Deficits In Infants Research Articles

Caffeine improves mitochondrial dysfunction in the white matter of neonatal rats with hypoxia-ischemia through deacetylation: a proteomic analysis of lysine acetylation.

White matter damage (WMD) is linked to both cerebral palsy and cognitive deficits in infants born prematurely. The focus of this study was to examine how caffeine influences the acetylation of proteins within the neonatal white matter and to evaluate its effectiveness in treating white matter damage caused by hypoxia-ischemia. We employed a method combining affinity enrichment with advanced liquid chromatography and mass spectrometry to profile acetylation in proteins from the white matter of neonatal rats grouped into control (Sham), hypoxic-ischemic (HI), and caffeine-treated (Caffeine) groups. Our findings included 1,999 sites of lysine acetylation across 1,123 proteins, with quantifiable changes noted in 1,342 sites within 689 proteins. Analysis of these patterns identified recurring sequences adjacent to the acetylation sites, notably YKacN, FkacN, and G * * * GkacS. Investigation into the biological roles of these proteins through Gene Ontology analysis indicated their involvement in a variety of cellular processes, predominantly within mitochondrial locations. Further analysis indicated that the acetylation of tau (Mapt), a protein associated with microtubules, was elevated in the HI condition; however, caffeine treatment appeared to mitigate this over-modification, thus potentially aiding in reducing oxidative stress, inflammation in the nervous system, and improving mitochondrial health. Caffeine inhibited acetylated Mapt through sirtuin 2 (SITR2), promoted Mapt nuclear translocation, and improved mitochondrial dysfunction, which was subsequently weakened by the SIRT2 inhibitor, AK-7. Caffeine-induced changes in lysine acetylation may play a key role in improving mitochondrial dysfunction and inhibiting oxidative stress and neuroinflammation.

Neurological and Visual Outcomes in Infants and Toddlers Following Therapeutic Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy

BackgroundThe majority of studies have investigated neurodevelopmental outcomes, whereas visual impairment is less explored in children with a history of neonatal (hypoxic-ischemic) encephalopathy. Our aim was to perform a detailed neurological and visual assessment and also to investigate the presence of cerebral visual impairment in infants and toddlers with neonatal encephalopathy. MethodsThirty participants with a history of neonatal encephalopathy, who had been hospitalized for therapeutic hypothermia, underwent a detailed neurological examination at age five to 36 months. Age-matched, 30 healthy children were also enrolled as a control group. All children in the study and control groups received neurological and a comprehensive ophthalmologic examination, including visual field and visual acuity. Presence of cerebral visual impairment was also evaluated clinically. ResultsRates of cerebral palsy, severe motor impairment, cognitive impairment, epilepsy, and cerebral visual impairment were found to be 20%, 10%, 15.3%, 10%, and 20%, respectively. When compared with healthy controls, oculomotor functions, pupillary light response, refractive parameters, anterior/posterior segment examinations, ocular visual impairment rates, and last, visual acuities were found similar. However, we found a statistically significant increase in visual field defects in our study group. ConclusionsIt could be better to perform a comprehensive ophthalmologic examination including visual field, visual acuity, and oculomotor functions by a pediatric ophthalmologist to accurately diagnose neurovisual deficits in infants following therapeutic hypothermia. Early identification and rehabilitation of the visual deficits might improve the neurodevelopment in these children.

Human cytomegalovirus induces significant structural and functional changes in terminally differentiated human cortical neurons.

Human cytomegalovirus (HCMV) is a highly prevalent viral pathogen that can cause serious neurological deficits in infants experiencing an in utero infection. Also, as a life-long infection, HCMV has been associated with several diseases in the adult brain. HCMV is known to infect early neural progenitor cells, but whether it also infects terminally differentiated neurons is still debated. Here, we differentiated human-induced pluripotent stem cells into neurons for 84-120 days to test the ability of HCMV to infect terminally differentiated neurons and assess the downstream functional consequences. We discovered that mature human neurons are highly permissive to HCMV infection, exhibited late replication hallmarks, and produced infectious virus. Moreover, infection in terminally differentiated neurons essentially eliminated neuron function. These results demonstrate that terminally differentiated human neurons are permissive to HCMV infection, which can significantly alter both structural and functional features of this mature neuron population.

The Benefits of Combining Bobath and Vojta Therapies in Infants with Motor Development Impairment-A Pilot Study.

Background: In infants presenting with motor development impairment, early kinesiotherapeutic interventions aim to normalise the pattern of movements and improve recovery. By applying Bobath and Vojta methods, we aimed to identify a combined approach regarding motor deficit in infants with neurological disabilities. Methods: We designed a prospective interventional study on 108 infants with motor developmental delay and applied Bobath, Vojta, or combined Bobath and Vojta therapy in three equal groups. Results: In the combined Bobath and Vojta group, complete motor recovery was achieved for 50% of the participants, with full recovery after six months, whereas in Bobath- or Vojta-only therapy groups, the total recovery for all participants was achieved at seven months. Regarding infants with muscular hypertonia, Bobath therapy initiation demonstrated complete recovery in 5 months in more than 50% of the cases, while for Vojta this was achieved in only 33.57% of the cases. Conclusions: The comparative evaluation conducted by analysing the data regarding the application of the Bobath and Vojta methods showed that combining these two therapies results in a shorter motor deficit recovery time than if a single therapy is applied. These findings have important implications for the selection of rehabilitation therapies in infants with neurological motor development issues.

Perturbed neurochemical and microstructural organization in a mouse model of prenatal opioid exposure: A multi-modal magnetic resonance study.

Methadone-based treatment for pregnant women with opioid use disorder is quite prevalent in the clinical environment. A number of clinical and animal model-based studies have reported cognitive deficits in infants prenatally exposed to methadone-based opioid treatments. However, the long-term impact of prenatal opioid exposure (POE) on pathophysiological mechanisms that govern neurodevelopmental impairment is not well understood. Using a translationally relevant mouse model of prenatal methadone exposure (PME), the aim of this study is to investigate the role of cerebral biochemistry and its possible association with regional microstructural organization in PME offspring. To understand these effects, 8-week-old male offspring with PME (n = 7) and prenatal saline exposure (PSE) (n = 7) were scanned in vivo on 9.4 Tesla small animal scanner. Single voxel proton magnetic resonance spectroscopy (1H-MRS) was performed in the right dorsal striatum (RDS) region using a short echo time (TE) Stimulated Echo Acquisition Method (STEAM) sequence. Neurometabolite spectra from the RDS was first corrected for tissue T1 relaxation and then absolute quantification was performed using the unsuppressed water spectra. High-resolution in vivo diffusion MRI (dMRI) for region of interest (ROI) based microstructural quantification was also performed using a multi-shell dMRI sequence. Cerebral microstructure was characterized using diffusion tensor imaging (DTI) and Bingham-neurite orientation dispersion and density imaging (Bingham-NODDI). MRS results in the RDS showed significant decrease in N-acetyl aspartate (NAA), taurine (tau), glutathione (GSH), total creatine (tCr) and glutamate (Glu) concentration levels in PME, compared to PSE group. In the same RDS region, mean orientation dispersion index (ODI) and intracellular volume fraction (VFIC) demonstrated positive associations with tCr in PME group. ODI also exhibited significant positive association with Glu levels in PME offspring. Significant reduction in major neurotransmitter metabolites and energy metabolism along with strong association between the neurometabolites and perturbed regional microstructural complexity suggest a possible impaired neuroadaptation trajectory in PME offspring which could be persistent even into late adolescence and early adulthood.

Continuous monitoring of cerebral blood flow during general anaesthesia in infants

BackgroundGeneral anaesthesia is associated with neurocognitive deficits in infants after noncardiac surgery. Disturbances in cerebral perfusion as a result of systemic hypotension and impaired autoregulation may be a potential cause. Our aim was to study cerebral blood flow (CBF) velocity continuously during general anaesthesia in infants undergoing noncardiac surgery and compare variations in CBF velocity with simultaneously measured near-infrared spectroscopy (NIRS), blood pressure, and heart rate. MethodsNeoDoppler, a recently developed ultrasound system, was used to monitor CBF velocity via the anterior fontanelle during induction and maintenance of general anaesthesia until the start of surgery, and during recovery. NIRS, blood pressure, and heart rate were monitored simultaneously and synchronised with the NeoDoppler measurements. ResultsThirty infants, with a median postmenstrual age at surgery of 37.6 weeks (range 28.6–60.0) were included. Compared with baseline, the trend curves showed a decrease in CBF velocity during induction and maintenance of anaesthesia and returned to baseline values during recovery. End-diastolic velocity decreased in all infants during anaesthesia, on average by 59%, whereas peak systolic- and time-averaged velocities decreased by 26% and 45%, respectively. In comparison, the reduction in mean arterial pressure was only 20%. NIRS values were high and remained stable. When adjusting for mean arterial pressure, the significant decrease in end-diastolic velocity persisted, whereas there was only a small reduction in peak systolic velocity. ConclusionsContinuous monitoring of CBF velocity using NeoDoppler during anaesthesia is feasible and may provide valuable information about cerebral perfusion contributing to a more targeted haemodynamic management in anaesthetised infants.

Real-life data on the effectiveness of extensively hydrolyzed protein-based formula and amino acid-based formula in regaining weight and height in infants on a cow's milk protein elimination diet.

To compare the effectiveness of extensively hydrolyzed protein-based formula (EHF) or amino acid-based formula (AAF) in reversing the weight and height deficit in infants on a cow's milk protein elimination diet. Infants from a retrospective cohort who were fed EHF (n = 17) or AAF (n = 16) for at least 2 months on a cow's milk protein elimination diet were included. The weight and height values recorded in the infants' medical records were obtained. The mean age of the infants at the start of EHF and AAF were 5.8 ± 2.6 and 4.4 ± 2.5 months, respectively (P = 0.061). There was no difference between the groups in terms of the monthly weight gain (373.0 ± 212.2 and 453.1 ± 138.5 g, P = 0.223, respectively, for EHF and AAF), while the monthly increase in height was greater in the group fed with AAF (1.3 ± 0.5 and 1.8 ± 0.6, P = 0.030). A comparison between the difference in the initial z-score and in the oral challenge test of weight-for-age (+0.7 ± 1.2 and +1.3 ± 1.4, P = 0.262, respectively, for the EHF and AAF groups), height-for-age (+0.2 ± 1.1 and +1.2 ± 1.8, P = 0.090), and body mass index (BMI)-for-age (+0.7 ± 1.3 and +0.7 ± 1.5, P = 0.971) did not reveal a statistically significant difference between the groups. Correlation coefficients showed that the greater the initial nutritional deficit, the greater the positive variation between the beginning of each formula and the oral challenge test. EHF and AAF provided similar increases in the weight-for-age, height-for-age, and BMI-for-age z-scores in both groups. The monthly increase in height was greater in infants who received AAF.

Egr2 contributes to age-dependent vulnerability to sevoflurane-induced cognitive deficits in mice.

Sevoflurane inhalation is prone to initiate cognitive deficits in infants. The early growth response-2 (Egr-2) gene is DNA-binding transcription factor, involving in cognitive function. In this study we explored the molecular mechanisms underlying the vulnerability to cognitive deficits after sevoflurane administration. Six-day-old (young) and 6-week-old (early adult) mice received anesthesia with 3% sevoflurane for 2 h daily for 3 days. We showed that multiple exposures of sevoflurane induced significant learning ability impairment in young but not early adult mice, assessed in Morris water maze test on postnatal days 65. The integrated differential expression analysis revealed distinct transcription responses of Egr family members in the hippocampus of the young and early adult mice after sevoflurane administration. Particularly, Egr2 was significantly upregulated after sevoflurane exposure only in young mice. Microinjection of Egr2 shRNA recombinant adeno-associated virus into the dentate gyrus alleviated sevoflurane-induced cognitive deficits, and abolished sevoflurane-induced dendritic spins loss and BDNF downregulation in young mice. On the contrary, microinjection of the Egr2 overexpression virus in the dentate gyrus aggravated learning ability impairment induced by sevoflurane in young mice but not early adult mice. Furthermore, we revealed that sevoflurane markedly upregulated the nuclear factors of activated T-cells NFATC1 and NFATC2 in young mice, which were involved in Egr2 regulation. In conclusion, Egr2 serves as a critical factor for age-dependent vulnerability to sevoflurane-induced cognitive deficits.

Scoring of brain magnetic resonance imaging and neurodevelopmental outcomes in infants with congenital heart disease

BackgroundAdvances in surgical techniques to tackle critical congenital heart diseases (CHD) have enhanced the survival rates and life expectancy of children born with heart disease. Studies to better acknowledge their neurodevelopmental trajectory have paramount implications. ObjectiveThe aim of this study is to examine the nature of brain MRI findings in infants born with critical congenital heart diseases needing intervention in the first 6 months of life, with the help of an MRI scoring system and correlation with long term neurodevelopmental outcomes. MethodsBrain MRI scans of eligible infants were extracted from database, reexamined to categorize, and score them into three main functional areas: cognitive/grey matter, motor/white matter, and visual. The scoring system also included stage of myelination and presence of punctate hemorrhages. The correlation of individual and total MRI scores with neurodevelopmental assessment using Bayley Scales for Infant and Toddler Development- version 3 (BSID III) were examined via logistic regression models while controlling for confounding variables. ResultMedian (IQR) MRI score was 6 (4–7) with grey matter score of 2 (1–4). Initial BSID III scores were 80 ± 15, 80 ± 18, and 81 ± 19 for cognitive, motor and language components, respectively. The MRI cognitive score had direct correlation with respiratory index prior to surgery (cc = 0.47, p = 0.03) and cross-clamping time (cc = 0.65, p = 0.001). It displayed a significant inverse correlation with language scores for BSID III at 9 months (R = -0.42, p = 0.04) which lost significance in subsequent visits. ConclusionThis pilot study proved the feasibility of correlating structural brain abnormalities in MRI with later brain developmental deficits in infants with CHD. We envision establishing a standardized MRI scoring system to be performed on a large multi-center cohort that would help better predict and measure brain injury in infants with CHDs.

Perinatal Opioid Exposure Results in Persistent Hypoconnectivity of Excitatory Circuits and Reduced Activity Correlations in Mouse Primary Auditory Cortex.

Opioid use by pregnant women results in neonatal opioid withdrawal syndrome (NOWS) and lifelong neurobehavioral deficits including language impairments. Animal models of NOWS show impaired performance in a two-tone auditory discrimination task, suggesting abnormalities in sensory processing in the auditory cortex. To investigate the consequences of perinatal opioid exposure on auditory cortex circuits, we administered fentanyl to mouse dams in their drinking water throughout gestation and until litters were weaned at postnatal day (P)21. We then used in vivo two-photon Ca2+ imaging in adult animals of both sexes to investigate how primary auditory cortex (A1) function was altered. Perinatally exposed animals showed fewer sound-responsive neurons in A1, and the remaining sound-responsive cells exhibited lower response amplitudes but normal frequency selectivity and stimulus-specific adaptation (SSA). Populations of nearby layer 2/3 (L2/3) cells in exposed animals showed reduced correlated activity, suggesting a reduction of shared inputs. We then investigated A1 microcircuits to L2/3 cells by performing laser-scanning photostimulation (LSPS) combined with whole-cell patch-clamp recordings from A1 L2/3 cells. L2/3 cells in exposed animals showed functional hypoconnectivity of excitatory circuits of ascending inputs from L4 and L5/6 to L2/3, while inhibitory connections were unchanged, leading to an altered excitatory/inhibitory balance. These results suggest a specific reduction in excitatory ascending interlaminar cortical circuits resulting in decreased activity correlations after fentanyl exposure. We speculate that these changes in cortical circuits contribute to the impaired auditory discrimination ability after perinatal opioid exposure.SIGNIFICANCE STATEMENT This is the first study to investigate the functional effects of perinatal fentanyl exposure on the auditory cortex. Experiments show that perinatal fentanyl exposure results in decreased excitatory functional circuits and altered population activity in primary sensory areas in adult mice. These circuit changes might underlie the observed language and cognitive deficits in infants exposed to opioids.

Early detection and treatment of attention deficits in preterm and at term infants with risk factors for brain damage

Cognitive deficits in infants born preterm and infants at term with risk factors for brain damage are a common outcome. Attention deficits in preterm infants are related to the development of attention-deficit/hyperactivity disorder (ADHD), and therefore, there is a need for earlier evaluations and treatment procedures that are implemented before the presence of signs of ADHD. MethodsWe studied preterm (74%) and term infants with the Infant Scale of Selective Attention (ISSA, Escala de Evaluación de la Atención Selectiva (EEAS), in Spanish). This scale evaluates both visual- and auditory-orienting attention. Two groups participated, one with attention deficits (n = 26) and another with regular performance (n = 36). An early attention-stimulation program (EASP) was implemented in the infant group with attention deficits from three to eight months of age. All infants underwent magnetic resonance imaging (MRI), and visual and auditory evoked responses were assessed. ResultsAll infants had prenatal and perinatal risk factors for brain damage and abnormal MRI findings, and the majority had abnormalities compatible with white matter injury. However, there were four infants with porencephalic cysts; 3 of them were in the treated group. At the beginning of the treatment, ISSA values showed differences between groups. These differences persisted for five months in the visual test and up to the sixth month in the auditory evaluation. Afterward, there were no significant differences, indicating that infants with attention deficits had satisfactorily responded to the treatment. ConclusionsThe ISSA is helpful for the early evaluation of visual and auditory attention. Infants with attention deficits react well enough after six months of EASP.

Pantothenate kinase-associated neurodegeneration (Hallerworden–Spatze disease): clinical aspects, diagnosis, treatment (literature review and own data)

Aim. To analyze current data of scientific literature on the etiology, pathogenesis, approaches to the diagnosis and treatment of rare orphan disease – pantothenate kinase-associated neurodegeneration and to describe the clinical case of this disease. Pantothenate kinase-associated neurodegeneration (PKAN) is a rare inherited autosomal recessive disorder caused by mutations in the PANK2 gene, which is located at the chromosomal locus: 20p13-p12.3. The article presents a literature review and a case report of the diagnosis and treatment of 8-year-old girl with pantothenate kinase-associated neurodegeneration who suffered from progressive motor impairment. Among the dominant clinical manifestations is a growing extrapyramidal motor disorder, the so-called “dystonic storm”, which can range from severe sensorimotor motor deficits in infants and young children to mild parkinsonism in adults. MRI signs in the form of specific changes in the T2-weighted mode, which detects typical areas of hyperintensive signal in globus pallidus, surrounded by a border of hypointensive signal (“tiger’s eye”) are particular important. Neuroimaging data most likely make possible to suspect a correct diagnosis, reducing the time and cost of additional examinations. There is no pathogenetic treatment of this disease now. The main directions of currently available symptomatic drug therapy are described. Clinical trials of detoxifying drugs that reduce iron levels in the body (chelation) and surgical treatments are currently underway. Conclusions. The presented clinical observation once again confirms the complexity of the diagnostic search for orphan diseases of the nervous system. A key place in the diagnosis of pantothenate kinase-associated neurodegeneration belongs to the neuroimaging methods and molecular genetic testing data.

Birth weight, growth, nutritional status and mortality of infants from Lambaréné and Fougamou in Gabon in their first year of life.

Malnutrition and low birth weight (LBW) are two common causes of morbidity and mortality among children in sub-Saharan Africa. Both malnutrition and LBW affect early childhood development with long term consequences that may vary in their degree depending on the geographical setting. This study evaluates growth, nutritional status and mortality of infants from Lambaréné and Fougamou in Gabon from a birth cohort of a malaria in pregnancy clinical trial (NCT00811421). A prospective longitudinal birth cohort conducted between 2009 and 2012, included infants that were followed up from birth until their first-year anniversary. The exposure of interest was low birth weight and the outcomes explored were growth represented by weight gain, the nutritional status including stunting, wasting and underweight, and the mortality. Scheduled follow-up visits were at one, nine and 12 months of age. Logistic regression was used to assess the association between low birth weight and growth and nutritional outcomes, and cox regression was used for mortality. A total of 907 live-born infants were included in the analysis. The prevalence of LBW was 13% (115). At one month of life, out of 743 infants 10% and 4% presented with stunting and underweight, respectively, while these proportions increased at 12 months of life to 17% and 21%, respectively, out of 530 infants. The proportion of infants with wasting remained constant at 7% throughout the follow-up period. Stunting and underweight were associated with LBW, adjusted odds ratio (aOR): 2.6, 95% confidence interval (95%CI): 1.4-4.9 and aOR: 4.5, 95%CI: 2.5-8.1, respectively. Preterm birth was associated with stunting, aOR: 2.7, 95%CI: 1.2-6.3 and underweight, aOR: 5.4, 95%CI: 1.7-16.1 at one month of life. Infants with LBW were at higher hazard of death during the first year of life, adjusted hazard ratio 4.6, 95%CI: 1.2-17.0. Low birthweight infants in Gabon are at higher risks of growth and nutritional deficits and mortality during the first year of life. Tailored interventions aiming at preventing adverse pregnancy outcomes including LBW, early detection and appropriate management of growth, and nutritional deficits in infants are necessary in Gabon.

Auditory deficits in infants at risk for dyslexia during a linguistic sensitive period predict future language

Developmental dyslexia, a specific difficulty in learning to read and spell, has a strong hereditary component, which makes it possible to examine infants for early predictors of the condition even prior to the emergence of detectable symptoms. Using magnetoencephalography (MEG), we found smaller and shorter neural responses to simple sounds in infants at risk for dyslexia at 6 as compared to 12 months of age, a pattern that was reversed in age-matched controls. The findings indicate atypical auditory processing in at-risk infants across the sensitive period for native-language phoneme learning. This pattern was robust and localized to the same cortical areas regardless of the modeling parameters/algorithms used to estimate the current distribution underlying the measured activity. Its localization to left temporal and left frontal brain regions indicates a potential impact of atypical auditory processing on early language learning and later language skills because language functions are typically lateralized to the left hemisphere. This interpretation is supported by our further finding that atypical auditory responses in at-risk infants consistently predicted syntactic processing between 18 and 30 months and word production at 18 and 21 months of age. These results suggest a possible early marker of risk for dyslexia in at-risk infants.

Association between fetal sex and maternal plasma microRNA responses to prenatal alcohol exposure: evidence from a birth outcome-stratified cohort

Most persons with fetal alcohol spectrum disorders (FASDs) remain undiagnosed or are diagnosed in later life. To address the need for earlier diagnosis, we previously assessed miRNAs in the blood plasma of pregnant women who were classified as unexposed to alcohol (UE), heavily exposed with affected infants (HEa), or heavily exposed with apparently unaffected infants (HEua). We reported that maternal miRNAs predicted FASD-related growth and psychomotor deficits in infants. Here, we assessed whether fetal sex influenced alterations in maternal circulating miRNAs following prenatal alcohol exposure (PAE). To overcome the loss of statistical power due to disaggregating maternal samples by fetal sex, we adapted a strategy of iterative bootstrap resampling with replacement to assess the stability of statistical parameter estimates. Bootstrap estimates of parametric and effect size tests identified male and female fetal sex-associated maternal miRNA responses to PAE that were not observed in the aggregated sample. Additionally, we observed, in HEa mothers of female, but not male fetuses, a network of co-secreted miRNAs whose expression was linked to miRNAs encoded on the X-chromosome. Interestingly, the number of significant miRNA correlations for the HEua group mothers with female fetuses was intermediate between HEa and UE mothers at mid-pregnancy, but more similar to UE mothers by the end of pregnancy. Collectively, these data show that fetal sex predicts maternal circulating miRNA adaptations, a critical consideration when adopting maternal miRNAs as diagnostic biomarkers. Moreover, a maternal co-secretion network, predominantly in pregnancies with female fetuses, emerged as an index of risk for adverse birth outcomes due to PAE.

Iron deficiency anaemia in pregnancy: A contemporary review.

Iron deficiency anaemia is a global health problem, which particularly affects pregnant women. Iron deficiency anaemia during pregnancy is associated with increased maternal and perinatal morbidity and mortality. Maternal iron deficiency may also be associated with neurocognitive deficits in infants. Iron requirements increase during pregnancy and are influenced by hepcidin, the master regulator of iron homeostasis. The enduring global burden of maternal anaemia suggests that currently employed iron supplementation strategies are suboptimal. Recent developments in our understanding of systemic and placental iron homeostasis may improve therapeutic effectiveness by altering the dose and frequency of oral iron. Intravenous iron appears to be a safe treatment to correct maternal anaemia rapidly but research on patient-centred outcomes and cost-effectiveness is needed. Future trials should be adequately powered to assess outcomes relevant to pregnant women.

Colocalization of Oxtr with Prader-Willi syndrome transcripts in the trigeminal ganglion of neonatal mice.

Prader-Willi syndrome (PWS) is caused by deficient expression of the paternal copy of several contiguous genes on chromosome 15q11-q13 and affects multiple organ systems in the body, including the nervous system. Feeding and suckling deficits in infants with PWS are replaced with excessive feeding and obesity in childhood through adulthood. Clinical trials using intranasal oxytocin (OXT) show promise to improve feeding deficits in infants with PWS. The mechanism and location of action of exogenous OXT are unknown. We have recently shown in neonatal mice that OXT receptors (OXTR) are present in several regions of the face with direct roles in feeding. Here we show that the trigeminal ganglion, which provides sensory innervation to the face, is a rich source of Oxtr and a site of cellular co-expression with PWS gene transcripts. We also quantified OXTR ligand binding in mice deficient in Magel2, a PWS gene, within the trigeminal ganglion and regions that are anatomically relevant to feeding behavior and innervated by the trigeminal ganglion including the lateral periodontium, rostral periodontium, tongue, olfactory epithelium, whisker pads and brainstem. We found that peripheral OXTR ligand binding in the head is mostly intact in Magel2-deficient mice, although it is reduced in the lateral periodontium (gums) of neonatal Magel2-deficient mice compared to wild-type controls. These data suggest that OXT via orofacial OXTR may play a peripheral role to modulate sensory-motor reflexes necessary for suckling and may be part of the mechanism by which intranasal OXT shows promise for therapeutic benefit in PWS.

Relationship between Stunting, Wasting, Underweight and Geophagy and Cognitive Function of Children.

The aim of this study was to investigate the relationship between anthropometric characteristics and both geophagy and cognitive function of children. The study prospectively followed singleton children whose mothers participated in the MiPPAD clinical trial in Allada, Benin, from birth to age 12 months. Anthropometric measurements were taken at birth and 9 and 12 months. Wasting, stunting and underweight were defined as weight-for-length, length-for-age and weight-for-age Z-scores less than -2, respectively. Cognitive and motor functions were assessed using the Mullen Scales of Early Learning. Parent-reported geophageous habits of children were collected when the children were 12 months. Multiple linear and logistic regressions were used to analyse the data. A total of 632 children (49.7% girls) were involved in the study. Stunting, wasting and underweight were observed in 14.1%, 13.6% and 17.7%, respectively, at 9 months and 17.3%, 12.7% and 17.2%, respectively, at 12 months. The prevalence of geophagy among the children was 48.2%. Impaired growth at 9 and 12 months was consistently associated with low cognitive and gross motor (GM) score. Children stunted at 9 months had lower GM scores at 12 months compared with their non-stunted peers (β = -3.48, 95% confidence interval -6.62 to -0.35). Stunting, wasting and underweight are associated with cognitive and GM deficits in infants. In this setting, impaired growth was not associated with geophagy. Further research evaluating geophagy and growth prospectively and concurrently from birth to 36 months is needed.

Novel word learning deficits in infants at family risk for dyslexia.

Children of reading age diagnosed with dyslexia show deficits in reading and spelling skills, but early markers of later dyslexia are already present in infancy in auditory processing and phonological domains. Deficits in lexical development are not typically associated with dyslexia. Nevertheless, it is possible that early auditory/phonological deficits would have detrimental effects on the encoding and storage of novel lexical items. Word-learning difficulties have been demonstrated in school-aged dyslexic children using paired associate learning tasks, but earlier manifestations in infants who are at family risk for dyslexia have not been investigated. This study assessed novel word learning in 19-month-old infants at risk for dyslexia (by virtue of having one dyslexic parent) and infants not at risk for any developmental disorder. Infants completed a word-learning task that required them to map two novel words to their corresponding novel referents. Not at-risk infants showed increased looking time to the novel referents at test compared with at-risk infants. These findings demonstrate, for the first time, that at-risk infants show differences in novel word-learning (fast-mapping) tasks compared with not at-risk infants. Our findings have implications for the development and consolidation of early lexical and phonological skills in infants at family risk of later dyslexia.

Antenatal exposure to antidepressant drugs and the risk of neurodevelopmental and psychiatric disorders: a systematic review.

This study investigated whether antenatal exposure to antidepressants (ADs) increases the risks of autism spectrum disorders (ASD), attention deficit/hyperactivity disorders (ADHD), schizophrenia and other mental illnesses, and cognitive and developmental deficits in infants or preschool children. PubMed, EMBASE, BIREME/BVS databases were searched to identify studies examining associations of ADs in pregnancy with neurodevelopmental and psychiatric disorders. Twenty studies addressed ASD and/or ADHD risks while 30 focused on developmental and cognitive deficits in infants or preschool children. Most studies detected no association of antenatal AD with ASD after adjustment of risk ratios for maternal depression or psychiatric disorders. Some studies showed that maternal depression, regardless of whether it is treated or untreated, increased ASD risks. Seven out of 8 studies found no increase in ADHD risk associated with antenatal exposure to selective serotonin reuptake inhibitors, the most commonly used AD. No consistent evidence was found linking AD in pregnancy to neurocognitive developmental deficits in infants or preschool children. A residual confounding by indication (depression severity) remained in almost all studies. This systematic review found no consistent evidence suggesting that ADs in pregnancy increase risks of ASD, ADHD, and neurocognitive development deficits. Some studies, however, found evidence that maternal depression increases ASD risks.