A preliminary study of the effects of stimulant medications on estimates of psycholinguistic abilities for children with attention-deficit/hyperactivity disorder.

Underlying deficits in inattention, hyperactivity, and/or impulsivity might contribute to suboptimal test-taking behaviours during language assessments that can lead to diagnostic errors. Considerations of potential medication effects on estimates of children's nonword repetition, sentence recall, tense-marking, and narrative abilities are warranted given long-standing enthusiasm for these indices to serve as clinical markers for developmental language disorder (DLD). A battery consisting of 1 nonverbal, 1 reading, and 6 verbal measures was administered twice to 26 children (6-9 years) with independently diagnosed combined-type attention-deficit/hyperactivity disorder (ADHD). All participants had been prescribed stimulant medications for the management of their ADHD symptoms and were assessed off- and on-medication, with order counter-balanced across participants. Half of the participants had concomitant DLD. Examiners were unaware of children's clinical status during assessments or when they were testing children who had received medication. Effect sizes were calculated for each measure. Significant score differences indicating a beneficial impact of stimulant medications on children's performances were observed on the recalling sentences subtest of the Clinical Evaluation of Language Fundamentals and the Picture Peabody Vocabulary Test. Adjustments may be needed when speech language pathologists use sentence recall or receptive vocabulary measures to make diagnostic decisions with children who have ADHD.

An IQ consortium analysis of starting dose selection for oncology small molecule first-in-patient trials suggests an alternative NOAEL-based method can be safe while reducing time to the recommended phase 2 dose.

The first-in-patient (FIP) starting dose for oncology agents should be reasonably safe and provide potential therapeutic benefit to the patient. For late-stage oncology patients, this dose is often based on the ICH S9 guidance, which was developed primarily based on experience with cytotoxic chemotherapeutic agents using the rodent STD10 or non-rodent HNSTD and an appropriate safety factor. With the increase in molecularly targeted chemotherapeutics, it is prudent to re-evaluate how the FIP dose is derived to ensure that the appropriate balance between risk and therapeutic benefit to the patient is achieved. Blinded data on 92 small molecule oncology compounds from 12 pharmaceutical companies who are members of the IQ DruSafe consortium were gathered to investigate if a NOAEL-based starting dose without a safety factor would have been tolerated in the FIP trial and if so, estimating how many dose escalation cohorts could have been reduced. Our analysis suggests that the NOAEL-based alternative starting dose would have been tolerated in most cases evaluated, with an anticipated mean reduction of 2.3 cohorts. Of the 12 cases where the alternative approach resulted in a starting dose that would have exceeded the MTD/RP2D, none of the nonclinical toxicities in these cases were considered irreversible and would be monitorable in all but one instance. Most non-tolerated cases were within two-threefold of the MTD/RP2D, with the clinical AEs considered manageable and mitigated by dose de-escalation. No one method of FIP dose calculation will likely be appropriate for all oncology small molecules and starting dose selection should be performed using a case-by-case approach. However, the NOAEL-based method that does not utilize a safety factor should be considered when appropriate to minimize the number of patients exposed to sub-therapeutic doses of an investigational oncology agent and accelerating development to RP2D.

Factors Impacting Implementation of Universal Screening of Developmental Language Disorder in Public Schools.

PURPOSE: Developmental language disorder (DLD) is an underidentified neurodevelopmental disorder that affects, on average, one out of 11 kindergarten-age children (ages 4-6 years). Children with DLD can face academic, behavioral, psychiatric, emotional, and social challenges. Universal screening is seen as an effective way for public school districts to increase DLD identification rates. However, little is known about factors impacting implementation of school-based universal screenings for DLD. We partnered with a large suburban school district in the Intermountain West region of the United States to gather detailed perspectives from school personnel regarding the barriers and facilitators to the implementation of universal screening in their district. METHOD: Using a two-phase mixed-methods design, we first conducted focus groups to identify potential barriers and facilitators to universal screening. We then used the qualitative data from the first phase to develop a 20-item survey to assess agreement with the focus group results among a wider group of district speech-language pathologists and kindergarten teachers from the school district. RESULTS: Our survey showed moderate levels of agreement with our focus group results. In particular, school personnel showed high levels of support for universal screening for DLD, with interesting interplay across various factors: (a) the negative impact of unmanageable workload on personnel under both referral- and universal-based identification formats, (b) the preference for paraprofessionals to administer screenings, (c) the role that Response to Intervention programs may play in offsetting workloads associated with universal screenings, and (d) the need for increased awareness and education about child language development and impairment among general education teachers and the public. CONCLUSION: Recommendations for incorporating these factors into more useful and applicable collaborative research-based efforts are presented. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.23661876.

Positive Predictive Values Associated With Adapting the Redmond Sentence Recall Measure Into a Kindergarten Screener for Developmental Language Disorder.

PURPOSE: Researchers estimate the prevalence of developmental language disorder (DLD) in 5-year-olds to be between 7% and 12%. Current identification systems in public schools typically favor referral identification formats over targeted or universal screenings. Public schools face unique challenges when assessing the value of screening measures for DLD that include real-world considerations such as administration, time, and resource constraints. This study used the positive predictive value (PPV) of the Redmond Sentence Recall (RSR) to assess its fidelity when administered by special education paraprofessionals. Our obtained PPV was compared across three areas: (a) previous studies that have utilized the RSR, (b) rates extrapolated from the participating school district's preexisting referral system from a previous study, and (c) expectations based on DLD prevalence. METHOD: Language screenings were conducted in two elementary schools using the RSR administered by school-based paraprofessionals trained on the screener protocol. One hundred sixty-four kindergarten students (age range: 5-6 years) were screened. Confirmatory testing was completed on all students who failed the screener. RESULTS: Of the 164 students screened, 19 failed the RSR (11.5%), and 14 met criteria (8.5%) for DLD (PPV = .74). Our PPV was similar to previously published studies that utilized the RSR using research assistants and was higher than the PPV associated with teacher-based referrals from the participating school district. CONCLUSION: The RSR represents a potentially useful screener for identifying children at risk for previously unidentified language disorders in public schools. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.22044479.

In Utero Antiretroviral Exposure and Risk of Neurodevelopmental Problems in HIV-Exposed Uninfected 5-Year-Old Children.

Studies have observed neurodevelopmental (ND) challenges among young children perinatally HIV-exposed yet uninfected (CHEU) with in utero antiretroviral (ARV) exposure, without clear linkage to specific ARVs. Atazanavir (ATV) boosted with ritonavir has been a preferred protease inhibitor recommended for pregnant women, yet associations of ATV with ND problems in CHEU have been reported. Studies among early school-age children are lacking. The pediatric HIV/AIDS cohort study (PHACS) surveillance monitoring for antiretroviral therapy (ART) toxicities (SMARTT) study evaluated 5-year-old monolingual English-speaking CHEU using the behavior assessment system for children, Wechsler preschool and primary scales of intelligence, and test of language development-primary. A score ≥1.5 standard deviations worse than population norms defined a signal within each domain. Analyses of risk for signals were stratified by timing of any ARV initiation. Associations between ARV exposure and risk of ND signals were assessed using proportional odds models, adjusting for confounders. Among 230 children exposed to ARVs at conception, 15% had single and 8% had multiple ND problems; ATV exposure was not associated with higher risk of signals [adjusted cumulative odds ratio (cOR) = 0.66, confidence interval (CI): 0.28-1.56]. However, among 461 children whose mothers initiated ARVs during pregnancy, 21% had single and 12% had multiple ND problems; ATV exposure was associated with higher risk of signals (cOR = 1.70, CI: 0.82-3.54). The specific regimen tenofovir/emtricitabine/ATV was associated with higher risk (cOR = 2.31, CI: 1.08-4.97) relative to regimens using a zidovudine/lamivudine backbone combined with non-ATV ARVs. It remains important to monitor neurodevelopment of CHEU during early childhood and investigate the impact and the role of timing of in utero exposure to specific ARVs.

Psycholinguistic profiling of children with sluggish cognitive tempo.

Language disorders are frequently comorbid with attention deficit/hyperactivity disorder (ADHD). Sluggish cognitive tempo (SCT), a second attention disorder, may potentially explain some of the links between language disorders and ADHD. In this study we examined the psycholinguistic abilities of 207 children (mean age 7;10) with and without clinically significant levels of SCT symptoms to determine the degree to which symptoms of language disorder co-occur in cases of SCT. Analyses of children's tense-marking, nonword repetition, and sentence recall indicated that deficits in these areas were not associated with SCT. Instead, SCT appears to be more closely aligned with features of social (pragmatic) communication disorder.

The Greentown Project: Building Evidence to inform Intervention Design for Juveniles Caught-up in Local Criminal Networks.

A small minority of juveniles are responsible for the majority of detected juvenile crime in Ireland. This situation presents significant policy concerns. The current paper, based on findings from a comparative analysis builds on a multi-step research design process to provide evidence-based knowledge to inform the design of a new targeted intervention. An initial social network analysis of national crime and intelligence data produced localized basic criminal network maps illustrating co-offending and intelligence relationships between adults and juveniles in specific Police sub-districts (Part 1). These network maps then provided an enquiry frame for interviews with members of the police forces in three case study locations (Part 2). A comparative analysis of the three studies (Part 3) identified diversity in network structure and inherent resilience. The analysis also identifies core similarities in juveniles' vulnerabilities and risks to recruitment. These factors are important considerations for an intervention seeking to disrupt networks and create safe "exit" environments for juveniles.

The Reliability of Short Conversational Language Sample Measures in Children With and Without Developmental Language Disorder.

PURPOSE: Language sample analysis (LSA) represents an ecologically valid method for diagnosing, identifying goals, and measuring progress in children with developmental language disorder (DLD). LSA is, however, time consuming. The purpose of this study was to determine the length of sample needed to obtain reliable LSA measures for children in kindergarten and first grade with typical language (TL) and DLD using automated analyses from the Systematic Analysis of Language Transcripts software. METHOD: Play-based conversational language samples collected on kindergarten to first-grade children with TL (n = 21) and DLD (n = 21) from a community-based sample were analyzed. Eight LSA measures were calculated from 1-, 3-, 5-, 7-, and 10-min sample cuts and compared to 20-min samples for reliability. RESULTS: Reliability estimates were similar for the TL and DLD groups except for errors and omissions, which showed overall higher levels of reliability in the DLD group and reached acceptable levels at 3 min. Percent grammatical utterances were reliable at 7 min in the DLD group and not reliable in shorter samples in the TL group. The subordination index was reliable at 10 min for both groups. Number of different words reached acceptable reliability at the 3-min length for the DLD group and at the 10-min length for the TL group. Utterances and words per minute were reliable at 3 min and mean length of utterance at 7 min in both groups. CONCLUSIONS: Speech-language pathologists can obtain reliable LSA measures from shorter, 7-min conversational language samples from kindergarten to first-grade children with DLD. Shorter language samples may encourage increased use of LSA. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.19529287.

Self-regulation in children with vocal fold nodules: A multilevel analysis.

INTRODUCTION: Vocal fold nodules (VNs) represent the most common cause of voice disorders in children. Phonotrauma related to chronic, repetitive, intense vocal activity is often cited as the proximate cause of VNs. However, diminished self-regulation (SR) may predispose some children toward extreme phonotraumatic voice use, thereby contributing secondarily to their development. This case-control study examined the association between features of SR and VNs in children. METHOD: Parents of children with VNs (N = 40, Age Mean = 7.5, SD = 2.03 years) and vocally normal, medical controls (VNCs; N = 40, Age Mean = 7.6, SD = 1.54 years) completed the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF2; Gioia, Isquith, Guy & Kenworthy, 2015), an inventory that evaluates components of SR in children. RESULTS: Children with VNs, as compared with the vocally normal control group, were described as (i) impulsive (i.e., scoring significantly worse on the Behavior Regulation Index, BRI; P < 0.001, Cohen's d = 0.86), and (ii) emotionally dysregulated (i.e., scoring significantly worse on the Emotional Regulation Index, ERI; P < 0.001, Cohen's d = 0.81). CONCLUSIONS: Diminished SR in some children with VNs may contribute to phonotraumatic vocal behaviors and potentially attenuate the effectiveness of voice therapy.

Design and optimisation of dendrimer-conjugated Bcl-2/xL inhibitor, AZD0466, with improved therapeutic index for cancer therapy.

Dual Bcl-2/Bcl-xL inhibitors are expected to deliver therapeutic benefit in many haematological and solid malignancies, however, their use is limited by tolerability issues. AZD4320, a potent dual Bcl-2/Bcl-xL inhibitor, has shown good efficacy however had dose limiting cardiovascular toxicity in preclinical species, coupled with challenging physicochemical properties, which prevented its clinical development. Here, we describe the design and development of AZD0466, a drug-dendrimer conjugate, where AZD4320 is chemically conjugated to a PEGylated poly-lysine dendrimer. Mathematical modelling was employed to determine the optimal release rate of the drug from the dendrimer for maximal therapeutic index in terms of preclinical anti-tumour efficacy and cardiovascular tolerability. The optimised candidate is shown to be efficacious and better tolerated in preclinical models compared with AZD4320 alone. The AZD4320-dendrimer conjugate (AZD0466) identified, through mathematical modelling, has resulted in an improved therapeutic index and thus enabled progression of this promising dual Bcl-2/Bcl-xL inhibitor into clinical development.

Spontaneous productions of infinitive clauses by English-speaking children with and without specific language impairment.

As a group, children with specific language impairment (SLI) have presented with lower levels of proficiency with infinitive clauses relative to comparison groups with typical language (TL). The presence of considerable individual variability within those affected by SLI, however, remains unexplained. Furthermore, the status of infinitive clause productions in children with language impairments that do not meet criteria for SLI, because of either low nonverbal abilities or other concomitant conditions, is unknown. Previous studies focused on children with SLI and have not included children who would fit into a broader developmental language disorder (DLD) designation. In this study, spontaneous language samples were collected on 30 children with DLD and 30 children with typical language skills, including those with low nonverbal abilities or other neurodevelopmental disorders (age range: 5;1-7;7). Samples were analyzed to examine potential predictors of children's infinitive clause use and their infinitive TO omission rates. Significant group differences were found for the number and accuracy of infinitive clauses produced. Consistent with previous reports examining children with SLI, considerable variability was found across cases of DLD. Maternal education and mean length of utterance (MLU) were significant predictors for children's infinitive clause use. Finite verb morphology composite scores and MLU were significant predictors of children's infinitive TO omission rates.

Clinical Intersections Among Idiopathic Language Disorder, Social (Pragmatic) Communication Disorder, and Attention-Deficit/Hyperactivity Disorder.

Purpose Estimates of the expected co-occurrence rates of idiopathic language disorder and attention-deficit/hyperactivity disorder (ADHD) provide a confusing and inconsistent picture. Potential sources for discrepancies considered so far include measurement and ascertainment biases (Redmond, 2016a, 2016b). In this research symposium forum article, the potential impact of applying different criteria to the observed co-occurrence rate is examined through an appraisal of the literature and an empirical demonstration. Method Eighty-five cases were selected from the Redmond, Ash, et al. (2019) study sample. Standard scores from clinical measures collected on K-3rd grade students were used to assign language impairment status, nonverbal impairment status, social (pragmatic) communication disorder status, and ADHD status. Criteria extrapolated from the specific language impairment (Stark & Tallal, 1981), developmental language disorder (Bishop et al., 2017), and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition language disorder (American Psychiatric Association, 2013) designations were applied. Results The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition language disorder designation and its separation of language disorder from the social (pragmatic) communication disorder designation provided the clearest segregation of idiopathic language deficits from elevated ADHD symptoms, showing only a 2% co-occurrence rate. In contrast, applying the broader developmental language disorder designation raised the observed co-occurrence rate to 22.3%. The specific language impairment designation yielded an intermediate value of 16.9%. Conclusions Co-occurrence rates varied as a function of designation adopted. The presence of pragmatic symptoms exerted a stronger influence on observed co-occurrence rates than low nonverbal abilities. Impacts on clinical management and research priorities are discussed. Presentation Video https://doi.org/10.23641/asha.13063751.

"Tell Me About Your Child": A Grounded Theory Study of Mothers' Understanding of Language Disorder.

Purpose The purpose of this study was to generate a theory grounded in data explaining caregivers' understanding of their child's language disorder and the perceived role of speech-language pathologists in facilitating this knowledge. Method This study employed grounded theory as a conceptual framework. Qualitative data were generated based on semistructured interviews conducted with 12 mothers of children who had received speech-language pathology services. Results The following themes emerged from the data analysis: (a) Many mothers reported receiving confusing or irrelevant diagnostic terms for language disorder, (b) mothers of children with language disorders were distressed about their children's language problems, (c) mothers did not always trust or understand their children's speech-language pathologist, and (d) mothers were satisfied with the interventions their child had been receiving. Mothers described their children's language disorder using a total of 23 labels, most of which were not useful for accessing meaningful information about the nature of their child's communication problem. Generally, mothers reported they did not receive language-related diagnostic labels from speech-language pathologists for their child's language disorder. Conclusions Two theories were generated from the results: (a) Lack of information provided to mothers about their child's language disorder causes mothers psychological harm that appears to be long lasting. (b) Difficulties in successfully relaying information about language disorders to parents result in negative perceptions of speech-language pathology. Implications and future directions are discussed. Supplemental Material https://doi.org/10.23641/asha.12177390.

Exploring gender as a potential source of bias in adult judgments of children with specific language impairment and attention-deficit/hyperactivity disorder.

The purpose of this follow-up study to Ludlow (2013) was to examine potential sources of variability within attributional ratings adults (age range: 21-73) assigned to child speakers affected by either Specific Language Impairment (SLI) or Attention-Deficit/Hyperactivity Disorder (ADHD). Factors considered were rater's gender [Rater Male (RM) or Rater Female (RF)], the reported gender of the speakers [Speaker Male (SM) or Speaker Female (SF)], and the type of neurodevelopmental disorder involved (SLI or ADHD). Eighty participants (40 male and 40 female) rated brief, transcribed, narratives previously produced in Ludlow (2013) by boys affected by either SLI, ADHD, or who had typical neurodevelopment (TN). Narratives were presented to raters as having been generated by either a boy or a girl. After reading each narrative, participants provided ratings in response to 15 questions about the narrative, the child speaker's attributes, and family background. Analyses revealed a significant main effect for speaker group, such that raters assigned more pejorative attributes to children with a disorder (ADHD = SLI < TN and ADHD < SLI < TN) across all dimensions. Significant speaker gender main effects (SM < SF) were limited to questions targeting the speaker's behavioral attributes. Results obtained in this study with transcription stimuli replicated previous reports that had used audio stimuli. These findings contribute to a growing body of research documenting the presence of robust, multidimensional, implicit, negative biases among most individuals towards children displaying language differences associated with common neurodevelopmental disorders.

Birth Prevalence of Congenital Cytomegalovirus Infection in HIV-Exposed Uninfected Children in the Era of Combination Antiretroviral Therapy.

OBJECTIVES: To estimate birth prevalence of congenital cytomegalovirus (cCMV) in HIV-exposed uninfected children born in the current era of combination antiretroviral therapy and describe cCMV-related neurodevelopmental and hearing outcomes. STUDY DESIGN: The Surveillance Monitoring for ART Toxicities cohort study follows HIV-exposed uninfected children at 22 sites in the US and Puerto Rico. Birth cCMV prevalence was estimated in a subset of participants who had blood pellets collected within three weeks of birth and underwent ≥1 of 6 assessments evaluating cognitive and language development including an audiologic examination between 1 and 5 years of age. Detection of CMV DNA by polymerase chain reaction testing of peripheral blood mononuclear cells was used to diagnose cCMV. Proportions of suboptimal assessment scores were compared by cCMV status using Fisher exact test. RESULTS: Mothers of 895 eligible HIV-exposed uninfected children delivered between 2007 and 2015. Most (90%) were on combination antiretroviral therapy, 88% had an HIV viral load of ≤400 copies/mL, and 93% had CD4 cell counts of ≥200 cells/µL. Eight infants were diagnosed with cCMV, yielding an estimated prevalence of 0.89% (95% CI, 0.39%-1.75%). After adjusting for a sensitivity of 70%-75% for the testing method, projected prevalence was 1.2%-1.3%. No differences were observed in cognitive, language and hearing assessments by cCMV status. CONCLUSIONS: Although birth cCMV prevalence in HIV-exposed uninfected children born to women with well-controlled HIV is trending down compared with earlier combination antiretroviral therapy-era estimates, it is above the 0.4% reported for the general US population. HIV-exposed uninfected children remain at increased risk for cCMV.

Heteroarylamide smoothened inhibitors: Discovery of N-[2,4-dimethyl-5-(1-methylimidazol-4-yl)phenyl]-4-(2-pyridylmethoxy)benzamide (AZD8542) and N-[5-(1H-imidazol-2-yl)-2,4-dimethyl-phenyl]-4-(2- pyridylmethoxy)benzamide (AZD7254).

Aberrant hedgehog (Hh) pathway signaling is implicated in multiple cancer types and targeting the Smoothened (SMO) receptor, a key protein of the Hh pathway, has proven effective in treating metastasized basal cell carcinoma. Our lead optimization effort focused on a series of heteroarylamides. We observed that a methyl substitution ortho to the heteroaryl groups on an aniline core significantly improved the potency of this series of compounds. These findings predated the availability of SMO crystal structure in 2013. Here we retrospectively applied quantum mechanics calculations to demonstrate the o-Me substitution favors the bioactive conformation by inducing a dihedral twist between the heteroaryl rings and the core aniline. The o-Me also makes favorable hydrophobic interactions with key residue side chains in the binding pocket. From this effort, two compounds (AZD8542 and AZD7254) showed excellent pharmacokinetics across multiple preclinical species and demonstrated in vivo activity in abrogating the Hh paracrine pathway as well as anti- tumor effects.

Redmond (2002) Revisited: Have Standardized Behavioral Rating Scales Gotten Better at Accommodating for Overlapping Symptoms with Language Impairment?

Seventeen years ago, Redmond reviewed five standardized behavioral rating scales and identified several aspects of their design that made them prone to mischaracterize language impairments as socioemotional behavioral disorders. The purpose of this report is to provide an update and extension of the original audit. We consulted test manuals to evaluate: (1) representation of children with language impairments in their standardization samples; (2) presence of language, or academic items within their inventories; (3) accommodations for administering the measure to children with language impairments; and (4) procedures for identifying inordinately punitive ratings. Overlapping language and academic symptoms continued to be a problem across current behavioral rating scales. Improvements since Redmond occurred in the representation of children with language impairments in standardization samples and in procedures for identifying inordinately punitive ratings. We discuss implications for clinical assessment, research programs, and instrument development.

Diagnostic Accuracy of Sentence Recall and Past Tense Measures for Identifying Children's Language Impairments.

Purpose Measures of linguistic processing and grammatical proficiency represent strong candidates for adaptation into language screeners for early elementary students. One key barrier, however, has been the lack of consensus around the preferred reference standard for assigning affected status. Diagnostic accuracies associated with sentence recall and past tense marking index measures were examined relative to 5 different reference standards of language impairment: receipt of language services, clinically significant levels of parental concern, low performance on language measures, a composite requiring at least 2 of these indicators, and a composite requiring convergence across all indicators. Method One thousand sixty grade K-3 students participated in school-based language screenings. All students who failed the screenings and a random sampling of those who passed were invited to participate in confirmatory assessments. The community-based sample was supplemented by a clinical sample of 58 students receiving services for language impairment. Two hundred fifty-four students participated in confirmatory testing. Examiners were naive to participants' status. Results Diagnostic accuracies for the sentence recall and past tense marking index measures varied across the different reference standards (areas under receiver operating characteristic curves: .67-.95). Higher levels of convergence occurred with reference standards based on behavioral measures. When affected status was defined by receipt of services and/or parental ratings, cases presented with higher levels of performance on the language measures than when affected status was based on behavioral criteria. Conclusion These results provide additional support for the adaptation of sentence recall and past tense marking to screen for language impairments in early elementary students. Supplemental Material https://doi.org/10.23641/asha.8285786.

Risk for Speech and Language Impairments in Preschool Age HIV-exposed Uninfected Children With In Utero Combination Antiretroviral Exposure.

BACKGROUND: Perinatally HIV-exposed but uninfected (HEU) children have elevated risk of late language emergence at 1 year of age, with possible links to in utero antiretroviral (ARV) exposure. We investigated possible risks for speech impairments (SIs) and language impairments (LI) in preschool monolingual HEU children in the United States. METHODS: Speech and language assessments were conducted as part of the Pediatric HIV/AIDS Cohort Study Surveillance Monitoring of ART Toxicities study at ages 3 (N = 208) and 5 (N = 429) years. Domains of speech, overall language, vocabulary and grammar were assessed. SI and LI were defined by standardized scores <15th percentile and categorized as primary (normal nonverbal IQ ≥ 85 without hearing loss) and concomitant (low nonverbal IQ and/or presence of hearing loss). Logistic regression models were used to estimate odds of SI and LI for different ARV exposures, adjusted for confounding variables. RESULTS: The risk for language impairments in HEU children was higher than population norms; risk for SIs was not elevated. Risk factors for impairments included male sex, black race and other socioeconomic measures, although these varied by age, primary (P) versus concomitant (C) impairment and by speech or language measure. Adjusted logistic regression models revealed lower and increased risk for specific ARVs. Tenofovir exposure was associated with increased risk for SI at 3 years of age but was associated with decreased risk for concomitant language impairment at 5 years of age. CONCLUSIONS: Further investigation of combination ARV exposure and speech/language impairment among preschool children is needed to confirm associations.