Spatial profiling of the placental chorioamniotic membranes reveals upregulation of immune checkpoint proteins during Group B infection in a nonhuman primate model.

Background: Preterm birth is a leading cause of neonatal mortality, which is often complicated by intrauterine infection and inflammation. We have established a nonhuman primate model of Group B (GBS, ) infection-associated preterm birth. Immune checkpoints are modulators of the immune response by activating or suppressing leukocyte function and are understudied in preterm birth.

Factors Influencing COVID-19 Vaccine Uptake among Spanish-Speaking Pregnant People.

The coronavirus disease 2019 (COVID-19) pandemic exposed the vulnerability of pregnant women to excess morbidity and mortality, as well as the disproportionate disease burden in certain racial, ethnic, and sociodemographic groups. Vaccine hesitancy represents a major threat to public health, and crafting messages that reach vulnerable groups and address their intersectionality remains a weakness for pandemic preparedness. We sought to investigate factors that influenced vaccine acceptance and social media ad response in a mixed-methods study of Spanish-speaking women living in the rural Western United States who were pregnant or recently pregnant between November 2022 and June 2023.

The prevalence and developmental course of auditory processing differences in autistic children.

Auditory processing differences, including hyper- or hyposensitivity to sound, aversions to sound, and difficulty listening under noisy, real-world conditions, are commonly reported in autistic individuals. However, the developmental course and functional impact of these auditory processing differences are unclear. In this study, we investigate the prevalence, developmental trajectory, and functional impact of auditory processing differences in autistic children throughout childhood using a longitudinal study design.

COVID-19 Vaccine Hesitancy among English-Speaking Pregnant Women Living in Rural Western United States.

This mixed-method study investigated vaccine hesitancy among pregnant women living in rural western United States and their response to social media ads promoting COVID-19 vaccine uptake. Thirty pregnant or recently pregnant participants who live in rural zip codes in Washington, Oregon, California, and Idaho were interviewed between November 2022 and March 2023. Interviews were transcribed and coded, while the ad ratings were analyzed using linear mixed models.

Impact of progesterone on innate immunity and cell death after influenza A virus H1N1 2009 infection of lung and placental cells in vitro.

The influenza A virus (IAV) 2009 H1N1 pandemic was associated with an increased risk of maternal mortality, preterm birth, and stillbirth. The underlying mechanism for severe maternal lung disease and stillbirth is incompletely understood, but IAV infection is known to activate innate immunity triggering the release of cytokines. Elucidating the impact of progesterone (P4), a key hormone elevated in pregnancy, on the innate immune and inflammatory response to IAV infection is a critical step in understanding the pathogenesis of adverse maternal-fetal outcomes.

Diminished antiviral innate immune gene expression in the placenta following a maternal SARS-CoV-2 infection.

Background: COVID-19 is caused by the SARS-CoV-2 virus and is associated with critical illness requiring hospitalization, maternal mortality, stillbirth, and preterm birth. SARS-CoV-2 has been shown to induce placental pathology. However, substantial gaps exist in our understanding of the pathophysiology of COVID-19 disease in pregnancy and the long-term impact of SARS-CoV-2 on the placenta and fetus.

Interaction of Treatment Intensity and Autism Severity on Frequency and Maturity of Spontaneous Communication in Toddlers with Autism Spectrum Disorder.

This study tested whether the effect of treatment intensity or treatment style on children's frequency and maturity of spontaneous communication varied by initial severity of disability. Eighty-seven toddlers with autism spectrum disorders were randomly assigned to either (a) 15 hrs per week of discrete trial teaching (DTT), (b) 25 hrs per week of DTT, (c) 15 hrs per week of a naturalistic developmental behavioral intervention (NDBI), or (d) 25 hrs per week of NDBI. Trained research staff implemented the 1:1 treatments in homes or educational centers over 12 months.

A Multisite Randomized Controlled Trial Comparing the Effects of Intervention Intensity and Intervention Style on Outcomes for Young Children With Autism.

Objective: This randomized, multisite, intent-to-treat study tested the effects of 2 levels of treatment intensity (number of hours) and 2 treatment styles on the progress of young children with autism spectrum disorder (ASD). We predicted that initial severity of developmental delay or autism symptoms would moderate the effects of intensity and style on progress in 4 domains: autism symptom severity, expressive communication, receptive language, and nonverbal ability.

Method: A total of 87 children with ASD, mean age 23.

Clinical characteristics of 46 pregnant women with a severe acute respiratory syndrome coronavirus 2 infection in Washington State.

Background: The impact of coronavirus disease 2019 on pregnant women is incompletely understood, but early data from case series suggest a variable course of illness from asymptomatic or mild disease to maternal death. It is unclear whether pregnant women manifest enhanced disease similar to influenza viral infection or whether specific risk factors might predispose to severe disease.

Objective: To describe maternal disease and obstetrical outcomes associated with coronavirus disease 2019 in pregnancy to rapidly inform clinical care.

A Broad Spectrum Chemokine Inhibitor Prevents Preterm Labor but Not Microbial Invasion of the Amniotic Cavity or Neonatal Morbidity in a Non-human Primate Model.

Leukocyte activation within the chorioamniotic membranes is strongly associated with inflammation and preterm labor (PTL). We hypothesized that prophylaxis with a broad-spectrum chemokine inhibitor (BSCI) would downregulate the inflammatory microenvironment induced by Group B Streptococcus (GBS, ) to suppress PTL and microbial invasion of the amniotic cavity (MIAC). To correlate BSCI administration with PTL and MIAC, we used a unique chronically catheterized non-human primate model of Group B Streptococcus (GBS)-induced PTL.

A Multisite Randomized Controlled Two-Phase Trial of the Early Start Denver Model Compared to Treatment as Usual.

Objective: This single-blind, randomized, multisite, intent-to-treat study was designed to replicate and extend Dawson et al.'s (Pediatrics. 2010;125: e17-e23) randomized controlled trial testing the effects of the Early Start Denver Model (ESDM), an intensive play- and routines-based intervention delivered in natural settings.

The Developmental Sequence and Relations Between Gesture and Spoken Language in Toddlers With Autism Spectrum Disorder.

In typical development, gestures precede and predict language development. This study examines the developmental sequence of expressive communication and relations between specific gestural and language milestones in toddlers with autism spectrum disorder (ASD), who demonstrate marked difficulty with gesture production and language. Communication skills across five stages (gestures, word approximations, first words, gesture-word combinations, and two-word combinations) were assessed monthly by blind raters for toddlers with ASD participating in an randomized control trial of parent-mediated treatment (N = 42, 12-30 months).

Cost Offset Associated With Early Start Denver Model for Children With Autism.

Objective: To determine the effect of the Early Start Denver Model (ESDM) for treatment of young children with autism on health care service use and costs.

Method: We used data from a randomized trial that tested the efficacy of the ESDM, which is based on developmental and applied behavioral analytic principles and delivered by trained therapists and parents, for 2 years. Parents were interviewed about their children's service use every 6 months from the onset of the intervention to follow-up (age 6 years).

The Relationship Between Early Neural Responses to Emotional Faces at Age 3 and Later Autism and Anxiety Symptoms in Adolescents with Autism.

Both autism spectrum (ASD) and anxiety disorders are associated with atypical neural and attentional responses to emotional faces, differing in affective face processing from typically developing peers. Within a longitudinal study of children with ASD (23 male, 3 female), we hypothesized that early ERPs to emotional faces would predict concurrent and later ASD and anxiety symptoms. Greater response amplitude to fearful faces corresponded to greater social communication difficulties at age 3, and less improvement by age 14.

Whole exome sequencing in extended families with autism spectrum disorder implicates four candidate genes.

Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders, characterized by impairment in communication and social interactions, and by repetitive behaviors. ASDs are highly heritable, and estimates of the number of risk loci range from hundreds to >1000. We considered 7 extended families (size 12-47 individuals), each with ≥3 individuals affected by ASD.

Transmission disequilibrium of small CNVs in simplex autism.

We searched for disruptive, genic rare copy-number variants (CNVs) among 411 families affected by sporadic autism spectrum disorder (ASD) from the Simons Simplex Collection by using available exome sequence data and CoNIFER (Copy Number Inference from Exome Reads). Compared to high-density SNP microarrays, our approach yielded ∼2× more smaller genic rare CNVs. We found that affected probands inherited more CNVs than did their siblings (453 versus 394, p = 0.

Atypical developmental patterns of brain chemistry in children with autism spectrum disorder.

Importance: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with symptoms emerging during early childhood. The pathophysiology underlying the disorder remains incompletely understood.

Objective: To examine cross-sectional and longitudinal patterns of brain chemical concentrations in children with ASD or idiopathic developmental delay (DD) from 3 different age points, beginning early in the clinical course.

Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.

Exome sequencing studies of autism spectrum disorders (ASDs) have identified many de novo mutations but few recurrently disrupted genes. We therefore developed a modified molecular inversion probe method enabling ultra-low-cost candidate gene resequencing in very large cohorts. To demonstrate the power of this approach, we captured and sequenced 44 candidate genes in 2446 ASD probands.

Individual common variants exert weak effects on the risk for autism spectrum disorders.

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk.

A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder.

Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants.

Evidence for broader autism phenotype characteristics in parents from multiple-incidence autism families.

The broader autism phenotype (BAP) was assessed in parents who have two or more children with autism spectrum disorder (ASD) (multiplex (MPX) autism), parents who have no more than one child with ASD (simplex autism), parents who have a child with developmental delay without ASD, and parents who have typically developing children. Clinicians, naive to parent group membership status, rated BAP characteristics from videotaped administration of the Broader Autism Phenotype Symptom Scale (BPASS). Differences among groups in BPASS scores in the four assessed domains (social motivation, conversational skills, expressiveness, and restricted interests) were examined using multivariate ANOVA and post hoc comparisons.

Genome-scan for IQ discrepancy in autism: evidence for loci on chromosomes 10 and 16.

Performance IQ (PIQ) greater than verbal IQ (VIQ) is often observed in studies of the cognitive abilities of autistic individuals. This characteristic is correlated with social and communication impairments, key parts of the autism diagnosis. We present the first genetic analyses of IQ discrepancy (PIQ-VIQ) as an autism-related phenotype.