV）所生的HIV暴露未感染（HEU）婴儿的数据。
方法：使用贝利婴儿和幼儿发展量表，第三版。 （Bayley-III），我们比较了PHIV与NPHIV妇女所生的HEU婴儿在1岁时的神经发育结局。包括那些在1岁时具有有效Bayley-III数据并在1982年之后出生的母亲。认知，语言和运动领域被评估为连续综合评分。线性混合效应模型适合估计各组之间Bayley-III得分的平均差异，并针对混杂因素进行了调整。
结果：550名艾滋病毒妇女分娩了678名HEU儿童（分别由PHIV和NPHIV妇女分娩的125和553名）。在未经调整的模型中，患有PHIV和NPHIV的妇女所生婴儿的每个Bayley-III域平均得分没有显着差异。调整后，患有PHIV的女性婴儿的语言综合评分较低（91.9 vs. 94.8，P = 0.05）和运动评分（93.7 vs. 96.8，P = 0.03），但认知综合评分没有差异。
结论：PHIV vs. NPHIV患儿所生婴儿的认知领域结局令人放心。早期语言和运动功能的差异尽管具有一定的临床意义，但突出了对PHIV女性儿童的神经发育进行长期监测的重要性。

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。