Newborn auditory brainstem response and sudden infant death syndrome.

Sudden infant death syndrome (SIDS)-the sudden and unexplained death of a seemingly healthy infant, <1 year old-may be associated with abnormalities in the brain regions that underlie breathing and arousal during sleep. While post-mortem studies suggest abnormalities in SIDS infants' brainstems, there are no studies of these infants' brainstem function before death. One way to assess the function of the brainstem is with auditory brainstem response (ABR), a routine hearing-screening method that noninvasively measures the brainstem's response to sound. We hypothesize that anomalies in newborns' ABR measures may predict SIDS. Indeed, previous studies identified abnormalities in ABR characteristics in small samples of near-miss SIDS infants hospitalized for infant apnea syndrome. However, there is a need to examine the ABRs of infants who died of SIDS. Therefore, in the current study, we propose integrating two secondary datasets to examine newborns' ABRs (N = 156,972), including those who later died of SIDS (n = ~42; .27 out of every 1000 infants), using existing archived records of neonatal ABR results from a sample of newborns born in Florida. We hypothesize that infants who die from SIDS are more likely than non-SIDS infants to have abnormal ABRs as newborns. Understanding the association between SIDS and ABR may facilitate more accurate identification of an infant's risk for SIDS at birth, enabling increased monitoring, which may facilitate interventions and improve survivorship.

Elevated risk for developmental disabilities in children with congenital heart defects.

BACKGROUND: This study examined risk for developmental disabilities in preschool-aged children with a congenital heart defect (CHD) at the population level. METHODS: Statewide birth, birth defects, and preschool developmental disability records were integrated. The final sample included 1,966,585 children (51.0% male). Children were grouped by type(s) of CHD: critical CHD, noncritical CHD, atrial septal defect, or no major birth defects (groups were mutually exclusive). RESULTS: Children with a CHD (any type) were at increased risk for developmental disability (any type) (RR 2.08, 95% CI 2.03-2.14, P < .001). Children in the critical CHD, noncritical CHD, and atrial septal defect groups were at increased risk for developmental delay, intellectual disability, language impairment, other health impairment, and any disability. Children in the atrial septal defect group were at increased risk for autism spectrum disorder and speech impairment. For all CHD groups, risk was greatest for other health impairment and intellectual disability. CONCLUSIONS: Increased risk for developmental disabilities was identified for children with less severe CHDs as well as for children with more severe (critical) CHDs. All children with CHDs should be closely monitored so that appropriate interventions can be initiated as early as possible to maximize learning outcomes.

Sensing echoes: temporal misalignment in auditory brainstem responses as the earliest marker of neurodevelopmental derailment.

Neurodevelopmental disorders are on the rise worldwide, with diagnoses that detect derailment from typical milestones by 3 to 4.5 years of age. By then, the circuitry in the brain has already reached some level of maturation that inevitably takes neurodevelopment through a different course. There is a critical need then to develop analytical methods that detect problems much earlier and identify targets for treatment. We integrate data from multiple sources, including neonatal auditory brainstem responses (ABR), clinical criteria detecting autism years later in those neonates, and similar ABR information for young infants and children who also received a diagnosis of autism spectrum disorders, to produce the earliest known digital screening biomarker to flag neurodevelopmental derailment in neonates. This work also defines concrete targets for treatment and offers a new statistical approach to aid in guiding a personalized course of maturation in line with the highly nonlinear, accelerated neurodevelopmental rates of change in early infancy.

Newborn Auditory Brainstem Responses in Children with Developmental Disabilities.

We integrated data from a newborn hearing screening database and a preschool disability database to examine the relationship between newborn click evoked auditory brainstem responses (ABRs) and developmental disabilities. This sample included children with developmental delay (n = 2992), speech impairment (SI, n = 905), language impairment (n = 566), autism spectrum disorder (ASD, n = 370), and comparison children (n = 128,181). We compared the phase of the ABR waveform, a measure of sound processing latency, across groups. Children with SI and children with ASD had greater newborn ABR phase values than both the comparison group and the developmental delay group. Newborns later diagnosed with SI or ASD have slower neurological responses to auditory stimuli, suggesting sensory differences at birth.

Prolonged Auditory Brainstem Response in Universal Hearing Screening of Newborns with Autism Spectrum Disorder.

Previous studies report prolonged auditory brainstem response (ABR) in children and adults with autism spectrum disorder (ASD). Despite its promise as a biomarker, it is unclear whether healthy newborns who later develop ASD also show ABR abnormalities. In the current study, we extracted ABR data on 139,154 newborns from their Universal Newborn Hearing Screening, including 321 newborns who were later diagnosed with ASD. We found that the ASD newborns had significant prolongations of their ABR phase and V-negative latency compared with the non-ASD newborns. Newborns in the ASD group also exhibited greater variance in their latencies compared to previous studies in older ASD samples, likely due in part to the low intensity of the ABR stimulus. These findings suggest that newborns display neurophysiological variation associated with ASD at birth. Future studies with higher-intensity stimulus ABRs may allow more accurate predictions of ASD risk, which could augment the universal ABR test that currently screens millions of newborns worldwide. LAY SUMMARY: Children with autism spectrum disorder (ASD) have slow brain responses to sounds. We examined these brain responses from newborns' hearing tests and found that newborns who were later diagnosed with autism also had slower brain responses to sounds. Future studies might use these findings to better predict autism risk, with a hearing test that is already used on millions of newborns worldwide.

Lead Exposure and Developmental Disabilities in Preschool-Aged Children.

CONTEXT: Lead is a preventable environmental toxin that has been previously associated with deficits in cognition, academic performance, attention, and behavior in children. Very few studies, however, have examined the relationship between exposure to lead and documented developmental disabilities. OBJECTIVE: This study examined the relative risk of lead exposure on developmental disabilities in preschool-aged children. DESIGN: A statewide lead surveillance data set containing blood lead level (BLL) was integrated with another statewide data set containing developmental disability classifications for special education placement for preschool-aged children. PARTICIPANTS: The participants were the 85 178 children (average age 2.6 years) whose records in both data sets were able to be linked. Forty-six percent of the participants had an identified developmental disability. MAIN OUTCOME MEASURE: Developmental disability classification served as the main outcome measure. RESULTS: A high BLL, defined as 5 µg/dL or more, was associated with significantly increased risk for developmental disabilities (risk ratio [RR] = 1.04; 95% CI = 1.01-1.08), particularly intellectual disability (RR = 1.58, 95% CI = 1.10-2.25) and developmental delay (DD; RR = 1.11, 95% CI = 1.06-1.17). CONCLUSIONS: The results of this study are consistent with previous research identifying an association between lead exposure and numerous intellectual and educational outcomes and demonstrate that high BLL is associated with meeting eligibility criteria for developmental disabilities in young children. Continued research, surveillance, and prevention efforts are needed to further reduce the negative impacts of lead on individuals and society. Reducing or eliminating lead exposure would improve outcomes for individual children (eg, better academic performance) and reduce the burden to society (eg, lower enrollments in special education systems).

Down regulation of macrophage IFNGR1 exacerbates systemic L. monocytogenes infection.

Interferons (IFNs) target macrophages to regulate inflammation and resistance to microbial infections. The type II IFN (IFNγ) acts on a cell surface receptor (IFNGR) to promote gene expression that enhance macrophage inflammatory and anti-microbial activity. Type I IFNs can dampen macrophage responsiveness to IFNγ and are associated with increased susceptibility to numerous bacterial infections. The precise mechanisms responsible for these effects remain unclear. Type I IFNs silence macrophage ifngr1 transcription and thus reduce cell surface expression of IFNGR1. To test how these events might impact macrophage activation and host resistance during bacterial infection, we developed transgenic mice that express a functional FLAG-tagged IFNGR1 (fGR1) driven by a macrophage-specific promoter. Macrophages from fGR1 mice expressed physiologic levels of cell surface IFNGR1 at steady state and responded equivalently to WT C57Bl/6 macrophages when treated with IFNγ alone. However, fGR1 macrophages retained cell surface IFNGR1 and showed enhanced responsiveness to IFNγ in the presence of type I IFNs. When fGR1 mice were infected with the bacterium Listeria monocytogenes their resistance was significantly increased, despite normal type I and II IFN production. Enhanced resistance was dependent on IFNγ and associated with increased macrophage activation and antimicrobial function. These results argue that down regulation of myeloid cell IFNGR1 is an important mechanism by which type I IFNs suppress inflammatory and anti-bacterial functions of macrophages.

General parity between trio and pairwise breeding of laboratory mice in static caging.

Changes made in the 8th edition of the Guide for the Care and Use of Laboratory Animals included new recommendations for the amount of space for breeding female mice. Adopting the new recommendations required, in essence, the elimination of trio breeding practices for all institutions. Both public opinion and published data did not readily support the new recommendations. In response, the National Jewish Health Institutional Animal Care and Use Committee established a program to directly compare the effects of breeding format on mouse pup survival and growth. Our study showed an overall parity between trio and pairwise breeding formats on the survival and growth of the litters, suggesting that the housing recommendations for breeding female mice as stated in the current Guide for the Care and Use of Laboratory Animals should be reconsidered.

Type I IFNs downregulate myeloid cell IFN-γ receptor by inducing recruitment of an early growth response 3/NGFI-A binding protein 1 complex that silences ifngr1 transcription.

The ability of type I IFNs to increase susceptibility to certain bacterial infections correlates with downregulation of myeloid cell surface IFNGR, the receptor for the type II IFN (IFN-γ), and reduced myeloid cell responsiveness to IFN-γ. In this study, we show that the rapid reductions in mouse and human myeloid cell surface IFNGR1 expression that occur in response to type I IFN treatment reflect a rapid silencing of new ifngr1 transcription by repressive transcriptional regulators. Treatment of macrophages with IFN-ß reduced cellular abundance of ifngr1 transcripts as rapidly and effectively as actinomycin D treatment. IFN-ß treatment also significantly reduced the amounts of activated RNA polymerase II (pol II) and acetylated histones H3 and H4 at the ifngr1 promoter and the activity of an IFNGR1-luc reporter construct in macrophages. The suppression of IFNGR1-luc activity required an intact early growth response factor (Egr) binding site in the proximal ifngr1 promoter. Three Egr proteins and two Egr/NGFI-A binding (Nab) proteins were found to be expressed in bone macrophages, but only Egr3 and Nab1 were recruited to the ifngr1 promoter upon IFN-ß stimulation. Knockdown of Nab1 in a macrophage cell line prevented downregulation of IFNGR1 and prevented the loss of acetylated histones from the ifngr1 promoter. These data suggest that type I IFN stimulation induces a rapid recruitment of a repressive Egr3/Nab1 complex that silences transcription from the ifngr1 promoter. This mechanism of gene silencing may contribute to the anti-inflammatory effects of type I IFNs.

Pregnancy 101: a call for reproductive and prenatal health education in college.

The objective of the study was to demonstrate the effectiveness of a college course in preconception health and prenatal development at improving reproductive health awareness in college students. Students enrolled in the course completed pretest and posttest assessments and a course evaluation. Students' self-perception of awareness of the positive and negative factors that can affect pregnancy increased from 13% at the beginning of the course to 89 and 93% at the end of the course, respectively. Correspondingly, students' knowledge of course-related information improved across nearly all areas assessed. The average score among students increased from 67 to 90% correct from pretest to posttest. Course evaluation results indicated that over 94% of students found the course to be beneficial and informative. College courses are a practical way to disseminate reproductive and prenatal health information. Educating college students in these areas has clear benefits to both individual students and society and, as such, merits increased attention in college curricula.

Differential effects of type I and II interferons on myeloid cells and resistance to intracellular bacterial infections.

The type I and II interferons (IFNs) play important roles in regulating immune responses during viral and bacterial infections and in the context of autoimmune and neoplastic diseases. These two IFN types bind to distinct cell surface receptors that are expressed by nearly all cells to trigger signal transduction events and elicit diverse cellular responses. In some cases, type I and II IFNs trigger similar cellular responses, while in other cases, the IFNs have unique or antagonistic effects on host cells. Negative regulators of IFN signaling also modulate cellular responses to the IFNs and play important roles in maintaining immunological homeostasis. In this review, we provide an overview of how IFNs stimulate cellular responses. We discuss the disparate effects of type I and II IFNs on host resistance to certain intracellular bacterial infections and provide an overview of models that have been proposed to account for these disparate effects. Mechanisms of antagonistic cross talk between type I and II IFNs are also introduced.

Study of clinical applications and safety for Pascal® laser photocoagulation in retinal vascular disorders.

PURPOSE: To establish safe laser parameter standards for 10-30 ms Pascal(®) laser in clinical practice and to evaluate clinical and visual outcomes using this 532-nm multi-spot photocoagulation system. METHODS: Retrospective observational case series of 313 patients treated between 2006 and 2008. Evaluation of eight groups: A - panretinal photocoagulation (PRP) for proliferative diabetic retinopathy (PDR); B - focal laser treatment for clinically significant diabetic macular oedema; C - grid laser for diffuse diabetic macular oedema; D - sector PRP for ischaemic branch retinal vein occlusions (I-BRVO); E - full PRP for ischaemic central retinal vein occlusions (I-CRVO); F - macular laser treatment for macular oedema secondary to non-ischaemic BRVO; G - full PRP for rubeosis iridis and/or neovascular glaucoma (NVG) secondary to I-BRVO, I - CRVO or PDR; H - laser retinopexy for retinal breaks/degenerations. RESULTS: Mean LogMAR visual acuity for all procedures improved postlaser (p = 0.065), and laser prevented visual loss in 85% eyes. Topical anaesthesia was only required. At mean follow-up of 5 months, 72% procedures had a successful clinical outcome. Significantly higher powers were required for PRP using Pascal(®) compared to conventional laser (p = 0.001) in PDR, I-BRVO, I-CRVO and NVG. Sixty-seven per cent of patients (15/20) were successfully treated with single-session 20-ms PRP using a mean 1952 burns. There were no laser-associated adverse effects or ocular complications associated with multi-spot PRP or macular Pascal(®) arrays. CONCLUSIONS: The clinical efficacy using 10- to 30-ms pulse duration Pascal(®) laser is comparable to conventional standard protocols used for the treatment of vascular retinal disorders. Higher power, 10- to 30-ms pulse duration laser may be safely and effectively used in clinical practice.

Infant responding to joint attention, executive processes, and self-regulation in preschool children.

Infant joint attention is related to behavioral and social outcomes, as well as language in childhood. Recent research and theory suggests that the relations between joint attention and social-behavioral outcomes may reflect the role of executive self-regulatory processes in the development of joint attention. To test this hypothesis two studies were conducted. The first, cross-sectional study examined the development of responding to joint attention (RJA) skill in terms of increasing executive efficiency of responding between 9 and 18 months of age. The results indicated that development of RJA was characterized by a decreased latency to shift attention in following another person's gaze and head turn, as well as an increase in the proportion of correct RJA responses exhibited by older infants. The second study examined the longitudinal relations between 12-month measures of responding to joint attention and 36-month attention regulation in a delay of gratification task. The results indicated that responding to joint attention at 12-months was significantly related to children's use of three types of self-regulation behaviors while waiting for a snack reward at 36 months of age. These observations are discussed in light of a developmental theory of attention regulation and joint attention in infancy.

Anticipatory smiling: linking early affective communication and social outcome.

In anticipatory smiles, infants appear to communicate pre-existing positive affect by smiling at an object and then turning the smile toward an adult. We report two studies in which the precursors, development, and consequences of anticipatory smiling were investigated. Study 1 revealed a positive correlation between infant smiling at 6 months and the level of anticipatory smiling at 8 and 10 months during joint attention episodes, as well as a positive correlation between anticipatory smiling and parent-rated social expressivity scores at 30 months. Study 2 confirmed a developmental increase in the number of infants using anticipatory smiles between 9 and 12 months that had been initially documented in the Study 1 sample [Venezia, M., Messinger, D. S., Thorp, D., & Mundy, P. (2004). The development of anticipatory smiling. Infancy, 6(3), 397-406]. Additionally, anticipatory smiling at 9 months positively predicted parent-rated social competence scores at 30 months. Findings are discussed with regard to the importance of anticipatory smiling in early socioemotional development.

Undergraduate student awareness of issues related to preconception health and pregnancy.

OBJECTIVES: To assess undergraduate student awareness of issues related to preconception health and pregnancy and to investigate gender differences. METHODS: Two-hundred forty-one undergraduate students (137 females, 104 males) completed a questionnaire designed to assess awareness of issues related to preconception health and pregnancy. RESULTS: Overall, students demonstrated a low to moderate level of awareness, correctly answering 64% of items. Individual student scores varied a great deal, ranging from 33% to 89% correct. Students who had previously taken a course containing information on pregnancy and/or child development correctly answered a greater percentage of items than those who had not taken such a course. Females had slightly, but statistically significantly, higher awareness scores than males. Students self-reported ratings of awareness of behaviors that are dangerous during pregnancy were associated with their composite scores on the questionnaire. Awareness across individual items varied a great deal. Students demonstrated a high level of awareness for substance use, a moderate level of awareness for sexually transmitted diseases and preconception care, and lower levels of awareness for folic acid, prenatal development, health, and pregnancy spacing. CONCLUSIONS: Efforts to improve preconception health should include increasing awareness of reproductive issues for both males and females. Existing efforts to provide information on reproductive health to students need to be expanded and new strategies developed. Particular attention should be paid to increasing awareness of the benefits of family planning, the early onset and rapid rate of organogenesis, the benefits of folic acid, and the importance of addressing health-related issues.

Individual differences and the development of joint attention in infancy.

This study examined the development of joint attention in 95 infants assessed between 9 and 18 months of age. Infants displayed significant test-retest reliability on measures of following gaze and gestures (responding to joint attention, RJA) and in their use of eye contact to establish social attention coordination (initiating joint attention, IJA). Infants displayed a linear, increasing pattern of age-related growth on most joint attention measures. However, IJA was characterized by a significant cubic developmental pattern. Infants with different rates of cognitive development exhibited different frequencies of joint attention acts at each age, but did not exhibit different age-related patterns of development. Finally, 12-month RJA and 18-month IJA predicted 24-month language after controlling for general aspects of cognitive development.

Infant joint attention, temperament, and social competence in preschool children.

Infant joint attention has been observed to be related to social-emotional outcomes in at-risk children. To address whether this relation is also evident in typically developing children, 52 children were tested at 12, 15, 24, and 30 months to examine associations between infant joint attention and social outcomes. Twelve-month initiating and responding to joint attention were related to 30-month social competence and externalizing behavior, even when accounting for 15-month temperament ratings, 24-month cognition and language, and demographic variables. These results suggest that, in addition to associations with language and cognition, infant joint attention reflects robust aspects of development that are related to individual differences in the emergence of social and behavioral competence in childhood.

Tracking preschool children with developmental delay: third grade outcomes.

Educational outcomes were evaluated for 2,046 preschool children identified with developmental delay. Results indicated that at third grade, 26% were in regular education and the remaining 74% were receiving special education services. The most common disability classifications at outcome were specific learning disabilities and educable mentally handicaps. Regular education, but not special education, children had higher retention rates than did the general population. The presence of one or more secondary exceptionalities in preschool was more common for special education than regular education children. Regular education and special education children did not differ on other factors studied. This study highlights the importance of developmental delay as an exceptionality category and advances our understanding of the long-term implications of such delay.

The temporal coordination of early infant communication.

The ability to coordinate expressive behaviors is crucial to the development of social and emotional communication. Coordination involves systematic sequencing of behaviors from two different modalities that have some temporal overlap. A bootstrapping procedure was used to determine whether preverbal 3- and 6-month-old infants sequence vocalizations, gazes at their mothers' faces, and facial expressions into pairs of coordinated patterns nonrandomly. Smiles and frowns were highly coordinated with vocalizations. Smiles were also coordinated with gazes at mothers' faces, which became stronger with age. Vocalizations were not coordinated with gazes at mothers' faces. These findings illustrate the manner in which infants temporally coordinate communicative actions and provide new evidence that facial expressions (particularly smiles) are central to early infant communications.

Responding to joint attention and language development: a comparison of target locations.

This study examined the importance of target location (within vs. outside the visual field) on the relation between responding to joint attention and subsequent language development in 47 normally developing infants. The results supported a developmental progression in the infants' ability to locate targets from within to outside the visual field. In addition, individual differences in 15-month-old infants' ability to correctly locate targets outside the visual field was a unique predictor of expressive language at 24 months. Infants' ability to locate targets outside the visual field may demonstrate increasing capacities for attention regulation, representational thinking, and social cognition that may facilitate language learning. The implications of this study are discussed with regard to the usefulness of measures of responding to joint attention for identifying early language and developmental delays.