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.

Methods and Challenges in a Cohort Study of Infants and Toddlers With Craniofacial Microsomia: The Clock Study.

OBJECTIVE: The Craniofacial microsomia: Longitudinal Outcomes in Children pre-Kindergarten (CLOCK) study is a longitudinal cohort study of neurobehavioral outcomes in infants and toddlers with craniofacial microsomia (CFM). In this article, we review the data collection and methods used to characterize this complex condition and describe the demographic and clinical characteristics of the cohort. SETTING: Craniofacial and otolaryngology clinics at 5 study sites. PARTICIPANTS: Infants with CFM and unaffected infants (controls) ages 12 to 24 months were recruited from the same geographical regions and followed to age 36 to 48 months. METHODS: Phenotypic, neurodevelopmental, and facial expression assessments were completed during the first and third waves of data collection (time 1 and time 3, respectively). Medical history data were taken at both of these time points and during an intermediate parent phone interview (time 2). RESULTS: Our cohort includes 108 cases and 84 controls. Most cases and controls identified as white and 55% of cases and 37% of controls identified as Hispanic. Nearly all cases had microtia (95%) and 59% had mandibular hypoplasia. Cases received extensive clinical care in infancy, with 59% receiving care in a craniofacial clinic and 28% experiencing at least one surgery. Study visits were completed at a study site (92%) or at the participant's home (8%). CONCLUSIONS: The CLOCK study represents an effort to overcome the challenges of characterizing the phenotypic and neurodevelopmental outcomes of CFM in a large, demographically and geographically diverse cohort.

Facial Expressiveness in Infants With and Without Craniofacial Microsomia: Preliminary Findings.

OBJECTIVE: To compare facial expressiveness (FE) of infants with and without craniofacial macrosomia (cases and controls, respectively) and to compare phenotypic variation among cases in relation to FE. DESIGN: Positive and negative affect was elicited in response to standardized emotion inductions, video recorded, and manually coded from video using the Facial Action Coding System for Infants and Young Children. SETTING: Five craniofacial centers: Children's Hospital of Los Angeles, Children's Hospital of Philadelphia, Seattle Children's Hospital, University of Illinois-Chicago, and University of North Carolina-Chapel Hill. PARTICIPANTS: Eighty ethnically diverse 12- to 14-month-old infants. MAIN OUTCOME MEASURES: FE was measured on a frame-by-frame basis as the sum of 9 observed facial action units (AUs) representative of positive and negative affect. RESULTS: FE differed between conditions intended to elicit positive and negative affect (95% confidence interval = 0.09-0.66, P = .01). FE failed to differ between cases and controls (ES = -0.16 to -0.02, P = .47 to .92). Among cases, those with and without mandibular hypoplasia showed similar levels of FE (ES = -0.38 to 0.54, P = .10 to .66). CONCLUSIONS: FE varied between positive and negative affect, and cases and controls responded similarly. Null findings for case/control differences may be attributable to a lower than anticipated prevalence of nerve palsy among cases, the selection of AUs, or the use of manual coding. In future research, we will reexamine group differences using an automated, computer vision approach that can cover a broader range of facial movements and their dynamics.

Characterizing facial features in individuals with craniofacial microsomia: A systematic approach for clinical research.

BACKGROUND: Craniofacial microsomia (CFM) is a congenital condition with wide phenotypic variability, including hypoplasia of the mandible and external ear. We assembled a cohort of children with facial features within the CFM spectrum and children without known craniofacial anomalies. We sought to develop a standardized approach to assess and describe the facial characteristics of the study cohort, using multiple sources of information gathered over the course of this longitudinal study and to create case subgroups with shared phenotypic features. METHODS: Participants were enrolled between 1996 and 2002. We classified the facial phenotype from photographs, ratings using a modified version of the Orbital, Ear, Mandible, Nerve, Soft tissue (OMENS) pictorial system, data from medical record abstraction, and health history questionnaires. RESULTS: The participant sample included 142 cases and 290 controls. The average age was 13.5 years (standard deviation, 1.3 years; range, 11.1-17.1 years). Sixty-one percent of cases were male, 74% were white non-Hispanic. Among cases, the most common features were microtia (66%) and mandibular hypoplasia (50%). Case subgroups with meaningful group definitions included: (1) microtia without other CFM-related features (n = 24), (2) microtia with mandibular hypoplasia (n = 46), (3) other combinations of CFM- related facial features (n = 51), and (4) atypical features (n = 21). CONCLUSION: We developed a standardized approach for integrating multiple data sources to phenotype individuals with CFM, and created subgroups based on clinically-meaningful, shared characteristics. We hope that this system can be used to explore associations between phenotype and clinical outcomes of children with CFM and to identify the etiology of CFM. Birth Defects Research (Part A) 106:915-926, 2016.© 2016 Wiley Periodicals, Inc.

Observed child and parent toothbrushing behaviors and child oral health.

BACKGROUND: Parent-led toothbrushing effectively reduces early childhood caries. Research on the strategies that parents use to promote this behavior is, however, lacking. AIM: To examine associations between parent-child toothbrushing interactions and child oral health using a newly developed measure, the Toothbrushing Observation System (TBOS). DESIGN: One hundred children ages 18-60 months and their parents were video-recorded during toothbrushing interactions. Using these recordings, six raters coded parent and child behaviors and the duration of toothbrushing. We examined the reliability of the coding system and associations between observed parent and child behaviors and three indices of oral health: caries, gingival health, and history of dental procedures requiring general anesthesia. RESULTS: Reliabilities were moderate to strong for TBOS child and parent scores. Parent TBOS scores and longer duration of parent-led toothbrushing were associated with fewer decayed, missing or filled tooth surfaces and lower incidence of gingivitis and procedures requiring general anesthesia. Associations between child TBOS scores and dental outcomes were modest, suggesting the relative importance of parent versus child behaviors at this early age. CONCLUSIONS: Parents' child behavior management skills and the duration of parent-led toothbrushing were associated with better child oral health. These findings suggest that parenting skills are an important target for future behavioral oral health interventions.

Hemifacial microsomia: from gestation to childhood.

Hemifacial microsomia (HFM) is a variable, complex malformation involving asymmetric hypoplasia of the face and ear. Little is known about the risk factors for or consequences of HFM. In this study, we describe 3 studies that have been or are currently being conducted to further our understanding of this malformation. The first completed study examined whether HFM risk is related to maternal exposures that may affect blood flow. In that case-control study, interview data from 230 mothers of children in the case group and 678 mothers of children in the control group suggested that maternal use of vasoactive medications in the first trimester, particularly in combination with cigarette smoking, was associated with increased risks of HFM. The second study is currently underway, in which we are evaluating whether HFM risk is related to genetic variation in pathways associated with vasculogenesis and hemostasis, using DNA collected in the first study. The third ongoing study observes children with HFM to identify psychosocial, cognitive, dental, and medical sequelae. When the children from the original case-control study are 6 or 7 years of age, mothers and teachers complete self-administered questionnaires that cover a wide range of psychosocial development domains. Preliminary analyses of 115 case and 314 control children suggest that children with HFM may have worse teacher-reported academic performance and possibly higher levels of internalizing behavior problems than control children. When data on the full study sample are available, further analyses will determine whether the preliminary findings remain and if they vary by HFM phenotype, parenting style, or indicators of social risk.

Dynamics of Face and Head Movement in Infants with and without Craniofacial Microsomia: An Automatic Approach.

BACKGROUND: Craniofacial microsomia (CFM) is a congenital condition associated with malformations of the bone and soft tissue of the face and the facial nerves, all of which have the potential to impair facial expressiveness. We investigated whether CFM-related variation in expressiveness is evident as early as infancy. METHODS: Participants were 113 ethnically diverse 13-month-old infants (n = 63 cases with CFM and n = 50 unaffected matched controls). They were observed in 2 emotion induction tasks designed to elicit positive and negative effects. Facial and head movement was automatically measured using a computer vision-based approach. Expressiveness was quantified as the displacement, velocity, and acceleration of 49 facial landmarks (eg, lip corners) and head pitch and yaw. RESULTS: For both cases and controls, all measures of expressiveness strongly differed between tasks. Case-control differences were limited to infants with microtia plus mandibular hypoplasia and other associated CFM features, which were the most common phenotypes and were characterized by decreased expressiveness relative to control infants. CONCLUSIONS: Infants with microtia plus mandibular hypoplasia and those with other associated CFM phenotypes were less facially expressive than same-aged peers. Both phenotypes were associated with more severe involvement than microtia alone, suggesting that infants with more severe CFM begin to diverge in expressiveness from controls by age 13 months. Further research is needed to both replicate the current findings and elucidate their developmental implications.

Speech, Language, and Communication Skills of Adolescents With Craniofacial Microsomia.

Purpose Youth with craniofacial microsomia (CFM) have anomalies and comorbidities that increase their risk for speech, language, and communication deficits. We examined these outcomes in youth with and without CFM and explored differences as a function of CFM phenotype and hearing status. Method Participants included youth ages 11-17 years with CFM (n = 107) and demographically similar controls (n = 306). We assessed speech intelligibility, articulation, receptive and expressive language, and parent and teacher report measures of communication. Hearing status was also screened at the study visit. Group differences were estimated using linear regression analyses with standardized effect sizes (ES) adjusted for demographic characteristics (adjusted ES) or negative binomial regression. Results Youth with CFM scored lower than unaffected peers on most measures of intelligibility, articulation, expressive language, and parent- and-teacher-rated communication. Differences were most pronounced among participants with CFM who had mandibular hypoplasia plus microtia (adjusted ES = -1.15 to -0.18). Group differences were larger in youth with CFM who failed the hearing screen (adjusted ES = -0.73 to 0.07) than in those who passed the hearing screen (adjusted ES = -0.34 to 0.27). Conclusions Youth with CFM, particularly those with mandibular hypoplasia plus microtia and/or hearing loss, should be closely monitored for speech and language concerns. Further research is needed to identify the specific needs of youth with CFM as well as to document the course of speech and language development in children with CFM.

Evaluation of prenatal diabetes mellitus and other risk factors for craniofacial microsomia.

OBJECTIVES: Craniofacial microsomia (CFM) is a congenital condition that typically involves hypoplasia of the ear and jaw. It is often associated with adverse effects such as hearing loss and sleep-disordered breathing. There is little research on its etiology. METHODS: We conducted a case-control study from maternal interview data collected from mothers of infants with and without CFM. The study included 108 children with and 84 children without CFM. Logistic regression with adjustment for demographic factors was used to evaluate associations between maternal exposures of interest and risk for CFM overall, as well as for different phenotypic sub-groups of children on the CFM spectrum. RESULTS: We found a statistically significant association between diabetes mellitus (DM) and CFM (OR 4.01, 95% CI 1.6-10.5). The association was slightly attenuated after adjustment for BMI. Higher parity was also associated with increased risk for CFM (OR 2.0, 95% CI 1.0-4.0). Vitamin A consumption and/or liver consumption was associated with a 70% lower risk compared with non-users (OR 0.3, 95% 0.1-0.8). Maternal age at the time of pregnancy was not associated with CFM. CONCLUSIONS: These analyses contribute evidence linking maternal DM with an elevated risk of having an infant with CFM, which is consistent with previous research and adds to the body of knowledge about the strength of this association. Further study is warranted to understand the potential mechanisms underlying the effect of DM in the developing embryo.

Automatic Action Unit Detection in Infants Using Convolutional Neural Network.

Action unit detection in infants relative to adults presents unique challenges. Jaw contour is less distinct, facial texture is reduced, and rapid and unusual facial movements are common. To detect facial action units in spontaneous behavior of infants, we propose a multi-label Convolutional Neural Network (CNN). Eighty-six infants were recorded during tasks intended to elicit enjoyment and frustration. Using an extension of FACS for infants (Baby FACS), over 230,000 frames were manually coded for ground truth. To control for chance agreement, inter-observer agreement between Baby-FACS coders was quantified using free-margin kappa. Kappa coefficients ranged from 0.79 to 0.93, which represents high agreement. The multi-label CNN achieved comparable agreement with manual coding. Kappa ranged from 0.69 to 0.93. Importantly, the CNN-based AU detection revealed the same change in findings with respect to infant expressiveness between tasks. While further research is needed, these findings suggest that automatic AU detection in infants is a viable alternative to manual coding of infant facial expression.

Intelligence and Academic Achievement of Adolescents with Craniofacial Microsomia.

BACKGROUND: The authors compared the IQ and academic achievement of adolescents with craniofacial microsomia (cases) and unaffected children (controls). Among cases, the authors analyzed cognitive functioning by facial phenotype. METHODS: The authors administered standardized tests of intelligence, reading, spelling, writing, and mathematics to 142 cases and 316 controls recruited from 26 cities across the United States and Canada. Phenotypic classification was based on integrated data from photographic images, health history, and medical chart reviews. Hearing screens were conducted for all participants. RESULTS: After adjustment for demographics, cases' average scores were lower than those of controls on all measures, but the magnitude of differences was small (standardized effect sizes, -0.01 to -0.3). There was little evidence that hearing status modified case-control group differences (Wald p > 0.05 for all measures). Twenty-five percent of controls and 38 percent of cases were classified as having learning problems (adjusted OR, 1.5; 95 percent CI, 0.9 to 2.4). Comparison of cases with and without learning problems indicated that those with learning problems were more likely to be male, Hispanic, and to come from lower income, bilingual families. Analyses by facial phenotype showed that case-control group differences were largest for cases with both microtia and mandibular hypoplasia (effect sizes, -0.02 to -0.6). CONCLUSIONS: The highest risk of cognitive-academic problems was observed in patients with combined microtia and mandibular hypoplasia. Developmental surveillance of this subgroup is recommended, especially in the context of high socioeconomic risk and bilingual families. Given the early stage of research on craniofacial microsomia and neurodevelopment, replication of these findings is needed. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Sleep outcomes in children with hemifacial microsomia and controls: a follow-up study.

OBJECTIVE: Children with craniofacial anomalies are at high risk for sleep-disordered breathing (SDB), yet its prevalence among children with craniofacial conditions is not known. Children with hemifacial microsomia (HFM) are likely particularly vulnerable to SDB as a result of underdevelopment of the mandible and oropharynx. Nevertheless, most children with HFM are not referred for sleep studies. We hypothesized that sleep outcomes would be worse in children with HFM versus control subjects. METHODS: We conducted a follow-up study among 124 case participants and 349 control subjects who previously participated in a study of HFM risk factors. Parents completed the Pediatric Sleep Questionnaire (PSQ) regarding symptoms of SDB and sleep habits. Regression models were adjusted for region, age, sex, race/ethnicity, and maternal education. RESULTS: Snoring was more commonly reported for children with HFM (29%) than for control subjects (17%). Compared with control subjects, children with HFM more often had symptoms consistent with SDB. On average, case participants' parents reported 1.9 times as many symptoms on the PSQ breathing scale and 1.3 times more symptoms on the PSQ sleepiness scale than did control subjects' parents, with little difference on the PSQ behavior scale. Parents of children with HFM reported 1.4 times more night awakenings than did control subjects' parents. CONCLUSIONS: Children with HFM experienced more snoring and other symptoms of SDB than did control subjects. Pediatricians should be aware of the increased vulnerability for SDB among children with mandibular or external ear underdevelopment or asymmetry and should refer to a sleep specialist as needed.