Prenatal exposure to polycyclic aromatic hydrocarbons and executive functions at school age: Results from a combined cohort study.

BACKGROUND: Executive functions develop rapidly in childhood, enabling problem-solving, focused attention, and planning. Exposures to environmental toxicants in pregnancy may impair healthy executive function development in children. There is increasing concern regarding polycyclic aromatic hydrocarbons (PAHs) given their ability to transfer across the placenta and the fetal blood-brain barrier, yet evidence from epidemiological studies is limited. METHODS: We examined associations between prenatal PAH exposure and executive functions in 814 children of non-smoking mothers from two U.S. cohorts in the ECHO-PATHWAYS Consortium. Seven mono-hydroxylated PAH metabolites were measured in mid-pregnancy urine and analyzed individually and as mixtures. Three executive function domains were measured at age 8-9: cognitive flexibility, working memory, and inhibitory control. A composite score quantifying overall performance was further calculated. We fitted linear regressions adjusted for socio-demographics, maternal health behaviors, and psychological measures, and examined modification by child sex and stressful life events in pregnancy. Bayesian kernel machine regression was performed to estimate the interactive and overall effects of the PAH mixture. RESULTS: The results from primary analysis of linear regressions were generally null, and no modification by child sex or maternal stress was indicated. Mixture analyses suggested several pairwise interactions between individual PAH metabolites in varied directions on working memory, particularly interactions between 2/3/9-FLUO and other PAH metabolites, but no overall or individual effects were evident. CONCLUSION: We conducted a novel exploration of PAH-executive functions association in a large, combined sample from two cohorts. Although findings were predominantly null, the study carries important implications for future research and contributes to evolving science regarding developmental origins of diseases.

Book-Sharing for Toddlers with Clefts (BOOST): Protocol for a randomized controlled trial of a remote intervention to promote language development in children with cleft palate.

BACKGROUND: Children with cleft palate, with or without cleft lip (CP±L), exhibit language delays on average compared to children without clefts. Interventions to address these disparities are scarce. In this multi-center study, Book Sharing for Toddlers with Clefts (BOOST), we will test a remote, parent-focused intervention to promote language development in children with CP±L. OBJECTIVES: The study will test two primary hypotheses. First, toddlers randomized to BOOST will exhibit better language outcomes than children receiving standard-of-care (SOC). Second, we hypothesize that the BOOST program's effect on language outcomes is mediated by the frequency and quality of parent-child reading interactions. METHODS: The study is a randomized-controlled trial comparing the BOOST group to a SOC comparison group. We will enroll N = 320 English and/or Spanish-speaking children ages 24-32 months with isolated CP±L (n = 160 per group). Both groups will receive children's books, and parents will record and upload videos of themselves reading the books with their children using a smartphone app developed for the study. Parents will also complete surveys asking whether they read to their children on five randomly selected days each week. In addition, the BOOST group will participate in 3 remote dialogic book-sharing intervention sessions via Zoom. We will code book-sharing videos to assess parents' target skill usage and children's expressive language. End-of-study assessments will include measures of child language outcomes (e.g., clinician-administered measures, parent reports, and naturalistic child language samples). RESULTS: Enrollment began in April 2024 and will continue through approximately April 2028. CONCLUSION: The BOOST study will address a critical gap in the literature on interventions to improve language in children with CP±L. The results will inform the care for toddlers with oral clefts and have potential applications for other populations.

Cognitive Outcomes of Children With Sagittal Craniosynostosis Treated With Either Endoscopic or Open Calvarial Vault Surgery.

Importance: Several studies have reported a higher incidence of neurodevelopmental delays and cognitive deficits in patients with single-suture craniosynostosis; however, there are few studies examining the associations of repair type with cognitive outcomes. Objective: To measure differences in neuropsychological outcomes between school-age children who were treated for sagittal craniosynostosis and unaffected controls and explore differences in cognitive function among children with sagittal craniosynostosis who were previously treated with either endoscopic strip craniectomy or open calvarial vault surgery. Design, Setting, and Participants: This cohort study was performed between 2018 and 2022. Eligible participants included patients aged 5 to 17 years who had previously been seen as infants or toddlers (<3 years) at 1 of 3 surgical centers for craniosynostosis repair with either endoscopic surgery or open calvarial vault surgery. A separate cohort of unaffected controls were included for comparison. Data analysis was conducted from November 2023 to February 2024. Exposures: Open calvarial vault surgery or endoscopic repair for single-suture craniosynostosis. Main Outcomes and Measures: The primary outcome was the Differential Ability Scales-II (DAS-II) General Conceptual Ability (GCA) score, an index for overall intellectual ability. Secondary outcomes included DAS-II subscale scores (Verbal Ability, Nonverbal Reasoning, Spatial Ability, Working Memory, and Processing Speed), and Patient-Reported Outcomes Measurement Information System (PROMIS) cognitive function scores. Results: A total of 81 patients with sagittal craniosynostosis (59 male [73%]; 22 female [27%]) and 141 controls (81 male [57%]; 60 female [43%]) were included. Of the 81 participants with sagittal craniosynostosis, 46 underwent endoscopic repair and 35 underwent open repair. Median (range) age at time of follow-up assessment was 7.7 (5.0-14.8) years for children with sagittal craniosynostosis and median age at assessment was 8.5 (7.7-10.5) years for controls. After controlling for age at assessment, sex, and socioeconomic status, there was no statistically significant or clinically meaningful difference in GCA scores between children who underwent endoscopic repair (adjusted mean score, 100; 95% CI, 96-104) and open repair (adjusted mean score, 103; 95% CI, 98-108) (P > .99). We found no significant difference in PROMIS scores between repair types (median [range] for endoscopic repair 54 [31-68] vs median [range] for open repair 50 [32-63]; P = .14). When comparing the treatment groups with the unaffected controls, differences in subscale scores for GCA and working memory were observed but were within normal range. Conclusions and Relevance: In this cohort study, there were no statistically or clinically significant differences in cognitive outcomes among school-age children by and type of surgical procedure used to repair nonsyndromic sagittal craniosynostosis. These findings suggest primary care clinicians should be educated about different options for craniosynostosis surgery to ensure early referral of these patients so that all treatment options remain viable.

School-age anthropometric and patient-reported outcomes after open or endoscopic repair of sagittal craniosynostosis.

OBJECTIVE: Several studies have compared perioperative parameters and early postoperative morphology between endoscope-assisted strip craniectomy with orthotic therapy (endoscopic repair) and cranial vault remodeling (open repair). To extend these results, the authors evaluated school-age anthropometric outcomes after these techniques across three institutions. METHODS: School-aged children (age range 4-18 years) with previously corrected isolated sagittal craniosynostosis were enrolled. Upon inclusion, 3D photographs and patient-reported outcomes were obtained, and the cephalic index and head circumference z-scores were calculated. Analyses of covariance models controlling for baseline differences and a priori covariates were performed. RESULTS: Eighty-one participants (median [range] age 7 [4-15] years) were included. The mean (95% CI) school-age cephalic index was significantly higher in the endoscopic cohort, though within the normal range for both groups (endoscopic 78% [77%-79%] vs open 76% [74%-77%], p = 0.027). The mean change in the cephalic index from preoperation to school age was significantly greater in the endoscopic group (9% [7%-11%] vs open 3% [1%-5%], p < 0.001). Compared to preoperative measurements, mean school-age head circumference z-scores decreased significantly more in the open cohort (-1.6 [-2.2 to -1.0] vs endoscopic -0.3 [-0.8 to -0.2], p = 0.002). Patient-reported levels of stigma were within the normal limits for both groups. CONCLUSIONS: Endoscopic and open repair techniques effectively normalize school-age anthropometric outcomes. However, endoscopic repair produces a clinically meaningful and significantly greater improvement in the school-age cephalic index, with maintenance of head growth. These findings demonstrate the importance of early referral by pediatricians and inform treatment decisions.

Greater Gestational Vitamin D Status is Associated with Reduced Childhood Behavioral Problems in the Environmental Influences on Child Health Outcomes Program.

BACKGROUND: Vitamin D deficiency is common in pregnancy. Vitamin D plays an important role in the developing brain, and deficiency may impair childhood behavioral development. OBJECTIVES: This study examined the relationship between gestational 25(OH)D concentrations and childhood behavior in the Environmental influences on Child Health Outcomes (ECHO) Program. METHODS: Mother-child dyads from ECHO cohorts with data available on prenatal (first trimester through delivery) or cord blood 25(OH)D and childhood behavioral outcomes were included. Behavior was assessed using the Strengths and Difficulties Questionnaire or the Child Behavior Checklist, and data were harmonized using a crosswalk conversion. Linear mixed-effects models examined associations of 25(OH)D with total, internalizing, and externalizing problem scores while adjusting for important confounders, including age, sex, and socioeconomic and lifestyle factors. The effect modification by maternal race was also assessed. RESULTS: Early (1.5-5 y) and middle childhood (6-13 y) outcomes were examined in 1688 and 1480 dyads, respectively. Approximately 45% were vitamin D deficient [25(OH)D < 20 ng/mL], with Black women overrepresented in this group. In fully adjusted models, 25(OH)D concentrations in prenatal or cord blood were negatively associated with externalizing behavior T-scores in middle childhood [-0.73 (95% CI: -1.36, -0.10) per 10 ng/mL increase in gestational 25(OH)D]. We found no evidence of effect modification by race. In a sensitivity analysis restricted to those with 25(OH)D assessed in prenatal maternal samples, 25(OH)D was negatively associated with externalizing and total behavioral problems in early childhood. CONCLUSIONS: This study confirmed a high prevalence of vitamin D deficiency in pregnancy, particularly among Black women, and revealed evidence of an association between lower gestational 25(OH)D and childhood behavioral problems. Associations were more apparent in analyses restricted to prenatal rather than cord blood samples. Interventions to correct vitamin D deficiency during pregnancy should be explored as a strategy to improve childhood behavioral outcomes.

A Multi-Cohort Examination of the Independent Contributions of Maternal Childhood Adversity and Pregnancy Stressors to the Prediction of Children's Anxiety and Depression.

Women's social experiences can have long-term implications for their offspring's health, but little is known about the potential independent contributions of multiple periods of stress exposures over time. This study examined associations of maternal exposure to adversity in childhood and pregnancy with children's anxiety and depression symptoms in a large, sociodemographically diverse sample. Participants were 1389 mother-child dyads (child age M = 8.83 years; SD = 0.66; 42% Black, 42% White; 6% Hispanic) in the ECHO-PATHWAYS Consortium's three U.S. pregnancy cohorts. Women reported their exposure to childhood traumatic events (CTE) and pregnancy stressful life events (PSLE). Children self-reported on their symptoms of anxiety and depression at age 8-9 years. Regression analyses estimated associations between maternal stressors and children's internalizing problems, adjusting for confounders, and examined child sex as a modifier. Exploratory interaction analyses examined whether geospatially-linked postnatal neighborhood quality buffered effects. In adjusted models, PSLE counts positively predicted levels of children's anxiety and depression symptoms ([ßAnxiety=0.08, 95%CI [0.02, 0.13]; ßDepression=0.09, 95%CI [0.03, 0.14]); no significant associations were observed with CTE. Each additional PSLE increased odds of clinically significant anxiety symptoms by 9% (95%CI [0.02, 0.17]). Neither sex nor neighborhood quality moderated relations. Maternal stressors during pregnancy appear to have associations with middle childhood anxiety and depression across diverse sociodemographic contexts, whereas maternal history of childhood adversity may not. Effects appear comparable for boys and girls. Policies and programs addressing prevention of childhood internalizing symptoms may benefit from considering prenatal origins and the potential two-generation impact of pregnancy stress prevention and intervention.

Prenatal bisphenol A exposure in relation to behavioral outcomes in girls aged 4-5 and modification by socio-demographic factors in The Infant Development and Environment Study (TIDES).

Bisphenol A (BPA) is a polymer used in the production of polycarbonate plastics and epoxy resins. An estrogen mimic, prenatal BPA exposure has been associated with several behavioral outcomes in children; however, the impact of maternal demographic and economic factors on associations between BPA and child behavioral outcomes have not been examined. The objective of this study was to examine associations between prenatal maternal urinary BPA and behavior in 4-5 year old girls, and to assess whether socio-demographic factors modify this relationship. Mothers enrolled in The Infant Development and Environment Study (TIDES) provided a single spot urine at enrollment (median gestational age 11 weeks) and completed the Behavior Assessment System for Children-2 (BASC-2) and Social Responsiveness Scale-2 (SRS-2) when their daughters were 4-5 years of age. Mother-daughter pairs with complete phthalate, BASC-2, SRS-2, and covariate data were included in this analysis (N = 244). BPA was detectable in 93 % of urine samples. We used multivariable linear regression analyses to estimate associations between maternal urinary log10-transformed BPA concentration and BASC-2 subscale and composite scores and SRS-2 Total Score. To examine the role of socioeconomic and demographic factors associated with study site, we stratified by TIDES center, comparing those enrolled at University of Rochester Medical Center (URMC), a predominately lower socioeconomic population, and those enrolled elsewhere: University of Washington, University of Minnesota, and University of California San Francisco, whose populations share similar higher socioeconomic demographic characteristics. Across all centers, no associations were seen between BPA and BASC-2 or SRS-2 scores. When stratifying by center, BPA was significantly associated with greater social impairment as measured by the SRS-2 Total Score (ß-coefficient [95 % confidence intervals]: 5.1 [1.0, 9.2]) in URMC participants (N = 61). In non-URMC participants (N = 183), BPA was significantly associated with lower BASC-2 Internalizing composite (-3.3 [-6.7, 0.0]) and Depression subscale scores (-3.4 [-6.7, 0.0]) while no associations were seen between BPA and SRS-2 scores. Our findings suggest that sociodemographic factors may modify the impacts of maternal prenatal BPA on developmental endpoints.

Community participation in youth with craniofacial microsomia.

PURPOSE: To examine differences in community participation and environmental support for youth with and without craniofacial microsomia. METHODS: This study involved secondary analyses of a subset of data (n = 396) from a longitudinal cohort study. Multiple linear and Poisson regression analyses and Wilcoxon Mann-Whitney tests were used to estimate differences in community participation and environmental support between youth with craniofacial microsomia and youth without craniofacial microsomia, stratified based on their history of education and health-related service use. Chi-square analyses were used to explore item-level group differences in change desired across community activities. RESULTS: Statistically significant differences were found in community participation frequency (ES = -0.52; p < 0.001), level of involvement (r = -0.16; p = 0.010), and desire for change in participation when comparing youth with craniofacial microsomia and non-affected peers not receiving services (p < 0.001). There were no statistically significant differences between youth with craniofacial microsomia and non-affected peers receiving services. CONCLUSIONS: Results suggest lower community participation in youth with craniofacial microsomia as compared to non-affected peers not receiving services. This may suggest opportunities for designing and testing interventions to promote community participation among youth with craniofacial microsomia, so as to support their transition to adulthood.Implications for rehabilitationYouth with craniofacial microsomia may have unmet rehabilitation needs related to their community participation.Rehabilitation professionals should pay attention to participation of youth with craniofacial microsomia in activities that place a higher demand on involvement with others.Rehabilitation professionals should appraise participation frequency and involvement of youths with craniofacial microsomia to gain accurate insight into their current community participation.

Behavioral and Social Functioning of Children With and Without Positional Plagiocephaly: Late Infancy to School Age.

Positional plagiocephaly and/or brachycephaly (PPB) is associated with cognition, motor, and other developmental outcomes, but little is known about the social-behavioral adjustment of children with PPB. The primary aim of this study was to compare the social-behavioral development of preschool and school-age children with and without PPB and to examine the potential moderating effects of PPB severity on group differences.Two hundred twenty children with a history of PPB and 164 controls participated in at least one behavioral assessment at 4-11 months, 18 months, 36 months, and 7 years. The frequencies of observed problem behaviors and social competence were estimated using the Child Behavior Checklist Ages 1.5-5 (CBCL/1.5-5), Caregiver-Teacher Report Form(C-TRF), CBCL/6-18, and Teacher Report Form.Children with PPB were similar to controls on the internalizing, externalizing, or total problems composites. At 7 years, CBCL/6-18 total competence scores were significantly lower in children with histories of PPB than controls. In analyses stratified by PPB severity, we found that children with moderate/severe PPB had slightly higher scores on the C-TRF internalizing scale at 36 months and lower total competence scores at age 7 years. Children who had a history of mild PPB were similar to controls on all outcomes.This study is the first to examine social and behavioral outcomes in a large cohort of children with and without a history of PPB. We found limited evidence of an association between PPB and parent and teacher-reported social-emotional and behavioral adjustment through early school-age.

Prediction of school-age IQ, academic achievement, and motor skills in children with positional plagiocephaly.

INTRODUCTION: Children with positional plagiocephaly and/or brachycephaly (PPB) are at risk of early developmental delay, but little is known about early life factors associated with school-age neurodevelopment. This study examined associations of demographic characteristics, prenatal risk factors and early neurodevelopment assessment with school-age IQ, academic performance, and motor development in children with PPB. METHODS: The study sample consisted of 235 school-age children with PPB followed since infancy. Outcome measures included IQ using the Differential Ability Scales-Second Edition, academic achievement as measured by the Wechsler Individualized Achievement Tests-Third Edition), and motor function using the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition. Linear regression was used to examine the incremental improvement of model fit of demographics, prenatal and early life characteristics, severity of PPB, and neurodevelopment at ages 7, 18, and 36 months as measured by the Bayley-3 on school-age scores. RESULTS: Mean age at school-age assessment was 9.0 years. Adjusted r2 for demographic, prenatal, and early life risk factors ranged from 0.10 to 0.22. Addition of PPB severity and Bayley-3 measures at ages 7 and 18 months did not meaningfully change model fit. Adjusted r2 after inclusion of Bayley-3 at 36 months ranged from 0.35 to 0.41. CONCLUSION: This study suggests that PPB severity and very early life neurodevelopment have little association with school-age neurodevelopment above and beyond demographic and early life risk factors. However, preschool-age neurodevelopmental assessment may still be useful in identifying children with PPB at risk for delay and who may benefit from early intervention.

Home Language Environment of Children With Orofacial Clefts as a Target for Intervention.

OBJECTIVE: To evaluate the home language environment (HLE) in children with orofacial clefts as a potential modifiable target for language and literacy intervention. DESIGN: Feasibility study examining longitudinal trends in HLE and responses to parent-focused literacy intervention. SETTING: Tertiary care children's hospital. PARTICIPANTS: HLE data were collected for 38 children with orofacial clefts between ages 7 and 23 months. Twenty-seven participants received parent-focused literacy intervention. INTERVENTIONS: Reach Out and Read, a literacy intervention, was introduced during a clinic visit. To assess response, participants were randomized to age at intervention (9, 18, or 24 months). MAIN OUTCOME MEASURES: Primary outcome measures included measurements from recordings in the home language environment of adult word count, child vocalizations, and conversational turns. RESULTS: Baseline (preintervention) results showed lower adult word count and conversational turns for caregivers and children with cleft lip and palate, as well as for those from lower socioeconomic groups. After the literacy intervention was introduced, this cohort showed increasing measures of child and caregiver vocalizations, particularly when introduced at 18 months. CONCLUSIONS: Although these results are preliminary, findings suggest that HLE characteristics vary as a function of children's cleft type as well as family socioeconomic status. Further, our caregiver-focused literacy intervention was feasible and resulted in short-term improvements in HLE. This is the first study to document HLE as a target for intervention in children with oral clefts. These findings support further research on HLE and caregiver-focused intervention to improve language/literacy outcomes for children with oral clefts.

Caregiver Perspectives on School Participation Among Students With Craniofacial Microsomia.

IMPORTANCE: Knowledge of unmet school participation needs for students with craniofacial microsomia (CFM) can inform decisions regarding intervention support. OBJECTIVE: To compare students with and without CFM on school participation (i.e., frequency, involvement, desire for participation to change) and caregivers' perceptions of environmental support for participation in occupations. DESIGN: Cross-sectional design using secondary analyses of a subset of data. SETTING: Multisite cohort study. PARTICIPANTS: Caregivers of students with CFM (n = 120) and of students without CFM (n = 315), stratified by history of education- and health-related service use. OUTCOMES AND MEASURES: School participation and environmental support, obtained with the Participation and Environment Measure-Children and Youth. RESULTS: Significant group differences were found in frequency of school participation (effect size [ES] = -0.38, 95% confidence interval [-0.64, -0.12], p = .005), level of involvement (ES = -0.14, p = .029), and desired change (p = .001), with students with CFM exhibiting greater participation restriction than students without CFM and no history of service use. No statistically significant group differences were found in environmental support for participation in the school setting. Item-level findings showed statistically significant higher desire for participation to change in three of five school occupations (odds ratio = 1.77-2.39, p = .003-.045) for students with CFM compared with students without CFM and no history of service use. CONCLUSIONS AND RELEVANCE: The results suggest that students with CFM experience restriction in participation at school. WHAT THIS ARTICLE ADDS: Students with CFM may benefit from targeted school-based interventions to optimize their inclusion.

Phthalate mixtures in pregnancy, autistic traits, and adverse childhood behavioral outcomes.

BACKGROUND: Prenatal exposure to multiple phthalates is ubiquitous, and yet few studies have evaluated these exposures as a mixture in relation to child autistic traits and behavioral problems. OBJECTIVES: To assess cumulative associations between prenatal phthalate mixtures and child behaviors, including effect modification by exposure timing and child sex. METHODS: Analyses included 501 mother/child pairs from the multicenter pregnancy cohort The Infant Development and Environment Study (TIDES). Nine maternal urinary phthalate metabolites were measured in early and late pregnancy, and behavior was assessed at ages 4-5 years using composite T scores for the Behavioral Assessment System for Children (BASC-2), which measures several dimensions of child behavior, and the Social Responsiveness Scale (SRS-2), which measures social impairment consistent with autistic traits. We utilized weighted quantile sum (WQS) regressions to examine pregnancy period-specific associations between phthalate mixtures and behavioral outcomes. Full-sample 95% WQS confidence intervals are known to be anti-conservative, so we calculated a confirmatory p-value using a permutation test. Effect modification by sex was examined with stratified analyses. RESULTS: A one-quintile increase in the early pregnancy phthalate mixture was associated with increased SRS-2 total score (coefficient = 1.0, confirmatory p = 0.01) and worse adaptive skills (coefficient = -1.0, confirmatory p = 0.06) in both sexes. In sex-stratified analyses, the early pregnancy phthalate mixture was associated with increased SRS-2 total score in boys (coefficient = 1.2, confirmatory p = 0.04) and girls (coefficient = 1.0, confirmatory p = 0.10) and worse BASC-2 adaptive skills score in girls (coefficient = -1.5, confirmatory p = 0.06), while the late pregnancy phthalate mixture was associated with increased BASC-2 externalizing score in boys (coefficient = 1.3, confirmatory p = 0.03). CONCLUSION: Our results suggest cumulative adverse associations between prenatal phthalate mixtures and multiple facets of childhood behavior.

Do Infant Motor Skills Mediate the Association Between Positional Plagiocephaly/Brachycephaly and Cognition in School-Aged Children?

OBJECTIVE: Positional plagiocephaly/brachycephaly (PPB) is associated with lower cognitive scores in school-aged children. This study tested the hypothesis that infant motor skills mediate this association. METHODS: Children with a history of PPB (cases, n = 187) and without PPB (controls, n = 149) were followed from infancy through approximately 9 years of age. Infant motor skills were assessed using the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-3), and cognition was assessed using the Differential Ability Scales, 2nd edition (DAS-2). The Bayley-3 motor composite was examined as a mediator of the association between PPB and DAS-2 general cognitive ability (GCA) scores. In secondary analyses, mediation models were examined for the DAS-2 verbal ability, nonverbal ability, and working memory scores; models using the Bayley-3 fine versus gross motor scores also were examined. RESULTS: Cases scored lower than controls on the DAS-GCA (ß = -4.6; 95% CI = -7.2 to -2.0), with an indirect (mediated) effect of ß = -1.5 (95% CI = -2.6 to -0.4) and direct effect of ß = -3.1 (95% CI = -5.7 to -0.5). Infant motor skills accounted for approximately 33% of the case-control difference in DAS-2 GCA scores. Results were similar for other DAS-2 outcomes. Evidence of mediation was greater for Bayley-3 gross motor versus fine motor scores. CONCLUSION: Infant motor skills partially mediate the association between PPB and cognition in school-aged children. Monitoring motor development and providing intervention as needed may help offset associated developmental concerns for children with PPB. IMPACT: To our knowledge, this study is the first longitudinal investigation of the development of children with and without PPB from infancy through the early school years and the first to examine motor skills as a mediator of cognitive outcomes in this population. The findings highlight the importance of early motor skills for other developmental outcomes. LAY SUMMARY: Infants' motor skills are related to the development of PPB and its association with later cognition. If your child has PPB, physical therapists may have an important role in assessing and providing treatment to promote motor development.

Cognitive, Motor, and Language Development of Preschool Children With Craniofacial Microsomia.

OBJECTIVE: To examine neurodevelopment in preschool-aged children with craniofacial microsomia (CFM) relative to unaffected peers. DESIGN: Multisite, longitudinal cohort study. SETTING: Tertiary care centers in the United States. PARTICIPANTS: We included 92 children with CFM ("cases") through craniofacial centers and clinics. Seventy-six children without CFM (controls) were included from pediatric practices and community advertisements. This study reports on outcomes assessed when participants were an average age of 38.4 months (SD = 1.9). MAIN OUTCOME MEASURES: We assessed cognitive and motor skills using the Bayley Scales of Infant and Toddler Development, third edition (Bayley-III), and language function using subtests from the Clinical Evaluation of Language Fundamentals-Preschool, second edition (CELF-P2). RESULTS: Case-control differences were negligible for Bayley-III cognitive (effect sizes [ES] = -0.06, P = .72) and motor outcomes (ES = -0.19, P = .25). Cases scored lower than controls on most scales of the CELF-P2 (ES = -0.58 to -0.20, P = .01 to .26). Frequency counts for "developmental delay" (ie, one or more scores > 1 SD below the normative mean) were higher for cases (39%) than controls (15%); however, the adjusted odds ratio = 1.73 (P = 0.21) was not significant. Case-control differences were most evident in children with microtia or other combinations of CFM-related facial features. CONCLUSIONS: Cognitive and motor scores were similar for preschool-aged children with and without CFM. However, children with CFM scored lower than controls on language measures. We recommend early monitoring of language to identify preschoolers with CFM who could benefit from intervention.

Behavioral Adjustment of Preschool Children With and Without Craniofacial Microsomia.

OBJECTIVE: The study aim was to assess behavioral adjustment in preschool children with and without craniofacial microsomia (CFM). DESIGN: Multisite cohort study of preschoolers with CFM ("cases") or without CFM ("controls"). PARTICIPANTS: Mothers (89%), fathers (9%), and other caregivers (2%) of 161 preschoolers. OUTCOME MEASURE: Child Behavior Check List (CBCL 1.5-5); linear regressions with standardized effect sizes (ES) adjusted for sociodemographic confounds. RESULTS: Child Behavior Check Lists for 89 cases and 72 controls (average age 38.3 ± 1.9 months). Children were male (54%), white (69%), and of Latino ethnicity (47%). Cases had microtia with mandibular hypoplasia (52%), microtia only (30%), or other CFM-associated features (18%). Nearly 20% of cases had extracranial anomalies. Composite CBCL scores were in the average range compared to test norms and similar for cases and controls. On the subscales, cases' parents reported higher Anxious/Depressed scores (ES = 0.35, P = .04), Stress Problems (ES = 0.40, P = .04), Anxiety Problems (ES = 0.34, P = .04), and Autism Spectrum Problems (ES = 0.41, P = .02); however, the autism subscale primarily reflected speech concerns. Among cases, more problems were reported for children with extracranial anomalies and certain phenotypic categories with small ES. CONCLUSIONS: Behavioral adjustment of preschoolers with CFM was comparable to peers. However, parental reports reflected greater concern for internalizing behaviors; thus, anxiety screening and interventions may benefit children with CFM. Among cases, more problems were reported for those with more complex presentations of CFM. Craniofacial microsomia-related speech problems should be distinguished from associated psychosocial symptoms during developmental evaluations.

Motor Function in School-Aged Children With Positional Plagiocephaly or Brachycephaly.

OBJECTIVE: To determine whether children with a history of positional plagiocephaly/brachycephaly (PPB) show persistent deficits in motor development. METHODS: In a longitudinal cohort study, we completed follow-up assessments with 187 school-aged children with PPB and 149 participants without PPB who were originally enrolled in infancy. Primary outcomes were the Bruininks-Oseretsky Test of Motor Proficiency-Second Edition (BOT-2) composite scores. RESULTS: Children with PPB scored lower than controls on the BOT-2. Stratified analyses indicated that differences were restricted to children who had moderate-severe PPB. No consistent differences were observed in children who had mild PPB. CONCLUSION: Children who had moderate-severe PPB in infancy show persistent differences in motor function. We suggest close developmental monitoring and early intervention to address motor deficits.

Prenatal sex hormones and behavioral outcomes in children.

Abnormal sex hormone levels in utero have been associated with child behavioral problems, but it is unclear if normal variation in prenatal sex hormones is associated with subsequent behavior in childhood. We assessed maternal sex hormones, including serum estrone (E1), estradiol (E2), estriol (E3), free testosterone (FT), and total testosterone (TT), during early pregnancy (gestational week 6-21 (mean = 11.1)) and evaluated child behavior at ages 4-5 using the Behavioral Assessment System for Children (BASC-2) and Social Responsiveness Scale (SRS-2) in 404 mother/child pairs (211 girls, 193 boys) within The Infant Development and Environment Study, a multi-site pregnancy cohort study. Associations between hormones and composite scores were evaluated using multiple linear regressions in both sexes combined, and separate models assessed effect modification by sex with the addition of interaction terms. A 10-fold increase in maternal FT or TT was associated in both sexes with a 4.3-point (95 % CI: 0.5, 8.2) or 4.4-point (0.8, 8.0) higher BASC-2 internalizing composite T score, respectively. In addition, a 10-fold increase in FT or TT was associated with a 3.8-point (0.04, 7.5) or 4.0-point (0.5, 7.5) higher behavioral symptoms index composite score. In models evaluating effect modification by sex, a 10-fold increase in E1 was associated with a 4.3-point (1.2, 7.4) decrease in adaptive skills composite score in girls only (interaction p = 0.04). We observed associations between testosterone and internalizing behaviors and behavioral symptoms index in both sexes, as well as a female-specific association between E1 and adaptive skills. Sex hormones during pregnancy may play a key role in influencing later-life behavior, and additional studies should further examine different periods of susceptibility to hormonal signals.

Maternal acetaminophen use during pregnancy and childhood behavioural problems: Discrepancies between mother- and teacher-reported outcomes.

BACKGROUND: Maternal acetaminophen use during pregnancy is common and has been associated with childhood behavioural problems among offspring, specifically hyperactivity and conduct problems. OBJECTIVE: Assessments of child behaviour in many previous studies have relied on maternal or parent report. Acknowledging that results of behavioural assessments vary between informants, we examined the association between maternal acetaminophen use during pregnancy and behaviour problems in childhood based on mother- and teacher-report. METHODS: A longitudinal study of 560 mother-child pairs with data on illnesses and medication use during pregnancy and neurodevelopmental assessments during childhood was conducted. Acetaminophen use during pregnancy was captured using a standardised maternal interview, completed 1 year after delivery on average. Measures of childhood (6-12 years of age) behaviour were obtained via mother- and teacher-report, using the Child Behaviour Checklist and Teacher Report Form. Linear and log-binomial models were used to calculate adjusted mean differences (MD) and risk ratios (RR), respectively and 95% confidence intervals (CI) for internalising, externalising, and total behaviour problems comparing acetaminophen users to non-users. Stabilized inverse probability weights were used to account for loss to follow-up, and adjustments for indication were made. RESULTS: Approximately 60% (n = 354) of women reported use of acetaminophen during pregnancy. Acetaminophen use during pregnancy was associated with an increase in total behaviour problem score and risk of clinical behaviour problems according to mother report (MD 2.2, 95% CI 0.3, 4.1 and RR 1.93, 95% CI 0.99, 3.76) but not according to teacher report. Weighting to account for participation did not alter results, while adjustment for indications of acetaminophen use greatly attenuated the associations with mother-reported total behaviour problem score and risk of clinical behaviour problems (MD 0.1, 95% CI -2.1, 2.3 and RR 1.31, 95% CI 0.67, 2.58). CONCLUSIONS: Acetaminophen use during pregnancy was weakly associated with mother-reported behaviour problems and not associated with teacher-reported problems.