Neurobehavioral Development Research Articles

The role of T-cells in neurobehavioural development: Insights from the immunodeficient nude mice

Mice homozygous for the nude mutation (Foxn1nu) are hairless and exhibit congenital dysgenesis of the thymic epithelium, resulting in a primary immunodeficiency of mature T-cells, and have been used for decades in research with tumour grafts. Early studies have already demonstrated social behaviour impairments and central nervous system (CNS) alterations in these animals, but did not address the complex interplay between CNS, immune system and behavioural alterations. Here we investigate the impact of T-cell immunodeficiency on behaviours relevant to the study of neurodevelopmental and neuropsychiatric disorders. Moreover, we aimed to characterise in a multidisciplinary manner the alterations related to those findings, through evaluation of the excitatory/inhibitory synaptic proteins, cytokines expression and biological spectrum signature of different biomolecules in nude mice CNS. We demonstrate that BALB/c nude mice display sociability impairments, a complex pattern of repetitive behaviours and higher sensitivity to thermal nociception. These animals also have a reduced IFN-γ gene expression in the prefrontal cortex and an absence of T-cells in meningeal tissue, both known modulators of social behaviour. Furthermore, excitatory synaptic protein PSD-95 immunoreactivity was also reduced in the prefrontal cortex, suggesting an intricate involvement of social behaviour related mechanisms. Lastly, employing biospectroscopy analysis, we have demonstrated that BALB/c nude mice have a different CNS spectrochemical signature compared to their heterozygous littermates. Altogether, our results show a comprehensive behavioural analysis of BALB/c nude mice and potential neuroimmunological influences involved with the observed alterations.

Association of Iron-Deficiency Anemia and Non-Iron-Deficiency Anemia with Neurobehavioral Development in Children Aged 6-24 Months.

(1) Background: Anemia has comprehensive adverse effects on the growth and development of children. In this study, we analyzed the potential effects of different types of anemia on early-life neurobehavioral development. (2) Methods: A total of 2601 children aged 6–24 months, whose parents agreed to participate in this study, underwent routine blood tests and neurobehavioral development assessment. The children’s parents or other primary caregivers were interviewed with a face-to-face questionnaire at the time of enrollment in the study. Anemia was determined by hemoglobin < 110 g/L and classified into iron-deficiency and non-iron-deficiency anemia according to the levels of serum ferritin, C-reactive protein, and alpha-1-acid glycoprotein. Neurobehavioral development was assessed by the China Developmental Scale for Children and divided into five domains: gross motor, fine movement, adaptability, language, and social behavior. The development quotient (DQ) was used to measure the level of total neurobehavioral development and each domain of neurobehavioral development. (3) Results: The prevalence of anemia in children aged 6–24 months was 26.45%, of which iron-deficiency anemia only accounted for 27.33%. Compared with children without anemia, those with iron-deficiency anemia had a significantly lower developmental quotient (DQ) for total neurobehavioral development and gross motor and adaptability development. The partial regression coefficients were −1.33 (95% CI −2.36, −0.29; p = 0.012), −1.88 (95% CI −3.74, −0.03; p = 0.047), and 1.48 (95% CI −2.92, −0.05; p = 0.042), respectively. Children with non-iron-deficiency anemia had significantly lower DQ for total neurobehavioral development and gross motor and fine movement development than those without anemia. The partial regression coefficients were −0.94 (95% CI −1.64, −0.25; p = 0.008), −1.25 (95% CI −2.48, −0.03; p = 0.044), and −1.18 (95% CI −2.15, −0.21; p = 0.017), respectively. There were no statistically significant differences in total neurobehavioral development and the five domains of neurobehavioral development between children with non-iron-deficiency and iron-deficiency anemia. The partial β values were 0.40 (95% CI −1.53, 2.33; p = 0.684), 0.21 (95% CI −1.39, 1.81; p = 0.795), 0.63 (95% CI −1.03, 2.28; p = 0.457), 0.16 (95% CI −1.78, 2.10; p = 0.871), 0.35 (95% CI −1.32, 2.01; p = 0.684), and 0.34 (95% CI −0.77, 1.46; p = 0.545), respectively. (4) Conclusions: Both iron-deficiency anemia and non-iron-deficiency anemia were negatively correlated with the neurobehavioral development of children. Negative correlations were found between iron-deficiency anemia and gross motor and adaptability development and between non-iron-deficiency anemia and gross motor and fine movement development.

Interventions to improve neurodevelopmental outcomes of children born moderate to late preterm: a systematic review protocol.

Introduction:Prematurity (birth before 37 +0 weeks' gestation) is associated with wide-ranging neurodevelopmental impairment. Prognosis among moderate to late (32 +0 to <37 +0 weeks' gestation) preterm infants (MLPT) is better compared to their counterparts born very preterm (<32 +0 weeks' gestation). However the risk of developmental impairment among MLPT, who make up about 84% of all preterm infants, is 2-3 times higher when compared to infants born at term. Early interventions have aimed to improve outcomes in preterm infants generally, but there are limited data on their need and effect in MLPT specifically. Prioritising research, long-term follow-up and early interventions targeted at ameliorating the impact of preterm birth among MLPT is required. Objectives:To conduct a systematic review of the type of early childhood interventions (from birth until 4 years of age) offered to MLPT children and to evaluate their impact on neurodevelopmental outcomes (cognitive, neurobehavioural and motor) as assessed in these children during childhood (until 18 years of age). Methods and analysis:A systematic literature search in Web of Science, Medline Ovid, PsycINFO, CINAHL and EMBASE will be conducted. Data on MLPT children receiving developmental interventions until the age of 4 years will be evaluated. Interventions may involve parents or primary caregivers. Primary outcomes are cognitive, neurobehavioural and motor development as measured from birth until the age of 18 years. The Cochrane Risk of Bias Assessment Tool will be used to evaluate the methodological quality of randomised controlled trials (RCTs) included in the review and will be graded as low, high or unclear risk of bias. The quality of non-RCTs will be evaluated with the Newcastle-Ottawa Scale. The quality of evidence for each outcome will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation Approach. Publication and reporting bias will be assessed using Egger's test and funnel plots respectively.

Placental gene network modules are associated with maternal stress during pregnancy and infant temperament.

Maternal psychosocial stress during pregnancy (MPSP) is a known contributor to maladaptive neurobehavioral development of the offspring; however, the underlying molecular mechanisms linking MPSP with childhood outcome remain largely unknown. Transcriptome-wide gene expression data were generated using RNA-seq from placenta samples collected in a multi-ethnic urban birth cohort in New York City (n=129). Weighted gene co-expression network analysis (WGCNA) was used to characterize placental co-expression modules, which were then evaluated for their associations with MPSP and infant temperament. WGCNA revealed 16 gene coexpression modules. One module, enriched for regulation of chromosome organization/gene expression, was positively associated with MPSP and negatively associated with Regulatory Capacity (REG), a component of infant temperament. Two other modules, enriched for cotranslational protein targeting and cell cycle regulation, respectively, displayed negative associations with MPSP and positive associations with REG. A module enriched with oxidative phosphorylation/mitochondrial translation was positively associated with REG. These findings support the notion that the placenta provides a functional in utero link between MPSP and infant temperament, possibly through transcriptional regulation of placental gene expression.

Exposure of pregnant rats to stress and/or sertraline: Side effects on maternal health and neurobehavioral development of male offspring

AimsSertraline (SE) is one of the most prescribed medications for treating gestational depression, anxiety and stress. However, little is known about its effects on nervous-system development in offspring. Therefore, this study investigated the somatic, reflex and neurobehavioral development of rats exposed to SE during pregnancy, associated or not with stress. Main methodsPregnant Wistar rats were assigned to the following groups (n = 10-8 rats/group): CO - control animals administered filtered water by gavage; SE - animals administered 20 mg/kg SE by gavage; ST - animals subjected to restraining stress and administered filtered water; ST/SE - animals subjected to restraining stress and administered 20 mg/kg SE. The treatment was administered between gestational days (GD) 13 to 20. Somatic and reflex developments were investigated in the male offspring from postnatal day (PND) 1 to 21. The elevated plus maze was performed on PND 25 and 80. The open field and light/dark box test were performed on PND 90 and 100, respectively. Key findingsBody weight reduction and vaginal bleeding were observed in pregnant rats exposed to SE. The male offspring of the SE group showed delay in incisor eruption, fur development and negative geotaxis. In addition, the SE group was less exploratory (anxious personality) compared to the CO and ST groups. SignificanceThe results obtained in the present study demonstrate that sertraline not only impairs maternal health, but also, associated or not with stress, can compromise the somatic, reflex and neurobehavioral development of male rats.

Interventions to improve neurodevelopmental outcomes of children born moderate to late preterm: a systematic review protocol

Introduction: Prematurity (birth before 37 +0 weeks’ gestation) is associated with wide-ranging neurodevelopmental impairment. Prognosis among moderate to late (32 +0 to <37 +0 weeks’ gestation) preterm infants (MLPT) is better compared to their counterparts born very preterm (<32 +0 weeks’ gestation). However the risk of developmental impairment among MLPT, who make up about 84% of all preterm infants, is 2-3 times higher when compared to infants born at term. Early interventions have aimed to improve outcomes in preterm infants generally, but there are limited data on their need and effect in MLPT specifically. Prioritising research, long-term follow-up and early interventions targeted at ameliorating the impact of preterm birth among MLPT is required.Objectives: To conduct a systematic review of the type of early childhood interventions (from birth until 4 years of age) offered to MLPT children and to evaluate their impact on neurodevelopmental outcomes (cognitive, neurobehavioural and motor) as assessed in these children during childhood (until 18 years of age).Methods and analysis: A systematic literature search in Web of Science, Medline Ovid, PsycINFO, CINAHL and EMBASE will be conducted. Data on MLPT children receiving developmental interventions until the age of 4 years will be evaluated. Interventions may involve parents or primary caregivers. Primary outcomes are cognitive, neurobehavioural and motor development as measured from birth until the age of 18 years. The Cochrane Risk of Bias Assessment Tool will be used to evaluate the methodological quality of randomised controlled trials (RCTs) included in the review and will be graded as low, high or unclear risk of bias. The quality of non-RCTs will be evaluated with the Newcastle-Ottawa Scale. The quality of evidence for each outcome will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation Approach. Publication and reporting bias will be assessed using Egger’s test and funnel plots respectively.

Evaluation of Severity of Infectious Pneumonia for Newborn Using Ultrasound Image under Adaptive Image Denoising Algorithm

This study was to analyze the ultrasound imaging characteristics of infectious pneumonia of newborn in different conditions and the differences in neurobehavioral development. An adaptive image denoising (AID) algorithm was constructed based on multiscale wavelet features. It was compared with the transform domain denoising (TDD) algorithm and spatial domain denoising (SDD) algorithm and applied to ultrasound images of newborns with infectious pneumonia. It was found that the peak signal-to-noise ratio (PSNR), structural similarity (SSIM), and feature similarity index (FSIM) of the constructed algorithm were higher than those of the TDD and SDD algorithms ( P &lt; 0.05 ). The ultrasound scores of newborns in noncritical group (group A, 1.54 ± 0.62 scores) were all lower than those of the critical group (group B, 3.96 ± 0.41 scores) and extremely critical group (group C, 4.25 ± 0.35 scores) ( P &lt; 0.05 ). The behavioral ability, passive muscle tension, active muscle tension, and original reflection of the newborns in group A were better than other groups ( P &lt; 0.05 ). It indicated that the constructed algorithm showed better denoising effect on ultrasound images, which could effectively evaluate the severity of newborns’ infectious pneumonia.

Vasopressin but Not Oxytocin Responds to Birth Stress in Infants.

ContextBirth triggers a large fetal neuroendocrine response, which is more pronounced in infants born vaginally than in those born by elective cesarean section (ECS). The two related peptides arginine vasopressin (AVP) and oxytocin (OT) play an essential role in peripheral and central stress adaptation and have a shared receptor mediating their function. Elevated cord blood levels of AVP and its surrogate marker copeptin, the C-terminal part of AVP prohormone, have been found after vaginal delivery (VD) as compared to ECS, while release of OT in response to birth is controversial. Moreover, AVP, copeptin and OT have not yet been measured simultaneously at birth.ObjectiveTo test the hypothesis that AVP but not OT levels are increased in infants arterial umbilical cord blood in response to birth stress and to characterize AVP secretion in direct comparison with plasma copeptin.MethodsIn a prospective single-center cross-sectional study, we recruited healthy women with a singleton pregnancy and more than 36 completed weeks of gestation delivering via VD or ECS (cesarean without prior uterine contractions or rupture of membranes). Arterial umbilical cord blood samples were collected directly after birth, centrifuged immediately and plasma samples were frozen. Concentrations of AVP and OT were determined by radioimmunoassay and that of copeptin by ultrasensitive immunofluorescence assay.ResultsA total of 53 arterial umbilical cord blood samples were collected, n = 29 from VD and n = 24 from ECS. Ten venous blood samples from pregnant women without stress were collected as controls. AVP and copeptin concentrations were significantly higher in the VD group than in the ECS group (both p < 0.001), median (range) AVP 4.78 (2.38–8.66) vs. 2.38 (1.79–3.88) (pmol/L), copeptin 1692 (72.1–4094) vs. 5.78 (3.14–17.97), respectively, (pmol/L). In contrast, there was no difference in OT concentrations (pmol/L) between VD and ECS, 6.00 (2.71–7.69) vs. 6.14 (4.26–9.93), respectively. AVP and copeptin concentrations were closely related (Rs = 0.700, p < 0.001) while OT did not show any correlation to either AVP or copeptin. In linear regression models, vaginal delivery and biochemical stress indicators, base deficit and pH, were independent predictors for both AVP and copeptin. OT was not linked to base deficit or pH.ConclusionVaginal birth causes a profound secretion of AVP and copeptin in infants. Whereas AVP indicates acute stress events, copeptin provides information on cumulative stress events over a longer period. In contrast, fetal OT is unaffected by birth stress. Thus, AVP signaling but not OT mediates birth stress response in infants. This unique hormonal activation in early life may impact neurobehavioral development in whole life.

Effects of Prenatal Exposure to Perfluorononanoic Acid on Neurobehavioral Development in Rat Offspring

BACKGROUND AND AIM: Perfluorononanoic Acid (PFNA), a kind of fluorinated aliphatic molecules, had been extensively used in industrial applications as a surface protectant and known to accumulate in humans and wildlife. Although PFNA had been adversely associated with the growth and development of wild-type mice, much less is known about the impact of short-term exposure to PFNA during gestation on neurobehavioral development in rat offspring. The purpose of this study was to investigate the effects of PFNA on the physical and neurobehavioral development in sprague-dawley rat offspring. METHODS: Dams were dosed daily via oral gavage during gestation days 1-19 with control, 0.02, 0.2, 1.0, and 5.0 mg/kg of PFNA. During postnatal day (PND) 1-21, a series of developmental test battery were conducted, including body weight, maturational milestones (pinnae unfolding, incisor eruption, hair growth and eye opening) and neurobehavioral reflex (surface righting reflex, negative geotaxis, and cliff avoidance tests). Morris water maze tests were performed to study the learning and memory ability of the rat offspring on PND 28. RESULTS:PFNA exposure during gestation resulted in lower weight (≥1.0 mg/kg), later eye opening and worse performance in negative geotaxis (5.0 mg/kg), but no associations were observed between PFNA exposure and other maturational milestones or neurobehavioral reflex. Further, morris water maze tests indicated damaged spatial learning and memory ability of offspring (≥0.2 mg/kg). CONCLUSIONS:Our study reveals that PFNA exposure during gestation produce multiple adverse effects on neuro-development in rat, research is needed to examine the potential mechanisms linked to the adverse effects of PFNA. KEYWORDS: perfluorononanoic acid, neurobehavioral development, rat offspring, prenatal exposure

Bacterial modification of the association between arsenic and autism-related social behavior scores

BACKGROUND AND AIM: The relationship between environmental exposures and neurodevelopmental outcomes has been characterized, but the modifying role of microbiome is unknown. We probed prior evidence in the New Hampshire Birth Cohort Study (NHBCS) suggesting relationships between arsenic and neurobehavioral development, which were both associated with the infant gut microbiome in separate studies. METHODS: Total arsenic was quantified in six-week-old toenail clippings of NHBCS participants. Three years postpartum, parents completed the Social Responsiveness Scale (SRS-2), which measures autism-related social behaviors on a continuous scale standardized to a mean of 50 (standard deviation 10) with higher scores indicating more maladaptive behavior. Metagenomic sequencing was performed on infant stools collected at six weeks and one year of age. The ten bacterial species and functions with the highest relative abundances at each time were dichotomized at the median. Separate linear models including interaction terms between exposure and each dichotomous microbiome feature were constructed to examine the modifying role of the microbiome on the arsenic-SRS-2 relationship, adjusting for five other trace elements (copper, manganese, lead, selenium, zinc) and sociodemographic characteristics. RESULTS:The 78 participants with exposure, outcome, and microbiome data, rated better on the SRS-2 than the normative population (mean=44, SD=5).The relative abundances of several functional pathways identified in six-week stool samples appeared to modify the arsenic-SRS-2 association, including the S-adenosyl-L-methionine (SAM) cycle; among infants with high relative abundance of SAM genes there was no association [β=-0.66, 95%CI (-2.41,1.08)], whereas among infants with low relative abundance there was suggestive evidence of an adverse association [β=2.24, 95%CI (-0.04,4.51)], pinteraction=0.046]. Effect modification by individual species in six-week stool samples and features of the one-year-old microbiome was also identified in preliminary analyses. CONCLUSIONS:Our findings indicate that the infant gut microbiome may alter neurodevelopmental susceptibility to environmental exposures. Potential effect modification by SAM genes suggests the gut microbiome may contribute to arsenic methylation/excretion. KEYWORDS: Microbiome, Children's environmental health, Neurodevelopmental outcomes, Chemical exposures

Interactions of agricultural pesticide use near home during pregnancy and adverse childhood experiences on adolescent neurobehavioral development in the CHAMACOS study

BackgroundStudies have documented independent adverse associations between prenatal and early-life exposure to environmental chemicals and social adversity with child neurodevelopment; however, few have considered these exposures jointly. The objective of this analysis is to examine whether associations of pesticide mixtures and adolescent neurobehavioral development are modified by early-life adversity in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort. MethodsWe used linear mixed effects Bayesian Hierarchical Models (BHM) to examine the joint effect of applications of 11 agricultural pesticides within 1 km of maternal homes during pregnancy and youth-reported Adverse Childhood Experiences (ACEs) with maternal and youth-reported internalizing behaviors, hyperactivity, and attention problems assessed via the Behavior Assessment for Children (BASC) (mean = 50, standard deviation = 10) at ages 16 and 18 years (n = 458). ResultsThe median (25th-75th percentiles) of ACEs was 1 (0–3); 72.3% of participants had low ACEs (0–2 events) and 27.7% had ACEs (3+ events). Overall, there was little evidence of modification of exposure-outcome associations by ACEs. A two-fold increase in malathion use was associated with increased internalizing behaviors among those with high ACEs from both maternal- (β = 1.9; 95% Credible Interval (CrI): 0.2, 3.7 for high ACEs vs. β = −0.1; 95% CrI: 1.2, 0.9 for low ACEs) and youth-report (β = 2.1; 95% CrI: 0.4, 3.8 for high ACEs vs. β = 0.2; 95% CrI: 0.8, 1.2 for low ACEs). Applications of malathion and dimethoate were also associated with higher youth-reported hyperactivity and/or inattention among those with high ACEs. ConclusionWe observed little evidence of effect modification of agricultural pesticide use near the home during pregnancy and adolescent behavioral problems by child ACEs. Future studies should examine critical windows of susceptibility of exposure to chemical and non-chemical stressors and should consider biomarker-based exposure assessment methods.

Effect of 9,12-Octadecadiynoic Acid on Neurobehavioral Development in Caenorhabditis elegans.

Human breast milk lipids have major beneficial effects: they promote infant early brain development, growth and health. To identify the relationship between human breast milk lipids and infant neurodevelopment, multivariate analyses that combined lipidomics and psychological Bayley-III scales evaluation were utilized. We identified that 9,12-octadecadiynoic acid has a significantly positive correlation with infant adaptive behavioral development, which is a crucial neurodevelopment to manage risk from environmental stress. To further clarify the biological function of 9,12-octadecadiynoic acid in regulating neurodevelopment, Caenorhabditis elegans (C. elegans) was used as a model to investigate the effect of 9,12-octadecadiynoic acid on neurobehavioral development. Supplementation with 9,12-octadecadiynoic acid from the L1 to L4 stage in larvae affected locomotive behaviors and foraging ability that were not socially interactive, implying that 9,12-octadecadiynoic acid is involved in regulating the serotonergic neuronal ability. We found that supplementary 0.1 μM 9,12-octadecadiynoic acid accelerated the locomotive ability and foraging ability via increasing the expression of serotonin transporter mod-1. Antioxidant defense genes, sod-1, sod-3 and cyp-35A2 are involved in 9,12-octadecadiynoic acid-induced motor neuronal activity. Nevertheless, supplementary 9,12-octadecadiynoic acid at concentrations above 1 μM significantly attenuated locomotive behaviors, foraging ability, serotonin synthesis, serotonin-related gene expressions and stress-related gene expression, resulting in the decreased longevity of worms in the experiment. In conclusion, our study demonstrates the biological function of 9,12-octadecadiynoic acid in governing adaptive behavioral development.

Sex Differences in Gut Microbial Development of Preterm Infant Twins in Early Life: A Longitudinal Analysis.

Infant gut microbiota plays a vital role in immune response, mediates neurobehavioral development and health maintenance. Studies of twins’ gut microbiota found that gut microbiota composition and diversity tend to be mature and stable with increasing postnatal age (PNA). Preterm infant gut microbiome shifts dramatically when they were staying in the neonatal intensive care unit (NICU). Compositions and shifting characteristics of gut microbiota among neonatal preterm twins and triplets during their early life are still unknown, which impedes a better understanding of the mechanism underpinning neurobehavioral development and precise intervention/health of preterm neonates. This longitudinal cohort study used a twins/triplets design to investigate the interaction of genetic (e.g., male vs. female) and environmental factors influencing the development of the gut microbiome in early life. We included 39 preterm infants, 12 were Female twins/triplets (Female T/T) including 3 twins pairs and 2 triplets, 12 were male twins (Male T) including 6 twins pairs, and 15 were mixed-sex twins/triplets (Mix T/T) including 6 twins pairs and 1 triplet (8 females and 7 males) during the first four weeks of NICU stay. Weekly gut microbiota patterns between females and males were compared by linear discriminant analysis (LDA) effect size (LEfSe). Metagenomics function of gut microbiota was predicted by using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Weekly function (KEGG pathways) differences between females and males were detected by using Statistical Analysis of Metagenomic Profiles (STAMP). Results found that female pairs and male pairs were significantly different in gut microbiome diversity, compositions, and predicted metabolic profiles, importantly, females and males were also significantly dissimilar within their co-twin/triplet pairs of the mixed-sex group, infants of co-twins/triplets shared more similar features than un-related infants from different twins’ pair. Future research developing personalized interventions for vulnerable high-risk infants should consider sex, and the interaction of sex and environmental factors.

Effects of prenatal exposure to persistent organic pollutants on neonatal Outcomes:A mother-child cohort (Shanghai, China)

Persistent organic pollutants (POPs), known as common environmental pollutants, which have adverse effects on neurobehavioral development, are widely applied in industry and agriculture. However, evidence about neurodevelopmental toxicity of POPs in humans is limited. This study aimed to explore the relationship between prenatal exposure to POPs and birth outcome of the newborn including birth length, weight, and head circumference. In this study, 1522 mother-child pairs were included in this study and cord blood samples were collected, which were detected to determine exposure level of 37 POPs in total. After delivery, the neonatal anthropometric indices detection (birth length, weight, and head circumference) was performed. According to the multivariate linear regression, the newborn with high detection rates (≥75 percentile) of hexachlorobenzene (HCB), beta-hexachlorocyclohexane (β-HCH), p,p’-dichlorodiphenyl dichloroethylene (p,p’-DDE) in the umbilical cord blood were demonstrated negative relationship with birth head circumference after adjusting for confounding factors, but not related with birth length and weight. After confirming that there was a nonlinear relationship between HCB and birth head circumference based on sex stratification through the generalized additive model (GAM), further two-piecewise linear regression model was conducted to explore the saturation threshold effect between HCB and birth head circumference, which showed cord serum HCB concentration greater than 0.5 μg/L was negatively associated with birth head circumference in girls. Our study provided evidence for the adverse influence of HCB, β-HCH and p,p'-DDE exposure during pregnancy on the birth head circumference of offspring. Although HCB induced reduction of birth head circumference was found in girls, the mechanism of gender difference remained unclear. Further studies are needed to explore the effect of POPs on the growth and development of offspring based on in vivo or in vitro experimental models.

Foetal mouth movements: Effects of nicotine.

To assess whether foetal mouth movement frequency changes across gestation and whether there are differences between cigarette and e-cigarette exposure conditions in comparison to a non-exposed group of foetuses. Pregnant women underwent 4-dimensional (4D) foetal ultrasound scans at 32weeks (106 scans) and 36weeks of gestational age (87 scans) at James Cook University Hospital, UK. The 4D scans were coded using the Fetal Observable Movement System (FOMS). Measures of maternal smoking status, stress, depression, anxiety, attachment and time of scan were also collected. There were four exposure groups: non-smokers, light smokers (<10 per day), heavy smokers (11-20per day) and e-cigarette users. No significant differences in relative frequency of mouth movements between the exposure groups at 32- and 36weeks of gestational age were found. Foetal mouth movements declined from 32 to 36weeks of gestation for non-exposed and e-cigarette-exposed foetuses. Due to variability in foetal behaviour, examining mouth movements alone may not be the most appropriate method for assessing group differences. However, in line with other research, mouth movement frequency declined between 32- and 36weeks of gestational age. A combination of foetal behavioural assessments is needed to assess the effects of cigarette and e-cigarette exposure on foetal neurobehavioural development.

A Comprehensive Approach to Rehabilitation Interventions in Patients with Angelman Syndrome: A Systematic Review of the Literature.

Angelman syndrome is a rare genetic disease affecting the central nervous system and neurobehavioral development causing severe mental, linguistic, and physical disabilities. The purpose of this review was to analyze the most recent evidence regarding the rehabilitation of subjects affected by this syndrome. The review was carried out in accordance with the preferred reporting items for systematic reviews and meta-analyses. A total of 3661 studies were identified in the databases. Once the inclusion/exclusion criteria were applied, 15 studies were considered for the paper’s preparation. The level of evidence of the studies was established according to the criteria of the Oxford Center for Evidence-Based Medicine—Levels of Evidence. From the selected studies, five rehabilitative approaches emerged: physiotherapy, applied behavioral analysis, toilet training, microswitch-cluster technology, and augmentative and alternative communication. Although the studies did not have a high level of evidence, the reported results appear to be encouraging and pave the way for further studies. It seems that individualized and multidisciplinary rehabilitation interventions help to improve patients’ autonomy and quality of life. In some studies, the caregivers’ role was fundamental to identify preferences and long-term improvements. Further studies on larger populations and with better methodological quality are needed to confirm the results.

Gestational Phthalate Exposure and Preschool Attention Deficit Hyperactivity Disorder in Norway.

Prenatal phthalate exposure has been linked to altered neurobehavioral development in both animal models and epidemiologic studies, but whether or not these associations translate to increased risk of neurodevelopmental disorders is unclear. We used a nested case-cohort study design to assess whether maternal urinary concentrations of 12 phthalate metabolites at 17 weeks gestation were associated with criteria for Attention Deficit Hyperactivity Disorder (ADHD) classified among 3-year-old children in the Norwegian Mother, Father and Child Cohort Study (MoBa). Between 2007 and 2011, 260 children in this substudy were classified with ADHD using a standardized, on-site clinical assessment; they were compared with 549 population-based controls. We modeled phthalate levels both linearly and by quintiles in logistic regression models adjusted for relevant covariates and tested for interaction by child sex. Children of mothers in the highest quintile of di-iso-nonyl phthalate (∑DiNP) metabolite levels had 1.70 times the odds of being classified with ADHD compared with those in the lowest quintile (95% confidence interval [CI] = 1.03 to 2.82). In linear models, there was a trend with the sum of di-2-ethylhexyl phthalate metabolites (∑DEHP); each natural log-unit increase in concentration was associated with 1.22 times the odds of ADHD (95% CI = 0.99 to 1.52). In boys, but not girls, mono-n-butyl phthalate exposure was associated with increased odds of ADHD (odds ratio [OR] 1.42; 95% CI = 1.07 to 1.88). Additional adjustment for correlated phthalate metabolites attenuated estimates. These results suggest gestational phthalate exposure may impact the behavior of children as young as 3 years.

Reporting on Australian childhood visual impairment: the first 10 years.

Visual impairment is rare but has significant impact on the neurobehavioural development and quality of life of children. This paper presents the key findings from the Australian Childhood Vision Impairment Register, which commenced in 2008 to report on children diagnosed with permanent visual impairment. Families consent to completing a data form related to their child and for contact with the child's ophthalmologist. Ophthalmologists complete and return a comprehensive data form on the child's primary and secondary ocular diagnoses, associated disabilities and health conditions, visual acuity and visual fields. Data is stored on a secure database and anonymised data is available to researchers and for planning purposes. Nine-hundred four children and their families provided informed consent for participation, with 57% males and 43% females. Most children spoke English in their home. Eighty-three percent of children were born full term, with a birth weight of >2500 g (81%). Children were commonly suspected to have visual impairment by a parent, with 68% of families receiving a diagnosis of visual impairment by their child's first birthday. The most common primary diagnoses were retinal dystrophy (17%), CVI (15%) and Albinism (11%). A secondary diagnosis of infantile nystagmus occurred in 33% of children. Additional disabilities and/or developmental delay were reported for 44% of children. Corrected binocular visual acuity was reported for 75% of children, with moderate visual impairment being most common. These findings contribute to knowledge of rare diseases affecting the eye and visual pathway and represent Australian childhood visual impairment.

Transplacental Transfer of Primaquine and Neurobehavioral Development of Prenatally Exposed Rats.

Primaquine (PQ) not only eliminates P. falciparum gametocytes but also kills liver dormant forms of P. vivax and P. ovale. Owing to these unique therapeutic properties, it is an essential drug. Although PQ has been used for over 70 years, its toxicological database has gaps such as the absence of studies on its reproductive and developmental toxicity and kinetics in pregnancy. This study investigated the transplacental transfer of PQ and the effects of intrauterine exposure on the postnatal growth, survival, and neurobehavioral development of the offspring. PQ kinetics and transplacental transfer were investigated in rats treated orally (40 mg.kg·bw−1) on gestation day (GD) 21. PQ was analyzed by high-performance liquid chromatography with diode array ultraviolet detection. To evaluate effects of intrauterine exposure on postnatal development, dams were treated orally with PQ (20 mg.kg·bw−1·d−1) or water (controls) on GD 0–21. Postnatal survival, body weight gain, somatic maturation, and reflex acquisition were evaluated. The open field test (OF) was conducted on PND 25. PQ concentration in the fetal plasma was nearly half that in maternal plasma. Except for increase in pregnancy loss, no effects of PQ were noted at term pregnancy and first days of life. Prenatal PQ did not affect postnatal weight gain nor did it impair somatic and neurologic development of the offspring. Pups born to PQ-treated dams showed reduced exploration and enhanced emotionality in the OF. PQ given in pregnancy, at doses greater than those recommended for malaria therapy, may affect pup postnatal survival and emotional behavior.

Incubation of Oxycodone Craving Following Adult-Onset and Adolescent-Onset Oxycodone Self-Administration in Male Rats.

Relapse is a major obstacle to curb the ongoing epidemic of prescription opioid abuse. We and others previously demonstrated that oxycodone seeking in adult rats progressively increases after abstinence from oxycodone self-administration (incubation of oxycodone craving). In humans, the onset of oxycodone use in adolescents may increase individuals’ vulnerability to later opioid addiction. However, little is known about incubation of oxycodone craving after adolescent-onset oxycodone self-administration in rats. In the first study, we trained single-housed adolescent (postnatal day 35 at start) and adult (postnatal day 77 at start) male Sprague–Dawley rats to self-administer oxycodone (0.1 mg/kg/infusion, 6 h/day for 10 days) and then tested oxycodone relapse on both abstinence day 1 and day 15. Given that social experience is critical for neurobehavioral development in adolescents, we performed the second study using group-housed adolescent and adult rats. In both studies, we observed no age differences in oxycodone self-administration and incubated oxycodone seeking on abstinence day 15. However, on abstinence day 1, we observed decreased oxycodone seeking in adolescents compared with adults. This pattern of data led to elevated incubation slopes in adolescent rats compared with adult rats. Finally, group-housed rats exhibited attenuated oxycodone seeking compared with single-housed rats on abstinence day 15, but not on day 1. Taken together, these data suggest that adolescents may be resistant to oxycodone relapse during early abstinence, but this resistance dissipates quickly during the transition between adolescent and young adulthood. In addition, group-housing plays a protective role against incubated oxycodone craving.