Preeclampsia, Fetal Growth Restriction, and 24-Month Neurodevelopment in Very Preterm Infants.

Importance: Preeclampsia has direct influences on a developing fetus and may impact postnatal health, and fetal growth restriction (FGR) is often seen co-occurring with preeclampsia. The development of children born very preterm after preeclampsia diagnosis with and without FGR is not well characterized. Objective: To examine the associations of preeclampsia and FGR with developmental and/or behavioral outcomes in a cohort of very preterm infants. Design, Setting, and Participants: In this cohort study, infants in the prospective Neonatal Neurobehavior and Outcomes in Very Preterm Infants study were enrolled between April 2014 and June 2016 from 9 US university-affiliated neonatal intensive care units (NICUs). Eligible infants were born before 30 weeks' gestation. Infants were excluded for any major congenital anomalies and for maternal age younger than 18 years or cognitive impairment impacting the ability to provide informed consent. Data analysis was performed from November 2023 to January 2024. Exposure: Maternal preeclampsia and FGR in very preterm infants. Main Outcomes and Measures: The Bayley-III cognition, motor, and language scores less than 85 (-1 SD) indicated developmental delay. Child Behavior Checklist/Preschool 1.5-5 T-scores greater than or equal to 64 for internalizing, externalizing, or total problems indicated clinical importance. Results: Of 704 infants enrolled, 529 (mean [SD] gestational age, 27.0 [1.9] weeks; 287 male [54.3%]) were studied at 24-month follow-up. A total of 94 infants' mothers had preeclampsia (23.2%), and 46 infants (8.7%) had FGR. In adjusted models, preeclampsia was not associated with Bayley-III (cognitive, B = 3.43 [95% CI, -0.19 to 6.66]; language, B = 3.92 [95% CI, 0.44 to 7.39]; motor, B = 1.86 [95% CI, -1.74 to 5.47]) or Child Behavior Checklist/Preschool 1.5-5 (internalizing, B = -0.08 [95% CI, -2.58 to 2.73]; externalizing, B = 0.69 [95% CI, -1.76 to 3.15]; total, B = 0.21 [95% CI, -2.48 to 2.91]) outcomes. FGR was associated with significantly lower Bayley-III scores (cognitive, B = -8.61 [95% CI, -13.33 to -3.89]; language, B = -8.29 [95% CI, -12.95 to -3.63]; motor, B = -7.60 [95% CI, -12.40 to -2.66]), regardless of preeclampsia status. Conclusions and Relevance: In this cohort study of preterm infants, preeclampsia was not associated with developmental and/or behavioral outcomes, but infants with FGR may be prone to developmental delays. These findings suggest future areas of research for understanding the roles of preeclampsia and FGR separately and together in early child development for preterm infants.

Corrigendum: Understanding profound autism: implications for stigma and supports.

[This corrects the article DOI: 10.3389/fpsyt.2024.1287096.].

Developmental characteristics and accuracy of autism screening among two-year-old toddlers in the ECHO program.

BACKGROUND: The Modified Checklist for Autism in Toddlers (M-CHAT) is a common pediatric screening tool with mixed accuracy findings. Prior evidence supports M-CHAT screening for developmental concerns, especially in toddlers born preterm. This study examined M-CHAT accuracy in a large, nationwide sample. METHODS: 3393 participants from the Environmental influences on Child Health Outcomes (ECHO) program were included. Harmonized M-CHAT (M-CHAT-H) results were compared with parent-reported autism diagnosis and autism-related characteristics to assess accuracy for term and preterm children, together and separately. Generalized estimating equations, clustering for ECHO cohort and controlling for demographic covariates, were used to examine associations between developmental and behavioral characteristics with M-CHAT-H accuracy. RESULTS: Sensitivity of the M-CHAT-H ranged from 36 to 60%; specificity ranged from 88 to 99%. Positive M-CHAT-H was associated with more developmental delays and behavior problems. Children with severe motor delays and more autism-related problems were more likely to have a false-negative M-CHAT-H. Children with fewer behavior problems and fewer autism-related concerns were more likely to have a false-positive screen. CONCLUSION: The M-CHAT-H accurately detects children at low risk for autism and children at increased risk with moderate accuracy. These findings support use of the M-CHAT-H in assessing autism risk and developmental and behavioral concerns in children. IMPACT: Previous literature regarding accuracy of the Modified Checklist for Autism in Toddlers (M-CHAT) is mixed but this study provides evidence that the M-CHAT performs well in detecting children at low risk for autism and consistently detects children with developmental delays and behavioral problems. The M-CHAT moderately detects children at increased risk for autism and remains a useful screening tool. This study examines M-CHAT accuracy in a large-scale, nationwide sample, examining associations between screening accuracy and developmental outcomes. These findings impact pediatric screening for autism, supporting continued use of the M-CHAT while further elucidating the factors associated with inaccurate screens.

Understanding profound autism: implications for stigma and supports.

Introduction: Societal perceptions and lack of understanding of autism spectrum disorder can be stigmatizing for autistic individuals and their families. This may be particularly the case for individuals who meet criteria for profound autism. Despite the considerable service needs of this marginalized group, there is little data on the prevalence of profound autism, nor on the experiences of those with profound autism and their families. Methods: The current study leveraged a mixed-methods approach to address these gaps. First, the prevalence of profound autism was examined in six samples-three from the United States and three from Western Europe. Second, inductive thematic analysis was used to code interviews from 20 caregivers of profoundly autistic adults. Results: The prevalence of profound autism varied widely across the six samples-from 11% to 48%. There were also notable differences between samples in prevalence by gender, race, and ethnicity. Two overarching themes were identified via inductive thematic analysis: Community Perceptions of Autism and Family Support Needs and Advocacy Challenges. Though caregivers were not directly asked about stigmatization during interviews, 85% of caregivers reported at least one instance of perceived stigma. Discussion: Future research should continue to examine the unique needs and stigmatization experiences of profoundly autistic individuals and their families across the life course.

Two-Year Autism Risk Screening and 3-Year Developmental Outcomes in Very Preterm Infants.

Importance: Use of the Modified Checklist for Autism in Toddlers, Revised With Follow-Up, a 2-stage parent-report autism risk screening tool, has been questioned due to reports of poor sensitivity and specificity. How this measure captures developmental delays for very preterm infants may provide support for continued use in pediatric care settings. Objective: To determine whether autism risk screening with the 2-stage parent-report autism risk screening tool at age 2 years is associated with behavioral and developmental outcomes at age 3 in very preterm infants. Design, Setting, and Participants: Neonatal Neurobehavior and Outcomes for Very Preterm Infants was a longitudinal, multisite cohort study. Enrollment occurred April 2014 to June 2016, and analyses were conducted from November 2022 to May 2023. Data were collected across 9 university-affiliated neonatal intensive care units (NICUs). Inclusion criteria were infants born less than 30 weeks' gestational age, a parent who could read and speak English and/or Spanish, and residence within 3 hours of the NICU and follow-up clinic. Exposures: Prematurity and use of the 2-stage parent-report autism risk screening tool at age 2 years. Main Outcomes and Measures: Outcomes include cognitive, language, motor composites on Bayley Scales for Infant and Toddler Development, third edition (Bayley-III) and internalizing, externalizing, total problems, and pervasive developmental disorder (PDD) subscale on the Child Behavior Checklist (CBCL) at age 3 years. Generalized estimating equations tested associations between the 2-stage parent-report autism risk screening tool and outcomes, adjusting for covariates. Results: A total of 467 children (mean [SD] gestational age, 27.1 [1.8] weeks; 243 male [52%]) were screened with the 2-stage parent-report autism risk screening tool at age 2 years, and outcome data at age 3 years were included in analyses. Mean (SD) maternal age at birth was 29 (6) years. A total of 51 children (10.9%) screened positive on the 2-stage parent-report autism risk screening tool at age 2 years. Children with positive screening results were more likely to have Bayley-III composites of 84 or less on cognitive (adjusted odds ratio [aOR], 4.03; 95% CI, 1.65-9.81), language (aOR, 5.38; 95% CI, 2.43-11.93), and motor (aOR, 4.74; 95% CI, 2.19-10.25) composites and more likely to have CBCL scores of 64 or higher on internalizing (aOR, 4.83; 95% CI, 1.88-12.44), externalizing (aOR, 2.69; 95% CI, 1.09-6.61), and PDD (aOR, 3.77; 95% CI, 1.72-8.28) scales. Conclusions and Relevance: Results suggest that the 2-stage parent-report autism risk screening tool administered at age 2 years was a meaningful screen for developmental delays in very preterm infants, with serious delays detected at age 3 years.

Neurobehavioral and Medical Correlates of Autism Screening: 2-Year Outcomes for Infants Born Very Preterm.

OBJECTIVE: To identify neonatal characteristics and 2-year neurodevelopmental outcomes associated with positive screening for risk of autism. STUDY DESIGN: Nine university-affiliated neonatal intensive care units (NICUs) enrolled infants born at <30 weeks of gestation. Infants underwent the NICU Network Neurobehavioral Scale examination before discharge and the Bayley Scales of Infant and Toddler Development, Third Edition, the Child Behavior Checklist, and the Modified Checklist for Autism in Toddlers, revised with follow-up (M-CHAT-R/F) at 2 years of corrected age. Generalized estimating equations examined associations between M-CHAT-R/F, neurobehavioral test results, and neonatal medical morbidities. RESULTS: At 2 years of corrected age, data were available for 466 of 744 enrolled infants without cerebral palsy. Infants with hypoaroused NICU Network Neurobehavioral Scale profiles were more likely to screen M-CHAT-R/F-positive (OR 2.76, 95% CI 1.38-5.54). Infants with ≥2 medical morbidities also were more likely to screen positive (OR 2.65, 95% CI 1.27-5.54). Children with positive M-CHAT-R/F scores had lower Bayley Scales of Infant and Toddler Development, Third Edition, Cognitive (t [451] = 5.43, P < .001, d = 0.82), Language (t [53.49] = 7.82, P < .001, d = 1.18), and Motor (t [451] = 7.98, P < .001, d = 1.21) composite scores and significantly greater Child Behavior Checklist Internalizing (t [457] -6.19, P < .001, d = -0.93) and Externalizing (t [57.87] = -5.62, P < .001, d = -0.84) scores. CONCLUSIONS: Positive M-CHAT-R/F screens at 2 years of corrected age were associated with neonatal medical morbidities and neurobehavioral examinations as well as toddler developmental and behavioral outcomes. These findings demonstrate the potential utility of the M-CHAT-R/F as a global developmental screener in infants born very preterm, regardless of whether there is a later autism diagnosis.

Prenatal and perinatal factors associated with neonatal neurobehavioral profiles in the ECHO Program.

BACKGROUND: Single-cohort studies have identified distinct neurobehavioral profiles that are associated with prenatal and neonatal factors based on the NICU Network Neurobehavioral Scale (NNNS). We examined socioeconomic, medical, and substance use variables as predictors of NNNS profiles in a multi-cohort study of preterm and term-born infants with different perinatal exposures. METHODS: We studied 1112 infants with a neonatal NNNS exam from the Environmental influences on Child Health Outcomes (ECHO) consortium. We used latent profile analysis to characterize infant neurobehavioral profiles and generalized estimating equations to determine predictors of NNNS profiles. RESULTS: Six distinct neonatal neurobehavioral profiles were identified, including two dysregulated profiles: a hypo-aroused profile (16%) characterized by lethargy, hypotonicity, and nonoptimal reflexes; and a hyper-aroused profile (6%) characterized by high arousal, excitability, and stress, with low regulation and poor movement quality. Infants in the hypo-aroused profile were more likely to be male, have younger mothers, and have mothers who were depressed prenatally. Infants in the hyper-aroused profile were more likely to be Hispanic/Latino and have mothers who were depressed or used tobacco prenatally. CONCLUSIONS: We identified two dysregulated neurobehavioral profiles with distinct perinatal antecedents. Further understanding of their etiology could inform targeted interventions to promote positive developmental outcomes. IMPACT: Prior research on predictors of neonatal neurobehavior have included single-cohort studies, which limits generalizability of findings. In a multi-cohort study of preterm and term-born infants, we found six distinct neonatal neurobehavioral profiles, with two profiles being identified as dysregulated. Hypo- and hyper-aroused neurobehavioral profiles had distinct perinatal antecedents. Understanding perinatal factors associated with dysregulated neurobehavior could help promote positive developmental outcomes.

Acoustic Cry Characteristics in Preterm Infants and Developmental and Behavioral Outcomes at 2 Years of Age.

Importance: Acoustic cry characteristics have been associated with severe medical problems in newborns. However, little is known about the utility of neonatal acoustic cry characteristics in the prediction of long-term outcomes of very preterm infants. Objectives: To evaluate whether acoustic characteristics of infant cry at neonatal intensive care unit (NICU) discharge are associated with behavioral and developmental outcomes at age 2 years in infants born very preterm. Design, Setting, and Participants: Infants born less than 30 weeks postmenstrual age (PMA) were enrolled from April 2014 through June 2016 as part of a multicenter (9 US university affiliated NICUs) cohort study and followed to adjusted age 2 years. Reported analyses began on September 2021. Data were analyzed from September 2021 to September 2022. Exposures: The primary exposure was premature birth (<30 weeks PMA). Main Outcomes and Measures: Cries were recorded during a neurobehavioral examination administered during the week of NICU discharge. Cry episodes were analyzed using a previously published computerized system to characterize cry acoustics. Year-2 outcomes included the Bayley-III Composite scores, Child Behavior Checklist (CBCL) and the Modified Checklist for Autism in Toddlers (M-CHAT R/F), dichotomized using clinically significant cutoffs (<85 on Bayley Language, Cognitive and/or Motor Composite scores, T-score >63 on the CBCL Internalizing, Externalizing and/or Total Problem Scales and total M-CHAT R/F score >2). Results: Analyzed infants (363 participants) were primarily male (202 participants [55.65%]) and had a mean [SD] gestational age of 27.08 [1.95] weeks). Cross-validated random forest models revealed that cry acoustics were associated with 2-year outcomes. Tests of diagnostic odds ratios (DOR) revealed that infants who exhibited total problem behavior CBCL scores greater than 63 at age 2 years were 3.3 times more likely (95% CI, 1.44-7.49) to be identified as so by random forest model estimates relative to other infants (scores ≤63); this association was robust to adjustment for family-wise type-I error rates and covariate measures. Similar associations were observed for internalizing (DOR, 2.39; 95% CI, 1.04-5.47) and externalizing (DOR, 2.25; 95% CI, 1.12-4.54) scores on the CBCL, clinically significant language (DOR, 1.71; 95% CI, 1.10-2.67) and cognitive (DOR, 1.70; 95% CI, 1.00-2.88) scores on the Bayley-III, and a positive autism screen on the M-CHAT (DOR, 1.91; 95% CI, 1.05-3.44). Conclusions and Relevance: In this cohort study of preterm infants, findings pointed to the potential use of acoustic cry characteristics in the early identification of risk for long-term developmental and behavioral deficits.

Moderators of Age of Diagnosis in > 20,000 Females with Autism in Two Large US Studies.

The objective of this study was to determine the clinical features that moderate a later age at ASD diagnosis in females in a large sample of females with ASD. Within two large and independent ASD datasets (> 20,000 females), females were first diagnosed with ASD 14-months later relative to males. This later age at diagnosis was moderated by a mild or atypical presentation, wherein repetitive behaviors were limited, IQ and language were broadly intact, and recognized symptoms emerged later in development. Females are at risk for a later age at ASD diagnosis and treatment implementation, and modification of early childhood ASD screening methods for females may be warranted.

Exploring communicative competence in autistic children who are minimally verbal: The Low Verbal Investigatory Survey for Autism (LVIS).

LAY ABSTRACT: Approximately one in three autistic children is unable to communicate with language; this state is often described as minimally verbal. Despite the tremendous clinical implications, we cannot predict whether a minimally verbal child is simply delayed (but will eventually develop spoken language) or will continue to struggle with verbal language, and might therefore benefit from learning an alternative form of communication. This is important for clinicians to know, to be able to choose the most helpful interventions, such as alternative forms of communication. In addition, the field lacks a standard definition of "minimally verbal." Even when we do agree on what the term means (e.g. fewer than 20 words), describing a child based on their lack of words does not tell us whether that child is communicating in other ways or how they are using those 20 words. To address these concerns, we developed the Low Verbal Investigatory Survey (LVIS), a one-page parent-report measure designed to help us characterize how minimally verbal autistic children are communicating. Parents of 147 children (aged 1-8 years) completed the LVIS. Here, we ask (1) whether the survey measures what it was designed to measure, that is, communicative ability in children without much spoken language, and (2) how the LVIS relates to cognitive and language ability, and symptoms of autism. Results suggest that this survey, which takes only 5 min to complete, is a good estimate of the child's communication skills. Furthermore, LVIS survey scores are correlated with other measures of language and cognitive abilities as well as autism symptomatology. The LVIS has the potential to save time and money in both clinical and research efforts to assess communication skills in minimally verbal autistic children.

Systematic Review: White Matter Microstructural Organization in Adolescents With Depression.

Objective: A growing body of literature has focused on the neural mechanisms of depression. Our goal was to conduct a systematic review on the white matter microstructural differences in adolescents with depressive disorders vs adolescents without depressive disorders. Method: We searched PubMed and PsycINFO for publications on August 3, 2022 (original search conducted in July 2021). The review was registered on PROSPERO (registration number: CRD42021268200), and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Eligible studies were original research papers comparing diffusion tensor/spectrum imaging findings in adolescents with vs without depression (originally ages 12-19 years, later expanded to 11-21 years). Studies were excluded if they focused on depression exclusively in the context of another condition, used only dimensional depressive symptom assessment(s), or used the same dataset as another included publication. Results: The search yielded 575 unique records, of which 14 full-text papers were included (824 adolescents with depression and 686 without depression). The following white matter regions showed significant differences in fractional anisotropy in at least 3 studies: uncinate fasciculus, cingulum, anterior corona radiata, inferior fronto-occipital fasciculus, and corpus callosum (genu and body). Most studies reported decreased, rather than increased, fractional anisotropy in adolescents with depression. Limitations include the possibility for selective reporting bias and risk of imprecision, given the small sample sizes in some studies. Conclusion: Our systematic review suggests aberrant white matter microstructure in limbic-cortical-striatal-thalamic circuits, and the corpus callosum, in adolescents with depression. Future research should focus on developmental trajectories in depression, identifying sources of heterogeneity and integrating findings across imaging modalities.

Sleep Problems and Autism Impairments in a Large Community Sample of Children and Adolescents.

Sleep problems are common in individuals with autism spectrum disorder (ASD). How sleep problems reflect specific ASD phenotypes is unclear. We studied whether sleep problems indexed functional impairment in a heterogeneous community sample of individuals with ASD. We analyzed 977 probands (233 females; age = 11.27 ± 4.13 years) from the Rhode Island Consortium for Autism Research and Treatment dataset, a unique public-private-academic collaboration involving all major points of service for families in Rhode Island. We found that individuals with a confirmed diagnosis of ASD were more likely to have sleep problems. However, across the whole sample and above and beyond a formal diagnosis, sleep problems were dimensionally associated with worse social impairment and poorer adaptive functioning. By using a large dataset reflective of the diversity of presentations in the community, this study underscores the importance of considering sleep problems in clinical practice to improve adaptive functioning in individuals with ASD.

Newborn Cry Acoustics in the Assessment of Neonatal Opioid Withdrawal Syndrome Using Machine Learning.

Importance: The assessment of opioid withdrawal in the neonate, or neonatal opioid withdrawal syndrome (NOWS), is problematic because current assessment methods are based on subjective observer ratings. Crying is a distinctive component of NOWS assessment tools and can be measured objectively using acoustic analysis. Objective: To evaluate the feasibility of using newborn cry acoustics (acoustics referring to the physical properties of sound) as an objective biobehavioral marker of NOWS. Design, Setting, and Participants: This prospective controlled cohort study assessed whether acoustic analysis of neonate cries could predict which infants would receive pharmacological treatment for NOWS. A total of 177 full-term neonates exposed and not exposed to opioids were recruited from Women & Infants Hospital of Rhode Island between August 8, 2016, and March 18, 2020. Cry recordings were processed for 118 neonates, and 65 neonates were included in the final analyses. Neonates exposed to opioids were monitored for signs of NOWS using the Finnegan Neonatal Abstinence Scoring Tool administered every 3 hours as part of a 5-day observation period during which audio was recorded continuously to capture crying. Crying of healthy neonates was recorded before hospital discharge during routine handling (eg, diaper changes). Exposures: The primary exposure was prenatal opioid exposure as determined by maternal receipt of medication-assisted treatment with methadone or buprenorphine. Main Outcomes and Measures: Neonates were stratified by prenatal opioid exposure and receipt of pharmacological treatment for NOWS before discharge from the hospital. In total, 775 hours of audio were collected and trimmed into 2.5 hours of usable cries, then acoustically analyzed (using 2 separate acoustic analyzers). Cross-validated supervised machine learning methods (combining the Boruta algorithm and a random forest classifier) were used to identify relevant acoustic parameters and predict pharmacological treatment for NOWS. Results: Final analyses included 65 neonates (mean [SD] gestational age at birth, 36.6 [1.1] weeks; 36 [55.4%] female; 50 [76.9%] White) with usable cry recordings. Of those, 19 neonates received pharmacological treatment for NOWS, 7 neonates were exposed to opioids but did not receive pharmacological treatment for NOWS, and 39 healthy neonates were not exposed to opioids. The mean of the predictions of random forest classifiers predicted receipt of pharmacological treatment for NOWS with high diagnostic accuracy (area under the curve, 0.90 [95% CI, 0.83-0.98]; accuracy, 0.85 [95% CI, 0.74-0.92]; sensitivity, 0.89 [95% CI, 0.67-0.99]; specificity, 0.83 [95% CI, 0.69-0.92]). Conclusions and Relevance: In this study, newborn acoustic cry analysis had potential as an objective measure of opioid withdrawal. These findings suggest that acoustic cry analysis using machine learning could improve the assessment, diagnosis, and management of NOWS and facilitate standardized care for these infants.

Cardiometabolic Pregnancy Complications in Association With Autism-Related Traits as Measured by the Social Responsiveness Scale in ECHO.

Prior work has examined associations between cardiometabolic pregnancy complications and autism spectrum disorder (ASD) but not how these complications may relate to social communication traits more broadly. We addressed this question within the Environmental Influences on Child Health Outcomes program, with 6,778 participants from 40 cohorts conducted from 1998-2021 with information on ASD-related traits via the Social Responsiveness Scale. Four metabolic pregnancy complications were examined individually, and combined, in association with Social Responsiveness Scale scores, using crude and adjusted linear regression as well as quantile regression analyses. We also examined associations stratified by ASD diagnosis, and potential mediation by preterm birth and low birth weight, and modification by child sex and enriched risk of ASD. Increases in ASD-related traits were associated with obesity (ß = 4.64, 95% confidence interval: 3.27, 6.01) and gestational diabetes (ß = 5.21, 95% confidence interval: 2.41, 8.02), specifically, but not with hypertension or preeclampsia. Results among children without ASD were similar to main analyses, but weaker among ASD cases. There was not strong evidence for mediation or modification. Results suggest that common cardiometabolic pregnancy complications may influence child ASD-related traits, not only above a diagnostic threshold relevant to ASD but also across the population.

Parental age and autism severity in the Rhode Island Consortium for Autism Research and Treatment (RI-CART) study.

Advanced parental age at offspring birth has been associated with autism spectrum disorder (ASD). The objective of the current study was to investigate associations between parental age at birth and autism severity. The Rhode Island Consortium for Autism Research and Treatment (RI-CART) study represents a community-based sample with a range of autism severity, including participants with and without ASD. This study involved participants (n = 1178) enrolled in RI-CART with available mother and father ages at birth. Primary data points included the age of mother and father at the participant's birth and results from the Autism Diagnostic Observation Schedule - Second Edition (ADOS-2). Mothers were 1.7 years older at the time of birth of the child with ASD, as compared to mothers of offspring without ASD. Fathers of children with ASD were 1.6 years older at the time of birth than fathers of children without ASD. The age of both parents at offspring birth displayed a positive, statistically significant association with overall ASD severity and the severity of restricted/repetitive behaviors. This finding was driven by the association between parental age and the severity of compulsions or rituals. Intelligence and adaptive functioning did not moderate the relationship between parental age and ASD severity. This study extends prior research to show that advanced parental age at birth is associated with the severity as well as the presence of ASD in offspring.

Testing the mid-range model: Attachment in a high risk sample.

Infant attachment is a key predictor of later socioemotional functioning, but it is not clear how parental responsivity to infant expressive behavior is associated with attachment outcomes. A mid-range model of responsivity holds that both unresponsive and highly reactive parental behaviors lead to insecure and disorganized attachment. We examined the relationship between maternal (and infant) contingent responsivity and attachment in a high-risk sample. Participants were 625 infant-mother pairs from a longitudinal study of children with and without prenatal drug exposure and variable levels of associated social risks. Infant-mother pairs participated in the Face-to-Face/Still-Face paradigm (FFSF) at 4-months and in the Strange Situation Procedure (SSP) at 18-months. A model incorporating both linear and quadratic responsivity effects indicated that mothers who were either very high (reactive) or very low (unresponsive) in responsivity were more likely to have infants with disorganized attachment outcomes. While maternal responsivity was associated with attachment disorganization, no associations between maternal responsivity, and attachment security/insecurity were detected. Infant responsivity to mother was not associated with attachment outcomes. The findings suggest the importance of mid-range levels of maternal responsivity in the development of organized attachment among infants facing high levels of prenatal and social risk.

Neurodevelopmental profiles of infants born <30 weeks gestation at 2 years of age.

BACKGROUND: Infants born <30 weeks postmenstrual age (PMA) are at increased risk for neurodevelopmental impairment by age 2. Prior studies report rates of impairment for individual outcomes separately. Our objective was to describe neurodevelopmental profiles of children born <30 weeks PMA, using cognitive, language, motor, and behavioral characteristics. METHODS: We studied 587 children from a multi-center study of infants born <30 weeks PMA. Age 2 outcomes included Bayley-III subscale scores, Child Behavior Checklist syndrome scores, diagnosis of cerebral palsy (CP), and positive screen for autism spectrum disorder (ASD) risk. We used latent profile analysis (LPA) to group children into mutually exclusive profiles. RESULTS: We found four discrete neurodevelopmental profiles indicating distinct combinations of developmental and behavioral outcomes. Two of the profiles included 72.7% of the sample with most having Bayley scores within the normal range. The other two profiles included the remaining 27.3% of the sample with most having Bayley scores outside of the normal range. Only one profile (11% of sample) was comprised of children with elevated behavioral problems. CONCLUSION: Child-centered analysis techniques could facilitate the development of targeted intervention strategies and provide caregivers and practitioners with an integrative understanding of child behavior. IMPACT: Most studies examining neurodevelopmental outcomes in very preterm children report rates of impairment for individual outcomes separately. Comprehensive, "child-centered" approaches that integrate across multiple domains can be used to identify subgroups of children who experience different types of neurodevelopmental impairments. We identified four discrete neurodevelopmental profiles indicating distinct combinations of developmental and behavioral outcomes in very preterm children at 24 months. "Child-centered" analysis techniques may provide clinically useful information and could facilitate the development of targeted intervention strategies for high-risk children.

Autism severity aggregates with family psychiatric history in a community-based autism sample.

The purpose of this study was to examine family psychiatric history in individuals with autism spectrum disorder (ASD) and its association with clinical presentation. Participants were 798 individuals with a clinical diagnosis of ASD, confirmed by the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), enrolled in Rhode Island Consortium for Autism Research and Treatment, a statewide research registry. Prior research suggests a specific behavioral phenotype in individuals with ASD who have family members with psychiatric diagnoses, including higher IQ and less severe language impairment. However, studies have not specifically investigated autism severity. We hypothesized that increased psychiatric family history would be associated with increased autism severity symptoms. Results show a strong association of increased burden of first-degree family psychiatric history with higher autism symptom severity as measured by Social Responsiveness Scale, Second Edition (SRS-2), but not with ADOS-2 severity scores, IQ, or adaptive functioning. These findings support the importance of investigating the contribution of psychiatric family history toward clinical ASD presentation. LAY SUMMARY: This study explored how family psychiatric history is related to clinical presentation of Autism Spectrum Disorder (ASD). Higher amounts of first-degree family psychiatric history was associated with higher autism symptom severity as measured by the Social Responsiveness Scale, Second Edition (SRS-2). The contribution of psychiatric family history requires ongoing investigation.

Epigenome-wide analysis identifies genes and pathways linked to acoustic cry variation in preterm infants.

BACKGROUND: Preterm birth places infants at higher risk of adverse long-term behavioral and cognitive outcomes. Combining biobehavioral measures and molecular biomarkers may improve tools to predict the risk of long-term developmental delays. METHODS: The Neonatal Neurobehavior and Outcomes in Very Preterm Infants study was conducted at nine neonatal intensive care units between April 2014 and June 2016. Cries were recorded and buccal swabs collected during the neurobehavioral exam. Cry episodes were extracted and analyzed using a computer system and the data were summarized using factor analysis. Genomic DNA was extracted from buccal swabs, quantified using the Qubit Fluorometer, and aliquoted into standardized concentrations. DNA methylation was measured with the Illumina MethylationEPIC BeadArray, and an epigenome-wide association study was performed using cry factors (n = 335). RESULTS: Eighteen CpGs were associated with the cry factors at genome-wide significance (α = 7.08E - 09). Two CpG sites, one intergenic and one linked to gene TCF3 (important for B and T lymphocyte development), were associated with acoustic measures of cry energy. Increased methylation of TCF3 was associated with a lower energy-related cry factor. We also found that pitch (F0) and hyperpitch (F0 > 1 kHz) were associated with DNA methylation variability at 16 CpG sites. CONCLUSIONS: Acoustic cry characteristics are related to variation in DNA methylation in preterm infants. IMPACT: Preterm birth is a major public health problem and its long-term impact on health is not well understood. Cry acoustics, related to prematurity, has been linked to a variety of medical conditions. Biobehavioral measures and molecular biomarkers can improve prediction tools for long-term developmental risks of preterm birth. Variation in epigenetic modulation in preterm infants provides a potential link between preterm birth and unfavorable developmental outcomes.